Imaging modalities to inform the detection and diagnosis of early caries

Abstract

Background

The detection and diagnosis of caries at the earliest opportunity is fundamental to the preservation of tooth tissue and maintenance of oral health. Radiographs have traditionally been used to supplement the conventional visual‐tactile clinical examination. Accurate, timely detection and diagnosis of early signs of disease could afford patients the opportunity of less invasive treatment with less destruction of tooth tissue, reduce the need for treatment with aerosol‐generating procedures, and potentially result in a reduced cost of care to the patient and to healthcare services.

Objectives

To determine the diagnostic accuracy of different dental imaging methods to inform the detection and diagnosis of non‐cavitated enamel only coronal dental caries.

Search methods

Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 31 December 2018); Embase Ovid (1980 to 31 December 2018); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 31 December 2018); and the World Health Organization International Clinical Trials Registry Platform (to 31 December 2018). We studied reference lists as well as published systematic review articles.

Selection criteria

We included diagnostic accuracy study designs that compared a dental imaging method with a reference standard (histology, excavation, enhanced visual examination), studies that evaluated the diagnostic accuracy of single index tests, and studies that directly compared two or more index tests. Studies reporting at both the patient or tooth surface level were included. In vitro and in vivo studies were eligible for inclusion. Studies that explicitly recruited participants with more advanced lesions that were obviously into dentine or frankly cavitated were excluded. We also excluded studies that artificially created carious lesions and those that used an index test during the excavation of dental caries to ascertain the optimum depth of excavation.

Data collection and analysis

Two review authors extracted data independently and in duplicate using a standardised data extraction form and quality assessment based on QUADAS‐2 specific to the clinical context. Estimates of diagnostic accuracy were determined using the bivariate hierarchical method to produce summary points of sensitivity and specificity with 95% confidence regions. Comparative accuracy of different radiograph methods was conducted based on indirect and direct comparisons between methods. Potential sources of heterogeneity were pre‐specified and explored visually and more formally through meta‐regression.

Main results

We included 104 datasets from 77 studies reporting a total of 15,518 tooth sites or surfaces. The most frequently reported imaging methods were analogue radiographs (55 datasets from 51 studies) and digital radiographs (42 datasets from 40 studies) followed by cone beam computed tomography (CBCT) (7 datasets from 7 studies). Only 17 studies were of an in vivo study design, carried out in a clinical setting. No studies were considered to be at low risk of bias across all four domains but 16 studies were judged to have low concern for applicability across all domains. The patient selection domain had the largest number of studies judged to be at high risk of bias (43 studies); the index test, reference standard, and flow and timing domains were judged to be at high risk of bias in 30, 12, and 7 studies respectively.

Studies were synthesised using a hierarchical bivariate method for meta‐analysis. There was substantial variability in the results of the individual studies, with sensitivities that ranged from 0 to 0.96 and specificities from 0 to 1.00. For all imaging methods the estimated summary sensitivity and specificity point was 0.47 (95% confidence interval (CI) 0.40 to 0.53) and 0.88 (95% CI 0.84 to 0.92), respectively. In a cohort of 1000 tooth surfaces with a prevalence of enamel caries of 63%, this would result in 337 tooth surfaces being classified as disease free when enamel caries was truly present (false negatives), and 43 tooth surfaces being classified as diseased in the absence of enamel caries (false positives). Meta‐regression indicated that measures of accuracy differed according to the imaging method (Chi²(4) = 32.44, P < 0.001), with the highest sensitivity observed for CBCT, and the highest specificity observed for analogue radiographs. None of the specified potential sources of heterogeneity were able to explain the variability in results. No studies included restored teeth in their sample or reported the inclusion of sealants.

We rated the certainty of the evidence as low for sensitivity and specificity and downgraded two levels in total for risk of bias due to limitations in the design and conduct of the included studies, indirectness arising from the in vitro studies, and the observed inconsistency of the results.

Authors' conclusions

The design and conduct of studies to determine the diagnostic accuracy of methods to detect and diagnose caries in situ are particularly challenging. Low‐certainty evidence suggests that imaging for the detection or diagnosis of early caries may have poor sensitivity but acceptable specificity, resulting in a relatively high number of false‐negative results with the potential for early disease to progress. If left untreated, the opportunity to provide professional or self‐care practices to arrest or reverse early caries lesions will be missed. The specificity of lesion detection is however relatively high, and one could argue that initiation of non‐invasive management (such as the use of topical fluoride), is probably of low risk.

CBCT showed superior sensitivity to analogue or digital radiographs but has very limited applicability to the general dental practitioner. However, given the high‐radiation dose, and potential for caries‐like artefacts from existing restorations, its use cannot be justified in routine caries detection. Nonetheless, if early incidental carious lesions are detected in CBCT scans taken for other purposes, these should be reported. CBCT has the potential to be used as a reference standard in diagnostic studies of this type.

Despite the robust methodology applied in this comprehensive review, the results should be interpreted with some caution due to shortcomings in the design and execution of many of the included studies. Future research should evaluate the comparative accuracy of different methods, be undertaken in a clinical setting, and focus on minimising bias arising from the use of imperfect reference standards in clinical studies.

Plain language summary

Dental imaging methods for the detection of early tooth decay

Why is it important to improve the detection of dental caries (tooth decay)? Dentists often aim to identify tooth decay that has already advanced to a level which needs a filling. If dentists were able to find tooth decay when it has only affected the outer layer of the tooth (enamel) then it is possible to stop the decay from spreading any further and prevent the need for fillings. It is also important to avoid a false‐positive result, when treatment may be given when caries is absent.

What is the aim of this review?
This Cochrane Review aimed to find out how accurate X‐ray images and other types of dental imaging are for detecting early tooth decay as part of the dental 'check‐up' for children and adults who visit their general dentist. Researchers in Cochrane included 77 studies published between 1986 and 2018 to answer this question.

What was studied in the review?
Three main types of dental imaging were studied in this review: analogue or digital radiographs (X‐rays) and three‐dimensional (3D) imaging (cone beam computed tomography (CBCT)). We studied decay on the occlusal surfaces (biting surfaces of the back teeth), the proximal surfaces (tooth surfaces that are next to each other), and smooth surfaces.

What are the main results of the review?
Researchers in Cochrane included 77 studies with a total of 15,518 tooth sites or surfaces, where typically 63% of tooth sites or surfaces had enamel caries. Some of these studies reported on more than one type of imaging, on both the permanent and primary ('milk') teeth or different tooth surfaces, and this gave us 104 sets of data to use. If these methods were to be used by a dentist for a routine dental examination, out of 1000 tooth sites or surfaces seen:
• the use of these methods will indicate that 336 tooth sites or surfaces will have early tooth decay, and of these, 43 (13%) will have no disease (incorrect diagnosis ‐ false positive);
• of the 664 tooth sites with a result indicating that early tooth decay is absent, 337 (51%) will have early tooth decay (incorrect diagnosis ‐ false negative).
This high proportion of false‐negative results means that early signs of decay will be missed. We found evidence that 3D imaging methods were better than analogue or digital radiographs at identifying early disease but that analogue radiographs were better at identifying disease‐free tooth surfaces.

Please see oralhealth.cochrane.org/imaging-modalities-inform-detection-and-diagnosis-early-caries.

How reliable are the results of the studies in this review?
We only included studies that assessed healthy teeth or those that were thought to have early tooth decay. This is because teeth with deep tooth decay would be easier to identify. However, there were some problems with how the studies were conducted. This may result in these methods appearing more accurate than they are, increasing the number of correct results. We judged the certainty of the evidence to be low due to how the studies selected their participants and the large number of studies that were carried out in a laboratory setting on extracted teeth, and the variation in the results.

Who do the results of this review apply to?
Studies included in the review were carried out in South America, Europe, Asia, and the US. A large number of studies examined extracted teeth, while clinical studies were completed in dental hospitals or general dental practices.

What are the implications of this review?
Low‐certainty evidence suggests that imaging for the detection or diagnosis of early tooth decay may result in a relatively high proportion of false‐negative results, with the potential for early disease to become more advanced. If left untreated, the opportunity to provide professional or self‐care practices to arrest or reverse early tooth decay will be missed.

How up‐to‐date is this review?
The electronic searches retrieved used studies published up to 31 December 2018.

Background

Cochrane Oral Health (COH) has undertaken several systematic reviews of diagnostic test accuracy (DTA) on methods to inform the detection and diagnosis of early dental caries. The suite of systematic reviews forms part of a UK National Institute for Health Research (NIHR) Cochrane Programme Grant Scheme and involved collaboration with the Complex Reviews Support Unit. The reviews follow standard Cochrane DTA methodology and are differentiated according to the index test under evaluation. A generic protocol serves as the basis for the suite of systematic reviews (Macey 2018).

Caries is an entire disease process, which can be stabilised and sometimes reversed if diagnosed and treated early on in the disease process (Fejerskov 2015; Pitts 2009).

Most high‐income countries around the world have evidenced a reduction in caries incidence in children and adolescents, and in some Scandinavian countries preventive programmes have almost eradicated caries, but such activities have not been widely replicated in other locations (Pitts 2017). The 2015 Global Burden of Disease study identified dental caries as the most prevalent, preventable condition worldwide (Feigin 2016; Kassebaum 2015), affecting 60% to 90% of children and the majority of adults of the world's population (Petersen 2005). Furthermore, despite a reduction in caries in some industrialised countries, the global incidence of untreated caries was reported to be 2.4 billion in 2010 (Feigin 2016; Kassebaum 2015; World Health Organization 2017) and continues to increase year on year. In the UK, statistics indicate that the primary reason for childhood (aged 5 to 9 years) hospital admissions is for the extraction of teeth (Public Health England 2014). Longitudinal studies have shown that those who experience caries early in childhood will have an increased risk of severe caries in later life, and that the disease trajectory will be steeper than those without early caries experience (Broadbent 2008; Hall‐Scullin 2017).

Untreated caries can lead to episodes of severe pain and infection, often requiring treatment with antibiotics. Dental anxiety, resulting from the failure to treat caries and the subsequent need for more invasive management, can adversely affect a person's future willingness to visit their dentist, leading to a downward spiral of oral disease (Milsom 2003; Thomson 2000). If left to progress, treatment options are limited to restoration or extraction, requiring repeated visits to a dental surgery or even to a hospital (Featherstone 2004; Fejerskov 2015; Kidd 2004).

The cost of treating caries is high. In the UK alone, the National Health Service (NHS) spends around GBP half a billion every year in treating the disease. Hidden costs also exist, and the related productivity losses are high, estimated at USD 27 billion globally in 2010 (Listl 2015).

Caries detection and diagnosis will most often be undertaken at a routine dental examination, by a general dental practitioner. However, caries detection can additionally be employed in secondary care settings, school, or community screening projects and epidemiology or research studies (Braga 2009; Jones 2017). The traditional method of detecting dental caries in clinical practice is a visual‐tactile examination often with supporting radiographic investigations. This combination of methods is believed to be successful at detecting caries that has progressed into dentine and reached a threshold where a restoration may be necessary (Kidd 2004). The detection of caries earlier in the disease continuum could lead to stabilisation of disease or even possible remineralisation of the tooth surface, thus preventing the patient from entering a lifelong cycle of restoration (Pitts 2017; Splieth 2020). However, early caries is difficult to detect visually, and the use of radiographs provides limited ability to detect small changes in dental enamel (Ismail 2007).

Detection and diagnosis at the initial (non‐cavitated) and moderate levels of caries is fundamental in achieving the promotion of oral health and prevention of oral disease (Fejerskov 2015; Ismail 2013). The prevalence of this early caries state is not often reported in dental epidemiology, with most reports preferring to focus on cavitated/dentinal lesions which may be easier to detect. For example, the most recent UK Adult Dental Health survey reported that 31% of the sample had untreated caries into dentine (Steele 2011; White 2012), and a US study reported levels of cavities at 15.30% in 12‐ to 19‐year olds (Dye 2015). However, one UK survey of children identified "clinical decay experience" which incorporates any enamel breakdown and all other form of caries and reported a prevalence of 63% in 15‐year olds (Vernazza 2016).

A wide variety of management options are available under NHS care at different thresholds of disease, ranging from non‐operative preventive strategies such as improved oral hygiene, a reduced sugar diet, and the application of topical fluoride, to minimally invasive treatments (e.g. sealing the affected surface of the tooth, or 'infiltrating' the demineralised tissue with resins), through to step‐wise caries removal and restoration for extensive lesions.

With advances in technology over the last two decades, alternative methods of detection have become available, such as digital radiography, fluorescence, transillumination, and electrical conductance‐based devices. The adjunctive use of such methods could support the detection and diagnosis of caries at an early stage of decay. In turn, early detection could lead to less invasive treatment with preservation of more tooth tissue, and potentially result in reduced cost of care to the patient and to healthcare services.

Target condition being diagnosed

The term dental caries is used to describe the mechanism which can ultimately lead to the breakdown of the tooth surface which results from an imbalance in the activity within the biofilm (or dental plaque) on the surface of the tooth within the oral cavity (Kidd 2016). This imbalance is due to bacterial breakdown of sugars in the diet which leads to the production of acid and demineralisation of the tooth. Disease progression can be moderated by improved oral hygiene practices together with the influx of fluoride through toothpaste and other available fluoride sources. However, the levels of sugar consumption observed in many populations will often outweigh the benefits of fluoride (Hse 2015). Ultimately, carious lesions may develop and destroy the structure of the tooth.

The most common surfaces for caries to manifest are on the biting (occlusal) surface or the tooth surface which faces an adjacent tooth (approximal surfaces); although smooth surfaces on the flat exterior of teeth adjacent to the tongue, cheeks, and lips can be affected. The severity of disease is defined by the depth of demineralisation of the tooth's structure and whether the lesion is active or arrested. Caries lesions confined to tooth enamel have the potential to be stabilised or even reversed. The progression of carious lesions into the deeper aspects of dentine and pulp of the tooth may be arrested, for example using silver diamine fluoride (Urquhart 2019), but will often require restorative treatment (Bakhshandeh 2018; Kidd 2004).

Variants of the DMFT (decayed, missing, and filled teeth) scale have typically been used in the assessment of disease severity in epidemiological and research studies. Within the D (decayed) component there are four clinically detectable thresholds applied as indicators for diagnosis and treatment planning, often labelled as D₁, D₂, D₃, and D₄ (Anaise 1984) (Additional Table 3). Typically the D₃ threshold, with only lesions extending into dentine classed as carious, has been used to determine the presence of caries (Pitts 1988; Shoaib 2009). These four categories have formed the basis for expanded indices based on visual characteristics such as the International Caries Detection and Assessment System (ICDAS) (Ekstrand 2007; Ismail 2007).

1. Classification of levels of caries levels.

DMFT classification	Definition (Pitts 2001)
0	Sound (non‐diseased)
D1	Non‐cavitated yet clinically detectable enamel lesions with intact surfaces
D2	Cavitated lesion penetrating the enamel or shadowing
D3	Cavity progressing past the enamel‐dentine junction into dentine
D4	Cavity progressing into pulp

DMFT = decayed, missing, and filled teeth.

Treatment of caries

There are many varied treatment options available to the dental clinician, dependent on the thresholds of observed disease. Initial caries can be addressed without surgical intervention using preventive and remineralising approaches such as plaque control, dietary advice, and application of fluoride (Kidd 2016). Minimally invasive treatments for initial caries are available, such as sealing the affected surface of the tooth, or 'infiltrating' the pores of the demineralised tissue with resins. Patients with severe caries may require step‐wise or selective caries removal and restoration of advanced lesions.

A caries management pathway, informed by diagnostic information, can be beneficial in guiding the clinician towards prevention or a treatment plan. One recently developed care pathway is the International Caries Classification and Management System (ICCMS) (Ismail 2015). The system presents three forms of management in the care pathway:

• when dentition is sound the clinician proceeds with preventive strategies to prevent sound surfaces from developing caries;

• non‐invasive treatment of the lesion to arrest the decay process and encourage remineralisation, preventing initial lesions from progressing to cavitated decay; and

• management of more severe caries through excavation and restoration or potentially extraction.

At the core of this care pathway is the ability to accurately detect early caries and optimise preventative strategies through excavation methods that preserve tooth tissue, and restoration or potential extraction in more severe cases. The detection and diagnosis of early caries remains challenging, and the likelihood of undiagnosed early disease is high (Ekstrand 1997). In such instances, the opportunity for preventing initial lesions from progressing to cavitated decay, or even reversing the disease process, is missed, and disease progresses to cavitated decay where restoration is required (Ekstrand 1998).

Index test(s)

The cornerstone of caries detection is a visual and tactile dental examination, and the ability of clinicians to accurately detect disease in this way has been researched for over half a century (Backer Dirks 1951). Tests may be suitable at different stages of the care pathway (Bloemendal 2004; Fyffe 2000), and the use of additional detection tools can support the detection, diagnosis, and monitoring process. The generic protocol (Macey 2018) provides information regarding alternative index methods of caries detection and diagnosis in this suite of Cochrane Reviews.

The use of dental imaging is a standard component of the clinical examination. The bitewing radiograph is a radiograph of the crowns of posterior teeth and their immediate supporting tissues. It is one of the most common dental diagnostic tools and is used to aid the diagnosis of caries or periodontal diseases and also to assess the integrity of existing restorations. Internationally, there is variation in the recall duration, but guidelines from the Faculty of General Dental Practice (UK), for example, suggest that bitewing radiographs are taken six monthly for people at high caries risk, annually for people at moderate caries risk, and at 12‐ to 18‐month intervals in children at low risk and 24‐month intervals for adults (Goodwin 2017).

The two most significant advances in this area within the last 20 years are the replacement of analogue imaging with digital imaging, and the introduction of cone beam computed tomography (CBCT), the latter providing the potential for three‐dimensional (3D) imaging. This review focuses on radiographic caries detection, and incorporates various adjuncts to the typical visual‐tactile examination including analogue and digital radiographs. Due to the high radiation dose, the utility of CBCT may rest in the use of 3D technology as a potential reference standard for in vivo studies.

Digital imaging can be direct or indirect. Direct digital imaging uses charge‐coupled devices to produce an instant chairside radiographic image. Indirect digital imaging using storage phosphor plates is less efficient and requires the additional step of a laser system to transform the X‐ray exposed phosphor into a visible image. However, despite the longer time taken to produce an image, indirect digital imaging has other advantages: it is easier to use, it has lower reject rates, and imaging plates are cheaper to replace than the direct imaging sensors. In addition, indirect digital imaging is more comfortable for patients and consequently, it is the first choice in the dental hospital for general use. Both direct and indirect imaging systems bring benefits over conventional analogue imaging and have replaced the need for the acquisition, storage, and disposal of hazardous chemicals, a dark room, the cost and storage of unexposed film, and the physical filing and security of patient hard‐copy films. Exposure factors can be set to a lower dose, as the post‐processing digital functionality allows for change in contrast, lightening and darkening, size of image, and easy magnification. These features all compensate for a reduction in spatial resolution, in comparison to film. Images can be stored in an electronic patient record, annotated and shared between clinicians. Progression of lesions, including early caries, can be evaluated on dual monitors, or split screens.

CBCT is an inherently digital system, that was designed as a lower dose alternative to the cross‐sectional imaging provided by conventional computed tomography (CT). It does not demonstrate soft tissue detail, but the tissue contrast of air, bone, and dental tissues make it the preferred modality for pre‐implant planning. In unrestored teeth, caries is believed to be well demonstrated, and due to the relief of superimposition provided by cross‐sectional imaging, more accurately shown than in film‐based (analogue) or digital imaging. However, the most significant artefact in CT or CBCT is that of beam hardening created by high attenuation objects such as dental restorations. Opaque streaks mask the adjacent tissues. Thus, CBCT is not recommended to be used to detect recurrent caries. However, the use of CT/CBCT is expensive and carries a higher radiation dose than that of conventional imaging, and is typically reserved for cases where significant clinical uncertainty remains following standard investigations. Despite the clinical benefits, the societal efficacy of CBCT is low and it is therefore not typically recommended as a modality for the routine detection of caries in specialist guideline documents.

Clinical pathway

The process proceeding from a dental patient attending for a routine examination and a caries assessment being undertaken potentially has four intertwined stages: screening, detection (case‐finding), diagnosis, and treatment planning. If the presenting patient is at some risk of disease but seemingly asymptomatic then this can be considered as a screening exercise (Wilson 1968) to detect initial caries in individuals who do not yet have symptoms. Since caries is a dynamic process the pure detection of the disease at a single time point is insufficient to inform the future care of the patient, and additionally the depth and severity of demineralisation, allied to a decision on the caries activity levels, are combined to reach a diagnosis (Ismail 2004; Nyvad 1997). This diagnosis then feeds into a caries management pathway once the patient's history, personal oral care, and risk factors have been considered. A comprehensive methodology has been developed, the International Caries Classification and Management System (ICCMS™), that "helps practitioners to intuitively and systematically collect and analyze personal and clinical data to develop comprehensive patient care plans" that go beyond restorative care (Ismail 2015). A version for use in clinical practice, CariesCare, has been developed by an international team (Martignon 2019).

Figure 1 presents the key elements of the ICCMS process and these reviews could inform the process at 'Keystone 3' where diagnosis is an indefinable component.

1.

Keystones of the International Caries Classification and Management System (ICCMS™).
Copyright© 2018 Ismail AI, Pitts NB, Tellez M. The International Caries Classification and Management System (ICCMS™) an example of a caries management pathway. BMC Oral Health 2015;15(Suppl 1):S9. Reproduced with permission.

Role of index test(s)

In clinical practice, a typical visual or visual‐tactile oral examination would always be undertaken as part of the clinical examination. Supplementing the visual‐tactile examination with radiographic methods (an 'add‐on') at appropriate time points can support the practitioner to resolve uncertainties regarding the presence or absence of early decay, and also to communicate the results of the clinical assessment to the patient. The information from caries detection (including assessment of severity of disease) will be an integral part of diagnosis, which additionally incorporates patient history, risk factors, and treatment planning protocols.

Alternative test(s)

Alternative tests include.

• Fluorescence: the breakdown of enamel alters the characteristics of its structure, when exposed to light‐inducing fluorescence diseased teeth respond differently to sound teeth. There is potential for mineral loss to be quantified and used to aid the diagnostic decision and treatment pathway (Angmar‐Månsson 2001; Matos 2011). Fluorescence is typically divided into laser fluorescence and light fluorescence (i.e. DIAGNOdent and quantitative light‐induced fluorescence (QLF) type devices) (Macey 2020).

• Visual or visual‐tactile examination: identifying caries according to visual appearance, aided by a dental mirror and probe, on clean and dry teeth.

• Fibre‐optic transillumination (FOTI): uses a light emitted from a handheld device which when placed directly onto the tooth illuminates the tooth (Pretty 2006). Any demineralisation should appear as shadows in the tooth due to the disruption of the tooth's structure (Macey 2021).

• Electrical conductance: the demineralisation of the tooth is reported to have an effect on the tooth's electrical conductance. This is measured by placing a probe on the tooth which measures any potentially higher conductivity which occurs due to carious lesions being filled with saliva (Tam 2001).

Rationale

Despite technological advances, the usual method of caries detection is currently based upon information from visual‐tactile clinical examination, with or without radiographs. Bader 2002 completed an extensive review of in vitro studies investigating the accuracy of visual examination, radiographs, fibre‐optic, electrical conductance, and fluorescence in the primary and permanent dentition. This review was limited to studies with a histological reference standard and grouped studies according to index test, disease threshold (enamel or dentinal lesions), and tooth surfaces (occlusal or proximal); a meta‐analysis was not undertaken and the authors graded the quality of the available evidence as low (Bader 2002). This review pre‐dates the development of meta‐analysis methods for DTA reviews recommended in the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy (Deeks 2013). More recently systematic reviews of caries detection have been completed which explore the use of fluorescence (Gimenez 2013), visual inspection (Gimenez 2015), and radiographs (Schwendicke 2015).

In this Cochrane Review we have included contemporary studies irrespective of publication language and status, and built upon existing research to incorporate methodological developments by: expanding the search strategy to capture all relevant evidence, applying appropriate hierarchical analysis (Dinnes 2016), and assessing the body of evidence using GRADE (Schünemann 2020; Schünemann 2020a) to facilitate the production of 'Summary of findings' tables.

Objectives

To establish the accuracy of imaging modalities to detect and inform the diagnosis of non‐cavitated enamel only coronal dental caries in children and adults. The specific research questions addressed in this Cochrane Review were:

• what is the diagnostic test accuracy of different methods for:

  • different purposes (case finding or detection and diagnosis in a clinical setting);

  • in different populations (children: primary/mixed dentition, adolescents: immature permanent dentition, or adults: mature permanent dentition);

  • when a comparison is made between different methods.

Secondary objectives

Where sufficient studies were available we investigated the following areas of potential heterogeneity:

• the use of different reference standards;

• tooth surface (occlusal, proximal, or smooth surface);

• prevalence of dentinal caries;

• participants or teeth with previously applied restorations (secondary caries) and pit and fissure sealants.

Methods

Criteria for considering studies for this review

Types of studies

We included diagnostic test accuracy (DTA) designs that were:

• studies with a single set of inclusion criteria that compared a diagnostic test with a reference standard. We included prospective studies that evaluated the diagnostic accuracy of single index tests, and studies that directly compared two or more index tests;

• randomised controlled trials (RCTs) of the diagnostic test accuracy of one or more index tests in comparison, or versus a no test option;

• 'case‐control' type accuracy studies where different sets of criteria were used to recruit those with or without the target condition, although prone to bias some novel systems may be identifiable through this design alone;

• reporting at either the patient, tooth, or tooth surface level, however only those reporting at the tooth surface level were included in the primary analysis;

• in vivo or in vitro studies.

In vitro studies are those in which teeth have been extracted prior to the initiation of the study, and assessed by the index test and reference standard (usually histology). This scenario is not representative of the typical clinical setting. In vivo studies recruit participants and carry out the index tests and reference standard on teeth in the oral cavity, usually without extraction of the teeth. A histology reference standard would not usually be employed in an vivo study with the exception of teeth indicated for orthodontic, periodontal, or third molar extraction, or for primary teeth close to exfoliation.

Studies were ineligible for inclusion where:

• artificially created carious lesions were used in the assessment;

• studies used and reported the results of two or more tests in combination; or

• an index test was used during the excavation of dental caries to ascertain the optimum depth of excavation.

Participants

Participants asymptomatic for dental caries who may have early, undetected caries at the point of recruitment. Studies that explicitly recruited participants with more advanced lesions that were obviously into dentine or frankly cavitated were excluded. Studies that recruited participants referred to secondary care for restorative treatment were also excluded as there is a likelihood that more advanced caries (into dentine or pulp) would be present and readily detectable without the need for the index tests investigated in this review.

Studies recruiting children, adolescents, and adults were all eligible for inclusion, as this allowed for the analysis of the diagnostic test accuracy of index tests for primary, mixed, and permanent dentition.

Index tests

We included intra and extraoral radiographic caries detection methods completed on intact teeth including:

• analogue (conventional) radiographs;

• digital radiographs; and

• cone beam computed tomography (CBCT).

These index tests could be used as a new adjunct to the typical clinical examination or as a replacement for aspects of the current standard examination (e.g. digital radiography to replace analogue radiograph).

Where studies used multiple examiners the most appropriate examiner to the research question was selected. For example, if the study used dental students, general dental practitioners, and restorative or radiography consultants, then the results of the general dental practitioner were extracted. In the scenario where multiple examiners were stated to have similar skills and experience, then the mean sensitivity and specificity values were extracted if available, otherwise the first set of reported results was extracted.

Target conditions

Coronal caries: initial stage decay, defined as initial or incipient caries or non‐cavitated enamel lesions. Specifically where there is a detectable change in enamel evident which is not thought to have progressed into dentine, on occlusal, approximal surfaces, or smooth surfaces.

Reference standards

A number of different reference standards have been used in primary DTA studies. The only way of achieving a true classification of caries presence and depth is to extract and section the tooth and then perform a histological assessment (Downer 1975; Kidd 2004). This approach is commonly undertaken on previously extracted teeth for in vitro studies but unethical for a healthy population in clinical (in vivo) studies. The only scenario where histology could be appropriate for studies undertaken in a primary or secondary care dental setting would be where a tooth has been identified as requiring extraction (ideally for a non‐caries related reason, such as orthodontic extraction, or third molar extraction), the index test could be applied prior to extraction, and followed by a histological reference standard.

The optimum reference standard was histology. Alternative, acceptable reference standards for this review included operative exploration, for patients with suspected early caries lesions, where a clinician removes caries with a dental burr (drill) in preparation for a restoration and reports the depth of decay for in vivo studies and enhanced visual examination (using a validated classification system) for patients where no initial decay is observed with the index test. Operative exploration was considered to be an acceptable reference standard on the understanding that in vivo studies require a separate reference standard for tooth sites not requiring treatment and verification bias would therefore be introduced. Enhanced visual examination with tooth separation was also considered an acceptable reference standard for approximal surfaces, but is the least preferred of all the options.

Studies that employed a composite reference standard based on the results of information from multiple sources were eligible for inclusion.

Search methods for identification of studies

Electronic searches

Cochrane Oral Health's Information Specialist conducted systematic searches in the following databases without language or publication status restrictions:

• MEDLINE Ovid (1946 to 31 December 2018) (Appendix 1);

• Embase Ovid (1980 to 31 December 2018) (Appendix 2).

Searching other resources

The following trial registries were searched for ongoing studies:

• US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 31 December 2018) (Appendix 3);

• World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch; searched 31 December 2018) (Appendix 4).

We searched the reference lists of included papers and previously published systematic reviews for additional publications not identified in the electronic searches.

Data collection and analysis

Selection of studies

Two review authors independently screened and assessed the results of all searches for inclusion. Any disagreements were resolved through discussion and, where necessary, consultation with another clinical or methodological member of the author team. Studies were excluded if they failed to present the data in the format of a 2 x 2 contingency table, or if they failed to report prevalence at the enamel threshold to enable a 2 x 2 table to be constructed. An adapted PRISMA flowchart was used to report the study selection process (McInnes 2018). Once agreement for inclusion was reached, the studies were categorised according to their index test, the tooth surface, and the dentition of the participants.

Data extraction and management

Two review authors extracted data independently and in duplicate using a piloted data extraction form based on the review inclusion criteria. Disagreements were resolved through discussion by the review team. Where data had been reported for multiple tooth surfaces or dentitions, data were extracted separately for each. We contacted study authors to obtain missing data or characteristics which were not evident in the published paper.

We recorded the following data for each study:

• sample characteristics (age, sex, socioeconomic status, risk factors where stated, number of patients/carious lesions, lesion location);

• setting (country, disease prevalence, type of facility);

• the type of index test(s) used (category, name, conditions (i.e. clean/dried teeth), positivity threshold);

• study information (design, reference standard, case definition, training and calibration of personnel);

• study results (true positive, true negative, false positive, false negative, any equivocal results, withdrawal).

Assessment of methodological quality

We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2) to assess the risk of bias and applicability of the primary diagnostic studies over the four domains of participant selection, index test, reference standard, and flow and timing (Whiting 2011). 'Review specific' descriptions of how the QUADAS‐2 items were contextualised and implemented are detailed in the accompanying checklist (Additional Table 4).

2. QUADAS‐2 tool.

Item	Response (delete as required)
Participant selection – Risk of bias
1) Was a consecutive or random sample of participants or teeth used?	Yes – where teeth or participants were selected consecutively or allocated to the study via a randomisation process No – if study described another method of sampling Unclear – if participant sampling is not described
2) Was a case‐control design avoided?	Yes – if case‐control clearly not used No – if study described as case‐control or describes sampling specific numbers of participants with particular diagnoses Unclear – if not clearly described
3) Did the study avoid inappropriate exclusions (e.g. inclusion of caries into dentine)?	Yes – if the study clearly reports that included participants or teeth were apparently healthy or caries into dentine were excluded No – if lesions were included that showed caries into dentine or exclusions that might affect test accuracy (e.g. teeth with no caries) Unclear – if not clearly reported
Could the selection of participants have introduced bias?
If answers to all of questions 1) and 2) and 3) was 'yes'	Risk is Low
If answers to any of questions 1) and 2) and 3) was 'no'	Risk is High
If answers to any of questions 1) and 2) and 3) was 'unclear'	Risk is Unclear
Participant selection – Concerns regarding applicability
1) Does the study report results for participants or teeth selected by apparent health or suspected early caries (i.e. studies do not recruit patients who are known to have advanced caries into dentine)?	Yes – if a group of participants or teeth has been included which is apparently healthy or indicative of early caries No – if a group of participants or teeth has been included which is suspected of advanced caries Unclear – if insufficient details are provided to determine the spectrum of participants or teeth
2) Did the study report data on a per‐patient rather than on a tooth or surface basis?	Yes – if the analysis was reported on a surface or tooth basis No – if the analysis was reported on a per‐patient basis Unclear ‐ if it is not possible to assess whether data are presented on a per‐patient or per‐tooth basis
3) Did the study avoid an in vitro setting which required the usage of extracted teeth?	Yes – if the participants were recruited prior to tooth extraction No – if previously extracted teeth were used in the analysis Unclear – if it was not possible to assess the source and method of recruiting of included participants/teeth
Is there concern that the included participants or teeth do not match the review question?
If answers to all of questions 1) and 2) and 3) was 'yes'	Risk is Low
If answers to any of questions 1) and 2) and 3) was 'no'	Risk is High
If answers to any of questions 1) and 2) and 3) was 'unclear'	Risk is Unclear
Index test ‐ Risk of bias (to be completed per test evaluated)
1) Was the index test result interpreted without knowledge of the results of the reference standard?	Yes – if the index test described is always conducted and interpreted prior to the reference standard result, or for retrospective studies interpreted without prior knowledge of the reference standard No – if index test described as interpreted in knowledge of reference standard result Unclear – if index test blinding is not described
2) Was the diagnostic threshold at which the test was considered positive pre‐specified?	Yes – if threshold was pre‐specified (i.e. prior to analysing the study results) No – if threshold was not pre‐specified Unclear – if not possible to tell whether or not diagnostic threshold was pre‐specified
For visual and radiograph tests only: 3) For studies reporting the accuracy of multiple diagnostic thresholds for the same index test or multiple index tests, was each threshold or index test interpreted without knowledge of the results of the others?	Yes – if thresholds or index tests were selected prospectively and each was interpreted by a different clinician or interpreter, or if study implements a retrospective (or no) cut‐off (i.e. look for deepest/most severe lesion first) No – if study states reported by same reader Unclear ‐ if no mention of number of readers for each threshold or if pre‐specification of threshold not reported N/A ‐ multiple diagnostic thresholds not reported for the same index test
Could the conduct or interpretation of the index test have introduced bias?
For visual and radiographic studies item 3) to be added
If answers to all of questions 1) and 2) was 'yes'	Risk is Low
If answers to any of questions 1) and 2) was 'no'	Risk is High
If answers to any of questions 1) and 2) was 'unclear'	Risk is Unclear
Index test ‐ Concerns regarding applicability
1) Were thresholds or criteria for diagnosis reported in sufficient detail to allow replication?	Yes – if the criteria for detection or diagnosis of the target disorder were reported in sufficient detail to allow replication No – if the criteria for detection or diagnosis of the target disorder were not reported in sufficient detail to allow replication Unclear ‐ if some but not sufficient information on criteria for diagnosis to allow replication were provided
2) Was the test interpretation carried out by an experienced examiner?	Yes – if the test clearly reported that the test was interpreted by an experienced examiner No – if the test was not interpreted by an experienced examiner Unclear – if the experience of the examiner(s) was not reported in sufficient detail to judge or if examiners described as 'Expert' with no further detail given
Is there concern that the included participants do not match the review question?
If the answer to question 1) and 2) was 'yes'	Concern is Low
If the answer to question 1) and 2) was 'no'	Concern is High
If the answer to question 1) and 2) was 'unclear'	Concern is Unclear
Reference standard ‐ Risk of bias
1) Is the reference standard likely to correctly classify the target condition?	Yes – if all teeth or surfaces underwent a histological or excavation reference standard No – if a final diagnosis for any participant or tooth was reached without the histological or excavation reference standards Unclear – if the method of final diagnosis was not reported
2) Were the reference standard results interpreted without knowledge of the results of the index test?	Yes – if the reference standard examiner was described as blinded to the index test result No – if the reference standard examiner was described as having knowledge of the index test result Unclear – if blinded reference standard interpretation was not clearly reported
Could the reference standard, its conduct, or its interpretation have introduced bias?
If answers to questions 1) and 2) was 'yes'	Risk is Low
If the answer to question 1) and 2) was 'no'	Concern is High
If the answer to question 1) and 2) was 'unclear'	Concern is Unclear
Reference standard ‐ Concerns regarding applicability
1) Does the study use the same definition of disease positive as the prescribed in the review question?	Yes ‐ same definition of disease positive used, or teeth can be disaggregated and regrouped according to review definition No ‐ some teeth cannot be disaggregated Unclear ‐ definition of disease positive not clearly reported
Flow and timing ‐ Risk of bias
1) Was there an appropriate interval between index test and reference standard (in vivo studies less than 3 months, in vitro no limit but must be stored appropriately)?	Yes ‐ if study reports index and reference standard had a suitable interval or storage method No ‐ if study reports greater than 3‐month interval between index and reference standard or inappropriate storage of extracted teeth prior to reference standard Unclear ‐ if study does not report interval or storage methods between index and histological reference standard
2) Did all participants receive the same reference standard?	Yes ‐ if all participants underwent the same reference standard No ‐ if more than 1 reference standard was used Unclear ‐ if not clearly reported
3) Were all participants included in the analysis?	Yes ‐ if all participants were included in the analysis No ‐ if some participants were excluded from the analysis Unclear ‐ if not clearly reported
If answers to questions 1) and 2) and 3) was 'yes'	Risk is Low
If answers to any one of questions 1) or 2) or 3) was 'no'	Risk is High
If answers to any one of questions 1) or 2) or 3) was 'unclear'	Risk is Unclear

N/A = not applicable; QUADAS‐2 = Quality Assessment of Diagnostic Accuracy Studies 2.

A 'Risk of bias' judgement ('high', 'low', or 'unclear') was made for each domain. Generally, where the answers to all signalling questions within a domain were judged as 'yes' (indicating low risk of bias for each question) then the domain was judged to be at low risk of bias. If any signalling question was judged as 'no', indicating a high risk of bias, the domain was scored as high risk of bias. This was followed by a judgement about concerns regarding applicability for the participant selection, index test, and reference standard domains. Results of the assessment of methodological quality are presented graphically.

Participant selection domain (1)

This domain refers to the selection of observations within the primary studies, either patient or tooth sample selection. The selection of patients has a fundamental effect on the estimated accuracy of an index test. The disease stages of sound and enamel should be represented in the sample and children, adolescents, and adults should be represented in the included studies to allow a complete appraisal of a test's potential to correctly classify disease in different populations.

It was acceptable for studies to focus on early enamel lesions for a specific surface (occlusal, approximal, or smooth) or dentition (primary or mixed, immature permanent, permanent). For a low risk of bias judgement, the inclusion of study participants or teeth meeting the eligibility criteria should be consecutive or random as inappropriate exclusions may lead to an over‐ or under‐estimation of the test's ability to detect disease. Additionally, the prevalence and severity of disease reported was used to inform the applicability of this test to a wider population.

Study results should be reported at a tooth or surface level, as opposed to patient level, due to the potential for the index test and reference standard to be reporting on different sites within the same mouth.

Index test domain (2)

The nature of the index tests and the visual presentation of the disease means that it should be feasible to ensure that the index test is conducted prior to the reference standard. The index test should be taken before the extraction of a tooth for any histological analysis or before in situ excavation of a tooth is undertaken. To minimise potential for bias, it is preferable for separate examiners to carry out the index test and reference standard. Where the index test is performed on previously extracted teeth, there should have been efforts made to replicate the setting of the oral cavity. This would often be achieved by placing teeth in a model which replicates the jaw and using either a water bath or plastic/resin block to replicate the effect of the cheek. The threshold of disease positive and negative should have been determined prior to analysis and be reflective of the participants recruited to the study.

Given the subjective nature of the interpretation of test results where thresholds of both initial and more severe assessments of disease are considered within a primary study, there may be potential for information bias. For example, if the assessor judgement is uncertain between caries into enamel or caries into dentine, the interpretation of the first threshold would influence the decision made on the second threshold. This can be mitigated by the use of different examiners to undertake separate assessments for each of the different thresholds.

Reference standard domain (3)

The reference standard assessment should be carried out by a different examiner to the index test, as the subjective interpretation of the reference standard could be compromised by knowledge of the index test results. However, where a tooth had been extracted, sectioned and prepared for histological evaluation it is extremely unlikely that an examiner would be able to recall the specific tooth or participant and the results from the index test results.

Time delays between index test and reference standard should be under three months for in vivo studies.

Ideally, each participating tooth or patient within a study should receive the same reference test. This is possible in the in vitro setting as each selected tooth can have a histological assessment applied. In vitro studies may have applied the same reference standard to all participants. If a study allocated participants or specific teeth to different reference standards then reasons for this allocation should have been clearly reported. All reference standards should have been completed without knowledge of the index test results.

Flow and timing domain (4)

The index test should have been conducted prior to the reference standard. If the reference standard used was tooth separation, radiograph, or excavation then there should be less than three months between index test and reference standard. Caries is a slow growing disease so minimal changes should be experienced within this time frame. All included teeth in the sample should receive both an index test and reference standard. Where studies report some teeth having an index test but not a reference standard, a reason should be clearly reported, such as teeth being broken during sectioning, this would not influence the risk of bias decision.

Statistical analysis and data synthesis

The threshold of interest was between sound teeth and early enamel caries. Estimates of diagnostic accuracy were expressed as sensitivity and specificity with 95% confidence intervals (CI) for each study and for each available data point if there were multiple index tests, dentition, or surfaces reported within a single study. When there were two or more test results reported in the same study, we included them as separate datasets. For both the overall analysis of all included datasets and the analysis of different imaging modalities we also indicated the 95% prediction regions as an indication of the region in which the sensitivity and specificity of a future study could be expected to lie given the results of the studies that have already been observed and included in the analysis.

Hierarchical models were used for data synthesis. The data were extracted for the target condition of early caries (caries into enamel) at the tooth site or surface level. This target condition has been consistently used across the suite of caries detection reviews. Study estimates of sensitivity and specificity were plotted on coupled forest plots and in receiver operating characteristic (ROC) space. Meta‐analysis was conducted which combined the results of studies for each index test using a bivariate model to estimate the summary values of sensitivity and specificity at a common threshold (Chu 2006; Reitsma 2005). Data were input to Review Manager 5 (Review Manager 2020) and displayed in coupled forest plots. Analysis was conducted using xtmelogit and the METANDI package in Stata (Harbord 2009; Stata 14; Takwoingi 2016), and the MetaDTA interactive web‐based tool (Freeman 2019). We used meta‐regression with xtmelogit to compare the accuracy of different imaging methods, study types, and dentitions separately. We added the different imaging methods, study designs (in vivo, in vitro) and dentition as covariates to the bivariate model, assuming equal variances, and used a likelihood ratio test to formally assess the significance of any model comparisons (Macaskill 2010; Takwoingi 2016). Initially we allowed the covariate effects to be assessed on both sensitivity and specificity. If a difference in sensitivity and or specificity was observed then further investigations were undertaken to determine whether the differences could be attributed to sensitivity or specificity, initially by assuming the same sensitivity but allowing specificity to vary and then assuming the same specificity but allowing sensitivity to vary (Takwoingi 2016). Where sufficient studies allowed we intended to explore the assumption of equal variances by performing a likelihood ratio test comparing the model that included the sensitivity and specificity covariates and assumed equal variances for each covariate with the model that included the sensitivity and specificity covariates but allowed for separate variances for the sensitivity and specificity of each covariate. Due to the large number of parameters to be estimated we had problems fitting these models, and consequently reverted to the assumption of equality of variances for the analyses.

Investigations of heterogeneity

The investigation of each potential source of heterogeneity was considered individually. Initially, a visual inspection of the clinical and methodological characteristics of the included studies, coupled forest plots, and summary ROC plots were used to form the basis of the assessment of heterogeneity. Where sufficient numbers of studies allowed, meta‐regression analyses were carried out to explore possible sources of heterogeneity. Formal model comparisons were undertaken as indicated in Statistical analysis and data synthesis.

The sources of heterogeneity (specified a priori) were the different reference standards used, tooth surfaces, prevalence of caries into dentine (classed as low (0% to 14%), medium (15% to 34%), and high prevalence (≥ 35%), as per the other reviews in this series), and studies including previously applied restorations (secondary caries) or pit and fissure sealants. Each potential source of heterogeneity was investigated separately.

Sensitivity analyses

Where a sufficient number of studies investigated the same index test, the following sensitivity analyses were performed to assess the impact on summary estimates of restricting the analyses according to the following criteria:

• low prevalence of dentine caries (i.e. less than 15%);

• low risk of bias for an index test;

• low risk of bias for a reference standard.

Assessment of reporting bias

Methods currently available to assess reporting or publication bias for diagnostic studies may lead to uncertainty and misleading results from funnel plots (Deeks 2005; Leeflang 2008), therefore we did not perform reporting bias tests in the reviews.

Summary of findings and assessment of the certainty of the evidence

We reported our results for our primary objective following GRADE methods (Schünemann 2020; Schünemann 2020a), and using the GRADEPro online tool (www.guidelinedevelopment.org). To enhance readability and understanding, we presented test accuracy results in natural frequencies to indicate numbers of false positives and false negatives. The certainty of the body of evidence was assessed with reference to the overall risk of bias of the included studies, the indirectness of the evidence, the inconsistency of the results, the imprecision of the estimates, and the risk of publication bias. We categorised the certainty of the body of evidence, as high, moderate, low, or very low.

Results

Results of the search

The search identified 5933 results. After an initial screen of titles and abstracts 123 studies were potentially eligible for inclusion. Upon closer inspection of the full papers this number reduced to the 77 studies which are included in this review (Figure 2). An inability to create a 2 x 2 table of the results and studies that stated their intention to include more advanced lesions that were obviously into dentine or frankly cavitated were the main reason for exclusion of studies. Studies and their reasons for exclusion are detailed in the Characteristics of excluded studies table.

2.

Study flow diagram.

We included 77 unique studies providing 104 datasets in the review. Two studies reported results for both the primary and permanent dentition (Ekstrand 2011; Souza 2014), three studies reported approximal and occlusal surfaces (Ariji 1998; Hintze 2003; Simon 2016). The results of multiple index tests were reported for 18 studies: 15 studies (Abesi 2012; Ariji 1998; Ashley 1998; Astvaldsdottir 2012; Costa 2002; Da Silva 2010; Erten 2005; Firestone 1998; Kalathingal 2007; Mitropoulos 2010; Pontual 2010; Ramezani 2016; Rathore 2012; Rockenbach 2008; Svanaes 2000) reported on two index tests, and three studies (Safi 2015; Senel 2010; Tarim 2014) reported on three index tests. Taking into account the multiplicity of dentitions, surfaces, and index tests within each study provided 104 datasets for the analysis, which reported a total of 15,518 tooth sites or surfaces. All included studies were published between 1986 and 2019 inclusive, with 44 (57%) studies conducted from 2010 onwards. Most studies were conducted in Brazil (35%), Germany (8%), Iran (8%), Denmark (6%), Switzerland (6%), Turkey (8%), and the US (6%). 17 (22%) studies were carried out in a clinical setting with an in vivo study design, 60 (78%) were classed as in vitro studies using extracted teeth.

A reference standard of histology was used in 64 studies (83%), excavation in 5 studies (6%), and an enhanced visual reference standard using separation with bands was used in 8 (10%) studies.

Most included studies assessed analogue radiography (51 studies and 55 datasets) followed by digital radiography (40 studies and 42 datasets), and cone beam computed tomography (CBCT) (7 studies and 7 datasets). 15 studies directly compared two tests of which 12 studies directly compared analogue and digital (Abesi 2012; Ariji 1998; Ashley 1998; Astvaldsdottir 2012; Costa 2002; Da Silva 2010; Erten 2005; Firestone 1998; Mitropoulos 2010; Pontual 2010; Rockenbach 2008; Svanaes 2000), and three studies compared digital with CBCT (Kalathingal 2007; Ramezani 2016; Rathore 2012). Three studies directly compared three tests, analogue, digital, and CBCT (Safi 2015; Senel 2010; Tarim 2014). 2 studies (4 datasets) reported on both the primary and permanent dentition, 55 studies (78 datasets) on the permanent dentition only, and 20 studies (22 datasets) on the primary dentition only. Most studies (42 studies and 57 datasets) reported on approximal surfaces only, with 31 studies (39 datasets) reporting results for the occlusal surfaces only. 3 studies (8 datasets) reported results for both the approximal and occlusal surfaces. We categorised the prevalence of caries into dentine, D₃ level, as high (> 35%) in 30 datasets (29%), medium (15% to 34%) in 40 datasets, and low (< 15%) in 22 studies. Insufficient information was available to make a judgement about the prevalence of D₃ caries in 12 datasets.

Our search identified some studies that had evaluated the use of dental imaging for the evaluation of secondary caries, but these were considered ineligible due to the inability to construct 2 x 2 tables for data at the enamel level, or tooth sites with artificially created lesions. No study intentionally included restored teeth in its sample or reported the inclusion of sealants that would allow us to evaluate early caries lesions.

Methodological quality of included studies

The methodological quality of the 77 included studies is summarised across the QUADAS‐2 domains in Figure 3 and the individual study results are shown in Figure 4. No studies were considered to be at low risk of bias across all four domains but 16 studies (21%) were judged to have low concern for applicability across all domains (Behere 2011; Cinar 2013; Freitas 2016; Hintze 2003; Jablonski‐Momeni 2017; Kockanat 2017; Kucukyilmaz 2015; Matos 2011; Mialhe 2003; Mortensen 2018; NCT02657538; Novaes 2009; Novaes 2010; Rocha 2003; Shimada 2014; Souza 2014). The patient selection domain had the highest proportion of high risk of bias studies (43 studies, 56%), we judged the index test, reference standard, and flow and timing domains to have a lower proportion of high risk of bias studies (30, 12, and 7 studies respectively). Applicability of patients and setting was of high concern in 58 (75%) studies, the conduct or interpretation of the index test was of high concern in 22 (29%) studies. There was low concern that the target condition as defined by the reference standard did not match the review question in all 77 studies.

3.

Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study.

4.

Risk of bias and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies.

Seven studies (9%) reported the use of random or consecutive sampling (Jablonski‐Momeni 2017; Matos 2011; Novaes 2009; Novaes 2010; Novaes 2012; Simon 2016; Souza 2018), 44 studies did not, instead choosing to select teeth, and in 26 studies it was not possible to determine how the sample of participants was obtained and an unclear judgement was made. All but one study (Senel 2010) avoided a case‐control study design. 44 studies (57%) avoided inappropriate exclusions, 32 (42%) failed to provide sufficient detail in the description of the sample population to satisfy us that exclusions were appropriate. Applicability of the sample to the population was of high concern for studies which investigated extracted teeth. As the objective of this review was to inform general clinical practice there may be concerns that results from laboratory‐based studies may have limited relevance to a clinical setting, and that extrapolation of results is inappropriate.

Index tests were interpreted without the knowledge of the reference standard in 72 (94%) studies, and with the knowledge of the reference standard in four studies due to: the same assessor applying/conducting the index test and reference standard (Rathore 2012), the index test being interpreted with knowledge of the reference standard (Lazarchik 1995), the index test preceding the reference standard (Matos 2011; Mortensen 2018). A pre‐specified threshold for interpretation of the index test was used in 74 (96%) studies. 22 (29%) studies were found to be of high concern regarding the applicability of the index test, this is due to examiners.

Of the 77 included studies we judged that the choice, conduct, or interpretation of the reference standard in 56 (73%) studies to be at low risk of bias, and 12 (16%) to be at high risk (Braun 2017; Espelid 1986; Jablonski‐Momeni 2012; Matos 2011; Mialhe 2003; Mortensen 2018; NCT02657538; Novaes 2009; Novaes 2010; Novaes 2012; Shimada 2014; Souza 2018). We judged 11 studies (14%) as unlikely to correctly classify our target condition of enamel caries (Bussaneli 2015; Espelid 1986; Jablonski‐Momeni 2017; Matos 2011; Mialhe 2003; Mortensen 2018; Novaes 2009; Novaes 2010; Novaes 2012; Shimada 2014; Souza 2018). This was typically due to the different reference standards used across the studies (e.g. excavation of teeth judged to require restoration, or the use of visual examination with or without separation of the proximal surfaces). It was unclear whether independent examiners assessed the reference standard in 30 (39%) studies however, we were satisfied that the reference standard examiner was independent in 44 (57%) studies. No studies were considered to be at high concern for applicability for this domain.

Sixty‐nine (90%) studies were judged to be at low risk of bias for patient flow. The time interval between administration of the index test and reference standard was unclear in 4 (5%) studies (Freitas 2016; Jablonski‐Momeni 2017; Senel 2010; Shimada 2014). There was variation in the reference standards in three studies due to different reference standards for suspected enamel and dentine caries (enhanced visual examination or excavation). 17 studies (22%) excluded some observations from the analysis (Ariji 1998; Astvaldsdottir 2012; Bahrololoomi 2015; Bussaneli 2015; Ekstrand 2011; Erten 2005; Goel 2009; Hintze 1996; Jablonski‐Momeni 2017; Ko 2015; Kockanat 2017; Matos 2011; Mialhe 2003; Mortensen 2018; Pontual 2010; Shimada 2014; Wenzel 2002). Where studies clearly reported that teeth did not receive the reference standard due to broken teeth during the sectioning procedure then this did not affect the overall bias result for this domain.

Findings

Table 1 reports the results of the 77 included studies which generated 104 datasets. We rated the certainty of the evidence as low and downgraded two levels in total for risk of bias due to limitations in the design and conduct of the included studies, indirectness arising from the in vitro studies, and inconsistency of the results.

Summary of findings 1. Summary of findings table ‐ main results.

Question	What is the diagnostic accuracy of radiographic methods for the detection and diagnosis of early dental caries?
Population	Asymptomatic children or adults presenting for clinical examination (clinical studies); extracted teeth of children or adults (in vitro studies). Clinical or in vitro studies which intentionally included dentine and frank cavitations for assessment were excluded
Index test	Intra and extraoral radiographic caries detection methods completed on intact teeth including: analogue (conventional) radiographs; digital radiographs; and CBCT
Comparator test	Estimates were compared across different radiographic methods. A separate review in this series explores the comparative accuracy of visual classification, fluorescence‐based, radiograph, and transillumination methods of detection and diagnosis
Target condition	Early dental caries (positivity threshold of early caries or beyond)
Reference standard	Histology, excavation, enhanced visual examination
Action	If dental caries can be detected at an early stage then remedial action can be taken to arrest or even reverse decay, and potentially prevent restorations
Diagnostic stage	Aimed at the general dental practitioner assessing regularly attending patients for early stage caries
Quantity of evidence	77 studies providing 104 datasets; 9331 lesions in 15,518 tooth sites or surfaces (median 63% prevalence)
Findings
Sensitivity (95% CI)a		0.47 (0.40 to 0.53)
Specificity (95% CI)a		0.88 (0.84 to 0.92)
Outcome	Numbers applied to a hypothetical cohort of 1000 tooth surfaces Effect per 1000 tooth surfaces assessed (95% CI)		Test accuracy Certainty of the evidence
	Pre‐test probability 28%b	Pre‐test probability 63%b
True positives (tooth surfaces with early enamel caries)	130 (113 to 148)	293 (254 to 332)	Sensitivity ‐ ⊕⊕⊝⊝ LOW Specificity ‐ ⊕⊕⊝⊝ LOW
False negatives (tooth surfaces incorrectly classified as not having early enamel caries)	150 (132 to 167)	337 (298 to 376)
True negatives (tooth surfaces without early enamel caries)	636 (606 to 660)	327 (312 to 339)
False positives (tooth surfaces incorrectly classified as having early enamel caries)	84 (60 to 114)	43 (31 to 58)
Limitations ‐ factors that may decrease the certainty of the evidence
Risk of bias	No studies were considered to be at low risk of bias overall. Across the 4 domains, the patient selection domain had the highest proportion of studies judged at high risk of bias (56%). We judged the index test, reference standard, and flow and timing domains to have a lower proportion of high risk of bias studies (39%, 16%, and 9% respectively). All but 1 study avoided a case‐control design, 57% avoided inappropriate exclusions, whilst only 9% reported the use of random or consecutive sampling. Most included studies were in vitro studies using histology as the reference standard, and likely to correctly classify the target condition, however some studies used an imperfect reference standard such as excavation or a visual examination with or without separation of the approximal surfaces
Applicability of evidence to question	16 studies (21%) were considered to have low concern for applicability across all domains. Applicability of patients and setting was of high concern in 75% of studies, mostly because they investigated extracted teeth and, as the objective of this review was to inform general clinical practice, there may be concerns that such results may have limited relevance to a clinical setting. The conduct or interpretation of the index test was of high concern in 29% of studies. There was low concern that the target condition as defined by the reference standard does not match the review question in all studies
Certainty of the evidence	We rated the certainty of the evidence as low, and downgraded 2 levels in total for risk of bias due to limitations in the design and conduct of the included studies, indirectness arising from the in vitro studies, and inconsistency of the results

^aThere was variability in the results of the individual studies, with sensitivities which ranged from 0 to 0.96 and specificities from 0 to 1.00. The variability in the results was partly explained by different methods evaluated.
^bHypothetical cohorts of 1000 tooth sites or surfaces are presented for numbers estimated at prevalence of 28% and 63% of enamel caries prevalence. Based on consultation with clinical colleagues, the lower prevalence figure addresses concerns that the higher prevalence value is not representative of the general population and is taken from the level of cavitated teeth in the UK Adult Dental Health Survey (Steele 2011). The higher prevalence figure is the median prevalence of early caries reported in the included studies.

CBCT: cone beam computed tomography; CI: confidence interval.

Radiological assessment was used to detect early/enamel caries in 15,518 tooth sites or surfaces, with a median prevalence in the included studies of 61%. The principal findings of this review are reported for all included datasets assessing a range of imaging modalities for detecting enamel caries. There was substantial variability in the accuracy estimates reported in the included studies. Sensitivities ranged from 0 to 0.96 and specificities from 0 to 1.00. The coupled forest plots of sensitivity and specificity for each of the included datasets are illustrated in Figure 5. For all radiographic methods the estimated summary sensitivity and specificity point was 0.47 (95% confidence interval (CI) 0.40 to 0.53) and 0.88 (95% CI 0.84 to 0.92), respectively. Figure 6 presents the summary receiver operating characteristic (SROC) plot with the summary point plotted along with the 95% confidence region and prediction region. The plot clearly illustrates the substantial variability in the estimates from the included studies, and this is further reflected in the wide 95% confidence region that covers very low values of sensitivity and specificity.

5.

Forest plot of 104 datasets from 77 studies.

6.

Summary receiver operating characteristic (SROC) plot of 104 datasets from 77 studies.

It should be noted that as 18 studies included in the meta‐analysis reported the use of more than one method on the same tooth surfaces, or a single method on different dentition or on different tooth surfaces, then there is some non‐independence of data in this analysis.

Different imaging modalities

We explored the comparative effects of the different methods using information from all 104 datasets (Table 2). The most frequently reported methods were analogue radiographs (55 datasets from 51 studies, 8589 tooth sites or surfaces) and digital radiographs (42 datasets from 40 studies, 5936 tooth sites or surfaces). The performance of CBCT was less frequently studied in only seven studies (7 datasets, 993 tooth sites or surfaces). The estimates of specificity were fairly consistent across the test types, but estimates for sensitivity were much lower for analogue and digital than for CBCT (Figure 7). However, the individual accuracy estimates and the 95% prediction regions clearly illustrate the substantial variability in estimates from the included studies and this is reflected in the wide 95% confidence regions for each of the imaging modalities. We explored the effect of different imaging modalities by including a covariate in the bivariate model to assess the effects on sensitivity or specificity or both. Assuming a common variance the summary points for sensitivity and specificity were:

Summary of findings 2. Summary of findings table ‐ comparison of tests.

Question	What is the diagnostic accuracy of radiographic methods for the detection and diagnosis of early dental caries?
Population	Asymptomatic children or adults presenting for clinical examination (clinical studies); extracted teeth of children or adults (in vitro studies). Clinical or in vitro studies which intentionally included dentine and frank cavitations for assessment were excluded
Index test	Intra and extraoral radiographic caries detection methods completed on intact teeth including: analogue (conventional) radiographs; digital radiographs; and CBCT For the purposes of this review the positivity threshold was caries in enamel
Comparator test	Estimates were compared across different radiographic methods. A separate review in this series explores the comparative accuracy of visual classification, fluorescence‐based, radiograph, and transillumination methods of detection and diagnosis
Target condition	Early dental caries (positivity threshold of early caries or beyond)
Reference standard	Histology, excavation, enhanced visual assessment
Action	If dental caries can be detected at an early stage then remedial action can be taken to arrest or even reverse decay, and potentially prevent restorations
Diagnostic stage	Aimed at the general dental practitioner assessing regularly attending patients for early stage caries
Quantity of evidence	77 studies providing 104 datasets; 9331 lesions in 15,518 tooth surfaces (median 63% prevalence)
Findings: analysis comparing analogue radiographs, digital radiographs, CBCT. Consequences in a cohort of 1000 tooth sites or surfaces
Test	Datasets	Tooth surfaces	Sensitivity (95% CI)	Specificity (95% CI)	Pre‐test probability 28%		Pre‐test probability 63%
					Missed	Overdiagnosis	Missed	Overdiagnosis
Analogue radiograph	55	8589	0.44 (0.38 to 0.50)	0.90 (0.86 to 0.93)	157 (139 to 174)	75 (53 to 104)	353 (312 to 392)	38 (27 to 53)
Digital radiograph	42	5936	0.49 (0.42 to 0.56)	0.87 (0.82 to 0.91)	143 (125 to 162)	92 (66 to 128)	323 (280 to 365)	47 (34 to 66)
CBCT	9	1081	0.60 (0.51 to 0.68)	0.81 (0.73 to 0.88)	112 (89 to 137)	134 (89 to 196)	253 (200 to 307)	69 (46 to 101)
The addition of test type to the model resulted in a meaningful difference to the sensitivity and specificity estimates: Chi2 = 32.44, df = 4, P < 0.001
Interpretation: these results should be interpreted taking into account the factors that limit the certainty of the evidence as indicated in Table 1
Using analogue as the reference standard: difference in sensitivity for CBCT = ‐0.16 (‐0.23 to ‐0.09), P < 0.001; digital = ‐0.04 (‐0.09 to ‐0.01), P = 0.018 difference in specificity for CBCT = 0.08 (0.02 to 0.14), P = 0.007; digital = 0.02 (‐0.01 to 0.06), P = 0.107

CBCT: cone beam computed tomography; CI: confidence interval; df: degrees of freedom.

7.

Forest plot of different imaging: analogue, digital, cone beam computed tomography (CBCT).

• 0.44 (95% CI 0.38 to 0.50) and 0.90 (95% CI 0.86 to 0.93) for analogue;

• 0.49 (95% CI 0.42 to 0.56) and 0.87 (95% CI 0.82 to 0.91) for digital;

• 0.60 (95% CI 0.51 to 0.68) and 0.81 (95% CI 0.73 to 0.88) for CBCT.

The summary points for all three methods are displayed in Figure 8. The addition of test type to the model resulted in a meaningful difference to the sensitivity or specificity estimates (Chi²(4) = 32.44, P < 0.001). Further investigation revealed a difference in the summary sensitivity values across the different methods (Chi²(2) = 22.04, P < 0.001), with highest sensitivity observed for CBCT, and a difference in the summary specificity values across the different methods (Chi²(2) = 11.33, P < 0.005), with highest specificity observed for analogue radiographs.

8.

Summary receiver operating characteristic (SROC) plot of different imaging: analogue, digital, cone beam computed tomography (CBCT).

As summary estimates differed according to imaging method, further exploration of the data was undertaken separately for the 97 analogue and digital datasets and for the seven CBCT datasets. This distinction has clinical applicability as CBCT are not routinely indicated for the diagnosis of caries and hence rarely undertaken by the general dental practitioner.

Different purposes (case finding or detection and diagnosis in a clinical setting)

Of the total 104 datasets, 87 datasets were obtained from in vitro studies (11,827 tooth sites or surfaces) and 17 from in vivo studies (3691 tooth sites or surfaces).

Of the 97 non‐CBCT datasets, 80 datasets were obtained from in vitro studies (10,834 tooth sites or surfaces) and 17 from in vivo studies (3691 tooth sites or surfaces) (Figure 9). We explored the effect of studies in a non‐clinical or clinical setting by including a covariate in the bivariate model to assess the effects on sensitivity or specificity or both. Assuming a common variance the summary points for sensitivity and specificity were:

9.

Forest plot of in vivo/in vitro (97 non‐cone beam computed tomography (non‐CBCT) datasets).

• in vitro 0.44 (95% CI 0.37 to 0.50) and 0.89 (95% CI 0.84 to 0.92);

• in vivo 0.56 (95% CI 0.43 to 0.69) and 0.89 (95% CI 0.78 to 0.95).

The summary points are illustrated in Figure 10. The addition of a covariate for in vivo or in vitro evaluation to the model did not result in any meaningful difference to the sensitivity or specificity estimates (Chi²(2) = 3.48, P = 0.18).

10.

Summary receiver operating characteristic (SROC) plot of in vivo/in vitro (97 non‐cone beam computed tomography (non‐CBCT) datasets).

We were unable to establish the effect of the reference standard for the seven CBCT datasets as all were in vitro studies.

Different dentition

Of the total 104 datasets, 80 datasets were obtained from studies evaluating the permanent dentition (11,424 tooth sites or surfaces) and 24 from the primary dentition (4094 tooth sites or surfaces).

Of the 97 non‐CBCT datasets with 14,525 tooth sites or surfaces, 73 datasets (10,431 tooth sites or surfaces) evaluated the permanent dentition and 24 (4094 tooth sites or surfaces) evaluated the primary dentition. A coupled forest plot (Figure 11) illustrates the reported sensitivity and specificity estimates. We explored the effect of the permanent or primary dentition by including a covariate for dentition in the bivariate model to assess the effects on sensitivity or specificity or both. Assuming a common variance the summary points for sensitivity and specificity were:

11.

Forest plot of dentition (97 non‐cone beam computed tomography (non‐CBCT) datasets).

• permanent dentition 0.44 (95% CI 0.37 to 0.51) and 0.90 (95% CI 0.85 to 0.93);

• primary dentition 0.52 (95% CI 0.40 to 0.63) and 0.87 (95% CI 0.77 to 0.93).

The summary points for the different dentitions are displayed in Figure 12. The addition of dentition to the model did not result in any meaningful difference to the sensitivity or specificity estimates (Chi²(2) = 1.34, P = 0.51).

12.

Summary receiver operating characteristic (SROC) plot of dentition (97 non‐cone beam computed tomography (non‐CBCT) datasets).

We were unable to establish the effect of dentition for the seven CBCT datasets as all datasets evaluated the permanent dentition.

Investigations of heterogeneity

Tests for heterogeneity were carried out separately for the analogue and digital datasets and the CBCT dataset. Where possible meta‐regression was used to explore the potential sources of heterogeneity.

Reference standard

Of the total 104 datasets, 91 datasets used a reference standard of histology (12,255 tooth sites or surfaces), eight used a visual reference standard (2450 tooth sites or surfaces), and five used excavation (813 tooth sites or surfaces).

Of the 97 non‐CBCT datasets, 84 used a reference standard of histology (11,262 tooth sites or surfaces), eight used a visual reference standard (2450 tooth sites or surfaces), and five used excavation (813 tooth sites or surfaces) (Figure 13). We explored the effects of excavation, histology, or enhanced visual assessment by including a covariate for reference standard in the bivariate model to assess the effects on sensitivity or specificity or both. Assuming a common variance the summary points for sensitivity and specificity were:

13.

Forest plot of reference standard (97 non‐cone beam computed tomography (non‐CBCT) datasets).

• excavation 0.51 (95% CI 0.27 to 0.74) and 0.96 (95% CI 0.80 to 0.99);

• histology 0.46 (95% CI 0.39 to 0.53) and 0.88 (95% CI 0.83 to 0.92);

• visual 0.47 (95% CI 0.29 to 0.66) and 0.91 (95% CI 0.77 to 0.97).

The summary points for the different reference standards are illustrated in Figure 14. The addition of the reference standard covariate to the model did not result in any meaningful difference to the sensitivity or specificity estimates (Chi²(4) = 2.98, P = 0.56).

14.

Summary receiver operating characteristic (SROC) plot of reference standard (97 non‐cone beam computed tomography (non‐CBCT) datasets).

We were unable to establish the effect of reference standard for the seven CBCT datasets as all used a reference standard of histology.

Tooth surface

Of the total 104 datasets, 61 evaluated proximal surfaces (11,089 tooth sites or surfaces) and 43 evaluated occlusal surfaces (4429 tooth sites or surfaces).

Of the 97 non‐CBCT datasets 58 (10,437) evaluated proximal surfaces and 39 (4088) evaluated occlusal surfaces (Figure 15). We explored the effect of the proximal or occlusal tooth surfaces by including a covariate for dentition in the bivariate model to assess the effects on sensitivity or specificity or both. Assuming a common variance the summary points for sensitivity and specificity were:

15.

Forest plot of tooth surface (97 non‐cone beam computed tomography (non‐CBCT) datasets).

• proximal tooth surfaces 0.47 (95% CI 0.39 to 0.55) and 0.89 (95% CI 0.84 to 0.93);

• occlusal tooth surfaces 0.45 (95% CI 0.35 to 0.54) and 0.88 (95% CI 0.80 to 0.93).

The summary points for the different reference standards are illustrated in Figure 16. The addition of tooth surface to the model did not result in any meaningful difference to the sensitivity or specificity estimates (Chi²(2) = 0.72, P = 0.70).

16.

Summary receiver operating characteristic (SROC) plot of tooth surface (97 non‐cone beam computed tomography (non‐CBCT) datasets).

Of the seven CBCT datasets, three (652 tooth sites or surfaces) evaluated proximal surfaces and four (341 tooth sites or surfaces) evaluated the occlusal surfaces. Assuming a common variance the summary points for sensitivity and specificity were:

• proximal surfaces 0.68 (95% CI 0.42 to 0.86) and 0.90 (95% CI 0.77 to 0.96);

• occlusal surfaces 0.76 (95% CI 0.55 to 0.89) and 0.54 (95% CI 0.31 to 0.75).

The addition of tooth surface to the model did not result in any meaningful difference to the sensitivity or specificity estimates (Chi²(2) = 5.68, P = 0.06).

Prevalence of caries into dentine (D₃)

The datasets were categorised according to the prevalence of caries into dentine with low (0% to 14%), medium (15% to 34%), and high prevalence (≥ 35%), as per the other reviews in this series. Where studies did not report the prevalence of dentine caries an estimation of the level was made wherever possible, based on the description in the paper and the reporting of the enamel prevalence. The prevalence of dentine caries was high in 30 datasets (3400 tooth sites or surfaces), medium in 40 datasets (5565 tooth sites or surfaces), and low in 22 datasets (4775 tooth sites or surfaces). The prevalence of dentine caries was not reported and could not be estimated in the remaining 12 datasets (1778 tooth sites or surfaces).

Of the 97 non‐CBCT datasets, the prevalence of dentine caries was high in 30 datasets (3400 tooth sites or surfaces), medium in 34 datasets (4632 tooth sites or surfaces), and low in 22 datasets (4775 tooth sites or surfaces). The prevalence of dentine caries was not reported and could not be estimated in the remaining 11 datasets (1718 tooth sites or surfaces) (Figure 17). For the purposes of analysis the high and unreported prevalence categories were combined.

17.

Forest plot of caries into dentine prevalence category (97 non‐cone beam computed tomography (non‐CBCT) datasets).

We explored the effect of the prevalence of caries into dentine by including a covariate in the bivariate model to assess the effects on sensitivity or specificity or both. Assuming a common variance the summary points for sensitivity and specificity were:

• low prevalence 0.36 (95% CI 0.25 to 0.47) and 0.91 (95% CI 0.85 to 0.95);

• medium prevalence 0.51 (95% CI 0.40 to 0.61) and 0.87 (95% CI 0.78 to 0.92);

• high or unreported prevalence 0.50 (95% CI 0.40 to 0.59) and 0.89 (95% CI 0.82 to 0.93).

The summary points are illustrated in Figure 18. The addition of D₃ prevalence category to the analysis did not result in a meaningful difference in sensitivity or specificity (Chi²(4) = 4.59, P = 0.33).

18.

Summary receiver operating characteristic (SROC) plot of caries into dentine prevalence category (97 non‐cone beam computed tomography (non‐CBCT) datasets).

We were unable to establish the effect of prevalence of caries into dentine for the seven CBCT datasets as all but one reported a category of medium prevalence.

Sensitivity analysis ‐ direct comparisons of test type

In a change to the protocol we were able to directly compare different tests based on data from studies which had applied more than one index test with a reference standard (within‐person analysis or paired studies). The methods for exploration of covariate effects on the accuracy estimates for the direct comparisons are as stated above.

Direct comparison of analogue and digital

Thirty‐two datasets from 15 studies (2152 tooth sites or surfaces) provided data to enable a direct comparison of analogue and digital methods of caries detection (Abesi 2012; Ariji 1998; Ashley 1998; Astvaldsdottir 2012; Costa 2002; Da Silva 2010; Erten 2005; Firestone 1998; Pontual 2010; Rockenbach 2008; Safi 2015; Senel 2010; Svanaes 2000; Tarim 2014; Mitropoulos 2010). The results from the bivariate analyses (same variance) were as follows (Figure 19):

19.

Summary receiver operating characteristic (SROC) plot of within‐person analysis analogue and digital radiographs.

• all 32 datasets sensitivity 0.44 (95% CI 0.33 to 0.56) and specificity 0.90 (95% CI 0.84 to 0.93), similar to values for the 97 datasets (sensitivity 0.46 (95% CI 0.40 to 0.51) and specificity 0.89 (95% 0.86 to 0.92));

• analogue sensitivity 0.41 (95% CI 0.30 to 0.53) and specificity 0.91 (95% CI 0.86 to 0.94);

• digital sensitivity 0.47 (95% CI 0.36 to 0.59) and specificity 0.88 (95% CI 0.83 to 0.92).

There was evidence of a difference in accuracy estimates according to test type (Chi²(2) = 10.34, P = 0.006). Further investigation revealed that there was a difference in sensitivity (Chi²(2) = 8.06, P = 0.005) but no difference in specificity (Chi²(2) = 2.27, P = 0.13).

Direct comparison of digital and CBCT

Twelve datasets from six studies (925 tooth sites or surfaces) provided data to enable a direct comparison of digital and CBCT methods of caries detection (Kalathingal 2007; Ramezani 2016; Rathore 2012; Safi 2015; Senel 2010; Tarim 2014). The results from the bivariate analyses (same variance) were as follows (Figure 20):

20.

Summary receiver operating characteristic (SROC) plot of within‐person analysis digital radiographs and cone beam computed tomography (CBCT).

• all 12 datasets sensitivity 0.73 (95% CI 0.61 to 0.82) and specificity 0.73 (95% CI 0.39 to 0.92);

• CBCT sensitivity 0.76 (95% CI 0.65 to 0.85) and specificity 0.69 (95% CI 0.35 to 0.90);

• digital sensitivity 0.69 (95% CI 0.57 to 0.80) and specificity 0.76 (95% CI 0.43 to 0.93).

There was evidence of a difference in accuracy estimates according to test type (Chi²(2) = 7.81, P = 0.02). Further investigation revealed that there was a difference in sensitivity (Chi²(2) = 5.09, P = 0.02) but no difference in specificity (Chi²(2) = 2.72, P = 0.10).

Direct comparison of analogue and CBCT

Six datasets from three studies (737 tooth sites or surfaces) provided data to enable a direct comparison of analogue and CBCT methods of caries detection (Safi 2015; Senel 2010; Tarim 2014). We were unable to pool the results and so the results of the individual studies are included in Figure 21.

21.

Summary receiver operating characteristic (SROC) plot of within‐person analysis analogue radiographs and cone beam computed tomography (CBCT).

Sensitivity analysis ‐ quality items

In the protocol we proposed sensitivity analysis was restricting studies to:

• low risk of bias for the index test domain;

• low risk of bias for the reference standard domain; and

• low prevalence of dentine caries (i.e. less than 35%).

The poor overall quality of many of the studies precluded any meaningful sensitivity analysis, as to do so would have meant discarding a substantial number of included studies from the analysis. For example, many studies failed to clearly report the level of cavitation that was present in the eligible population from which participants were recruited for the obtained sample. Descriptions of the inclusion criteria used in many of the studies were vague at best.

For all radiographic methods across the 104 datasets the estimated summary sensitivity and specificity point was 0.47 (95% CI 0.40 to 0.53) and 0.88 (95% CI 0.84 to 0.92) respectively.

Thirty‐five datasets were judged as low risk of bias for the index test (Abesi 2012; Astvaldsdottir 2012; Attrill 2001; Diniz 2010; Diniz 2011; Ekstrand 2011; Erten 2005; Espelid 1986; Firestone 1998; Haak 2003; Haiter‐Neto 2007; Haiter‐Neto 2008; Haiter‐Neto 2009; Huysmans 1997; Isidor 2009; Kalathingal 2007; Kockanat 2017; Kulczyk 2014; Kutcher 2006; Lussi 2006; Mendes 2006; Mialhe 2003; Mitropoulos 2010; Neuhaus 2011; Pakkala 2012; Rockenbach 2008; Schulze 2004; Shimada 2014; Simon 2016; Souza 2014; Souza 2018; Svanaes 2000; Tarim 2014; Xavier 2011; Zangooei 2010). Restricting the analysis to these datasets resulted in estimates of sensitivity and specificity of 0.51 (95% CI 0.43 to 0.61) and 0.88 (95% CI 0.82 to 0.92), a marginal change to the overall estimates.

Twenty‐one datasets were judged as high or unclear risk of bias for the reference standard (Apostolopoulou 2009; Bahrololoomi 2015; Braun 2017; Bussaneli 2015; Bussaneli 2015a; Costa 2002; Espelid 1986; Jablonski‐Momeni 2012; Jablonski‐Momeni 2017; Ko 2015; Matos 2011; Mialhe 2003; Mortensen 2018; NCT02657538; Neuhaus 2011; Novaes 2009; Novaes 2010; Novaes 2012; Shimada 2014; Souza 2018; Tonkaboni 2019). Removing these datasets from the analysis resulted in estimates of sensitivity and specificity of 0.51 (95% CI 0.45 to 0.57) and 0.87 (95% CI 0.83 to 0.90), a marginal change to the overall estimates.

The reported or imputed prevalence of dentine caries was low (< 15%) in 22 datasets (Behere 2011; Haiter‐Neto 2007; Haiter‐Neto 2008; Haiter‐Neto 2009; Hintze 1996; Hintze 2003; Huysmans 1997; Isidor 2009; Ko 2015; Matos 2011; Mialhe 2003; NCT02657538; Novaes 2009; Novaes 2010; Pakkala 2012; Pontual 2010; Rocha 2003; Souza 2014 (two datasets); Souza 2018; Xavier 2011). Restricting the analysis to these 22 datasets, the sensitivity and specificity estimates of these datasets was 0.34 (95% CI 0.25 to 0.45) and 0.91 (95% CI 0.87 to 0.94), a meaningful decrease in the overall sensitivity estimate.

Discussion

Summary of main results

Radiographs have long been used as a vital tool in the detection of dental caries by the general dental practitioner and other dental professionals. This systematic review specifically investigated the ability of analogue and digital radiographs, and cone beam computed tomography (CBCT) to detect early or enamel caries, with the rationale that once caries at this level is observed, then caries management strategies can be deployed to restrict disease progression and limit the need for future restorations. Many potentially eligible studies did not meet the inclusion criteria for this review even though they investigated an index test of interest with an appropriate reference standard, the reason being that they did not report the data in a 2 x 2 table or in a format to enable a 2 x 2 table to be constructed. Despite these limitations, 104 datasets from 77 studies were available for analysis.

We judged the overall certainty of the evidence to be low, and downgraded two levels in total for study limitations, indirectness due to the many in vitro studies included, and inconsistency of the results.

There are inherent difficulties in conducting diagnostic accuracy studies to detect and inform the diagnosis of caries, not least the choice of a suitable reference standard. The preferred reference standard is histology, but this requires a tooth to be extracted and sectioned prior to microscopic investigation. Clearly this is not achievable in a clinical study unless participants have teeth that have previously been indicated for orthodontic or third molar extraction or extraction due to periodontal disease. In younger children or adolescents clinical studies may be undertaken on teeth that are due to exfoliate. Such studies may evoke applicability concerns due to the specific subpopulations studied who may not necessarily be representative of the wider population. There are therefore difficult trade‐offs to be made between patient selection, applicability of study participants, and choice of reference standard which means that designing a study which minimises risk of bias and maximises applicability is particularly difficult. No studies in this review were judged as low risk of bias with low concern for applicability for all domains. Participant selection was the domain where we observed the highest percentage of studies judged to be at high risk of bias. The sample patients, teeth, or surfaces should be recruited consecutively or randomly with clearly reported methods to avoid any suggestion that observations are included that are more complex or straightforward to diagnose which would clearly introduce potential bias to the sample. There were also substantial applicability concerns for this domain, due to many studies being undertaken in an in vitro setting. We judged only 45% of studies as low risk of bias for the index test domain, for reasons including a lack of independence of examiners for multiple assessments within the same study, or in vitro studies that did not create a model for the teeth that attempted to recreate the soft tissues and facial structure. Specifically, the placement/position of teeth should be comparable to teeth within the jaw, and an attempt made to recreate the effect that the cheek would have on the efficacy of a radiograph. This was most often achieved with a water bath or a plastic or resin barrier being placed between the tooth and the radiograph device. Applicability was of high concern for in vitro studies that failed to replicate a clinical context.

We judged most studies to be at low risk of bias for the reference standard. This was due to the volume of in vitro studies which used a reference standard of histology. The studies that used enhanced visual methods as a reference standard were deemed to be at high risk of bias for this domain.

The main findings of this review are reported overall for all technologies and irrespective of study design and patient characteristics.

• For all included studies, the summary estimates were sensitivity of 0.47 (95% confidence interval (CI) 0.40 to 0.53) and specificity 0.88 (95% CI 0.84 to 0.92). There was substantial variability observed in the accuracy estimates of the individual studies, especially for sensitivity. This was reflected in the 95% prediction region which indicated that the estimates of sensitivity and specificity of a future study could fall within a broad range given the results of the studies that have already been observed and included in this analysis. It should be noted that 18 studies included in this meta‐analysis reported the use of more than one method on the same tooth surfaces, or a single method on different dentition or on different tooth surfaces, therefore there is some non‐independence of data in this analysis. In a hypothetical cohort of 1000 tooth sites or surfaces with a prevalence of 63% (the median prevalence observed in studies included in the meta‐analysis), the sensitivity of 0.47 and specificity of 0.88 would result in 337 not being identified as having early caries when actually there was caries present (false negatives) and 43 being identified as having caries when it did not exist (false positives) (Table 1). The consequences of these misclassifications are concerning. The false‐negative results imply that patients who would be considered for treatment would not receive it, and an opportunity to prevent the further development of a carious lesion would be missed. Given the recall period for routine dental examinations and the slow growing nature of the disease the clinician may be reassured that the lesion would be identified at the patient's next appointment. However, guidelines of the Faculty of General Dental Practice (UK) and other professional bodies recommend appropriate time intervals between radiographs, and so subsequent clinical examinations are unlikely to be undertaken with the radiograph adjunct. The false‐positive results for enamel caries would mean that topical fluoride or other minimally invasive treatments would be deployed when not required, the impact on the patient would be low. The prevalence applied to this scenario is potentially inflated due to many of the included studies being based on extracted teeth. Using the median prevalence of caries of any severity from a national epidemiological study (Steele 2011) the median prevalence is lower, 28%. When this lower prevalence is applied to a hypothetical cohort of 1000 tooth sites or surfaces, the revised numbers are 150 being incorrectly classified as healthy and 84 as having caries when the true disease state of the tooth site or surface is sound.

• Differences on summary estimates according to analogue, digital, and CBCT were observed (Chi²(2) = 32.44, P < 0.001). Further investigation revealed a difference in the summary sensitivity values across the different technologies (Chi²(2) = 22.04, P < 0.001) and in specificity values (Chi²(2) = 11.33, P < 0.005), with the highest sensitivity observed for CBCT and the highest specificity observed for analogue radiographs (Table 2). As with the overall analysis, there were concerns regarding the broad range of the 95% prediction interval and expectations for future studies with all three modalities. All subsequent analyses were undertaken separately for the analogue and digital devices and for the CBCT modalities. CBCT was included in the analysis to provide a complete overview of all relevant technologies, however this method would not typically be undertaken for the detection of enamel caries due to the high doses of radiation that patients would be exposed to.

• There was no meaningful difference in observed accuracy estimates obtained from the in vivo or in vitro settings (Chi²(2) = 3.48, P = 0.18). One reason for the variability in any observed sensitivity estimates could be whether the study was undertaken in a laboratory setting and evaluated extracted teeth (in vitro) or whether it was a clinical based study on teeth in situ (in vivo). In vivo studies are closest to evaluating the use of different technologies for diagnosis on a presenting patient. In vitro studies more closely mimic case finding or case detection. There was no meaningful difference observed in the investigations of study setting. Specificity results were virtually identical but the sensitivity was slightly higher in the in vivo studies (0.56 (95% CI 0.43 to 0.69)) than for the in vitro studies (0.44 (95% CI 0.37 to 0.50)). This may have been a result of the imperfect reference standards used in the in vivo setting which may have failed to identify the same cases of caries as the radiograph and therefore create an inflated sensitivity. It would be reasonable to assume that better quality radiographic standards can be expected in an in vivo research project than in everyday practice, and therefore the in vivo results reported in this review can be considered an optimum level of performance, and, in reality, diagnostic accuracy may be expected to be poorer and more variable.

• Summary values of sensitivity and specificity values were according to dentition, tooth surface, reference standard, and prevalence of dentinal caries in the study sample.

  • As the depth of enamel is thinner and as caries progresses more rapidly in the primary dentition, leading to more severe decay with greater expedience, we considered it important to explore potential differences in results according to the primary and permanent dentition. The need for prevention in permanent teeth is even more important as individuals aim to retain permanent teeth across their lifespan. Most studies evaluated permanent teeth, but there were no meaningful differences observed in the summary estimates of the primary or permanent dentition.

  • The tooth surface result is interesting as the radiograph is particularly valuable as a tool for detecting caries on proximal surfaces which are difficult to access. These surfaces cannot be easily viewed when performing a visual assessment and other types of technologies or devices (investigated in this series of Cochrane Reviews) are difficult to apply to proximal surfaces, so radiographs are considered to be of particular benefit to the clinician for this aspect of the clinical examination. On the occlusal surface the invaginated anatomy of the fissure means that early caries occurs on the walls of the fissure in its depth. In this area an X‐ray beam has to potentially travel through much more sound enamel and dentine buccal and lingual to the lesion before it hits the radiographic film or sensor, which would attenuate the X‐ray beam, making early detection radiographically very difficult. On the proximal surface however, as the tooth tissues curve toward the contact with the adjacent tooth, this sound tooth tissue buccal and lingual to an early lesion is much less, with much less attenuation of the X‐ray beam occurring making it potentially easier to detect proximal lesions radiographically. In this meta‐analysis the proportion of studies with a prevalence of dentine lesions > 15% was far higher in the studies evaluating the occlusal surfaces than those evaluating the proximal surfaces, making the classification task easier on the occlusal surfaces than may ordinarily be observed in clinical practice. The performance on occlusal surfaces may therefore, in part, be an artefact of a higher proportion of more severe decay in the study samples.

  • The results suggest that there is no difference between the ability of radiographs to detect caries on the occlusal or proximal surfaces with analogue or digital radiographs, or with CBCT. For CBCT however, the specificity for the occlusal surfaces 0.54 (95% CI 0.31 to 0.75) was markedly lower than for the proximal surfaces 0.90 (95% CI 0.77 to 0.96).

  • No differences were observed according to reference standard or prevalence of dentinal caries in the study sample.

Strengths and weaknesses of the review

The strengths of this review are the comprehensive literature search and rigorous application of appropriate methodology which ensured that all screening, inclusion decisions, and data extraction were performed in duplicate and with clinical and methodological expertise. A clear and reproducible method was used for the application of methodological quality decisions and data analysis. The relatively large volume of data enabled meta‐analysis using hierarchical bivariate methods which have been shown to be mathematically superior to simpler methods commonly used in systematic reviews of diagnostic test accuracy in oral health (Dinnes 2016). We elected to initially consider all studies irrespective of study design and patient characteristics, and to formally investigate covariates of interest through meta‐analysis, in contrast to the qualitative approach taken in other systematic reviews.

This systematic review builds upon existing literature. Bader 2002 completed a systematic review of radiograph devices (alongside visual, fluorescence, and other methods), but limited the inclusion criteria to studies where the index test was verified by a histological reference standard. Only two included studies reported on the assessment of enamel lesions. This Cochrane Review is a significant update which broadens the available reference standards to include visual and excavation in addition to histology, and substantially increases the number of included studies that have reported data at the enamel threshold. A later review by Gomez 2013 also investigated a variety of methods for caries detection, limited to non‐cavitated carious lesions. Study quality was assessed using a caries‐specific rating scale but no meta‐analysis was carried out. Potential sources of heterogeneity were explored but no formal analysis was undertaken.

Of most relevance to this review, Schwendicke 2015 presented a comprehensive review of radiograph techniques at three levels of dentine lesions, cavitated lesions, and any lesions. This review included 117 studies with a search date current up to September 2014. Our review updates this review but focuses on the enamel threshold of disease so although reporting a lower number of studies, the number of included studies reporting data at the enamel threshold has increased. In contrast to the Schwendicke 2015 review, the use of the bivariate methodology for the estimation of summary points and formal investigation of potential sources of heterogeneity through meta‐regressions is of substantial benefit, along with assessment of the certainty of the evidence. However, our final conclusion is similar, that digital and analogue radiographs show limited sensitivity for detecting early caries, in contrast to CBCT.

One weaknesses of this review is the large volume of ineligible studies due to insufficient information to extract or construct a 2 x 2 table for estimates of sensitivity and specificity. In the fluorescence review of this series (Macey 2020) we observed that 55 out of the 133 studies that were otherwise eligible for inclusion in the review did not permit the construction of a 2 x 2 table. There is no reason to expect that the proportion of potentially eligible studies for this review would be different. Many potentially eligible studies did not present the numbers of true positives, true negative, false positives, and false negatives at the enamel threshold. Instead they reported sensitivity, specificity, and area under the curve as their primary results, and often did not include prevalence of caries at the enamel threshold.

A significant source of bias particularly evident in the in vitro studies was that the participants or teeth were selected, with the potential that teeth were selected where the spectrum of disease was not representative and where classification of disease was artificially facilitated leading to inflated accuracy estimates.

The inclusion criteria of the review were selected to ensure that the focus was placed on the early detection of caries or caries limited to enamel. With the best of intentions studies could easily attempt to recruit sound or non‐cavitated teeth but when investigated with a thorough/complete reference standard, it become apparent that some tooth sites or surfaces, when viewed during participant selection, actually harboured dentinal caries. The concern of the review team was that if studies intentionally recruited dentinal lesions, then there would be a simplification of the detection and diagnostic decision as more advanced lesions obviously into dentine or frankly cavitated are generally easier to detect than earlier lesions which are limited to enamel. A further complication arose where some studies were poorly reported or lacked clarity on the selection criteria that they imposed on their sample. We took the position that unless the authors clearly stated that frank or dentinal cavities were intentionally included, then we were unable to exclude the study from the review. Due to incomplete reporting in the primary studies this decision has been difficult to apply consistently and a consequence is that some well‐reported studies have been excluded due to their clarity of reporting, whereas studies which may have intentionally included dentinal lesions but failed to explicitly report this fact have been included. To our best efforts this has been accounted for in the QUADAS‐2 assessment. We accept that this may leave the review open to criticism, however we would reiterate that this review intended to synthesise the evidence on early lesions and the inclusion of frank or dentinal cavities was not applicable to this question. The analysis by prevalence of caries at the dentinal level allowed us to investigate the effect of the inclusion of tooth sites or surfaces with dentinal decay. This analysis indicated that there was no meaningful difference in the accuracy estimates of studies with high or low prevalence of dentinal caries, and we can therefore conclude that the results of this review are robust, and the results confirm this to be the case.

An area of concern arose where the reference standard was histology or enhanced visual assessment and it was not clearly reported whether the same examiners conducted the index test and reference standard assessments. This issue was logged in the characteristics tables but our interpretation was that this would not affect the conduct or interpretation of the histological reference standard as it was hard to see how an examiner would remember the specific detail of a radiograph and recall it during the examination of a sectioned tooth. It is also important to note that for an enhanced visual assessment to be considered acceptable as a reference standard, then separators needed to be applied to allow the approximal surface to be clearly viewed.

Applicability of findings to the review question

Clearly there are concerns regarding the clinical applicability of the findings of this review. This is highlighted by the fact that the meta‐analysis is dominated by in vitro studies which are not conducted in a clinical setting which is representative of general dental practice. There is also concern that some of the in vitro studies also failed to make a reasonable attempt to replicate the conditions found in the oral cavity. However, the formal analysis concluded that there was no observed differences in the summary estimates from in vivo or in vitro studies.

We did not include any studies that evaluated caries at the enamel threshold adjacent to existing restorations (none were found in the search looking at enamel caries), and it is very unlikely that caries adjacent to existing restorations within the same tooth would be restricted to enamel.

Authors' conclusions

Implications for practice.

It was our intention that the results of this review be directly applicable to the general dental practitioner. Ideally, clinicians would have all diagnostic tests or devices available to them and use the most appropriate one according to clinical need. This is not achievable for most dental practices with finite resources and an existing infrastructure which would almost always feature a radiographic device. There is uncertainty as to whether the accuracy of these radiographs, specifically the sensitivity, is sufficient to detect and inform the diagnosis of early caries for clinicians. This finding does not detract from the benefits of using radiographs as an adjunct to the conventional visual‐tactile examination for detecting and diagnosing severe levels of disease. However, if clinicians are attempting to prescribe preventative measures for patients on a needs‐based approach then the radiograph will not be a useful part of this decision‐making process.

Although the evidence is more limited, cone beam computed tomography (CBCT) shows considerably more promise in being able to detect enamel level lesions but has limited applicability to a typical clinical setting. The high levels of radiation linked to CBCT would make it difficult to justify this as a course of action to detect early lesions. Although any lesion detected as an incidental finding on a CBCT taken for another purpose should be reported. Additionally, the issue of beam‐hardening artefacts from restorations is a constant problem, as is patient movement during scanning. CBCT equipment varies widely in image quality, for example in voxel dimensions amongst other parameters, and the results of this review from a relatively small number of studies using specific machines means that the results are not as easily transferable as those of analogue and digital radiography. The utility of three‐dimensional (3D) technology (CBCT) may lie as a potential reference standard for in vivo studies.

Implications for research.

This review indicates that there is limited evidence to suggest that analogue or digital radiographs are sufficiently sensitive to detect early enamel caries, but that performance for specificity is better. We do not see the need for this to be researched further. However, there are important shortcomings across the included studies, and within‐person comparative studies carried out in a clinical setting that focus on minimising bias arising from the use of imperfect reference standards in clinical studies would be useful additions to the evidence base. It is of vital importance that any future research studies report the data in a clear concise method and follow the STARD checklist (Bossuyt 2003; Bossuyt 2015), ideally with a cross‐tabulation of the index test and reference standard with a minimum requirement of three categories of each which could be titled: sound/caries free, early/enamel caries, and advanced/dentine caries. Many studies subdivided these latter two categories into inner and outer enamel/dentine caries, this allowed us to extract true‐positive, false‐positive, false‐negative, and true‐positive results to a greater level of severity of disease.

There is potential for automating disease classification in dental imaging through the use of artificial intelligence (e.g. Garcia Cantu 2020), and this area is worthy of further research.

What's new

Date	Event	Description
16 December 2021	Amended	Minor edit to external source of support

History

Review first published: Issue 3, 2021

Appendices

Appendix 1. MEDLINE Ovid search strategy

1. Dental caries/
2. (caries or carious).mp.
3. (teeth adj5 (cavit$ or decay$ or lesion$ or deminerali$ or reminerali$ or fissure$)).mp.
4. (tooth adj5 (cavit$ or decay$ or lesion$ or deminerali$ or reminerali$ or fissure$)).mp.
5. (dental adj5 (cavit$ or decay$ or lesion$ or deminerali$ or reminerali$ or fissure$)).mp.
6. (enamel adj5 (cavit$ or decay$ or lesion$ or deminerali$ or reminerali$ or fissure$)).mp.
7. (dentin$ adj5 (cavit$ or decay$ or lesion$ or deminerali$ or reminerali$ or fissure$)).mp.
8. or/1‐7
9. exp radiography, dental/
10. ((dental or oral or teeth or tooth or mouth or caries) adj5 (x‐ray$ or xray$ or radiograph$ or radiology or bitewing$ or tomograph$)).mp.
11. "bitewing radiograph$".mp.
12. ((diagnos$ or detect$) and caries and radiograph$).mp.
13. 9 or 10 or 11 or 12
14. 8 and 13

Appendix 2. Embase Ovid search strategy

1. Dental caries/
2. (caries or carious).mp.
3. (teeth adj5 (cavit$ or decay$ or lesion$ or deminerali$ or reminerali$ or fissure$)).mp.
4. (tooth adj5 (cavit$ or decay$ or lesion$ or deminerali$ or reminerali$ or fissure$)).mp.
5. (dental adj5 (cavit$ or decay$ or lesion$ or deminerali$ or reminerali$ or fissure$)).mp.
6. (enamel adj5 (cavit$ or decay$ or lesion$ or deminerali$ or reminerali$ or fissure$)).mp.
7. (dentin$ adj5 (cavit$ or decay$ or lesion$ or deminerali$ or reminerali$ or fissure$)).mp.
8. or/1‐7
9. exp Dental radiology/
10. ((dental or oral or teeth or tooth or mouth or caries) adj5 (x‐ray$ or xray$ or radiograph$ or radiology or bitewing$ or tomograph$)).mp.
11. "bitewing radiograph$".mp.
12. ((diagnos$ or detect$) and caries and radiograph$).mp.
13. 9 or 10 or 11 or 12
14. 8 and 13

Appendix 3. US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) search strategy

Expert Search interface: ( caries OR tooth decay OR dental decay OR cavities OR carious ) AND ( radiograph OR x‐ray OR xray OR tomography OR bitewing ) AND ( diagnosis OR diagnose OR detect OR detection )

Appendix 4. World Health Organization International Clinical Trials Registry Platform search strategy

caries AND radiograph OR caries AND x‐ray OR caries AND xray OR caries AND tomography OR caries AND bitewing

Data

Presented below are all the data for all of the tests entered into the review.

Tests. Data tables by test.

Test	No. of studies	No. of participants
1 All	78	15518
2 Analogue	52	8589
3 Digital	41	5936
4 CBCT	7	993
5 All non‐CBCT	77	14525

1. Test.

All

2. Test.

Analogue

3. Test.

Digital

4. Test.

CBCT

5. Test.

All non‐CBCT

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Abesi 2012.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: sound, early/enamel lesions, no cavitation, no restorations on approximal surfaces, no extensive buccal or lingual caries, no dental wear, no presence of fractures or anomalies and cavity in approximal surfaces Teeth: posterior, permanent Sealants: unclear Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Iran Setting: extracted teeth Number of participants/teeth/sites: 48 teeth/72 sites Prevalence: enamel 0.36, dentine 0.18
Index tests	Category of test: conventional and digital radiography Model set‐up: teeth embedded in blocks of Paris plaster in an anatomical position to establish approximal surfaces in contact. Each block consisted of 4 teeth, in which 2 interdental contacts including 6 interdental surfaces existed; 2 non‐contacted surfaces were not considered in the study. A 24 mm plexiglass plate was placed between the tube extension and the teeth to simulate soft tissue Sequence of test(s): 1) conventional, 2) 1 of 2 digital methods in a random order, 3) histology. Panel of observers appear to have been blinded by coding of images, randomly ordered digital images and 2‐week separation of viewing sessions Examiner training and calibration: 4 oral and maxillofacial radiologists acted as observers, all of whom had at least 5 years experience in caries diagnosis on digital images and film. No calibration ‐ diagnosis was a consensual decision Threshold applied: R0 = sound; R1 = radiolucency restricted to the enamel; R2 = radiolucency reaching the dentino‐enamel junction and the outer half of the dentine; R3 = radiolucency into the inner half of the dentine Device specifics: conventional and digital images of the teeth were acquired using 3 intraoral modalities: E‐speed film, CCD: 19‐38 microns pixel size and 13‐26 line‐pairs/mm (lp/mm) resolution and PSP receptor: 85‐167 micron pixel size and 6‐8 lp/mm resolution. Standardised conditions were used: DC intraoral X‐ray unit, at 60 kVp, 8 mA and 0.2 s for E‐speed, 10 mm tooth‐receptor distance, 30 cm target‐to‐receptor distance, rectangular collimation, paralleling technique. A 24 mm plexiglass plate was placed between the tube extension and the teeth to simulate soft tissue. A stabilizer device was used to maintain the projection geometry. Then all the films were simultaneously developed by an automatic processor using Tetenal developer and fixer solution, according to the manufacturer’s instructions. For digital exposure, it should be noted that all adjustment conditions for teeth and radiography apparatus were similar to before, the only difference was in the exposure time which was reduced to approximately 0.08 s
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: assessment was by an oral and maxillofacial pathologist Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: "serially sectioned... into 400 μm thick sections in the mesio‐distal direction so as to pass through the height of contour" Target condition: sound surfaces (absence of caries = R0) versus surfaces with lesions (presence of caries = R1, R2, R3)
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper; used conventional radiography data and the data for the charge‐coupled device digital radiography
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Apostolopoulou 2009.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions Teeth: primary molars Sealants: excluded Restorations: excluded Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Greece Setting: extracted teeth Number of participants/teeth/sites: 24 teeth/111 sites Prevalence: enamel 0.98, dentine 0.22
Index tests	Category of test: conventional radiograph Model set‐up: not reported Sequence of test(s): index tests (visual, radiograph and DIAGNOdent) performed prior to reference standard Examiner training and calibration: not reported: "One examiner performed all examination methods" Threshold applied: not clearly stated for radiographs, but enamel and dentine levels are stated in the results Device specifics: "..using the Endo Ray film holder and were developed in a Durr X‐Ray Film Processor – XR 04"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: sound, enamel, dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Unclear
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Ariji 1998.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: not reported (only states 'unrestored') Teeth: premolars and molars Sealants: not reported Surface: occlusal and approximal (reported separately Ariji 1998a)
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Japan Setting: extracted teeth Number of participants/teeth/sites: 150 teeth (118 in analyses)/118 occlusal sites and 236 approximal sites Prevalence: enamel = occlusal 0.83 and approximal 0.77; dentine = occlusal 0.38 and approximal 0.41
Index tests	Category of test: conventional and digital radiography (Pana Digital system using CCD) Model set‐up: pairs of teeth mounted in plaster blocks. To simulate the parallel or bitewing technique, the X‐ray beam was projected perpendicular to the tooth and the CCD sensor or film. A 10 mm thick acrylic plate was used to mimic soft tissue Sequence of test(s): unclear what order they were assessed but reference standard was last. Unclear if examiners would have been influenced by doing multiple assessments on each surface or if it was actually blinded Examiner training and calibration: 6 radiologists; calibration not mentioned Threshold applied: 0 = sound surface, 1 = enamel caries less than halfway through enamel, 2 = enamel caries penetrating at least halfway through enamel, but not involving dentino‐enamel junction, 3 = caries of enamel and dentine definitely at or through the dentino‐enamel junction extending less than halfway to the pulp cavity, 4 = caries of enamel and dentine penetrating more than halfway through the dentine toward the pulp cavity Device specifics: the X‐ray generator used was an MTX‐90. It was set at 60 kVp and 10 mA, with a total beam filtration of 1.5 mm aluminium equivalent. The beam was collimated to a 6 cm diameter with a short 15 cm cone. The distance between the focus and the sensor or film was set at 40 cm. For the evaluation of intraoral X‐ray film, Ektaspeed Plus was used. The films were processed in a Pantomat P10 using Kodak Readymatic chemistry. Exposure time was set at 0.3 s for the Pana Digital sensor and 0.6 s for the Ektaspeed Plus film so as to provide adequate image density according to our preliminary test: i.e., the densities from 1.0 for the light zone (enamel) to 3.5 for the dark zone (background or bone marrow) and the corresponding pixel levels from 64 to 237 in the 256 gray level
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: not reported Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: serially cut into sections 500‐700 µm thick in a mesio‐distal plane oriented parallel to the long axis of the tooth crown Target condition: 0 = sound surface, 1 = enamel caries less than halfway through enamel, 2 = enamel caries penetrating at least halfway through enamel, but not involving dentino‐enamel junction, 3 = caries of enamel and dentine definitely at or through the dentino‐enamel junction extending less than halfway to the pulp cavity, 4 = caries of enamel and dentine penetrating more than halfway through the dentine toward the pulp cavity
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 32 (32 of 150 teeth excluded due to lack of agreement between the reference standard assessors = high number, and could potentially be biasing the results if one examiner is generally more correct than the other)
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		High risk

Ariji 1998a.

Study characteristics
Patient Sampling	Identical to Ariji 1998, added to allow analysis of approximal surfaces
Patient characteristics and setting
Index tests
Target condition and reference standard(s)
Flow and timing
Comparative
Notes

Ashley 1998.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions Teeth: permanent premolars and molars Sealants: excluded Restorations: excluded Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: UK Setting: extracted teeth Number of participants/teeth/sites: 103 teeth/103 sites Prevalence: enamel 0.60, dentine 0.36
Index tests	Category of test: conventional and digital radiograph Model set‐up: "A jig was constructed to hold the occlusal plane of each tooth parallel to the X‐ray beam and perpendicular to the film or imaging plate. Each tooth was held in the jig by its own individual removable mould to allow switching between a film or imaging plate without altering the relationship of the tooth to the X‐ray beam, the film or imaging plate. The jig incorporated a 1 cm thickness of Perspex placed above the tooth to simulate the buccal soft tissues" Sequence of test(s): index tests (conventional and digital radiograph) performed prior to reference standard Examiner training and calibration: 1 examiner Threshold applied: sound, enamel, dentine Device specifics: "standard radiographic film (Kodak Ektaspeed, Kodak Limited, Herts, UK) and direct digital imaging (Orion Corporation Soredex‐Finndent, Finland)"; "The X‐ray machine (Gendex GX 1000, Gendex Corporation, Illinois, USA) was set at 65 kVp and 10 mA, with a focal point to film/imaging plate distance of 30 cm. Exposure times were 0.22 s for the conventional film and 0.08 s for the Digora system. Radiographs were viewed under constant conditions at x 1.5 magnification. Digital images were viewed on a 21‐inch monitor (Dell Computer Corporation, Austin, TX, USA) using the Digora software"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: sound, enamel, dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Astvaldsdottir 2012.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions: "The approximal surfaces of the selected teeth presented a range of conditions, from sound to non‐cavitated and cavitated caries lesions" Teeth: permanent premolars Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Sweden Setting: extracted teeth Number of participants/teeth/sites: 56 teeth/112 sites Prevalence: enamel 0.64, dentine 0.15
Index tests	Category of test: conventional and digital radiograph Model set‐up: "the cone was placed at a distance of approximately 3 cm from the teeth and 5 cm from the film or the sensor. To simulate soft tissue, a 22 mm plexiglas was positioned directly in front of the cone" Sequence of test(s): index tests (radiographs and transillumination) performed prior to reference standard Examiner training and calibration: 8 experienced examiners Threshold applied: sound outer/inner enamel, outer/inner dentine Device specifics: ‐ conventional: "using Planmeca intraoral radiographic equipment (Planmeca, Helsinki, Finland) and Kodak Ektaspeed plus films, with settings of 70 kV and 7mA and an exposure time of 0.25 s" ‐ digital: "a Sigma direct digital sensor and Cliniview software (Instrumentarium, Tuusula, Finland), was used. The settings were 60 kV and 7 mA, with an exposure time of 0.20 s"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: sound, enamel, dentine
Flow and timing	Participants with index test but no reference standard: 15 surfaces out of 112 damaged during preparation of reference standard Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Low risk

Attrill 2001.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions Teeth: primary molars Sealants: no Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: UK Setting: extracted teeth Number of participants/teeth/sites: 58 teeth Prevalence: enamel 0.60, dentine 0.52
Index tests	Category of test: conventional radiograph Model set‐up: no specific detail regarding set‐up Sequence of test(s): index tests (visual, DIAGNOdent, and radiograph) performed prior to reference standard Examiner training and calibration: none, experienced examiners Threshold applied: 0–9 sound/early enamel caries, 10–17 enamel caries, 18–99 dentinal caries Device specifics: "Four teeth were radiographed per standard intra‐oral film (Kodak Ektaspeed, Kodak Ltd, Herts, UK) and were mounted such that the occlusal plane of each tooth was parallel to the X‐ray beam and perpendicular to the film or imaging plate. The exposure was taken from the buccal aspect"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: yes Multiple tests: no Site selection: sectioned teeth Target condition: sound, enamel, dentine (outer third), dentine (mid and inner)
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	A threshold was applied to the index test which categorised early enamel caries with sound surfaces, therefore the data are not appropriate for meta‐analysis
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Bahrololoomi 2015.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions: "intact or had incipient and inconspicuous caries with or without color change were selected" Teeth: permanent molars Sealants: no Surface: occlusal
Patient characteristics and setting	Age: 7 to 13 years Sex: not reported Ethnicity: not reported Country: Iran Setting: dental school Number of participants/teeth/sites: 31 participants/115 teeth (6 of theses were excluded "due to patient dropout" so the became 109 teeth) Prevalence: enamel 0.94, dentine 0.37
Index tests	Category of test: conventional radiograph Model set‐up: clinical setting Sequence of test(s): index tests (visual, radiograph, DIAGNOdent) performed prior to reference standard Examiner training and calibration: not reported Threshold applied: R0 = no radiolucency, R1 = radiolucency detected in the enamel, but not beyond the dentino‐enamel junction, R2 = radiolucency detected and extended into the dentine Device specifics: ".. bitewing radiographs were taken ... at 70kV, 8 mA and 0.36 s exposure settings using E speed 22×35 mm dental films (Kodak, Rochester, USA) in XCP film holder and processed using a dental film processor.... Images were initially examined and scored (R0–R2) by a pedodontist on a negatoscope and then confirmed by a radiologist"
Target condition and reference standard(s)	Category: excavation ‐ in cases with obvious or ambiguous caries Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: excavated suspicious site Target condition: sound, enamel, dentine
Flow and timing	Participants with index test but no reference standard: unclear whether all surfaces were excavated and if not then what the reference standard was Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Examiner 2 results used for analysis
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	No
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Unclear
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		High risk

Behere 2011.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: "tooth surfaces were either discolored or were apparently caries‐free" Teeth: permanent premolars and molars Sealants: not reported Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: India Setting: extracted teeth Number of participants/teeth/sites: 50 teeth/100 surfaces Prevalence: enamel 0.24, dentine 0.04
Index tests	Category of test: digital radiograph with 2 interpretations of radiographic images (i) visual and (ii) Logicon caries detector Model set‐up: "extracted teeth were inserted in foam blocks and placed in a jig" Sequence of test(s): visual, then radiograph Examiner training and calibration: not reported Threshold applied: sound, enamel, dentine Device specifics: "using the Kodak RVG 5000 digital radiography system with the Satelec X‐Mind AC intraoral X‐ray machine (X‐ray tube: Toshiba DG073B, focal spot size: 0.7 mm, exposure time range: 0.08‐3.2 seconds in 17 steps, filtration: 0.8 mm of Al) operating at 70 kVp, 8 mA, 0.8 seconds and a focal spot‐to‐image receptor distance of 40 cm"
Target condition and reference standard(s)	Category: histology ‐ "magnified photographic image" of sectioned tooth Sequence of index test and reference standard: index prior to reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: sound, enamel, dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Braga 2009.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions Teeth: primary molars Sealants: not reported Restoration: excluded Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 84 participants/131 sites Prevalence: enamel 0.63, dentine 0.26
Index tests	Category of test: conventional radiograph Model set‐up: "teeth were placed in arch models" Sequence of test(s): index tests (visual, radiograph,then DIAGNOdent pen) prior to reference standard Examiner training and calibration: yes, trained: "Two examiners carried out all examinations" Threshold applied: sound, enamel, outer/middle/inner third of dentine Device specifics: "using bitewing holders (Han‐Shin PF 682; Jon Ind, São Paulo, Brazil). The X‐ray machine (Spectro 70 X; Dabi Atlante, Ribeirão Preto, Brazil) was set to 70 kV, 8 mA, and the exposure time was 0.3 s. Kodak Insight radiographic films (22⫻35 mm, Eastman Kodak, Rochester, NY) were used, the focus‐to‐film distance was 40 cm"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: sound, enamel (outer), enamel (inner), dentine (outer), dentine (inner)
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Braun 2017.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: "Visually intact tooth surfaces" Teeth: permanent molars and premolars Sealants: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Germany Setting: extracted teeth Number of participants/teeth/sites: 84 teeth Prevalence: enamel 0.77, dentine 0.40
Index tests	Category of test: digital ‐ VistaScan ‐ image plate scanner Model set‐up: "mounted on a 3 9 4 mm plate for digital X‐ray images (Ref.‐No. 2130‐042‐00, Duerr Dental, Bietigheim‐ Bissingen, Germany)" Sequence of test(s): index tests (visual then radiograph) performed prior to reference standard Examiner training and calibration: 2 independent examiners, same examiner for visual and radiograph Threshold applied: R0 = sound, R1 = caries radiolucency in enamel, R2 = caries radiolucency in the outer half of dentine, R3 = caries radiolucency in the inner half of dentine with or without apparent pulp involvement Device specifics: each tooth was mounted on a 3 x 4 mm plate for the digital X‐ray images (VistaScan, Duerr Dental, Bietigheim‐Bissingen, Germany) at 60 kV and 7 mA, with an exposure time of 0.08 s
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: assumed index test then reference standard but not clearly stated, potential that reference standard could have informed index test Training of examiner: experienced examiners Blinding to index test: same examiners as index test Multiple tests: no Site selection: sectioned teeth Target condition: H0 = no caries, H1 = caries extending up to outer half of enamel, H2 = caries extending up to inner half of enamel but not into dentine, H3 = caries extending up to outer half of dentine, H4 = caries extending up to inner half of dentine with or without apparent pulp involvement
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	No
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Bussaneli 2015.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions Teeth: permanent premolars and molars Sealants: no Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 102 teeth Prevalence: enamel 0.70, dentine 0.19
Index tests	Category of test: conventional radiograph Model set‐up: "teeth were mounted individually on a dental model" Sequence of test(s): index tests (radiograph, near‐infrared then DIAGNOdent pen and QLF) prior to reference standard Examiner training and calibration: 2 experienced examiners Threshold applied: "the absence of radiolucency (0), with enamel radiolucency (1), with radiolucency in the outer half of the dentin (2), and with radiolucency on the inner half of the dentin (3)" Device specifics: "a positioner placed at a distance of 23 cm between the film and the head of the unit, operating at 70 kVp, 8 mA (Spectro 70X Seletronic) (DabiAtlante, Ribeirão Preto, Brazil), and an exposure time of 0.30 s, using an ultrafast single film (Kodak Insight, 22 × 35 mm, Kodak, Rochester, USA), processed automatically (Dent‐X 9000, Dent‐X, Emsford, USA) and mounted on identified slide"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: healthy, enamel, lesion at the dentino‐enamel junction or dentinal
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 8 teeth excluded from results as near‐infrared device failed to return a result, therefore excluded from all tests
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		High risk

Bussaneli 2015a.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions: "These presented a sound occlusal surface, or had signs suggesting the presence of caries lesion, such as white spots, pigmentations, and cavities" Teeth: primary molars Sealants: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 77 teeth Prevalence: enamel 0.63, dentine level not available
Index tests	Category of test: conventional radiograph Model set‐up: in vitro study of occlusal surfaces, set‐up not described Sequence of test(s): index tests (visual, then radiograph) prior to reference standard Examiner training and calibration: experienced examiners: "Paediatric Dentistry (Group A), with at least 10 years of experience in clinical practice" Threshold applied: (0) sound, (1) absence of radiolucency, (2) radiolucency in the external half of enamel, (3) in the internal half of enamel, (4) radiolucency in the external half of dentine, and (5) radiolucency in the internal half of dentine Device specifics: Ultraspeed films (Kodak Insight, 22 9 35 mm, Kodak, Rochester, USA) and an X‐ray appliance (Spectro 70X, Dabi‐Atlante, Ribeirao Preto, Brazil) were used, operating at 70 kVp, 8 mA, and exposure time of 0.3 s. The radiographs were processed in an automatic processor (Dent‐X 9000, Dent‐X, Emsford, USA)
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: experienced examiners Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: healthy, outer half of enamel, inner enamel and outer third of dentinal, mid‐dentine and inner dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Focused on group A ‐ experienced examiners, rather than group B ‐ second year dental students; group A greater applicability to our research question
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Cinar 2013.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions Teeth: primary molars Sealants: no Restorations: excluded: "Teeth with any restoration, fissure sealants or fissures with brownish pigments were excluded from the study" Surface: occlusal
Patient characteristics and setting	Age: 9 to 11 years Sex: not reported Ethnicity: not reported Country: Turkey Setting: dental hospital Number of participants/teeth/sites: 44 sites Prevalence: 0.75 enamel, 0.20 dentine
Index tests	Category of test: conventional radiograph Model set‐up: clinical setting Sequence of test(s): index tests (visual, radiograph, then DIAGNOdent pen) prior to reference standard Examiner training and calibration: not reported: "assessment with visual examination and LF were performed twice each by the same examiners with a 2‐week interval between measurements" Threshold applied: sound, enamel, outer/middle/inner third of dentine Device specifics: "The radiographic films (Ekstraspeed Plus; Kodak, Rochester, NY, USA) were held by KwikbiteH film holders (Kwikbite; Hawe Neos Dental, Bioggio, Switzerland). The X‐ray machine was set at 70 kV, 8 mA and the exposure time was set at 0.25 s. Radiographs were developed in an automatic film processor"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: sound, outer enamel, inner enamel, dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Yes
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Costa 2002.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions Teeth: permanent molars and premolars Sealants: excluded Restorations: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 50 teeth Prevalence: 0.65 enamel, 0.31 dentine
Index tests	Category of test: conventional and digital radiograph Model set‐up: set in plaster blocks Sequence of test(s): index tests (visual, DIAGNOdent and radiograph) prior to reference standard Examiner training and calibration: not reported ‐ assessments were performed twice each by the same examiners with a week interval between measurements Threshold applied: sound, enamel, dentine Device specifics: ‐ conventional: 50 kVp, 10 mA, Kodak Ultraspeed ‐ digital: sensor CCD, using image enhancement and inversion of shades
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: sound, enamel, dentine
Flow and timing	Participants with index test but no reference standard: 1 (damaged during sectioning) Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Da Silva 2010.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: early/enamel lesions, no restored teeth Teeth: primary first and second upper and lower molars Sealants: no Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 50 teeth/50 sites Prevalence: enamel 0.56, dentine 0.38
Index tests	Category of test: conventional and digital radiography Model set‐up: no attempt to replicate an in vivo setting Sequence of test(s): 1) radiography (does not specify if there was an order in which conventional and digital were done), 2) visual, 3) histology. Examiners may have been influenced by assessing the digital and conventional radiographs at the same time Examiner training and calibration: 2 dental radiologists with minimum of 5 years experience. To ensure calibration, a training exercise was completed before each observation session. Instructions were provided and observers became familiar with the image scoring to be used Threshold applied: 0 = no radiolucency, 1 = radiolucency confined to the enamel, 2 = radiolucency in the outer third of the dentine, 3 = radiolucency in the middle third of the dentine, 4 = radiolucency reaching the pulpal third of the dentine Device specifics: a dental X‐ray unit operating at 7 mA and 70 kVcp was used for all exposures. Exposure times were selected individually for each system (film or digital) to provide adequate image densities. Film images were made with InSight film at 0.3 s. Films were processed with an automatic processor at 25°C, with a 5 min processing cycle. Digital radiographic images were obtained with a charge‐coupled device sensor (Dixi 3) using an exposure time of 0.2 s
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: done by an oral pathologist Blinding to index test: yes ‐ different examiner (histology assumed to be blind regardless) Multiple tests: no Site selection: teeth were embedded into acrylic resin and sectioned in a mesio‐distal direction Target condition: D0 = no caries, D1 = caries lesion limited to the outer half of the enamel, D2 = caries extending into inner half of the enamel, but not to amelo‐dentinal junction, D3 = caries limited to the outer half of the dentine, D4 = caries involving the inner half of the dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper; we used the data for observer 1
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Diniz 2010.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: sound, early/enamel lesions, no teeth caries and non‐caries defects on buccal, lingual, and proximal surfaces Teeth: permanent molars Sealants: unclear Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Switzerland Setting: extracted teeth Number of participants/teeth/sites: 166 teeth/166 sites Prevalence: enamel 0.95, dentine 0.46
Index tests	Category of test: conventional radiographs Model set‐up: embedded in wax blocks; 0.5 cm wide plastic mould was placed to simulate soft tissues Sequence of test(s): 1) radiography, 2) histology Examiner training and calibration: groups of Brazilian (n = 5) and Swiss (n = 5) final‐year dental students, groups of Brazilian (n = 5) and Swiss (n = 5) dentists with 5 to 7 years experience (i.e. 20 examiners in total); no additional training or calibration in interpretation of radiographs Threshold applied: no radiolucency (0), radiolucency in enamel (1), radiolucency in the outer half of dentine (2), and radiolucency in the inner half of dentine (3) Device specifics: standardised bitewing radiographs taken using fixed apparatus with a film holder, an X‐ray machine, and double Kodak Insight films at 65 kV, 7 mA, and exposure time of 0.09 s. Source‐to‐film distance 22 cm. All radiographs processed by an automatic X‐ray film developer XR 24 Pro, placed in transparent cards, and identified
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: not reported Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: teeth ground longitudinally. To confirm the grinding process, teeth were analysed under microscope at magnification of x 3.2. When test site reached, papers of grain size 30, 18, and 10 μm were used. Occlusal cut surfaces were photographed, and it was ensured that the caries lesion was not ground away Target condition: D0 = no caries, D1 = caries extending up to halfway through the enamel, D2 = caries in the inner half of enamel, D3 = caries limited to the outer half of dentine, D4 = caries extending into the inner half of dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper; we used the examiner group D data (Swiss dentists with 5‐7 years of experience, as dental students' ratings not applicable to real‐life scenario)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Diniz 2011.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: sound, early/enamel lesions, cavitated (level of cavitation not reported), no sealants, no restorations, no hypoplasia, no fluorosis, no caries lesions on smooth or proximal surfaces Teeth: permanent premolars and molars Sealants: no Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 104 teeth/104 sites Prevalence: enamel 0.94, dentine = not possible to calculate due to no clear threshold between enamel and dentine caries
Index tests	Category of test: conventional radiographs Model set‐up: no attempt to replicate an in vivo setting Sequence of test(s): 1) visual, 2) radiography, 3) treatment decision (visual and radiography scores made available to the examiner), 4) histology. Although same examiners also did visual tests: "The examiners were blinded during the X‐ray examination, and they did not have access to the test tooth" Examiner training and calibration: 4 dentists from Department of Paediatric Dentistry: 2 adjunct professors with 15 years' postgraduate experience and 2 PhD students with 8 years' postgraduate experience. Training carried out for ICDAS but not for radiography Threshold applied: (0) no radiolucency, (1) radiolucency in enamel, (2) radiolucency in the outer half of dentine, (3) radiolucency in the inner half of dentine Device specifics: standardised bitewing radiographs taken of all teeth using a fixed apparatus with a film holder, with a distance of 23 cm from the X‐ray tube, an X‐ray machine, and a single ultraspeed film at 70 kVp, 8 mA, and exposure time of 0.30 s
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: 2 experienced examiners and any disagreements re‐examined and consensus reached Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: "teeth longitudinally sectioned through centre of each test site... resulting in two sections corresponding to the test site. The section with a more severe lesion was analysed" Target condition: D0 = no caries, D1 = caries lesion limited to outer half of enamel, D2 = caries extending into inner half of enamel or outer half of dentine, D3 = caries limited to middle third of dentine, and D4 = caries involving inner half of dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity (mean of the 4 assessors was reported) and prevalence reported in paper
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Diniz 2012.

Study characteristics
Patient Sampling	Method of sampling: selected: "88 patients who each had at least one posterior tooth scheduled for extraction" Included conditions: no cavitation and early lesions: "ranged from having macroscopically intact occlusal surfaces to different stages of noncavitated and cavitated carious lesions" Teeth: permanent molars and premolars Sealants: excluded Restorations: excluded Surface: occlusal
Patient characteristics and setting	Age: 18 to 35 years Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 88 participants/105 teeth Prevalence: enamel 0.95, dentine 0.26
Index tests	Category of test: conventional radiograph Model set‐up: clinical setting Sequence of test(s): index tests (visual, radiograph, then fluorescence devices) prior to reference standard Examiner training and calibration: 1 experienced examiner ‐ masked from results of fluorescence device Threshold applied: sound, enamel, outer/inner dentine Device specifics: "a BW radiograph positioner and ultraspeed radiographic film at 70 peak kilovolts and 10 milliamperes with an exposure time of 0.6 seconds"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: 2 trained examiners Blinding to index test: unclear Multiple tests: no Site selection: marked on photographs then sectioned teeth Target condition: sound, inner/outer enamel, inner/outer dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Ekstrand 2011.

Study characteristics
Patient Sampling	Method of sampling: selected: "collected from plastic boxes of thousands of extracted and exfoliated teeth" Included conditions: no cavitation and early lesions: "ranged from having macroscopically intact occlusal surfaces to different stages of noncavitated and cavitated carious lesions" Teeth: primary: molars, canines, and incisors, and permanent: molars, premolars, and canines Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Bogotá, Colombia Setting: extracted teeth Number of participants/teeth/sites: "132 sound/carious proximal surfaces from 106 primary teeth and 160 sound/carious proximal surfaces from 140 permanent teeth" Prevalence: ‐ primary: enamel 0.82, dentine 0.64 ‐ permanent: enamel 0.78, dentine 0.33
Index tests	Category of test: conventional radiograph Model set‐up: not reported Sequence of test(s): index tests (visual, radiograph) prior to reference standard (the order of teeth and radiographs in the 1st examination was changed in the 2nd) Examiner training and calibration: 3 examiners trained on a 3‐day ICDAS course, "the training concerned discussion of the radiographic scoring system and calibration was done on 25 bitewing radiographs" Threshold applied: 0 = sound, 1 = radiolucency restricted to the outer half of the enamel, 2 = radiolucency in the inner half of the enamel or at maximum to the outer third of the dentine, 3 = radiolucency reaching the middle third of the dentine, 4 = radiolucency in the inner third of the dentine Device specifics: "Radiographs (speed group F, Kodak Insight Dental Film) were made of the selected teeth (70 kV, 7.5 mA, exposure time of 0.35 s for incisors, canines and premolars and 0.5 s for molars)"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: experienced examiner Blinding to index test: unclear Multiple tests: no Site selection: marked on photographs then sectioned teeth Target condition: "0 = sound surfaces, 1 = demineralization in the outer half of the enamel, 2 = demineralization involving the area between the inner half of the enamel and outer third of the dentine, 3 = demineralization reaching the middle third of the dentine, 4 = demineralization involving the inner third of the dentine"
Flow and timing	Participants with index test but no reference standard: "Due to breakdown of the tooth under the preparation, the histological examination was done on 112 primary surfaces and on 151 permanent surfaces" Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Low risk

Erten 2005.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: sound, early/enamel lesions, small cavitations Teeth: permanent premolars and molars Sealants: unclear Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Turkey Setting: extracted teeth Number of participants/teeth/sites: 40 teeth/80 sites (78 in histology examination due to damage during sectioning) Prevalence: enamel 0.45, dentine 0.37
Index tests	Category of test: conventional (3 separate types of film: Ultraspeed, Ektaspeed Plus, and Insight) and digital radiography (radiovisiography) Model set‐up: the roots of the teeth were embedded in Optosil, polyvinyl siloxane blocks simulating the anatomic contacts of 2 premolars and 2 molars. Soft tissue was simulated by using a 1 cm acrylic resin block Sequence of test(s): 1) radiographs were arranged randomly so do not appear to be in a particular sequence, 2) histology Examiner training and calibration: 1 oral and maxillofacial radiologist, 1 restorative clinician, and 1 endodontic clinician; each observer given instructions and a demonstration on how to code the radiographs Threshold applied: 1 = caries definitely absent; 2 = caries probably absent; 3 = unsure; 4 = caries probably present; 5 = caries definitely present (applicability concerns) Device specifics: films were exposed with a Trophy CCX X‐ray machine operating at 70 kVp, 8 mA, with a filtration of 2.5 mm equal aluminium, 0.8 mm x 0.8 mm focal spot, and 16 inch focal spot film distance. Insight films were exposed for 0.16 s (40% of the exposure required for Ultraspeed films). Ultraspeed films were exposed for 0.40 s, and Ektaspeed Plus films were exposed for 0.24 s. (Exposure times were chosen from the guideline for Kodak intraoral dental films for a machine operating at 70 kVp, 8 mA, and 16 inch focal spot film distance with automatic processing.) Films were processed in an automatic roller transport machine with freshly made chemicals. Digital images were taken with an RVG system (2000 model, Trophy Radiology) with a 16 inch sensor focal spot distance at 0.08 s of exposure time
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: not reported Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: teeth were sectioned in a mesio‐distal direction Target condition: not reported but prevalence at start of results section reports histology as: caries free; lesions localised in enamel; lesions localised in the outer dentine; lesions in the inner half of the dentine
Flow and timing	Participants with index test but no reference standard: 2 of 80 surfaces damaged during sectioning (insufficient to cause bias) Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper; we used the mean sensitivity/specificity of the 3 observers; used the Ultraspeed film for conventional radiography
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Low risk

Espelid 1986.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: no hypoplasia or other non‐carious defects Teeth: permanent premolars and molars Sealants: unclear Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Norway Setting: extracted teeth Number of participants/teeth/sites: 151 teeth/151 sites Prevalence: enamel 0.81, dentine 0.44
Index tests	Category of test: conventional radiographs (film) Model set‐up: in vivo setting not fully replicated (not placed in a block to replicate approximal tooth‐to‐tooth surfaces but a 10 mm wide plexiglass container filled with water was used to simulate soft tissues) Sequence of test(s): 1) visual tactile, 2) radiograph, 3) excavation Examiner training and calibration: 7 experienced dentists; no training or calibration mentioned Threshold applied: R1 = sound, R2 = not more than halfway into enamel, R3 = up to dento‐enamel junction, R4 = into the outer third of dentine, R5 = between outer third and half of dentine, R6 = more than halfway into dentine Device specifics: radiographed using double‐pack film and a dental X‐ray machine. Exposures made at 65 kV and 15 mA with exposure time 5/8's of a second at an object‐focus distance of 30 cm and object‐film distance of 2 cm. The horizontal projection was tangential to the approximal surface. A 10 mm wide plexiglass container filled with water was used to simulate soft tissues. Radiographs interpreted under standardised conditions, using an X‐ray viewer with a x2 magnifying lens
Target condition and reference standard(s)	Category: 1) visual‐tactile for identification of any lesion, 2) any lesions detected by visual‐tactile were excavated to assess the depth Sequence of index test and reference standard: visual‐tactile was before radiography and excavation was after radiography Training of examiner: not reported Blinding to index test: yes ‐ visual‐tactile done before radiography (unclear if blind at dentine threshold as it was unclear if it was the same 2 assessors for excavation) Multiple tests: yes ‐ visual‐tactile plus excavation if a lesion was present Site selection: not reported Target condition: for visual‐tactile at the enamel threshold: S1 = sound, S2 = lesion without cavitation, S3 = small cavitation, S4 = lesion showing both discolouration and a small cavity, S5 = lesion showing both discolouration and a big cavity; for assessment of lesion depth by excavation: L1 = sound, L2 = not more than halfway into enamel, L3 = up to dento‐enamel junction, L4 = into the outer third of dentine, L5 = between outer third and half of dentine, L6 = more than halfway into dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from crosstabs; used the numbers reported in figure 1 above the bold means (i.e. the observer who made fewest positive caries diagnoses)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Firestone 1998.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no mechanical damage (no other information reported) Teeth: permanent premolars and molars Sealants: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: USA Setting: extracted teeth Number of participants/teeth/sites: 52 teeth/102 sites Prevalence: enamel 0.66, dentine (no data)
Index tests	Category of test: conventional and digital radiography (digital with CariesFinder ‐ knowledge‐based image analysis and clinical decision support system) Model set‐up: "teeth positioned in near proximal contact in phantom blocks containing 3 teeth each... this arrangement of teeth was not considered to impose special conditions on the practitioners; soft‐tissue‐equivalent phantom formed of solid water putty was used" Sequence of test(s): 1) visual inspection with x6 magnification verified by thin‐section microradiography, 2) radiography (half the assessors viewed conventional first and the other half digital first ‐ then after 2 weeks they viewed the other) Examiner training and calibration: 16 general dental practitioners; no training or calibration reported Threshold applied: 'definitely yes', 'probably yes', 'probably not', 'definitely not' for the presence of caries, and 'yes' or 'no' for whether the surface in question should be restored = concerns over applicability Device specifics: 2 sets of bitewing radiographic images of the teeth, one using the Sens‐A‐Ray receiver (digital) and the other using Kodak D‐speed size‐2 film. The exposure parameters for the Sens‐A‐Ray were 65 kVp, 10 mA, 0.8 s; those for the film were 65 kVp, 10 mA, 1.25 s. The detector (film or Sens‐A‐Ray) to source distance was 24 inches (61 cm). In order to achieve ideal projection geometry, a General Electric 1000 X‐ray tube head was secured relative to the film exposure site
Target condition and reference standard(s)	Category: histology ‐ visual inspection with x6 magnification verified by thin‐section microradiography Sequence of index test and reference standard: reference standard appears to have been done prior to the radiographic viewings Training of examiner: not reported (done by 2 dental school faculty) Blinding to index test: yes ‐ done by different examiners to those who did the index test Multiple tests: yes Site selection: not reported Target condition: caries was defined as the presence of a 'white‐spot' or 'brown‐spot' lesion or a rough surface or surface cavitation. Cavitation was defined for the purpose of the study as a loss of smooth enamel surface integrity to an extent that would accommodate at least a number 1/4 round bur
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Freitas 2016.

Study characteristics
Patient Sampling	Method of sampling: selected ‐ convenience sample in basic health unit Included conditions: "The approximal surfaces ranged from sound to different stages of non‐cavitated and cavitated carious lesions" Teeth: "primary molar that was in an advanced stage of root resorption" Sealants: not reported Surface: approximal
Patient characteristics and setting	Age: 8 to 12 years Sex: not reported Ethnicity: not reported Country: Brazil Setting: health unit Number of participants/teeth/sites: 56 participants/89 teeth/166 surfaces Prevalence: enamel 0.68, dentine ‐ not possible to calculate as threshold combines inner enamel and outer third of dentine, highest prevalence would be 0.5
Index tests	Category of test: conventional bitewing Model set‐up: clinical setting Sequence of test(s): index tests (visual then radiograph) on 2 occasions but the same bitewing was used from the patient's records; performed prior to reference standard Examiner training and calibration: experienced researcher, who was previously trained and calibrated, same examiner for visual and radiograph Threshold applied: 0 = no radiolucency visible; 1 = radiolucency visible in the enamel; 2 = radiolucency visible in the dentine but restricted to the outer third of the dentine; 3 = radiolucency extending to the middle third of the dentine; and 4 = radiolucency in the pulpal third of the dentine Device specifics: "using radiographic positioners (Jon Han‐Shin PF 682, Jon Ind, São Paulo, Brazil) and E‐speed radiographic film (22 by 35 mm, Kodak Ektaspeed, Eastman Kodak, Rochester, NY, USA). The X‐ray machine (Spectro 70X, Dabi Atlante, Ribeirão Preto, São Paulo, Brazil) was set to 70 kV, 8 mA, and an exposure time of 0.3 seconds, and the focus‐to‐film distance was set to 40 cm"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: 2 experienced and trained examiners, who did not participate in the clinical examinations, evaluated each tooth section independently, Blinding to index test: separate examiner to index test Multiple tests: no Site selection: sectioned teeth Target condition: "zero ‐ no caries; one ‐ carious lesion limited to the outer half of the enamel; two ‐ caries extending into the inner half of the enamel or outer half of the dentin; three ‐ caries limited to the middle third of the dentin; and four ‐ caries involving the inner half of the dentin"
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: "monitored until natural exfoliation two weeks later; or scheduled for extraction" therefore unclear on time delay between index tests and reference standard Participants receiving both tests but excluded from results: 0
Comparative
Notes	Concern regarding unclear threshold between enamel and dentine lesions, since we are reporting at the enamel level the applicability remains low concern for the reference standard
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk

Goel 2009.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early enamel lesions Teeth: primary first and second molars Sealants: excluded Restorations: excluded Surface: occlusal
Patient characteristics and setting	Age: 8 to 12 years Sex: not reported Ethnicity: not reported Country: India Setting: index test performed in a clinical setting prior to extraction Number of participants/teeth/sites: 84 teeth/83 sites Prevalence: enamel 0.54, dentine 0.43
Index tests	Category of test: conventional bitewing Model set up: clinical setting Sequence of test(s): index tests (radiograph, visual and DIAGNOdent) performed prior to reference standard Examiner training and calibration: not reported Threshold applied: sound, enamel, inner/mid/outer dentine Device specifics: not reported
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: sound, inner/outer enamel, inner/outer dentine
Flow and timing	Participants with index test but no reference standard: 1 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Low risk

Haak 2003.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: sound, early/enamel lesions, small cavitation (no carious cavitations exceeding 2 mm in diameter), no approximal restorations Teeth: premolars and molars Sealants: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Germany Setting: extracted teeth Number of participants/teeth/sites: 160 teeth/320 sites Prevalence: enamel 0.67, dentine 0.37
Index tests	Category of test: digital bitewing radiographs Model set‐up: 20 pairs of upper and lower jaw quadrant blocks were mounted with approximal tooth surfaces in contact. Each block consisted of 2 premolars and molars with similar anatomical size and form. Canines and third molars were added with plastic teeth and the roots were embedded in plaster of Paris. No misalignments were simulated to avoid radiographic overlapping. Soft tissue was simulated by 14 mm of dental wax placed in front of the specimen Sequence of test(s): 1) radiography (different display methods in random order and sessions 1‐week apart), 2) histology Examiner training and calibration: 5 university dentists who were used to routinely diagnosing digital radiographs for at least 2 years; no training or calibration mentioned Threshold applied: (radiolucency) 0 = no lesion; 1 = 1st half of enamel; 2 = 2nd half of enamel; 3 = 1st quarter of dentine; 4 = 2nd quarter of dentine; 5 = inner half of dentine Device specifics: technical specifications of the sensor were: active area, 26 x 34 mm²; pixel size, 19.5 x 19.5 µm²; matrix, 880 x 692 pixels. A Heliodent DS dental X‐ray unit at 60 kVp and 7 mA was used to expose the sensor for 0.08 s. Screen resolution was set at 1024 x 768 pixels; colour was set to a 16‐bit depth. Visible display size of the TFT monitor was 23 x 30.6 cm² compared with a visible area of the CRT display of 26.2 x 35 cm²
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: not reported Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: all approximal surfaces were enclosed in epoxy resin and serially sectioned in a mesio‐distal direction into 300 µm sections Target condition: disease‐positive results were defined for 2 different validation thresholds: histological presence of caries (I) and dentine caries (II)
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper; used the overall mean sensitivity/specificity for the 2 monitor types and 3 image sizes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Haiter‐Neto 2007.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: sound and early lesions Teeth: permanent canines, premolars and molars Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 80 teeth/160 surfaces Prevalence: enamel 0.38, dentine 0.06
Index tests	Category of test: digital radiographs Model set‐up: "teeth mounted in 20 blocks of silicone with 4 test teeth (2 premolars and 2 molars) and 1 non‐test tooth (a canine). Placed the non‐test canine at the head of the block to secure approximal contact for the first premolar test tooth. A 12 mm acrylic plate was placed between the source of the X‐radiation and the teeth to simulate soft tissue" Sequence of test(s): index test prior to reference standard; examiners blinded to different index tests by random ordering and 1‐day separation of viewing sessions Examiner training and calibration: observers with at least 5 years experience with radiographic caries diagnosis Threshold applied: 1 = caries definitely absent; 2 = caries probably absent; 3 = unsure if caries is present or absent; 4 = caries probably present; 5 = caries definitely present Device specifics: "a radiographic unit with rectangular collimation operating at 65 kilovolts peak and 10 milliamperes"; "acquired the digital images by using the two PSP systems (Digora FMX and Digora Optime 8‐bit resolution) and the two CMOS systems (Schick CDR and Schick CDR Wireless). The exposure times for the selected images were as follows: 0.34 seconds (molars) and 0.30 seconds (premolars) for Digora FMX, 0.42 seconds (both molars and premolars) for Digora Optime and 0.26 seconds (molars) and 0.22 seconds (premolars) for Schick CDR and Schick CDR Wireless"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard follows index test Training of examiner: not reported Blinding to index test: unclear if same examiners but histology so assumed blinded Multiple tests: no Site selection: sectioned teeth Target condition: 0 = sound; 1 = caries in enamel; 2 = caries one‐third or less into dentine; 3 = caries more than one‐third into dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Used the data for Digora Optime as it was the newer version and therefore offering the greatest potential for clinical relevance
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Haiter‐Neto 2008.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: sound and early lesions Teeth: permanent canines, premolars, and molars Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 80 teeth/160 surfaces Prevalence: enamel 0.36, dentine 0.06
Index tests	Category of test: digital radiographs (comparing 7 different solid‐state intraoral digital receptors) Model set‐up: "teeth mounted in 20 blocks of silicone with 4 test teeth (2 premolars and 2 molars) and 1 non‐test tooth (a canine). Placed the non‐test canine at the head of the block to secure approximal contact for the first premolar test tooth. A 12 mm acrylic plate was placed between the source of the X‐radiation and the teeth to simulate soft tissue" Sequence of test(s): index test prior to reference standard; examiners blinded to different index tests by random ordering and 1‐day separation of viewing sessions Examiner training and calibration: observers with at least 5 years experience with radiographic caries diagnosis Threshold applied: 1 = caries definitely absent; 2 = caries probably absent; 3 = unsure if caries is present or absent; 4 = caries probably present; 5 = caries definitely present Device specifics: "using a radiographic unit with rectangular collimation operating at 65 kilovolts peak and 10 milliampere"; "digital images by using the two PSP systems (Digora FMX and Digora Optime 8‐bit resolution) and the two CMOS systems (Schick CDR and Schick CDR Wireless). The exposure times for the selected images were as follows: 0.34 seconds (molars) and 0.30 seconds (premolars) for Digora FMX, 0.42 seconds (both molars and premolars) for Digora Optime and 0.26 seconds (molars) and 0.22 seconds (premolars) for Schick CDR and Schick CDR Wireless"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard follows index test Training of examiner: not reported Blinding to index test: unclear if same examiners but histology so assumed blinded Multiple tests: no Site selection: sectioned teeth Target condition: 0 = sound; 1 = caries in enamel; 2 = caries one‐third or less into dentine; 3 = caries more than one‐third into dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Used the data for CDR‐APS
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Haiter‐Neto 2009.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: sound and early lesions Teeth: permanent canines, premolars, and molars Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 80 teeth/160 surfaces Prevalence: enamel 0.37, dentine 0.06
Index tests	Category of test: digital radiographs (comparing original 8‐bit images from the Vistascan storage phosphor plate system with images enhanced with specific filters) Model set‐up: "teeth mounted in 20 blocks of silicone with 4 test teeth (2 premolars and 2 molars) and 1 non‐test tooth (a canine). Placed the non‐test canine at the head of the block to secure approximal contact for the first premolar test tooth. A 12 mm acrylic plate was placed between the source of the X‐radiation and the teeth to simulate soft tissue" Sequence of test(s): index test prior to reference standard; examiners blinded to different index tests by random ordering and 1‐day separation of viewing sessions Examiner training and calibration: observers with at least 5 years experience with radiographic caries diagnosis Threshold applied: 1 = caries definitely absent; 2 = caries probably absent; 3 = unsure if caries is present or absent; 4 = caries probably present; 5 = caries definitely present Device specifics: "The Vistascan system software provides 3 types of predefined filters: a Fine filter and 2 caries‐specific filters, Caries1 and Caries2. The original images were enhanced by the 3 types of filters separately and saved in non‐compressed file format"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard follows index test Training of examiner: not reported Blinding to index test: unclear if same examiners but histology so assumed blinded Multiple tests: no Site selection: sectioned teeth Target condition: 0 = sound; 1 = caries in enamel; 2 = caries one‐third or less into dentine; 3 = caries more than one‐third into dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Used the data for the original images
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Hintze 1996.

Study characteristics
Patient Sampling	Method of sampling: not reported Included conditions: not reported Teeth: permanent premolars and molars Sealants: not reported Surface: approximal (at the enamel threshold) and occlusal (only reported at the dentine threshold)
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Denmark Setting: extracted teeth Number of participants/teeth/sites: 116 teeth/224 proximal sites (103 occlusal ‐ data not used) Prevalence: enamel 0.26, dentine 0.10
Index tests	Category of test: conventional radiograph ‐ 4 types of film assessed (we reported data for Ultra, Ekta, and M2 films as they all had the same results) Model set‐up: attempts made to replicate in vivo setting (blocks of teeth in a line and acrylic block was placed between the cone and the tooth block to produce a soft‐tissue equivalent scattering effect) Sequence of test(s): 1) radiography, 2) histology Examiner training and calibration: not reported Threshold applied: 1 = definitely present; 2 = probably present; 3 = unsure; 4 = probably not present; 5 = definitely not present Device specifics: radiograph of each tooth in the blocks taken on Ultra, Ekta, Plus, and M2 dental X‐ray films, by a GX 1000 X‐ray unit operating at 70 kV and 15 mA. The collimator was rectangular with a size corresponding to the area of the films. The target‐film distance was 30 cm, and exposure time was 0.42 s for Ultra, 0.26 s for Ekta and Plus, and 0.34 s for M2. A 12 mm acrylic block was placed between the cone and the tooth block to produce a soft‐tissue equivalent scattering effect. The tooth blocks were placed identically and in direct contact with the films during exposure. The films were developed in a Durr automatic processor
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: not reported Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: serially sectioned in 700 µm thick planes orientated mesio‐distally of the tooth crowns Target condition: sound, caries in enamel, and caries in dentine (beneath the enamel‐dentine junction). In the occlusal surfaces a positive diagnosis (disease) was defined as caries in the dentine. In the proximal surfaces a positive diagnosis was defined as caries in the enamel or deeper (we only used proximal data)
Flow and timing	Participants with index test but no reference standard: 13 (13 of 116 teeth damaged during sectioning but unlikely to bias results) Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from true‐positive/false‐positive rates and prevalence reported in paper; these data were only for proximal surfaces as the occlusal surfaces were only reported at dentine level; 4 types of film assessed ‐ we reported data for Ultra, Ekta, and M2 films (all had same results)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Low risk

Hintze 2003.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: not reported Teeth: canines, premolars, and molars Sealants: not reported Surface: approximal and occlusal surfaces in each tooth were scored
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Denmark Setting: extracted teeth Number of participants/teeth/sites: 198 teeth: 373 approximal sites and 158 occlusal Prevalence: ‐ approximal: enamel 0.56, dentine 0.14 ‐ occlusal: enamel 0.91, dentine 0.54
Index tests	Category of test: conventional radiograph ‐ 4 types of film assessed (we reported data for Ultra, Ekta, and M2 films as they all had the same results) Model set‐up: "teeth were mounted in blocks of silicone with 3 test teeth and 2 non‐test teeth in each block. The non‐test teeth were placed at each end of the block to create approximal contacts for the test teeth" Sequence of test(s): visual, radiograph then histology Examiner training and calibration: not reported Threshold applied: sound, enamel, outer/inner dentine Device specifics: "using an Oralix DC X‐ray unit (Gendex, Des Plaines, Ill, USA) with rectangular collimation at 60 kVp, 7 mA and a 32 cm focus‐film distance. A 12 mm acrylic plate was placed between the tube and the teeth to simulate soft tissue. Each test tooth was radiographed with an Ektaspeed Plus film"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard followed index tests Training of examiner: not reported Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: serially sectioned in 700 µm thick planes Target condition: sound, caries in enamel, and caries in dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Huysmans 1997.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: sound, early/enamel lesions, cavitation (no information on level of cavitation), no restorations Teeth: canines, premolars, and molars Sealants: not reported Surface: approximal (at the enamel threshold) and occlusal (only reported at the dentine threshold)
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: unclear (The Netherlands or Denmark) Setting: extracted teeth Number of participants/teeth/sites: 220 teeth/410 approximal sites (189 occlusal ‐ data not used) Prevalence: enamel 0.36, dentine 0.10 (approximal surfaces)
Index tests	Category of test: digital radiography (5 different exposure times) Model set‐up: "sets of 5 teeth were positioned in a row with contacting approximal surfaces, the roots embedded in impression putty blocks.... and 12 mm thick tissue equivalent material was placed between the tube extension and the teeth" Sequence of test(s): 1) radiography (examiners assessed radiographs of the same teeth at different exposure times but there were 410 approximal surfaces and each exposure time set of radiographs was viewed on different days, therefore no bias concerns), 2) histology Examiner training and calibration: not reported Threshold applied: caries was scored on a 5‐point confidence scale: 1= definitely not present, 2 = probably not present, 3 = unsure, 4 = probably present, 5 = definitely present (= concerns over applicability) Device specifics: each block was radiographed in 2 parts (tooth 1‐3, and tooth 3‐5) using the Digora system. The large image plate (3 x 4 cm) was used for all images, and 12 mm thick tissue equivalent material was placed between the tube extension and the teeth. The exposure parameters were as follows: 60 kVp, 15 mA and 66 cm focus to image plate distance. An electronic timer was used to make a complete set of images at each of 5 different exposure times: 0.08, 0.16, 0.26, 0.5, and 2.0 s
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: not reported Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: teeth embedded in acrylic resin and cut into mesio‐distal sections of 700 to 800 µm thickness. The highest score from the several sections of a tooth was used as the true status of the assessed surface Target condition: 0 = sound, 1= caries lesion in outer half of enamel, 2 = caries lesion in inner half of enamel up to and including the amelodentinal junction, 3 = caries lesion in outer half of dentine, 4 = caries lesion in inner half of dentine
Flow and timing	Participants with index test but no reference standard: 13 occlusal surfaces not used due to presence of restorations or damage during sectioning ‐ but we did not include data for occlusal surfaces Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper; these data were only for approximal surfaces as the occlusal surfaces were only reported at dentine level; 5 different exposure times assessed ‐ we report data for 0.08 s (other times of 0.16, 0.26, 0.5, and 2.0 s all had very similar results); we used the data for the mean of the 3 observers
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Isidor 2009.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: sound and early lesions Teeth: permanent canines, premolars, and molars Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 80 teeth/160 surfaces Prevalence: enamel 0.38, dentine 0.06
Index tests	Category of test: digital radiographs (comparing 5 flat panel monitors) Model set‐up: "teeth mounted in 20 blocks of silicone with 4 test teeth (2 premolars and 2 molars) and 1 non‐test tooth (a canine). Placed the non‐test canine at the head of the block to secure approximal contact for the first premolar test tooth. A 12 mm acrylic plate was placed between the source of the X‐radiation and the teeth to simulate soft tissue" Sequence of test(s): index test prior to reference standard; examiners blinded to different index tests by random ordering and 1‐day separation of viewing sessions Examiner training and calibration: observers with at least 5 years experience with radiographic caries diagnosis Threshold applied: 1 = caries definitely absent; 2 = caries probably absent; 3 = unsure if caries is present or absent; 4 = caries probably present; 5 = caries definitely present Device specifics: "using a Gendex DC X‐ray unit with a rectangular collimation operating at 65 kV and 10 mA"; "The blocks were stabilized in a jig to create a focus‐to‐digital receptor distance of 32 cm, a central beam orientation perpendicular to the tooth and a tooth‐to‐receptor distance of 2 cm"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard follows index test Training of examiner: not reported Blinding to index test: unclear if same examiners but histology so assumed blinded Multiple tests: no Site selection: sectioned teeth Target condition: 0 = sound; 1 = caries in enamel; 2 = caries one‐third or less into dentine; 3 = caries more than one‐third into dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Used the data for Eizo FlexScan MX190 because it is the most recent monitor
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Jablonski‐Momeni 2012.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: no restorations Teeth: permanent posterior teeth Sealants: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Germany Setting: extracted teeth Number of participants/teeth/sites: 84 teeth/84 sites Prevalence: enamel 0.85, dentine 0.48
Index tests	Category of test: digital bitewing radiographs Model set‐up: teeth were placed in rows (3 teeth in each row) in suitable moulds; no mention of method used to simulate presence of soft tissue Sequence of test(s): 1) visual, 2) laser fluorescence using DIAGNOdent, 3) fluorescence‐based camera (VistaCam), 4) radiography, 5) excavation (unclear whether the same examiners did all the index tests ‐ if they did, this could have influenced the interpretation of the radiographs if they were viewed in the same order and around the same time) Examiner training and calibration: 2 investigators (doctoral student and an experienced investigator) Threshold applied: 0 = no radiolucency, 1 = radiolucency in the outer half of enamel, 2 = radiolucency in the inner half of enamel, up to the enamel‐dentine junction, 3 = radiolucency in the outer half of dentine, 4 = radiolucency in the inner half of dentine Device specifics: radiographs were taken of all teeth using the Gendex dental X‐ray machine at 65 kV, 6.5 mA, and exposure time of 0.12 s. All radiographs were processed by the Digora Optime image scanner
Target condition and reference standard(s)	Category: excavation Sequence of index test and reference standard: reference standard last Training of examiner: not reported Blinding to index test: unclear if same examiners ‐ if the same, could have been influenced by multiple index tests Multiple tests: no Site selection: occlusal surfaces were photographed digitally. 1 site within the pit and fissure system of each tooth was marked on black and white images of the tooth surface for ease of relocation Target condition: the lesions' depths were divided up into the following categories: sound tooth surface (score 0), caries in the enamel (clinical score 1), caries down to the enamel‐dentine junction (clinical score 2), and caries in the first third of dentine (clinical score 3), caries down to the second third of dentine or near pulp, or pulp already effected (clinical score 4)
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from cross tabs
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Jablonski‐Momeni 2017.

Study characteristics
Patient Sampling	Method of sampling: "selected sequentially from regular dental screenings" Included conditions: sound or early enamel lesions: "criteria for inclusion were persons with an indication justifying dental radiographs or for whom radiographs were already available that were not older than 3 months"..."Approximal surfaces with ICDAS codes higher than 2, or enamel changes not due to caries, were not included in the study" Teeth: permanent premolars and molars Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: mean 29.5 years (range 18 to 45) Sex: 9 male, 9 female Ethnicity: not reported Country: Germany Setting: routine examination in dental clinic Number of participants/teeth/sites: 19 participants/161 teeth/193 sites Prevalence: enamel 0.62, dentine not reported (according to visual assessment results)
Index tests	Category of test: digital radiograph Sequence of test(s): visual, radiograph, after visual assessment Examiner training and calibration: "The radiographs were adjudged by consensus by the examiners" Threshold applied: D0 = no radiolucency; D1 = radiolucency in the outer half of the enamel; D2 = radiolucency in the inner half of the enamel ± enamel‐dentine junction Device specifics: "digital X‐ray machine (Heliodent DS, Sirona Bensheim, Germany) using a CCD intraoral sensor and a sensor holder"
Target condition and reference standard(s)	Category: visual: "teeth were separated prior to the visual examination using a dental wedge, but without additional separation of the teeth using orthodontic separation elastics" Sequence of index test and reference standard: near‐infrared not likely to effect results of reference standard Training of examiner: same examiners as index test, but tests interpreted independently Blinding to index test: performed prior to near‐infrared Multiple tests: visual and radiograph performed before near‐infrared, same examiners for all, but visual assessed before radiograph Site selection: all surfaces Target condition: sound, superficial enamel demineralisation, enamel breakdown, dentine caries
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 8 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Low risk

Kalathingal 2007.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: sound, early/enamel lesions Teeth: molars and premolars Sealants: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: USA Setting: extracted teeth Number of participants/teeth/sites: 20 teeth/40 sites Prevalence: enamel 0.45, dentine 0.25
Index tests	Category of test: digital intraoral radiographs and cone beam local computed tomography Model set‐up: 2 adult dentate mandibles served to position the extracted teeth in a natural arch form; sockets were modified to accommodate the sample teeth. 2 1.0 cm thick wax slabs were used to simulate soft tissue Sequence of test(s): 1) radiography (viewed in separate sessions in random order and at least 1 week apart = blinding), 2) histology Examiner training and calibration: 2 radiologists, 2 radiology residents, 2 operative dentistry residents, and 2 experienced general dentists. Observers also received written and verbal instructions Threshold applied: observers asked to judge the presence or absence of a caries lesion by using the following 5‐point scale: 1 = caries definitely absent; 2 = caries probably absent; 3 = unsure if caries is absent or present; 4 = caries probably present; 5 = caries definitely present. Observers were encouraged to make full use of the scale. An arbitrary cut‐off was created between scores 3 and 4, with scores 1, 2, and 3 representing a negative finding (caries absent), and scores 4 and 5 representing a positive finding (caries present) = concerns over applicability Device specifics: the X‐ray source was a conventional intraoral X‐ray unit operated at 60 kVp and 7 mA. The object was mounted on a computer controlled rotation stage at a distance of 54 cm from the focal spot. A collimator was placed at the opening of the X‐ray tube and another one was placed close to the object. The images were acquired with a Sidexis sensor at 12 bits per pixel (4096 gray levels) and a pixel size of 40 x 40 micrometers. The distance between the object and the detector was 11 cm. 100 basis images were acquired along a 180° arc. The angular disparity between individual basis images was 1.8°. The region of interest was composed of a cylindrical volume containing 3 teeth. Volume data were computed from the basis projections by using a filtered back projection CT reconstruction algorithm. Axial slices of 332 x 332 pixels were reconstructed with a slice thickness of 40 µm. 5 consecutive axial slices were averaged to reduce noise and increase contrast, resulting in a slice thickness of 0.2 mm. A final axial slice thickness of 0.4 mm was achieved using the Grouped ZProjector plugin in ImageJ. Parasagittal slices were reconstructed in ImageJ and combined into an image stack after 3‐slice averaging
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: same 8 examiners that did the index test had training and calibration with the same training set Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: each tooth was sectioned. A majority of the teeth were cut 4 times, resulting in 2 slices of 0.5 to 1.0 mm, and 2 thicker buccal and lingual segments Target condition: 0 = no caries; 1 = caries in outer half of enamel; 2 = caries extending to inner half of enamel; 3 = caries extending into dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper; used the data for the mean of the 8 observers
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Ko 2015.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: severity condition unclear: "proximal surfaces with extensive caries involving more than half of the proximal surface were excluded" Teeth: permanent molars and premolars Sealants: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: South Korea Setting: extracted teeth Number of participants/teeth/sites: 100 teeth (5 were damaged so only 95 reported in results) Prevalence: enamel 0.80, dentine 0.14
Index tests	Category of test: digital radiograph Model set‐up: "Pairs were formed with marginal ridges in contact to simulate the oral relationship with resin.....and putty" Sequence of test(s): visual then radiograph followed by QLF Examiner training and calibration: 1 calibrated dentist Threshold applied: no radiolucency, radiolucency restricted to the outer half of the enamel, radiolucency involved inner half of enamel ‐ up to (including) dentino‐enamel junction, radiolucency confined to outer half of dentine, radiolucency involved inner half of dentine with/without apparent pulpal involvement Device specifics: "using the dental X‐ray machine (Kodak 2200 Intraoral X‐ray System, Eastman Kodak Co., Rochester, NY, USA) at 60 kV and 7 mA and exposure time of 0.096 s"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: "enamel demineralization or a narrow surface zone of opacity", enamel or outer/inner dentine caries
Flow and timing	Participants with index test but no reference standard: 5 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Low risk

Kockanat 2017.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: non‐cavitated; "occlusal surfaces of the teeth had minimal macroscopic destruction" Teeth: primary molars Sealants: unclear Surface: occlusal
Patient characteristics and setting	Age: 9 to 12 years Sex: not reported Ethnicity: not reported Country: Turkey Setting: in vivo study conducted in dental hospital, followed by in vitro after extraction Number of participants/teeth/sites: 120 teeth (144 teeth were examined and measurements made with caries detection devices, but 120 of the 144 teeth were reported; due to inconsistencies in caries measurement results), clarification provided by study author Prevalence: enamel 0.78, dentine 0.32
Index tests	Category of test: digital radiograph Model set‐up: clinical setting Sequence of test(s): digital radiographies were obtained in order to determine the time of exfoliation during patient selection; followed by: visual, Sopro, DIAGNOdent pen then CarieScan pro Examiner training and calibration: unclear, 2 independent examiners Threshold applied: (0) no visible radiolucency; (1) radiolucency in the enamel; (2) radiolucency in the dentine, involving the surface or the outer third of the dentine, and (3) radiolucency in the dentine, involving the inner third of the dentine Device specifics: "using an X‐ray machine (X Mind, Acteon, La Ciotat, France) and phosphorous plates (PSP!X, Acteon, La Ciotat, France) at 70 kVp, 8 mA, and exposure time of 0.16 s"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: not reported Blinding to index test: not reported Multiple tests: no Site selection: sectioned teeth Target condition: sound, outer half of enamel, inner half of enamel, outer half of dentine, deep dentine
Flow and timing	Participants with index test but no reference standard: 24 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data used for examiner 1, with the comparison of in vivo index test versus histology Study authors contacted for clarification of study data
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		High risk

Kucukyilmaz 2015.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: non‐cavitated and early lesions Teeth: primary molars Sealants: unclear Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Turkey Setting: in vivo study conducted in dental hospital, followed by in vitro after extraction Number of participants/teeth/sites: 200 teeth Prevalence: enamel 0.82, dentine 0.33
Index tests	Category of test: digital radiograph Model set‐up: in vivo study so radiographs taken prior to extraction Sequence of test(s): visual, radiograph, DIAGNOdent, ECM completed in vivo and in vitro before sectioning of teeth Examiner training and calibration: 2 examiners trained by third experienced examiner Threshold applied: no radiolucency, outer half of enamel radiolucency, radiolucency in the inner half of the enamel, radiolucency inner/outer dentine Device specifics: "the Trophy ETX device and Kodak RVG 5000 Digital Radiography System"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: not reported Blinding to index test: not reported Multiple tests: no Site selection: sectioned teeth Target condition: sound, outer half of enamel, inner half of enamel, outer half of dentine, deep dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	First examiner and in vivo results used for data extraction
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Kulczyk 2014.

Study characteristics
Patient Sampling	Method of sampling: selected: "102 non‐cavitated human pre‐molar and molar teeth, extracted for orthodontic reasons, were chosen for this study" Included conditions: non‐cavitated Teeth: permanent premolars and molars Sealants: unclear Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Poland Setting: extracted teeth Number of participants/teeth/sites: 102 teeth/136 surfaces Prevalence: enamel 0.45, dentine 0.18
Index tests	Category of test: CBCT Model set‐up: "Pre‐molar and molar teeth were placed in blocks of silicone with approximal contacts consisting three visually non‐cavitated teeth and with the one mesial– occlusal–distal amalgam‐filled tooth in between" Sequence of test(s): CBCT prior to sectioning of teeth Examiner training and calibration: "two experienced dental radiologists each with a minimum 5 years’ experience in the radiology field" Threshold applied: "1, caries definitely not present; 2, caries probably not present; 3, unsure if caries is present or absent; 4, caries probably present; and 5, caries definitely present"; "The observations and scoring were performed for enamel and dentine during separate sessions" Device specifics: "CBCT unit (NewTom 3G; FOV, 9 inches; pixel size, 0.25 mm) at a fixed setting of 110 kV, automatically adjusted milliamperes and a scanning time of 36 s. Volumetric CBCT data were reconstructed and sectioned at 0.25 mm in the mesiodistal tooth plane, by means of proprietary NewTom software"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: not reported Blinding to index test: not reported Multiple tests: no Site selection: sectioned teeth Target condition: "sound surface, carious demineralization to half the thickness of enamel, carious demineralization completely through the enamel, demineralization through the enamel and into one‐third of the dentin and, finally, deeper dentin demineralization"
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data used for surface B (not adjacent to amalgam) for observer 1
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Kutcher 2006.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: not reported Teeth: molars and premolars Sealants: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: USA Setting: extracted teeth Number of participants/teeth/sites: 40 teeth/80 sites Prevalence: enamel 0.63, dentine 0.30
Index tests	Category of test: digital bitewing radiographs (3 different viewing situations ‐ in terms of level of lighting) Model set‐up: attempted to replicate an in vivo setting, but no mention of method used to simulate presence of soft tissue (= concerns over applicability) Sequence of test(s): 1) radiography (sessions were at least 2 weeks apart and sequence was random = blinding), 2) histology Examiner training and calibration: 6 senior dental students and 6 full‐time dental faculty members. Observers given written and verbal instructions before each observation session Threshold applied: a 5‐point confidence scale was used, with the following definitions: 1 = caries definitely absent, 2 = caries probably absent, 3 = unsure if caries absent or present, 4 = caries probably present, and 5 = caries definitely present (= concerns over applicability) Device specifics: imaged with storage phosphor plates using bitewing projection geometry. Plates were scanned at a resolution of 300 dpi and saved in lossless TIF format. Observers were encouraged to expand the image to its actual pixel size and to use software magnifying and brightness adjustment tools as desired. Other adjustments were not permitted. Study images were displayed on the same laptop computer for all sessions
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: not reported Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: 400 µm thick sections of the teeth were examined with a dissecting microscope Target condition: presence or absence of caries as well as caries depth was determined
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper; used the data for the mean of the 6 faculty observers (i.e. not the student observers); used the 'dim' light condition as this seems like the most clinically relevant (other conditions were both in bright light but 1 was hooded)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Lazarchik 1995.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: not reported Teeth: permanent premolars and molars Sealants: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: unclear Setting: extracted teeth Number of participants/teeth/sites: 100 teeth Prevalence: "79% caries with 67% dentin caries"
Index tests	Category of test: conventional radiograph Model set‐up: embedded in plaster blocks Sequence of test(s): index then reference Examiner training and calibration: 15 dental students, 14 senior dental students, 15 dental school staff, brief introduction provided Threshold applied: caries: definitely/probably present, definitely/probably not present Device specifics: Kodak Ultraspeed 50 kVp, 10 mA
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index then reference Training of examiner: not reported Blinding to index test: not reported Multiple tests: no Site selection: sectioned teeth Target condition: "depth of caries"
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Unclear
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	No
If a threshold was used, was it pre‐specified?	Unclear
If multiple tests were applied were different examiners used for each (in vivo)?
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Lussi 2006.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation Teeth: permanent molars Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Switzerland Setting: extracted teeth Number of participants/teeth/sites: 75 teeth/150 sites Prevalence: enamel 0.59, dentine 0.25
Index tests	Category of test: conventional bitewing Model set‐up: "The tooth under study was then placed in‐between two teeth mannequin. The roots were embedded in composite to arrange these three teeth in a manner that simulated contact points of adult teeth. Soft tissue was not simulated" Sequence of test(s): index tests (radiograph, visual and DIAGNOdent) performed prior to reference standard Examiner training and calibration: "examined by 5 experienced dentists on a backlit screen" Threshold applied: "no radiolucency, radiolucency in the outer, inner half of enamel or in dentine" Device specifics: "using Kodak Insight films (22 x 35 mm, Kodak, Rochester, Minn., USA). The X‐ray machine (HDX Dental EZ, USA) was set to 65 kV and 7 mA and an exposure time of 0.14 s was used"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: sound, inner/outer enamel, inner/outer dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Matos 2011.

Study characteristics
Patient Sampling	Method of sampling: random Included conditions: sound, early/enamel lesions, no frank occlusal cavitations, no restorations, no presence of hypoplastic pits, no presence of large carious lesions on smooth or proximal surfaces Teeth: primary molars Sealants: not reported Surface: occlusal
Patient characteristics and setting	Age: mean 7.3 years (range 4 to 12 years) Sex: 30 males, 38 females Ethnicity: not reported Country: Brazil Setting: university dental hospital (in vivo) Number of participants/teeth/sites: 68 participants/407 teeth/407 sites Prevalence: enamel 0.92, dentine 0.05
Index tests	Category of test: conventional bitewing radiography (film) Model set‐up: in vivo (= low concern for applicability) Sequence of test(s): 1) visual, 2) radiography, 3) laser fluorescence DIAGNOdent pen, 4) fluorescence camera (VistaProof), 5) operative treatment/excavation (only if dentine caries diagnosed for methods 1 or 2) Examiner training and calibration: 2 examiners did all tests. 1 benchmark examiner trained them with 3 patients (21 sites) for each method, but no calibration procedure. The 2 examiners were PhD students with previous experience in using the methods in research and clinical practice. Benchmark examiner was a senior lecturer with extensive experience in using these methods in several research projects Threshold applied: no radiolucency visible (0), radiolucency visible in enamel (1), radiolucency visible in dentine but restricted to the outer half of dentine (2), and radiolucency extending to the inner half of dentine (3) (= low concern for applicability) Device specifics: the X‐ray machine was set to 70 kV and 8 mA, and the exposure time was 0.3 s. The radiographs were taken with bitewing holders and the focus‐to‐film distance was 40 cm
Target condition and reference standard(s)	Category: for enamel caries: visual (ICDAS); for dentine caries: operative treatment (excavation) ‐ based on diagnosis of dentine caries from the visual and/or radiographic test Sequence of index test and reference standard: as above (see index test) Training of examiner: as above (see index test) Blinding to index test: no (for enamel caries, the reference standard (visual) was first and therefore interpreted without knowledge of the index test; dentine caries, as diagnosed by visual and/or radiographic tests, was verified by excavation so there may have been some influence) Multiple tests: yes Site selection: drawing of the occlusal surface was made to indicate the selected site for each tooth Target condition: ICDAS: 0 (sound tooth), 1 (first visual change in enamel), 2 (distinct visual change in enamel), 3 (localized enamel breakdown), 4 (underlying dark shadow from dentine), 5 (distinct cavity with visible dentine), and 6 (extensive distinct cavity with visible dentine) and radiography scoring (see index test) ‐ verified by checking the cavity with an explorer to distinguish between carious or sound dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 24 surfaces not included in enamel caries analysis due to lack of agreement between the examiners when using the visual reference standard; those suspected of dentine caries also had excavation to verify this and therefore this was not the same for those suspected of only having enamel caries
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper; used the data for examiner 1
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	No
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	No
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		High risk

Mendes 2006.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: non‐cavitated Teeth: primary molars Sealants: not reported Restorations: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 79 teeth/110 sites Prevalence: enamel 0.75, dentine 0.25
Index tests	Category of test: conventional bitewing Model set up: not reported Sequence of test(s): visual, then DIAGNOdent, then radiograph; prior to reference standard Examiner training and calibration: each method assessed in separate sessions by 2 examiners Threshold applied: sound, enamel, inner/outer dentine Device specifics: Insight 22 x 35 mm, Spectro 70 Xd set at 70 kV, 8 mA, 0.3 s exposure
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: not reported Multiple tests: no Site selection: marked on tooth then sectioned Target condition: sound, outer half of enamel, inner half of enamel, outer half of dentine, deep dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Mialhe 2003.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: unclear: "low caries prevalence (DMFT = 1.4)" Teeth: permanent premolars and molars Sealants: not reported Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: 13 to 15 years, Sex: not reported Ethnicity: not reported Country: Brazil Setting: school‐based recruitment Number of participants/teeth/sites: 70 participants/199 teeth (in the final sample) Prevalence: enamel (no cavitation) 0.85; dentine (cavitation) 0.14
Index tests	Category of test: conventional radiograph Sequence of test(s): index tests performed prior to reference standard Examiner training and calibration: 1 examiner for each test (visual, radiograph, and FOTI) Threshold applied: sound, outer/inner enamel, outer/inner dentine Device specifics: "using Kodak Ekta Speed Plus film (Kodak, Rochester, New York, USA) and film holders (Indusbello, Londrina, Parana, Brazil). The film was developed in an automatic processor (Gendex GXP, Gendex Corporation, Illinois, USA)"
Target condition and reference standard(s)	Category: visual after separation: "an orthodontic rubber ring (G&H Wire Company, Greenwood, IN) was placed with dental floss tied around the contact point of the teeth surfaces in which carious lesions had been detected. The rings were removed 24 h later and the surfaces were cleaned with dental floss and dried before examination" Sequence of index test and reference standard: index test followed reference standard Training of examiner: 3 examiners jointly decided Blinding to index test: unlikely Multiple tests: no Site selection: visual assessment of surface Target condition: sound no cavitation, cavitation
Flow and timing	Participants with index test but no reference standard: 20 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	No
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		High risk

Mitropoulos 2010.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: sound, early/enamel lesions, no cavitation (no distinct enamel breakdown on either 1 or both of their proximal surfaces) Teeth: molars and premolars Sealants: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Greece Setting: extracted teeth Number of participants/teeth/sites: 20 teeth/40 sites Prevalence: enamel 0.60, dentine 0.45
Index tests	Category of test: 1) conventional radiography; 2) digital radiography; 3) microcomputed tomography Model set‐up: does not appear to have been any attempt to replicate an in vivo setting (= concerns over applicability) Sequence of test(s): 1) visual, 2) radiography and histology (precise sequence not stated ‐ but classified blindly and with a 10‐day break between viewings for each modality) Examiner training and calibration: 2 experienced dentists with an interest in cariology. Calibration performed through a prior pilot study, in which 8 proximal surfaces (not included in main study) were examined with each modality and consensus agreement was achieved Threshold applied: 0 = no lesion, E1 = demineralisation confined to outer half of the enamel, E2 = demineralisation extending to the inner half of the enamel, D1 = demineralisation extending to dentine Device specifics: ‐ conventional and digital: for conventional, an F‐speed film was used and the X‐ray unit was set in 60 kV and 7 mA with 0.139 s exposure time. For digital, same X‐ray unit and a CCD sensor were used at 70 kV, 7 mA and 0.096 s exposure time, with the sensor set on the high‐resolution mode ‐ microcomputed tomography: digital sectional images were acquired with a microcomputed tomography scanner under the following irradiation conditions: 100 kV accelerating voltage, 98 mA beam current, 1 mm Al filter, 8.09 mm pixel size at 1024 x 1024 resolution, 1808 rotation at 0.238 step, 6 s exposure time per step and averaging by 2 frames. The duration of the full scan time was depended on the size of the examined teeth and ranged from 1.5 to 2 hours
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: as above (see index test) Training of examiner: as above (see index test) Blinding to index test: yes ‐ although not clear if reference standard was last, they were "classified blindly... with a 10‐day intermission among the different modalities" Multiple tests: no Site selection: "longitudinally bisected... in the centre of the suspected carious lesion" Target condition: 0 = no lesion, E1 = caries extended to outer half of the enamel, E2 = caries extending to the inner half of the enamel, D1 = caries extending to dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from cross tabs; used the data for examiner 1
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Mortensen 2018.

Study characteristics
Patient Sampling	Method of sampling: sites selected in each participant Included conditions: non‐cavitated and enamel lesions: "various stages of occlusal caries" Teeth: permanent molars Sealants: unclear Surface: occlusal
Patient characteristics and setting	Age: 20 to 66 years Sex: 21% male Ethnicity: not reported Country: Denmark Setting: university setting: patients, employees, and students Number of participants/teeth/sites: 57 participants/60 sites Prevalence: enamel 0.97, dentine 0.45 (ICDAS 3 and above)
Index tests	Category of test: bitewing unsure of conventional or digital Model set‐up: clinical setting Sequence of test(s): index test then reference standard, ordered: ECM (CarieScan), then DIAGNOdent pen then visual and bitewing radiograph Examiner training and calibration: experienced and trained Threshold applied: 0 = no radiolucency, 1 = radiolucency of the outer half of the enamel, 2 = radiolucency of the inner half of the enamel, 3 = radiolucency limited to the outer third of the dentine, 4 = radiolucency reaching the middle third of the dentine, 5 = radiolucency reaching the inner third of dentine, clinically cavitated, 6 = radiolucency into the pulp, clinically cavitated Device specifics: not described
Target condition and reference standard(s)	Category: visual (ICDAS) Sequence of index test and reference standard: reference standard follows ECM and DIAGNOdent pen Training of examiner: experienced examiners Blinding to index test: no Multiple tests: no, only visual used Site selection: first examiner labelled the location on a plan Target condition: ICDAS 1 to 5
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0 Unclear patient flow, 5 dropped out, of which 2 were excluded, 3 failed to attend repeat examinations
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	No
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	No
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Low risk

NCT02657538.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: sound or early enamel lesions: "at least one non‐restored interdental surface with either an approximal enamel caries and/or a sound tooth surface in the posterior teeth" Teeth: permanent premolars and molars Sealants: not reported Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: minimum age of 15 years; mean age: 27.5 years, range of age: 18 to 37 years Sex: 11 male, 24 female Ethnicity: not reported Country: Switzerland Setting: dental hospital ‐ restorative department Number of participants/teeth/sites: 35 participants/70 teeth Prevalence: enamel 0.56, dentine 0.03
Index tests	Category of test: digital radiograph Sequence of test(s): radiograph and NIR transillumination performed prior to tooth separation but assessed after tooth separation, with blinding to results of reference standard Examiner training and calibration: 2 investigators ‐ calibration performed for ICDAS and DIAGNOcam, unclear for radiograph Threshold applied: 0: sound surfaces; 1: first visible signs of enamel caries; 2: established caries lesion without any contact to the enamel‐dentine junction; 3: established enamel caries with an isolated spot reaching the enamel‐dentine junction; 4: dentine caries penetrating the enamel‐dentine junction linearly (broad contact to the enamel‐dentine junction); 5: deep dentine caries lesion with visible shadow in the dentine. The rating of the bitewing radiographs was done from D0 to D4 Device specifics: radiograph methods not clearly described
Target condition and reference standard(s)	Category: visual ‐ with additional impression of separated surfaces Sequence of index test and reference standard: NIR not likely to effect results of reference standard Training of examiner: same examiners as index test Blinding to index test: unclear Multiple tests: visual and radiograph performed before NIR, same examiners for all, but visual assessed before radiograph Site selection: all surfaces Target condition: ICDAS II criteria
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Currently unpublished, authors provided draft publication
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	No
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Neuhaus 2011.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: not reported Teeth: primary molars (first and second) Sealants: not reported Restorations: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Switzerland Setting: extracted teeth Number of participants/teeth/sites: 37 teeth/37 sites Prevalence: enamel 0.73, dentine 0.24
Index tests	Category of test: conventional bitewing Model set‐up: not reported Sequence of test(s): index tests (visual, DIAGNOdent devices then radiograph) then reference standard Examiner training and calibration: unclear: "examined independently" Threshold applied: sound, enamel, inner/outer dentine Device specifics: "using an X‐ray machine (HDX Dental EZ, USA) and double Kodak Insight films (22 × 35 mm, Kodak, Rochester, MN, USA) at 65 kV, 7 mA and an exposure time of 0.09 s"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: not reported Multiple tests: no Site selection: unclear Target condition: sound, outer half of enamel, inner half of enamel, outer half of dentine, deep dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Novaes 2009.

Study characteristics
Patient Sampling	Method of sampling: random Included conditions: no cavitation and early lesions Teeth: primary molars (first and second) Sealants: unclear Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: 5 to 12 years, mean 7.7 Sex: 21 male, 29 female Ethnicity: not reported Country: Brazil Setting: dental hospital Number of participants/teeth/sites: 50 participants/621 sites Prevalence: enamel 0.41, dentine 0.03
Index tests	Category of test: conventional bitewing Model set‐up: clinical setting Sequence of test(s): index tests (visual, radiograph, DIAGNOdent pen) then reference standard Examiner training and calibration: no formal calibration, 2 examiners carried out all examinations Threshold applied: sound, enamel, inner/middle/outer dentine Device specifics: "The X‐ray machine (Spectro 70 X, Dabi Atlante, Ribeirão Preto, Brazil) was set to 70 kV, 8 mA and the exposure time was 0.3 s. The radiographs were taken with bitewing holders (Jon Han‐Shin PF 682, Jon Ind., São Paulo, Brazil), and the focus‐to‐film distance was 40 cm. Kodak insight radiographic films (22 x 35 mm, Eastman Kodak, Rochester, USA) were used"
Target condition and reference standard(s)	Category: visual ‐ separators Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: approximal surface Target condition: sound, white spot, cavitated
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: 1 week to allow for separation of teeth Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Novaes 2010.

Study characteristics
Patient Sampling	Method of sampling: randomly selected, although precise methods are unclear Included conditions: no cavitation and early lesions Teeth: primary molars Sealants: unclear Surface: approximal: "exams were performed on the distal face of first primary molars, the mesial face of second primary molars and also the distal face of second primary molars"
Patient characteristics and setting	Age: 4 to 12 years, mean 7.25 Sex: 32 male, 44 female Ethnicity: not reported Country: Sao Paulo, Brazil Setting: dental hospital Number of participants/teeth/sites: 76 participants/168 teeth/592 sites Prevalence: enamel 0.81, dentine 0.05
Index tests	Category of test: conventional radiographs Model set‐up: clinical setting Sequence of test(s): index tests (randomly ordered: visual, radiograph, DIAGNOdent pen) then reference standard Examiner training and calibration: trained but no calibration Threshold applied: sound, enamel, dentine Device specifics: "X‐ray machine (Spectro 70 X, Dabi Atlante, Ribeirão Preto, Brazil) was set to 70 kV, 8 mA, and the exposure time was 0.3 s. The radiographs were taken with bitewing holders (Jon Han‐Shin PF 682, Jon Ind., São Paulo, Brazil), and the focus‐to‐film distance was 40 cm. Kodak Insight radiographic films"
Target condition and reference standard(s)	Category: visual ‐ separators Sequence of index test and reference standard: index tests then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: approximal surface Target condition: sound, white spot, cavitated
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: 1 week to allow for separation of teeth Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Novaes 2012.

Study characteristics
Patient Sampling	Method of sampling: randomly selected, although precise methods are unclear: "randomly selected using the enrolment or history form of each child" Included conditions: no cavitation and early lesions Teeth: primary molars: "first and second was present" Sealants: unclear Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: 4 to 12 years, mean 7.4 Sex: 32 male, 44 female Ethnicity: not reported Country: Sao Paulo, Brazil Setting: dental hospital: "children seeking dental treatment" suggests there will be some caries Number of participants/teeth/sites: 76 participants/344 sites Prevalence: enamel 0.8
Index tests	Category of test: conventional bitewing Model set‐up: clinical setting Sequence of test(s): index tests (visual, radiograph, DIAGNOdent pen) then reference standard Examiner training and calibration: trained but no calibration, assessed independently by 2 trained examiners Threshold applied: sound, or enamel: "radiolucency visible in the enamel was classified as the presence of caries lesions" Device specifics: "with bitewing holders (Jon Han‐Shin PF 682, Jon Ind., São Paulo, Brazil). Kodak Insight radiographic films (22 × 35 mm, Eastman Kodak, Rochester, USA) were used"
Target condition and reference standard(s)	Category: visual ‐ separators Sequence of index test and reference standard: index tests then reference standard Training of examiner: yes Blinding to index test: unclear Multiple tests: no Site selection: approximal surface Target condition: sound and caries (including: white spot, cavitation)
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: 1 week to allow for separation of teeth Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Novaes 2012a.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: unclear Teeth: primary molars: "recently extracted primary molars were selected" Sealants: not reported Restorations: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Sao Paulo, Brazil Setting: extracted teeth Number of participants/teeth/sites: 77 teeth/113 sites Prevalence: enamel 0.57, dentine 0.17
Index tests	Category of test: conventional bitewing Model set‐up: fixed on a silicon base Sequence of test(s): index tests (radiograph, visual, DIAGNOdent, VistaProof) then reference standard Examiner training and calibration: trained but no calibration, assessed independently by 2 trained examiners Threshold applied: sound, inner/outer enamel, inner/outer dentine Device specifics: "X‐ray machine (Spectro 70X; Dabi Atlante, Ribeirao Preto, Brazil) at 70 kV, 8 mA and Kodak Insight radiographic films (22 x 35 mm; Eastman Kodak, Rochester, MN, USA) were used. The exposure time was 0.3 s, and the focus‐to‐film distance was 40 cm"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: not reported Blinding to index test: not reported Multiple tests: no Site selection: sectioned teeth Target condition: "D0 – no caries; D1 – caries lesion limited to the outer half of the enamel, D2 – caries extending into the inner half of the enamel, D3 – caries limited to the outer half of the dentine, D4 – caries involving the inner half of the dentine"
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Pakkala 2012.

Study characteristics
Patient Sampling	Method of sampling: unclear: "One hundred extracted human premolars and molars were used for the experiment" Included conditions: unclear: "None had approximal lesion cavitation" Teeth: permanent premolars and molars Sealants: not reported Restorations: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Denmark Setting: extracted teeth Number of participants/teeth/sites: 100 teeth/160 sites Prevalence: enamel 0.37, dentine 0.03
Index tests	Category of test: conventional bitewing (study investigates 3 different screens) Model set‐up: "mounted in 20 silicone blocks of 5 teeth each: 1 canine (non‐test tooth), 2 premolars and 2 molars. They were placed in an anatomical position with approximal surfaces in contact. The blocks were placed in a jig to provide a central beam orientation" Sequence of test(s): index tests (radiograph) then reference standard Examiner training and calibration: "Two dentists in their first year of specialist training in oral radiology and a specialist" Threshold applied: "0 = no lesion, 1 = a carious lesion extending no further than half the depth of the enamel, 2 = a carious lesion extending deeper than half the depth of the enamel and 3 = a carious lesion extending into the dentine" Device specifics: "a storage phosphor plate system (Digora FMX, Soredex, Helsinki, Finland)... radiographed individually under standard conditions (65 kVp, 10 mA, paralleling technique, rectangular collimation with a 20‐millimetre tooth receptor distance and a 320‐millimetre focus‐to‐receptor distance) with an intraoral X‐ray unit (Gendex 1000 DC X‐ray unit, Gendex, Des Moines, Ill, USA)"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: not reported Blinding to index test: not reported Multiple tests: no Site selection: sectioned teeth Target condition: sound and enamel/dentine caries
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Dell screen used with 15 Lux level in results, as closest to those commonly used in practice
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Pontual 2010.

Study characteristics
Patient Sampling	Method of sampling: unclear: "a sample of 80 unrestored extracted human permanent teeth, 40 premolars and 40 molars, was used in this study" Included conditions: "without cavitations and ranged from sound to varying degrees of demineralization" Teeth: permanent premolars and molars Sealants: not reported Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 80 teeth/152 sites Prevalence: enamel 0.42, dentine 0
Index tests	Category of test: conventional bitewing and digital bitewing (3 types Digora blue and white, DenOptix) Model set‐up: "mounted in a block of silicone in an anatomical position"; "A 15 mm acrylic plate was placed between the tube and the teeth to simulate soft tissue" Sequence of test(s): index tests (conventional then digital radiograph) then reference standard Examiner training and calibration: "17 observers viewed the conventional and digital radiographs" Threshold applied: "0, sound; 1, caries restricted to the outer half of the enamel; 2, caries in the inner half of the enamel up to the enamel–dentine junction; 3, caries in dentine" Device specifics: "teeth were radiographed with Insight film (Eastman Kodak, Rochester, NY)"; "The X‐ray unit was a GE 1000 X‐ray machine (General Electric Company, Milwaukee, WI), operating at 70 kVp, 10 mA" ‐ conventional: "exposure time used for the Insight film was 0.35 s, which resulted in a density of 1.0" ‐ digital: "the exposure time was as follows: 0.25 s for Digora (blue plate), 0.13 s for Digora (white plate) and 0.20 s for DenOptix"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: not reported Blinding to index test: not reported Multiple tests: no Site selection: sectioned teeth Target condition: sound and enamel/dentine caries
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 8 "The histological examination of the sample showed that eight of the carious lesions extended into the dentine. These eight surfaces were excluded from the sample, since the purpose of the present study was to evaluate the radiographic detection of enamel approximal caries" The reasons for the excluded samples is clear and provides analysis which directly responds to our research question, so low risk of bias
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Low risk

Ramezani 2016.

Study characteristics
Patient Sampling	Method of sampling: not reported Included conditions: "sound to discolored with no macroscopic cavitations" Teeth: permanent molars ‐ removed for periodontal reasons Sealants: not applicable Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Iran Setting: extracted teeth Number of participants/teeth/sites: 88 teeth Prevalence: enamel 0.93, dentine 0.33
Index tests	Category of test: digital and CBCT Model set‐up: "mounted inside the Ross wax. For reconstruction of soft tissues, teeth were put in water" Sequence of test(s): index tests (radiographs and CBCT) performed prior to reference standard Examiner training and calibration: "Three independent observers" Threshold applied: "1’= Radiolucency reaching the pulpal third of the dentine, 2’= Radiolucency in the middle third of the dentine, 3’= Radiolucency in the outer third of the dentine, 4’= Radiolucency confined to the enamel, 5’= No radiolucency" Device specifics: "Digital radiographs were obtained using digital sensor size 2 (Minary, Sordex, Tussula, Finland) and periapical radiographic device (Soredex company, Helsinki, Finland). Exposure condition was standard (T = 0/06 s, KVP = 60, mA = 7.20 cm tube‐tooth distance). The sensors were scanned in an Optime scanner (Sordex company, Helsinki, Finland). Images were saved in Scanora software"; "CBCT data was acquired from NewTom 3G system (Verona, Italy) in an FOV of 6 inches and voxel size of 200 µm with the standard condition (T = 0.6 s, KVP = 110, mAs = 1.80)"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: assumed index test then reference standard but not clearly stated, potential that reference standard could have informed index test Training of examiner: not reported Blinding to index test: unclear whether same examiners as index test Multiple tests: no Site selection: sectioned teeth Target condition: same 5‐point scale as the index test
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Rathore 2012.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: sound or early lesions: "Any teeth that had large cavitated surfaces or restorations were excluded" Teeth: permanent premolar and molar Sealants: not reported Restorations: exclusions Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: US Setting: extracted teeth Number of participants/teeth/sites: 60 teeth Prevalence: enamel 0.45
Index tests	Category of test: CBCT and digital radiograph Model set‐up: "human dried mandible with a set of teeth placed in wax was used to simulate the patient's dental structures and soft tissues"; "The mandible was surrounded by a plexiglass box to simulate soft tissues" Sequence of test(s): index tests images (CBCT then radiograph) viewed at same time as reference standard Examiner training and calibration: "two radiologists, two radiology residents and two general dentists" Threshold applied: 1 = caries definitely absent, 2 = caries probably absent, 3 = unsure if caries absent or present, 4 = caries probably present and 5 = caries definitely present. "...scores of 1, 2 and 3 representing a negative finding (caries absent) and scores of 4 and 5 representing a positive finding (caries present)" Device specifics: ‐ CBCT: "using the Galileos (Sirona) CBCT unit"; "exposure parameters for the CBCT were set at 85 kVp and 21 mAs, with a total exposure time of 2–4 s" ‐ digital radiograph: "using a Planmeca (Planmeca Oy, Helsinki, Finland) intraoral source and a (Gendex Dental Systems, Hatfield, PA) photostimulable phosphor (PSP) imaging system. The exposure parameters for this system were set at 70 kVp and 3.2 s" Note: "Six observers viewed all the images from both the modalities"; "The observers had the flexibility to scroll through the entire volume of images for each of the 60 teeth" ‐ this suggests that the same observer viewed index test and reference standard and the results of the reference standard could affect the index test
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: not reported Blinding to index test: not reported Multiple tests: no Site selection: sectioned teeth Target condition: sound and caries
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: 1 week to allow for separation of teeth Participants receiving both tests but excluded from results: 0
Comparative
Notes	Mean values from table 1 in paper used for data extraction
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	No
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Rocha 2003.

Study characteristics
Patient Sampling	Method of sampling: selected: "Fifty occlusal sites were selected for this study" Included conditions: no cavitation and early lesions Teeth: primary molars Sealants: excluded Restorations: excluded Surface: occlusal
Patient characteristics and setting	Age: 10 to 11 years Sex: not reported Ethnicity: not reported Country: Brazil Setting: children with teeth close to exfoliation Number of participants/teeth/sites: 29 participants/50 sites Prevalence: enamel 0.58, dentine 0.14
Index tests	Category of test: conventional bitewing Model set‐up: clinical setting Sequence of test(s): DIAGNOdent, visual, radiograph followed by reference standard Examiner training and calibration: previously trained: "independently by 2 previously trained examiners" Threshold applied: sound, enamel, outer/mid/inner dentine Device specifics: "using a Siemens Heliodent 60B apparatus (60 kV, 10 mA, 0.4 s; Siemens, Munich, Germany) with bitewing positioners (Jon Han‐Shin PF 682, Jon Ind., Sao Paulo, Brazil) and Kodak Insight No 2 radiographic films (Eastman Kodak, Rochester, USA)"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test conducted before reference standard Training of examiner: not reported Blinding to index test: yes Multiple tests: no Site selection: sectioned tooth Target condition: sound, outer enamel, inner enamel and first third dentine middle and inner dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Rockenbach 2008.

Study characteristics
Patient Sampling	Method of sampling: unclear: "included 51 molars and 24 premolars, sound or with small proximal cavities, and without restorations" Included conditions: no cavitation and early lesions Teeth: permanent molars and premolars Sealants: not reported Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 75 teeth set in 25 different models consisting of 3 teeth each, this produced 4 proximal surfaces per model, therefore 100 sites reported Prevalence: enamel 0.72, dentine 0.23
Index tests	Category of test: conventional bitewing and 3 versions of digital bitewing Model set‐up: "affixed in blocks of silicone surrounded by an approximately 10 mm thick layer around the roots. Dental wax of 10 mm thickness was placed in front of the teeth to simulate soft‐tissue" Sequence of test(s): radiographs followed by reference standard: "interpreted individually by one examiner in three different viewing sessions considering all imaging modalities. A period of at least one week separated each viewing session and the radiographs were selected randomly" Examiner training and calibration: not reported Threshold applied: sound, enamel, dentine Device specifics: "Timex‐70X DRS (Gnatus, Ribeirão Preto, SP, Brazil) X‐ray machine, operating with 70 kVp, 7 mA and with HVL of 2.5 mm Al. The focus‐film distance was 40 cm" ‐ conventional: "were obtained utilizing periapical film no. 2, IP‐21 InSight (Eastman Kodak Co., Rochester, NY, USA). The exposure time used was 0.40 s" ‐ digital: "phosphor plates (31´41 mm) of the DenOptixTM system (Gendex®, Des Plaines, IL, USA). The exposure time used was 0.50 s"; "the digital system Digora® (Soredex, Orion Co., Helsinki, Finland) which also used storage phosphor plates. The exposure time used was 0.32 s. The imaging plates (30´40 mm) were scanned in the Digora® scanner"; "the CygnusRay MPS system (Progeny, Buffalo Grove, IL, EUA) with a charge‐coupled device"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test conducted before reference standard Training of examiner: "Microscopic analysis was performed by two observers, both experienced in histological assessments" Blinding to index test: not reported Multiple tests: no Site selection: sectioned tooth Target condition: sound, enamel and dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Conventional (film) and Digora used for data analysis
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Rodrigues 2008.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions Teeth: permanent molars Sealants: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Switzerland Setting: extracted teeth Number of participants/teeth/sites: 119 teeth Prevalence: enamel 0.93, dentine 0.54
Index tests	Category of test: conventional radiograph Sequence of test(s): DIAGNOdent, DIAGNOdent pen, VistaProof, visual, radiograph all prior to reference standard Examiner training and calibration: experienced Threshold applied: sound, enamel, inner/outer dentinal Device specifics: "X‐ray machine (HDX Dental EZ, USA) and double Kodak Insight films (22 x 35 mm, Kodak, Rochester, Minn., USA) at 65 kV, 7 mA and exposure time of 0.09 s. An automatic X‐ray film developer XR 24 Pro (Dürr Dental)"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests conducted before reference standard Training of examiner: not reported Blinding to index test: yes Multiple tests: no Site selection: sectioned teeth Target condition: sound, enamel, outer dentine, inner dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Safi 2015.

Study characteristics
Patient Sampling	Method of sampling: not reported Included conditions: sound or non‐cavitated Teeth: permanent molars and premolars Sealants: not applicable Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Iran Setting: extracted teeth Number of participants/teeth/sites: 42 teeth/84 surfaces Prevalence: enamel 0.36, dentine 0.23
Index tests	Category of test: conventional and digital bitewings, and CBCT Model set‐up: "three test teeth and one non‐test tooth in silicone blocks"; "In the use of intraoral modalities, a 12 mm acrylic plate was applied as fake soft tissue [9] between the tube and the mounted tooth. During the CBCT exposures, a water phantom [3] was placed around the blocks to resemble soft tissue" Sequence of test(s): index tests (radiographs and CBCT) performed prior to reference standard Examiner training and calibration: 4 expert independent observers, working independently Threshold applied: no caries, enamel, inner/outer dentine Device specifics: ‐ bitewing: "1) Digora‐fmx with blue plates [Sordex, Helsinki, Finland] and 2) Kodak (Espeed) Insight film (size2) [Eastman Kodak Company, Rochester, NY, USA]. The digital pictures were taken at 70 kvp, 8 mA but the exposure time was reduced to 0.08 s. The focus‐tooth and tooth‐receptor distances were 32 and 2 cm, respectively. The software used for processing PSPs was Digora for windows 2.8. The conventional images were exposed with an X‐ray unit operated at 70 kvp, 8 mA and exposure time of 0.16 s. The focus‐tooth length was 32 cm and the tooth ‐ receptor distance was 2 cm" ‐ CBCT: "Newtom VGI [Quantitative Radiology, Verna, Italy] in selected FOV 6×6cm, high resolution at a fixed 110 kvp setting and auto‐adjusted milliamperes. The blocks were scanned for 36 s"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: assumed index test then reference standard Training of examiner: "experienced maxillofacial pathologist" Blinding to index test: yes, separate examiner Multiple tests: no Site selection: sectioned teeth Target condition: same 5‐point scale as the index test
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Schulze 2004.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: sound, early/enamel lesions, no cavitations, no restorations Teeth: 10 molars, 9 premolars, 15 canines, 86 incisors Sealants: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Germany Setting: extracted teeth Number of participants/teeth/sites: 120 teeth/240 sites Prevalence: enamel 0.33, dentine (no data)
Index tests	Category of test: conventional radiography ‐ compared 3 different types of film Model set‐up: "each pair was mounted side by side.... in such a way that an interproximal contact was resembled." Consequently, the sample comprised 240 approximal sides, of which only 120 (50%) were in tooth‐to‐tooth contact (= concerns over applicability). A soft tissue scatter equivalent of 14 mm thick PMMA was placed in the path of the beam Sequence of test(s): 1) radiography (in random order with viewing sessions at least 24 hours apart = blinding), 2) histology Examiner training and calibration: 10 dentists of the Dental School Mainz (postgraduate working experience: 1 to 8 years; mean: 3.5 years); training/calibration not mentioned Threshold applied: 1 = definitely no lesion present, 2 = probably no lesion present, 3 = uncertain whether or not a lesion is present, 4 = probably lesion present, 5 = definitely lesion present (= concerns over applicability) Device specifics: focus‐to‐object distance was 255 mm and the focus‐to‐film distance was 265 mm. By placing each pair of teeth separately with its wax mount in the corresponding notch of the optical bench, a projection geometry was obtained in which the central X‐ray passed orthogonally through the interproximal contact. To obtain information on the appropriate exposure times for each film, 1 pair of incisors was exposed over a wide time range (0.08 to 0.40 seconds) with each film type. Darkest and brightest areas of each film were measured with an optical densitometer and the exposure time that resulted in maximum optical density values of approximately 2.0 as recommended by ISO 5799‐1991 was selected for each film. For all pairs of teeth, the resulting times for the evaluated radiographs were 0.20 seconds for Ultraspeed, 0.12 seconds for Ektaspeed and 0.10 seconds for Insight. All pairs of teeth were then exposed with all film types under these conditions and subsequently automatically processed in fresh solution
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: reference standard last Training of examiner: not reported Blinding to index test: yes ‐ assumed as it is histology Multiple tests: no Site selection: each tooth was hemisectioned in mesio‐distal direction perpendicular to the X‐ray beam in such a way that visible stained carious lesions were separated centrally. In case of no clinically visible carious lesion, hemisectioning was performed through the middle of the interproximal side of each tooth Target condition: 9 depth categories: 0 = no lesion, 1 = lesion depth 0.1 mm through 0.3 mm, 2 = lesion depth 0.4 mm through 0.6 mm, 3 = lesion depth 0.7 mm through 0.9 mm, 4 = lesion depth 1.0 mm through 1.2 mm, 5 = lesion depth 1.3 mm through 1.5 mm, 6 = lesion depth 1.6 mm through 1.8 mm, 7 = lesion depth 1.9 mm through 2.1 mm, 8 = lesion depth greater than 2.1 mm. The cut‐off point for the diagnosis 'carious lesion' was defined as microscopically visible lesion either in enamel or in dentine or in both structures, i.e., 'carious lesion' included all categories ≥ 1
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data calculated from sensitivity/specificity and prevalence reported in paper; used mean sensitivity/specificity (from the 10 assessors) reported in table II; used the data for the first column (Ultraspeed film)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Schulze 2008.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: "Unrestored teeth showing either no carious approximal lesions or a very superficial non‐cavitated lesion" Teeth: permanent 33 incisors, 10 canines, 13 premolars, and 44 molars Sealants: not reported Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Germany Setting: extracted teeth Number of participants/teeth/sites: 100 teeth/100 surfaces Prevalence: enamel 0.51, dentine 0.17: "the sample comprised 51 healthy teeth and 49 teeth"
Index tests	Category of test: digital radiographs (study investigated different compression rates of file images) Model set‐up: "Pairs in contact were fixed with their root tips in small plaster cubes"; "A soft‐tissue equivalent of polymethylmethacrylate, 12 mm thick, was positioned just in front of the object" Sequence of test(s): index tests (radiograph) then reference standard Examiner training and calibration: calibration performed on 2 images: "Ten experienced observers (range of working experience = 2–15 years, mean = 6.7 years)" Threshold applied: "1 = certainly no carious lesion present, 2 = probably no carious lesion present, 3 = uncertain, 4 = probably carious lesion present, 5 = certainly carious lesion present" Device specifics: "Using a dental CCD (charged‐coupled device) sensor (full size, Sirona Dental Systems, Bensheim, Germany) the paired tooth samples were exposed (0.05 s) at 60 kV and 7 mA"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: experienced examiners Blinding to index test: unclear Multiple tests: no Site selection: approximal surface Target condition: "0, healthy surface, no lesion; 1, enamel carious lesion; 2, lesion in outer half of dentine; 3, lesion in inner half of dentine"
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Senel 2010.

Study characteristics
Patient Sampling	Method of sampling: not reported: "230 human premolar and molar teeth with and without caries that had been extracted for periodontal or orthodontic reasons" Included conditions: non‐cavitated and early lesions ‐ possibly cavitated but unclear Teeth: permanent molar and premolars Sealants: no Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Turkey Setting: extracted teeth Number of participants/teeth/sites: 230 teeth/276 surfaces Prevalence: enamel = 0.49, dentine = 0.34
Index tests	Category of test: conventional and digital bitewing radiographs, CBCT Model set‐up: "Teeth were embedded in acrylic blocks in groups of five"; "A 1 cm thick acrylic block was placed behind the teeth in each block in order to simulate soft tissue" Sequence of test(s): visual, conventional bitewing radiographs followed by 2 types of digital radiograph and CBCT, then reference standard Examiner training and calibration: 2 examiners used, intraobserver agreement investigated within study Threshold applied: no radiolucency visible; radiolucency visible in enamel; radiolucency visible in dentine, radiolucency in pulp Device specifics: all radiographs used a "Trophy Trex X‐ray unit (Croissy, Beaubourg, France) operated at 65 kVp and 8 mA with a standardized paralleling technique and a focus–receptor distance of 20 cm" ‐ conventional: "using Kodak E speed (size 2) film (Kodak, Rochester, NY) with an image exposure time of 0.40 s" ‐ digital 1: "Progeny Vision DX (size 1) direct digital intraoral CCD sensor (Progeny Dental, Buffalo Grove, IL) with an image exposure time of 0.2 s" ‐ digital 2: "Digora Optime (Soredex, Tuusula, Finland) PSP digital intraoral system" ‐ CBCT: "ILUMA ultra cone beam CT scanner (Imtec Imaging, Ardmore, OK) with a 24.4619.5 cm amorphous silicon flat‐panel image detector and a cylindrical volume of reconstruction up to 21.1 6 14.2 cm. Images were obtained at 120 kVp, 3.8 mA and a voxel size of 0.3 mm, with an exposure time of 40 s"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test before reference standard Training of examiner: "consensus of one of the researchers and a histology specialist" Blinding to index test: not reported, suggests 1 of the examiners used for index tests also examined histology Multiple tests: no Site selection: sectioned teeth Target condition: sound, enamel, or dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Digora Optime test used for results as system has been commonly used in other studies
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	No
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Shimada 2014.

Study characteristics
Patient Sampling	Method of sampling: selected: "Ninety‐one unrestored proximal surfaces of premolars and molars, with/without the possibility of caries, were selected for this study" Included conditions: non‐cavitated and early lesions Teeth: permanent molar and premolars Sealants: no Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: 21 to 64 years (mean 28) Sex: not reported Ethnicity: not reported Country: Japan Setting: Tokyo Medical and Dental University Number of participants/teeth/sites: 53 participants/91 surfaces Prevalence: enamel = 0.67, dentinal = 0.38
Index tests	Category of test: conventional bitewing radiographs Model set‐up: clinical setting Sequence of test(s): visual, bitewing radiographs and OCT, then reference standard Examiner training and calibration: "five dentists each with over 25 years of experience in cariology"; "one experienced examiner (YS) discussed SS‐OCT imaging with the six dentists in a 1‐hour session" Threshold applied: sound, superficial enamel demineralisation, localised enamel breakdown, superficial dentinal caries, deep dentinal caries Device specifics: "group E‐speed films (Kodak Insight Dental Film, Carestream, Atkanta, GA) using a bitewing film holder (X‐Ray Holders, KerrHawe SA, Bioggio, Switzerland) with a 60‐kV X‐ray unit (Sirona Heliodent MD, Siemens, Munich, Germany)" Note: same examiner used for each index test assessment but an attempt made to randomise order of assessments to create some blinding between tests, therefore low risk of bias
Target condition and reference standard(s)	Category: excavation of severe caries, the remainder were visual Sequence of index test and reference standard: index test partly informs reference standard Training of examiner: not reported Blinding to index test: not possible Multiple tests: yes, visual and radiograph; plus excavation Site selection: occlusal surface under investigation Target condition: no caries, enamel, or dentine
Flow and timing	Participants with index test but no reference standard: 6 excluded from results since the approximal surface could not be viewed Participants with reference standard but no index test: 0 Time interval between tests: unclear Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	No
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	No
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		High risk

Simon 2016.

Study characteristics
Patient Sampling	Method of sampling: systematically sampled from attending population, no clear reporting of inclusion criteria regarding the caries status in sampled teeth Included conditions: participants scheduled for orthodontic extractions Teeth: permanent premolars Sealants: not reported Restorations: not reported Surface: occlusal and approximal
Patient characteristics and setting	Age: 12 to 60 years Sex: not reported Ethnicity: not reported Country: US Setting: extracted teeth used for radiographs Number of participants/teeth/sites: 40 participants teeth/109 sites Prevalence: ‐ occlusal: enamel 0.82, dentine not reported ‐ approximal: enamel 0.28, dentine not reported
Index tests	Category of test: digital radiography Model set‐up: "samples were mounted in black orthodontic acrylic blocks (Great Lakes Orthodontics, Tonawanda, NY)" Sequence of test(s): index tests in the clinical setting in the following order: (i) conventional photos; (ii) cross‐polarized near‐IR; (iii) occlusal NIR; (iv) approximal NIR. Digital radiographs followed in the in vitro setting Examiner training and calibration: 1 examiner assessed the NIR and another the radiographs, each was an experienced dentists with over 20 years experience Threshold applied: S = sound; E1 = outer half of enamel; E2 = inner half of enamel; D1 = inner half of dentine; D2 = second half of dentine Device specifics: "using a CareStream 2200 System (Kodak, Rochester, NY) operating at 60 kV"
Target condition and reference standard(s)	Category: histology ‐ polarized light microscopy (PLM) was used for histological examination Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: sound, inner/outer enamel, inner/outer dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Occlusal surfaces reported here
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Souza 2013.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: "occlusal surfaces varying from sound to having different stages of carious lesions" Teeth: primary molars Sealants: no Restorations: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 79 teeth (42 first molars and 37 second molars) Prevalence: enamel 0.76, dentine 0.35
Index tests	Category of test: conventional radiographs Model set‐up: "teeth were mounted individually on a dental model" Sequence of test(s): visual, radiograph, DIAGNOdent, DIAGNOdent pen and VistaProof, then reference standard Examiner training and calibration: "Two experienced examiners independently assessed the teeth" Threshold applied: sound, enamel, outer/mid/inner dentine Device specifics: "using an X‐ray machine (Spectro 60X, Dabi Atlante) and Kodak insight films (22 × 35 mm, Eastman Kodak, Rochester, NY, USA) at 60 kV, 10 mA, and exposure time of 0.2 s. All radiographs were processed by an automatic X‐ray film developer (Dent‐X 9000, Dent‐X, Elmsford, NY, USA)"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test before reference standard Training of examiner: "experienced senior researcher, who did not take part in the examination" Blinding to index test: not reported Multiple tests: no Site selection: sectioned teeth Target condition: enamel, or dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Souza 2014.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions Teeth: permanent Sealants: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 51 teeth/102 surfaces Prevalence: ‐ permanent: enamel 0.48, dentine 0.34 ‐ primary: enamel 0.35, dentine 0.10
Index tests	Category of test: conventional bitewing Model set‐up: "The teeth were fixed with a condensation silicone (Zetaplus, Zhermack SpA, Badia Polesine, Italy). Care was taken to simulate tooth contacts as best as possible, using dental floss to confirm" Sequence of test(s): index tests (radiograph and DIAGNOdent pen (random order)) performed prior to reference standard Examiner training and calibration: experienced Threshold applied: "(0) no radiolucency visible; (1) radiolucency visible in the outer half of the enamel; (2) radiolucency visible in the inner half of the enamel; (3) radiolucency in the outer half of the dentin; and (4) radiolucency in the inner half of dentin" Device specifics: "X‐ray machine (Spectro 60X, Dabi Atlante, Ribeirão Preto, São Paulo, Brazil) and Kodak insight films (22 mm × 35 mm, Eastman Kodak, Rochester, NY, USA) at 60 kV, 10 mA and an exposure time of 0.2 s and 0.4 s for primary and permanent teeth, respectively"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: separate examiner to index test Multiple tests: no Site selection: sectioned teeth Target condition: sound, inner/outer enamel, inner/outer dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Permanent teeth entered here, should enter a second record for primary teeth (true positive = 45, false positive = 64, false negative = 5, true negative = 30)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Souza 2018.

Study characteristics
Patient Sampling	Method of sampling: randomly selected Included conditions: no cavitation and early lesions (large carious lesions excluded) Teeth: primary molars Sealants: not reported Surface: approximal
Patient characteristics and setting	Age: 5 to 9 years Sex: 26 girls, 20 boys Ethnicity: not reported Country: Brazil Setting: clinical setting ‐ dental hospital Number of participants/teeth/sites: 46 participants/195 surfaces Prevalence: enamel 0.41, dentine 0.13
Index tests	Category of test: digital radiograph Sequence of test(s): index tests (fluorescence and radiograph) prior to reference standard Examiner training and calibration: trained and calibrated examiners Teeth cleaning prior to examination: rotating brush and floss Tooth drying prior to examination: unclear Threshold applied: 0 = no caries; 1 = radiolucency extending to the outer half of the enamel; 2 = radiolucency extending to the inner half of the enamel; 3 = radiolucency extending to the outer half of the dentine; 4 = radiolucency extending to the inner half of the dentine Device specifics: "The intraoral X‐ray unit (Dentsply Sirona Dental, York, Pennsylvania USA) was set at 60 kV, 7 mA, using an exposure time of 0.30 s."
Target condition and reference standard(s)	Category: visual after separation Sequence of index test and reference standard: index test then reference standard Training of examiner: agreement reached between 2 examiners Blinding to index test: unclear ‐ same examiner as index test but a week between examinations Multiple tests: no Site selection: approximal surface after separation Target condition: sound, inner/outer enamel, inner/outer dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: 1 week Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Soviero 2012.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: "no enamel developmental defects"; "Proximal surfaces with extensive cavities involving more than half of the proximal surface were excluded" Teeth: primary molars Sealants: not reported Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 25 teeth/48 surfaces Prevalence:enamel 0.81, dentine 0.33
Index tests	Category of test: conventional radiographs and microCT Model set‐up: "mounted in silicone to mimic the contact points" Sequence of test(s): index tests (visual, radiograph, microCT) then reference standard Examiner training and calibration: experienced in clinical and radiographic caries diagnosis and were trained to operate the microCT Threshold applied: sound, outer/inner enamel, outer/inner dentine Device specifics: "using Ektaspeed film n8 2 (Kodak, Rochester, USA), at 70 kV, 8 mA and 0.4 s exposure time (DabiAtlante, Ribeirao Preto, Brasil)"; "Skyscan 1076 MicroCT (Skyscan, Kontich, Belgium) at 100 kV, 100 mA, 9.05 mm pixel size, with Al 1.0 mm filter, rotation step of 0.38 and frame averaging of 4. Mean time of scanning was 1:27 h. Reconstruction was done using NRecon software (Skyscan, Kontich, Belgium)
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: experienced examiners Blinding to index test: unclear Multiple tests: no Site selection: approximal surface Target condition: sound, outer/inner enamel, outer/inner dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: "from two to three weeks" Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Svanaes 2000.

Study characteristics
Patient Sampling	Method of sampling: selected: "a mixture of sound and carious proximal surfaces without adjacent amalgam restorations" Included conditions: sound and early lesions, unclear whether dentinal lesions were involved Teeth: permanent premolars and molars Sealants: not reported Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Norway Setting: extracted teeth Number of participants/teeth/sites: 120 teeth/240 surfaces Prevalence:enamel 0.57, dentine 0.23
Index tests	Category of test: conventional and digital bitewing radiographs Model set‐up: "embedded in a circular, revolving holder with their approximal surfaces in contact" Sequence of test(s): index tests (radiographs) then reference standard Examiner training and calibration: "Three specialists in oral radiology and six postgraduate students training in oral radiology acted as observers" Threshold applied: "C1: caries in the outer half of enamel; C2: caries in the inner half of enamel; C3: caries in the outer half of dentin, and C4: caries in the inner half of dentin" Device specifics: "Ektaspeed Plus (Eastman Kodak, Rochester, N.Y., USA) dental X‐ray films and Digora® (Soredex Medical Systems, Helsinki, Finland) storage phosphor image plates were exposed simultaneously" Note: "The reading order for the observers was randomized and a period of at least 2 weeks separated the sessions"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: experienced examiners Blinding to index test: unclear Multiple tests: no Site selection: approximal surface Target condition: sound, outer/inner enamel, outer/inner dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Tarim 2014.

Study characteristics
Patient Sampling	Method of sampling: unclear Included conditions: non‐cavitated and early lesions: "large cavitated surfaces and dental restorations were not included" Teeth: permanent molars Sealants: excluded Restorations: excluded Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Turkey Setting: extracted teeth Number of participants/teeth/sites: 125 teeth/surfaces Prevalence: enamel 0.75, dentine 0.29
Index tests	Category of test: 4 radiographic tests: 1) conventional, 2) digital (CMOS sensor), 3) digital (PSP plate), 4) CBCT Model set‐up: mounted in a block of silicone paste Sequence of test(s): unclear but assumed to be completed in the order listed above and prior to reference standard, but interpreted in a random order Examiner training and calibration: "Two observers (one pedodontist and one oral and maxillofacial radiologist) independently viewed the image groups in random order", the radiologist had 10 years experience and trained the other examiner Threshold applied: 0 = no caries; 1 = radiolucency extending to the outer half of the enamel; 2 = radiolucency extending to the inner half of the enamel; 3 = radiolucency extending to the outer half of the dentine; 4 = radiolucency extending to the inner half of the dentine Device specifics: ‐ conventional: "using size 2 (3 x 4 mm) F‐speed film (CFSPEEDX, Medex Medical Imaging, Nice, France) and standardized bitewing projection geometry was used. The intraoral X‐ray unit (eXTtend; MyRay, Imola, Italy) was operated at 65 kV, 7 mA with 2.5 mm aluminium equivalent filtration" ‐ digital (CMOS sensor): "using the same intraoral X‐ray unit, but with a size 1 (37 x 24 mm) CMOS sensor (DIGORA Toto; SOREDEX, Milwaukee, Wisc., USA) with the same standardized projection geometry. The CMOS sensors were exposed for 0.12 s" ‐ digital (PSP plate): "using the same intraoral X‐ray unit, but with size 2 (31 x 41 mm) VistaScan blue storage phosphor plates (Dürr Dental, Bietigheim‐Bissingen, Germany) with the same standardized projection geometry. The PSP plates were exposed for 0.12 s" ‐ CBCT: "using a NewTom 5G CBCT system (Verona, Italy) with a 6 x 6 cm field of view in the high‐resolution denture scan mode. The voxel size was 0.075 mm at a fixed 110 kVp setting, automated adjusted milliamperes and a scan time of 36 s. The volumetric data from the CBCT system were reconstructed and sectioned into 0.075‐mm pieces" Images were randomised there was a delay between digital and conventional interpretation, so low risk of bias can be applied despite the same examiner interpreting different tests
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: "experience from several previous in vitro studies" Blinding to index test: unclear but suggests a different examiner Multiple tests: no Site selection: sectioned teeth Target condition: sound, inner/outer enamel, inner/outer dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	CMOS digital sensor used in results for digital
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Tonkaboni 2019.

Study characteristics
Patient Sampling	Method of sampling: not reported Included conditions: "Teeth with large proximal cavitated carious lesions with extensive tooth destruction were excluded and replaced" Teeth: permanent molars and premolars Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Iran Setting: extracted teeth Number of participants/teeth/sites: 108 teeth/324 sites reported Prevalence: contact area and higher ‐ enamel 0.42, dentine 0.35
Index tests	Category of test: conventional radiograph Model set‐up: teeth were mounted in a putty impression Sequence of test(s): index tests (visual, radiograph, VistaCam) then reference standard Examiner training and calibration: not reported Teeth cleaning prior to examination: brushed and scaled Tooth drying prior to examination: yes but technique not reported Threshold applied: 0 = no caries; 1 = radiolucency extending to the outer half of the enamel; 2 = radiolucency extending to the inner half of the enamel; 3 = radiolucency extending to the outer half of the dentine; 4 = radiolucency extending to the inner half of the dentine Device specifics: "using Kodak2200 intraoral Xray system (Eastman, Kodak Co., Rochester, NY, USA) and size 2 Insight film (Eastman Kodak Company, Paris, France). The exposure time was 0.16 s and a CCX intraoral unit with 0.8 mm focal spot, 8 mA, 70 kVp, and aluminum filter was used"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test before reference standard Training of examiner: not reported Blinding to index test: no Multiple tests: no Site selection: sectioned teeth Target condition: sound, outer enamel, inner enamel, outer dentine, inner dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data used from results of site at the contact area or higher
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Virajsilp 2005.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions Teeth: permanent molars Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Thailand Setting: extracted teeth Number of participants/teeth/sites: 72 teeth Prevalence: enamel 0.83, dentine 0.51 (although methods state that molars without obvious cavities were recruited)
Index tests	Category of test: conventional bitewing Model set‐up: not reported Sequence of test(s): index tests (visual, DIAGNOdent, radiograph) then reference standard Examiner training and calibration: not reported Threshold applied: sound, enamel, dentine Device specifics: using Kodak Ultraspeed and the Gendex GX 1000 dental X‐ray machine, at 60 kV, 10 mA and a 0.26 s exposure
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test before reference standard Training of examiner: not reported Blinding to index test: yes Multiple tests: no Site selection: sectioned through highest DIAGNOdent value Target condition: sound, outer enamel, inner enamel, outer dentine, inner dentine
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Unclear
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Wenzel 2002.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: not reported Teeth: permanent incisors, canines, premolars, and molars Sealants: not reported Restorations: included Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Denmark Setting: extracted teeth Number of participants/teeth/sites: 190 teeth/363 surfaces (17 surfaces excluded from analysis) Prevalence:enamel 0.38, dentine 0.24
Index tests	Category of test: digital radiographs ‐ 3 different sensors Model set‐up: "A 12‐mm acrylic plate was placed between the tube and the tooth block to simulate soft tissue" Sequence of test(s): index tests then reference standard Examiner training and calibration: 2 experienced radiologist and 2 dental students Threshold applied: "0 = sound, 1 = caries in enamel, 2 = caries into dentine" Device specifics: "using an Oralix DC X‐ray unit (Gendex, Des Plaines, IL, USA) with rectangular collimation operated at 60 kVp, 7 mA and a 32‐cm focus‐film distance" 3 different digital sensors: "Each test tooth was radiographed with the Trophy (Trophy Radiologie, Paris, France) charge‐coupled device (CCD)‐based sensor systems (RVG RadioVisioGraphy): an older, but widely sold sensor from 1994, here called RVGold (Fig. 1A) and a more recent sensor from 2000, which has a higher resolution, here called RVGnew"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: "Two experienced observers made a consensus" Blinding to index test: unclear Multiple tests: no Site selection: approximal surface Target condition: 0 = sound, 1 = caries in enamel, 2 = caries into dentine
Flow and timing	Participants with index test but no reference standard: 13, explanations provided (8 restorations, 4 damaged, and 5 severe occlusal caries) Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data used from student 1 and RVG (old)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		High risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		Low risk

Xavier 2011.

Study characteristics
Patient Sampling	Method of sampling: selected Included conditions: no cavitation and early lesions: "healthy and carious lesions compatible with the direct visual inspection (white spot, brown spot and a small cavity" Teeth: permanent premolars and molars Sealants: not reported Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 56 teeth (28 premolars and 28 molars)/112 surfaces Prevalence: enamel 0.09, dentine 0.05
Index tests	Category of test: conventional radiographs, plus multiple digital scans of conventional radiograph Model set‐up: "Dental stone plaster was mixed with broken rice in the same proportion by volume and was placed in the mould to simulate the trabecular bone", a support was "made from acrylic and was composed of a tube and an articulated base that can standardize the inclination to 8u of the X‐ray locator and a 1.5 cm thick plate, also in acrylic. This acrylic plate was placed between the tube and the model, with the capacity for absorption of the Xrays, similar to soft tissues of the face" Sequence of test(s): index tests then reference standard Examiner training and calibration: "three experienced examiners after an orientation on the purposes of this study" Threshold applied: "S = no carious lesion in the proximal area; NC = non‐conclusive image of carious lesions; and C = with carious lesions on the proximal surface. When the areas were classified as C, they were resorted into levels of depth; E = radiolucency restricted to the enamel without reaching the amelodentine junction; J 5 radiolucency strictly to the enamel, reaching the amelodentine junction; and D 5 radiolucency extended to the dentine" Device specifics: "taken with Insight films (EastmanKodak Co., Rochester, NY) from the same box, with a properly calibrated X‐ray machine, Kaycor X‐707 (Yoshida Dental Manufacturing Co., Tokyo, Japan), operating at 70 kV and 7 mA and with a time exposure of 0.40 s" then "digital images of the radiographs (Figure 1) were obtained with the use of six pieces of equipment, which were two scanners: Canon scanner table model CanonScan D646U (Canon USA Inc., Newport News, VA) and a Genius ColorPage HR7X (KYE Systems Corp. America, Doral, FL); and four cameras: Canon Powershot G2 (Canon USA Inc.); Nikon Coolpix 8700 (Nikon Inc., Melville, NY); Canon RebelXT with a Canon objective 100 mm f2, 8 Macro USM AF d58 (Canon USA Inc.); and a Nikon D70s model with a Nikon objective 105 mm f2, 8 Macro USM AF (Nikon Inc.)"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: approximal surface Target condition: "the lesion was restricted to the enamel (when restricted to the deeper half of the total thickness of the surface enamel); the lesion was at the amelodentine junction (when it reaches the deeper half of the total thickness of the enamel and not more than 0.5 mm deeper into the dentine); and the lesion was in the dentine (when it extends beyond the 0.5 mm into dentine)"
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Conventional radiograph used for data, mean value
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	No
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

Zangooei 2010.

Study characteristics
Patient Sampling	Method of sampling: unclear: "The sample consisted of 51 unrestored teeth with non‐cavitated interproximal surfaces based on visual inspection" Included conditions: no cavitation and early lesions: "Tooth surfaces ranged from sound to discolored" Teeth: premolars Sealants: not reported Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Iran Setting: extracted teeth Number of participants/teeth/sites: 51 teeth Prevalence: enamel 0.71
Index tests	Category of test: digital bitewing radiographs Model set‐up: "three teeth were mounted in dental stone blocks"; "an optical bench was constructed, consisting of a positioning ring (Rinn Corporation, USA) for the X‐ray tube in combination with the corresponding film holder mounted on a wooden platform" Sequence of test(s): index tests then reference standard: "Observers viewed images in 2 viewing sessions for the two imaging modes, with a 2‐week interval" Examiner training and calibration: "three observers (a maxillofacial radiologist, an operative dentistry specialist and a dentist) were recruited for this study" Threshold applied: "presence or absence of caries in the proximal surface" Device specifics: "using a dental X‐ray unit (ELITYS Trophy, TRX 708, CROISSY BEAUBOURG, France) for all exposures operating at 70 kVp, 8 mA, and 0.0.1 sec with 2.0 mm aluminium equivalent filtra‐tioN"
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index tests then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: no Site selection: approximal surface Target condition: presence or absence of caries in the proximal surface
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 0 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Results from 'gray scale' process used in data analysis
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
If multiple tests were applied were different examiners used for each (in vivo)?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk

CBCT = cone beam computed tomography; CCD = charged‐coupled device; DEJ = dentino‐enamel junction; DMFT = (decayed, missing, and filled teeth) scale; ECM = electronic caries monitor; FOTI = fibre optic transillumination; ICDAS = International Caries Detection and Assessment System; kV = kilovolts; kVp = kilovoltage peak; lp/mm = line‐pairs/mm; mA = milliamperes; microCT = microcomputed tomography; NIR = near‐infrared; OCT = optical coherence tomography; QLF = quantitative light‐induced fluorescence; s = seconds.

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Abdinian 2015	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table at the enamel caries threshold
Abdinian 2017	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table at the enamel caries threshold
Abdinian 2018	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table at the enamel caries threshold
Alomari 2014	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table ‐ data presented at the dentine level
Alomari 2015	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table ‐ data presented at the dentine level
Arslan 2014	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table at the enamel caries threshold
Berkhout 2007	Sample unsuitable ‐ included dentinal lesions
Blazejewska 2016	Reference standard unsuitable ‐ approximal surfaces were investigated but a visual reference standard was applied, to be included tooth separation should have been performed
Bussaneli 2015c	Proximal caries; radiographs results used as reference standard and included in visual review of this series
Chawla 2012	Not possible to extract data, figures in table 3 do not provide false‐negative results, agreement of sound teeth does not correspond to presentation of ROC curve to allow for derivation of full 2 x 2 table
Cortes 2000	Sample unsuitable ‐ included frank cavitation
Coutinho 2014	Not possible to calculate prevalence at D1 or D3 due to reporting of reference standard as sound or cavitated
da Silva Neto 2008	Sample unsuitable ‐ appeared to include dentine cavitation
Dehghani 2017	Not possible to extract data, there were prevalence details but sensitivities/specificities were greater than 1
Diniz 2016	Sample unsuitable ‐ included cavitated margins
Espelid 1994	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table at the enamel caries threshold, figure 1 reported pooled data for all 10 dentists and table 1 reported the dentine threshold only
Hietala‐Lenkkeri 2014	Index test not suitable ‐ radiograph not applied as an index test
Holtzman 2010	Insufficient detail provided on radiograph equipment and methods so could not classify
Holtzman 2014	Sample unsuitable ‐ included up to ICDAS 4
Jan 2016	Sample unsuitable ‐ "cavitated and non‐cavitated carious teeth selected across ICDAS‐II 0 through 6"
Kamburoglu 2012	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table as it is unclear what threshold was used in study results
Katge 2016	Suitable sample, index test, and reference standard but unable to a construct 2 x 2 table at the enamel caries threshold
Kavvadia 2008	Reference standard only reported on excavated teeth, therefore a 2 x 2 table of the sample could not be constructed
Kavvadia 2012	Reference standard only reported on excavated teeth, therefore a 2 x 2 table of the sample could not be constructed
Kim 2017	Radiograph used as reference standard
Kordic 2003	Table 1 confirmed that dentinal caries were included in the sample
Krzyzostaniak 2015	We could not complete a 2 x 2 table with certainty from data provided
Kuhnisch 2009	Data reported at dentine caries only for radiographs
Laitala 2017	Reference standard unsuitable ‐ approximal surfaces were investigated but a visual reference standard was applied, to be included tooth separation should have been performed
Lara‐Capi 2017	Not a DTA study ‐ compared visual, transillumination, and bitewing, with none as a reference standard
Matalon 2003	Sample unsuitable ‐ dentinal surfaces recruited
Menem 2017	Sample unsuitable ‐ methods state that 30 sites were recruited with cavitated lesions, authors confirmed these to be dentinal
Milosavljevic 2016	Suitable sample, index test, and reference standard but unable to construct a 2 x2 table at the enamel caries threshold
Nair 2001	Sample unsuitable ‐ included frank cavitation
Nascimento 2018	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table at the enamel caries threshold
Nikneshan 2015	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table at the enamel caries threshold
Ricketts 1997	Sample included frank cavitation
Schaefer 2018	Unable to use data, lack of clarity regarding the inclusion of sealant and restorations
Shwetha 2017	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table at the enamel caries threshold
Sinanoglu 2014	Unclear how Table 6 results of sensitivity and specificity were calculated, whether these were only reporting the participants that underwent excavation or a hybrid reference standard was applied to assess all participants
Singh 2016	Suitable sample, index test, and reference standard but unable to construct a 2 x 2 table at the enamel caries threshold
Terry 2016	Reference standard unsuitable ‐ "a consensus of two experts consisting of board‐certified oral and maxillofacial radiologists, with 47 years' and 24 years' of experience, respectively" ‐ they used the same radiographic images as the index test
White 1997	Selected teeth for the sample which had "lesions penetrating the dentine"
Wojtowicz 2003	Sample unsuitable ‐ 20% teeth included in sample had dentinal caries
Yoon 2017	Reference standard unsuitable ‐ radiograph used as the reference standard
Young 2009	Unable to construct a 2 x 2 table for results at the enamel threshold. Results were presented for "lesions limited to enamel" but it is not clear how those surfaces which were identified as dentine caries by the index test would have been treated in the analysis

DTA = diagnostic test accuracy; ICDAS = International Caries Detection and Assessment System; ROC = receiver operating characteristic.

Differences between protocol and review

• One of the objectives was removed because the search produced a large body of evidence for the primary time point in clinical process so we decided it would add unnecessary complexity to investigate the additional objective of the value of each index test at different positions in the clinical pathway.

• Sensitivity analysis: in a change to the protocol we were able to directly compare different tests based on data from studies which had applied more than one index tests with a reference standard (paired studies).

Contributions of authors

All review authors collaborated in the conception of the review purpose and design.

Drafting the protocol and final draft of the review: Tanya Walsh (TW) and Richard Macey (RM).
Developing the search strategy: TW and RM.
Co‐ordination of contributions from the co‐authors: TW and RM.
Screening of papers against eligibility criteria: RM, TW, Philip Riley (PR), Helen Worthington (HW), and Anne‐Marie Glenny (AMG).
Obtained data on published, ongoing, and unpublished studies: RM.
Appraising the quality of papers: RM, TW, PR, HW, Ting‐Li Su (TLS), and AMG.
Extracting data for the review: RM, TW, PR, HW, TLS, and AMG.
Entering data into Review Manager 5: RM.
Analysis of data: TW.
Provided clinical guidance during all phases of the review: Falk Schwendicke (FS), Janet Clarkson (JC), Anita Sengupta (AS), and David Ricketts (DR).

Sources of support

Internal sources

• Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK

• Manchester Academic Health Sciences Centre (MAHSC) and the NIHR Manchester Biomedical Research Centre, UK

External sources

• National Institute for Health Research (NIHR), UK

  This project was funded by the National Institute for Health Research (NIHR Cochrane Programme Grant 16/114/23 'Detection and Diagnosis of Common Oral Diseases: Diagnostic Test Accuracy of Tests of Oral Cancer and Caries'). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care

• NIHR, UK

  This project was supported by the NIHR, via Cochrane Infrastructure funding to Cochrane Oral Health. The views and opinions expressed herein are those of the review authors and do not necessarily reflect those of the Evidence Synthesis Programme, the NIHR, the NHS, or the Department of Health and Social Care

• Cochrane Oral Health Global Alliance, Other

  The production of Cochrane Oral Health reviews has been supported financially by our Global Alliance since 2011 (oralhealth.cochrane.org/partnerships-alliances). Contributors in the last 2 years have been the American Association of Public Health Dentistry, USA; AS‐Akademie, Germany; the British Association for the Study of Community Dentistry, UK; the British Society of Paediatric Dentistry, UK; the Canadian Dental Hygienists Association, Canada; the Centre for Dental Education and Research at All India Institute of Medical Sciences, India; the National Center for Dental Hygiene Research & Practice, USA; New York University College of Dentistry, USA; and Swiss Society of Endodontology, Switzerland

Declarations of interest

Tanya Walsh: none known. I am Statistical Editor with Cochrane Oral Health.
Richard Macey: none known.
Philip Riley: none known. I am Deputy Co‐ordinating Editor of Cochrane Oral Health.
Anne‐Marie Glenny: none known. I am Joint Co‐ordinating Editor of Cochrane Oral Health.
Falk Schwendicke: I have a conflict of interest when it comes to artificial intelligence (AI)‐based diagnostics. This, however, is beyond the remit of this review.
Helen V Worthington: none know. I am Emeritus Co‐ordinating Editor of Cochrane Oral Health.
Janet E Clarkson: none known. I am Joint Co‐ordinating Editor of Cochrane Oral Health.
David Ricketts: none known.
Ting‐Li Su: none known.
Anita Sengupta: none known.

Edited (no change to conclusions)