Visual or visual‐tactile examination to detect and inform the diagnosis of enamel caries

Richard Macey; Tanya Walsh; Philip Riley; Anne-Marie Glenny; Helen V Worthington; Lucy O'Malley; Janet E Clarkson; David Ricketts

doi:10.1002/14651858.CD014546

. 2021 Jun 14;2021(6):CD014546. doi: 10.1002/14651858.CD014546

Visual or visual‐tactile examination to detect and inform the diagnosis of enamel caries

Richard Macey ¹, Tanya Walsh ^1,^✉, Philip Riley ², Anne-Marie Glenny ¹, Helen V Worthington ², Lucy O'Malley ¹, Janet E Clarkson ³, David Ricketts ⁴

Editor: Cochrane Oral Health Group

PMCID: PMC8428329 PMID: 34124773

Abstract

Background

The detection and diagnosis of caries at the initial (non‐cavitated) and moderate (enamel) levels of severity is fundamental to achieving and maintaining good oral health and prevention of oral diseases. An increasing array of methods of early caries detection have been proposed that could potentially support traditional methods of detection and diagnosis. Earlier identification 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 visual classification systems for the detection and diagnosis of non‐cavitated coronal dental caries for different purposes (detection and diagnosis) and in different populations (children or adults).

Search methods

Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 30 April 2020); Embase Ovid (1980 to 30 April 2020); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 30 April 2020); and the World Health Organization International Clinical Trials Registry Platform (to 30 April 2020). We studied reference lists as well as published systematic review articles.

Selection criteria

We included diagnostic accuracy study designs that compared a visual classification system (index test) with a reference standard (histology, excavation, radiographs). This included cross‐sectional 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 considered. Studies that explicitly recruited participants with caries into dentine or frank cavitation 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

We extracted data independently and in duplicate using a standardised data extraction and quality assessment form based on QUADAS‐2 specific to the review context. Estimates of diagnostic accuracy were determined using the bivariate hierarchical method to produce summary points of sensitivity and specificity with 95% confidence intervals (CIs) and regions, and 95% prediction regions. The comparative accuracy of different classification systems was conducted based on indirect comparisons. Potential sources of heterogeneity were pre‐specified and explored visually and more formally through meta‐regression.

Main results

We included 71 datasets from 67 studies (48 completed in vitro) reporting a total of 19,590 tooth sites/surfaces. The most frequently reported classification systems were the International Caries Detection and Assessment System (ICDAS) (36 studies) and Ekstrand‐Ricketts‐Kidd (ERK) (15 studies). In reporting the results, no distinction was made between detection and diagnosis. Only two studies were at low risk of bias across all four domains, and 15 studies were at low concern for applicability across all three domains. The patient selection domain had the highest proportion of high risk of bias studies (49 studies). Four studies were assessed at high risk of bias for the index test domain, nine for the reference standard domain, and seven for the flow and timing domain. Due to the high number of studies on extracted teeth concerns regarding applicability were high for the patient selection and index test domains (49 and 46 studies respectively).

Studies were synthesised using a hierarchical bivariate method for meta‐analysis. There was substantial variability in the results of the individual studies: sensitivities ranged from 0.16 to 1.00 and specificities from 0 to 1.00. For all visual classification systems the estimated summary sensitivity and specificity point was 0.86 (95% CI 0.80 to 0.90) and 0.77 (95% CI 0.72 to 0.82) respectively, diagnostic odds ratio (DOR) 20.38 (95% CI 14.33 to 28.98). In a cohort of 1000 tooth surfaces with 28% prevalence of enamel caries, this would result in 40 being classified as disease free when enamel caries was truly present (false negatives), and 163 being classified as diseased in the absence of enamel caries (false positives). The addition of test type to the model did not result in any meaningful difference to the sensitivity or specificity estimates (Chi²(4) = 3.78, P = 0.44), nor did the addition of primary or permanent dentition (Chi²(2) = 0.90, P = 0.64). The variability of results could not be explained by tooth surface (occlusal or approximal), prevalence of dentinal caries in the sample, nor reference standard. Only one study intentionally included restored teeth in its sample and no studies reported the inclusion of sealants.

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 results.

Authors' conclusions

Whilst the confidence intervals for the summary points of the different visual classification systems indicated reasonable performance, they do not reflect the confidence that one can have in the accuracy of assessment using these systems due to the considerable unexplained heterogeneity evident across the studies. The prediction regions in which the sensitivity and specificity of a future study should lie are very broad, an important consideration when interpreting the results of this review. Should treatment be provided as a consequence of a false‐positive result then this would be non‐invasive, typically the application of fluoride varnish where it was not required, with low potential for an adverse event but healthcare resource and finance costs.

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. Studies to determine the diagnostic accuracy of methods to detect and diagnose caries in situ are particularly challenging. Wherever possible future studies should be carried out in a clinical setting, to provide a realistic assessment of performance within the oral cavity with the challenges of plaque, tooth staining, and restorations, and consider methods to minimise bias arising from the use of imperfect reference standards in clinical studies.

Plain language summary

Visual or visual‐tactile examination for the diagnosis of dental caries

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 minimise the number of false‐positive results when treatment may be given when caries is absent, and improved visual detection methods may reduce such occurrences.

What is the aim of this review?

The aim of this Cochrane Review was to find out how accurate visual classification systems are for detecting early tooth decay as part of the dental 'check‐up' for children and adults who visit their dentist. Researchers in Cochrane included 67 studies to answer this question.

What was studied in the review?

Two main visual classification systems were studied in this review: the International Caries Detection and Assessment System (ICDAS) and the Ekstrand‐Ricketts‐Kidd (ERK) system. A third group of visual classifications is reported and labelled as 'Other' because the studies did not report what system was used. 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?

The review included 67 studies with a total of 19,590 teeth. Some studies reported on more than one type of classification system, this gave us 71 sets of data to use. The results of these studies indicate that, in theory, if the visual classification systems were to be used by a dentist for a routine dental examination in a group of 1000 tooth sites/surfaces, of whom 350 (28%) have early tooth decay:

• the use of a visual classification system will indicate that an estimated 403 will have early tooth decay, and of these, 163 (40%) will not have tooth decay (false positive ‐ incorrect diagnosis); • of the 597 tooth sites/surfaces with a result indicating that tooth decay is not present, 40 (7%) will have early tooth decay (false negative ‐ incorrect diagnosis).

A diagram of these results can be found at oralhealth.cochrane.org/visual-examination-classification-systems-results-0331c. In this example, visual classification systems produce a high proportion of false‐positive results. Treatment in the absence of disease is likely to be non‐invasive such as the application of high fluoride toothpaste, or oral health advice and guidance from the dentist, but will incur financial cost to the patient or healthcare provider.

We found no evidence from the data collected that the classification systems differed in their accuracy.

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 the visual classification systems appearing more accurate than they really are, increasing the number of correct visual classification results. We judged the certainty of the evidence to be low due to how the studies selected their participants, the large number of studies that were carried out in a laboratory setting on extracted teeth, and variation in results.

Who do the results of this review apply to?

Studies included in the review were carried out in Brazil, Europe, Japan, and Australia. A large number of studies performed the tests on extracted teeth, while clinical studies were completed in dental hospitals, general dental practices, or schools. Studies were from the years 1988 to 2019.

What are the implications of this review?

We observed substantial variation in the results, which is perhaps unsurprising as the use of these classification systems involve interpretation by the user. There is considerable uncertainty in the likely performance of a future study. Further research studies should be carried out in a clinical setting.

How up‐to‐date is this review?

Review authors searched for and used studies published up to 30 April 2020.

Summary of findings

Background

Cochrane Oral Health (COH) has undertaken several Cochrane Reviews of diagnostic test accuracy (DTA) on the detection and diagnosis of dental caries (Fee 2020; Macey 2020; Macey 2021; Macey 2021a; Walsh 2021). The suite of systematic reviews forms part of a UK National Institute for Health Research (NIHR) Cochrane Programme Grant 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 served 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). In some Scandinavian countries, preventive oral health 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 has 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, the global incidence of untreated caries was reported to be 2.4 billion in 2010 (Feigin 2016; Kassebaum 2015; World Health Organization 2017) and despite a reduction in caries in some industrialised countries, the global incidence of caries has increased by 14% in the five years to 2015 to over half a billion people (Feigin 2016). In the UK, recent 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 usually be undertaken at a routine dental examination, by a general dental practitioner, in patients who are presenting asymptomatically. However, caries detection can additionally be employed in secondary care settings, school or community screening projects and epidemiology or research studies (Braga 2009b; 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 restoration is 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). 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). Caries diagnosis is a complex process involving the staging of the disease process (severity), assessment of the location of the lesion (whether in a plaque stagnation area or not), understanding caries risk factors for the individual patient and lesion and assessment of lesion activity, but pivotal to the diagnostic process is the early identification of caries, namely caries detection, which is the focus of this suite of reviews.

Detection and diagnosis at the initial (non‐cavitated) and moderate (enamel) levels of caries is fundamental in achieving the promotion of oral health and prevention of oral disease (Fejerskov 2015; Ismail 2013). Dental caries if left unchecked is likely to progress in severity based upon the amount of demineralisation that has taken place within the lesion and the depth of penetration of the lesion into the tooth tissues. These two factors are not necessarily linearly related but both will dictate whether a lesion develops a frank hole or discontinuity of the tooth surface (cavitation). As such, a lesion may be confined to enamel in depth and may (rarely) or may not be cavitated based upon the amount of demineralisation and similarly the same argument can apply to lesions extending into dentine histopathologically. Thus lesion depth estimation and surface topography are important features to capture in caries detection. The prevalence of this early caries state is not often reported in dental epidemiology, 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 treatment options are available at these different thresholds of disease, these include:

non‐operative preventive strategies such as improved oral hygiene, reduced sugar diet, and application of topical fluoride;
minimally invasive treatments such as sealing the affected surface of the tooth, or 'infiltrating' the softer demineralised tissue with resins for initial caries;
operative interventions such as step‐wise caries removal and restoration for extensive lesions.

With advances in technology over the last two decades, alternative methods of caries detection have become available, such as advancements in radiography and the development of fluorescence, transillumination, and electrical conductance devices. These could potentially aid the detection and diagnosis of caries at an early stage of decay. This would afford the patient the opportunity of a less invasive treatment with less destruction of tooth tissue and potentially result in a reduced cost of care to the patient and to healthcare services. Furthermore, the ability to accurately detect early caries and prevent early caries lesions from progressing has become increasingly important in reducing the need to undertake/undergo invasive treatment which may require the use of aerosol generating procedures (AGPs).

Target condition being diagnosed

Caries is an entire disease process, which can be arrested and sometimes reversed if diagnosed early enough (Fejerskov 2015; Pitts 2009). 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 production of acid and demineralisation of the tooth. Disease progression can be moderated by 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 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 presenting at levels into tooth enamel have potential to be stabilised or even reversed, whereas the progression of carious lesions into the dentine and pulp of the tooth will often require restoration (Bakhshandeh 2018; Kidd 2004).

Assessment of disease severity traditionally used in epidemiological and research studies has employed some variant of the DMFT (decayed, missing, and filled teeth) scale. 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 has been used to determine the presence of caries (Pitts 1988; Shoaib 2009).

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

Name of scoring system	Description	Scale
ICDAS	Classifies the severity and activity of lesions on primary and permanent teeth; occlusal, approximal or smooth; and those adjacent to restorations. The surface is the unit of interest. Examination uses a dental mirror, ball‐ended probe and 3‐in‐1 syringe to dry surfaces. There are 2 digits, the surface condition and the caries state (we will focus on the caries state numbering here). Codes also suggest treatment of management methods. Codes 1‐2 the white/brown spot lesions (non‐cavitated) require non‐invasive treatment. Codes 3‐4 the shadowed enamel cavitation may require restorations. Codes 5‐6 the dentine cavitation may require more severe treatment or extraction (Ismail 2007; Pitts 2001)	0: sound 1: first visual change in enamel 2: distinct visual change in enamel 3: localised enamel breakdown 4: underlying dark shadow from dentine 5: distinct cavity with visible dentine 6: extensive distinct cavity with visible dentine
ERK	Aimed to detect and classify 'hidden caries' that are visible on bitewing radiographs but often has no obvious visual signs of caries. The scale relies on the classification of enamel translucency before and after drying, in addition to opacity, discolouration which may be indicative of underlying caries in the dentine (Ekstrand 1997)	0: no or slight changes in enamel translucency (after drying) 1: opacity or discolouration hardly visible on wet surface but distinctly visibile when dry 2: opacity or discolouration visible without drying 3: localised enamel breakdown 4: cavitation exposing dentine
Nyvad	Based on surface characteristics rather than lesion depth to identify 2 levels of severity ‐ non‐cavitated and cavitated, the former focusing on enamel lesions. Examination should be performed on teeth free of dental plaque, surfaces should be dried for 10 to 15 seconds. A sharp explorer is generally used to assess the texture and roughness of the lesion; translucency/opacity, location, and colour can be assessed visually. Can be used on occlusal, approximal and smooth surfaces, also includes scores for secondary and root caries (Zandona 2019)	0 = sound: normal enamel translucency and texture 1 = active non‐cavitated: whitish, or yellowish appearance; feel rough when explorer is gently moved across the surface 2 = active cavitated (surface discontinuity): localised surface defect (microcavity) in enamel only 3 = active cavitated (surface discontinuity): present similar surface characteristics but will feel softer rather than rougher, cavity easily observed 4 = inactive cavitated (intact surface): whitish, brownish or black; shiny, feels hard and smooth 5 = inactive caries (surface discontinuity): localised surface defect (microcavity) in enamel only 6 = inactive caries (cavity): easily visible cavity, surface black, shiny and hard 7 = filling (sound surface) 8 = filling + active caries non‐cavitated 9 = filling + inactive caries (Nyvad 1999)

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) or 2) or 3) was 'no'	Risk is High
Studies moved from low to unclear 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) or 2) or 3) was 'no'	Risk is High
Studies moved from low to unclear 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) or 2) was 'no'	Risk is High
Studies moved from low to unclear 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) or 2) was 'no'	Concern is High
Studies moved from low to unclear if the answer to question 1) or 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) or 2) was 'no'	Concern is High
Studies moved from low to unclear if the answer to question 1) or 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
Studies moved from low to unclear if answers to any of questions 1) or 2) or 3) was 'unclear'	Risk is Unclear

Test	Study ID	Prevalence of enamel caries	Prevalence of caries into dentine	Dentition	Reference standard	Surface	Setting	Multisite
ICDAS	Achilleos 2013	0.95	High	Permanent	Histology	Occlusal	In vitro	No
ERK	Akarsu 2006	0.77	High	Permanent	Excavation	Occlusal	Dental hospital	No
Other visual	Ashley 1998	0.6	High	Permanent	Histology	Occlusal	In vitro	No
ERK	Bahrololoomi 2015	0.94	High	Primary	Excavation	Occlusal	Dental hospital	No
ICDAS	Bottenberg 2016	0.75	High	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Braga 2009	0.63	Medium	Primary	Histology	Approximal	In vitro	Yes
ICDAS	Braga 2010	0.52	Medium	Primary	Histology	Occlusal	In vivo ‐ non‐clinic setting	No
Other visual	Braga 2010 2 test	0.52	Medium	Primary	Histology	Occlusal	In vivo ‐ non‐clinic setting	No
ICDAS	Braun 2017	0.77	High	Permanent	Histology	Occlusal	In vitro	No
Other visual	Bussaneli 2015	0.71	High	Primary	Separation	Approximal	Dental hospital	No
ICDAS	Bussaneli 2015a	0.63	Low	Primary	Histology	Occlusal	In vitro	No
ICDAS	Campos 2017	0.96	High	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Carvalho 2018	0.73	High	Permanent	Radiograph	Occlusal	In vitro	No
ICDAS	Castilho 2016	0.81	Low	Permanent	Histology	Occlusal	Clinic	No
ICDAS	Chawla 2012	0.61	Medium	Primary	Histology	Approximal	In vitro	No
ERK	Cinar 2013	0.75	Medium	Primary	Histology	Occlusal	Dental hospital	No
Other visual	Costa 2002	0.65	Medium	Permanent	Histology	Occlusal	In vitro	No
ERK	Da Silva 2010	0.56	High	Primary	Histology	Occlusal	In vitro	No
ICDAS	Diniz 2009	0.96	High	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Diniz 2011	0.94	Medium	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Diniz 2012	0.95	Medium	Permanent	Histology	Occlusal	Dental hospital	No
ICDAS	Diniz 2019	0.75	High	Primary	Histology	Occlusal	In vitro	No
ICDAS	Ekstrand 2007	0.72	High	Primary	Histology	Occlusal	In vitro	No
ICDAS	Ekstrand 2011	0.78	High	Primary	Histology	Approximal	In vitro	Yes
ICDAS	Ekstrand 2011a	0.78	Medium	Permanent	Histology	Approximal	In vitro	Yes
ERK	Erten 2005	0.63	Medium	Permanent	Histology	Occlusal	In vitro	No
Other visual	Forgie 2003	0.86	High	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Freitas 2016	0.68	Medium	Primary	Histology	Approximal	Clinic	Yes
ERK	Goel 2009	0.54	High	Primary	Histology	Occlusal	Clinic	No
Other visual	Haak 2002	0.67	High	Permanent	Histology	Approximal	In vitro	Yes
Other visual	Hintze 2003	0.26	Low	Permanent	Histology	Approximal	In vitro	Yes
Other visual	Hintze 2003a	0.91	High	Permanent	Histology	Occlusal	In vitro	No
ERK	Huth 2010	0.66	High	Permanent	Excavation	Approximal	Clinic	No
ICDAS	Iranzo‐Cortes 2017	0.77	Medium	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Iranzo‐Cortes 2018	0.68	Not reported	Primary	Histology	Occlusal	In vitro	No
ICDAS	Jablonski‐Momeni 2008	0.76	High	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Jablonski‐Momeni 2012	0.84	High	Permanent	Excavation	Occlusal	In vitro	No
Other visual	Kim 2017	0.61	Medium	Permanent	Radiograph	Approximal	Clinic	No
ICDAS	Ko 2015	0.8	Medium	Permanent	Histology	Approximal	In vitro	No
ICDAS	Kockanat 2017	0.78	Medium	Primary	Histology	Occlusal	Clinic	No
Other visual	Kucukyilmaz 2015	0.82	Medium	Primary	Histology	Occlusal	Clinic	No
ERK	Kuhnisch 2009	0.89	High	Permanent	Histology	Occlusal	In vitro	No
Other visual	Kuhnisch 2009a	0.82	High	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Laitala 2017	0.2	Low	Permanent	Radiograph	Approximal	Clinic	Yes
ERK	Mendes 2006	0.75	Medium	Primary	Histology	Occlusal	In vitro	Yes
ICDAS	Mitropoulos 2010	0.6	High	Permanent	Histology	Approximal	In vitro	Yes
Other visual	Nakagawa 2013	0.75	Medium	Primary	Histology	Smooth	In vitro	Yes
Other visual	Nakajima 2014	0.74	Medium	Primary	Histology	Occlusal	In vitro	Yes
ICDAS	Neuhaus 2011	0.73	Medium	Primary	Histology	Occlusal	In vitro	No
ICDAS	Neuhaus 2015	0.87	Medium	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Novaes 2009	0.41	Low	Primary	Separation	Approximal	Clinic	Yes
ICDAS	Novaes 2010	0.81	Low	Primary	Separation	Approximal	Clinic	Yes
ICDAS	Novaes 2012	0.57	Medium	Primary	Histology	Occlusal	In vitro	Yes
Other visual	Paula 2011	0.88	Medium	Permanent	Histology	Occlusal	In vitro	Yes
ERK	Pereira 2011	0.57	Medium	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Qudeimat 2019	0.9	Medium	Permanent	Histology	Occlusal	In vitro	No
ERK	Rocha 2003	0.58	Low	Primary	Histology	Occlusal	Clinic	No
ICDAS	Rodrigues 2008	0.93	High	Permanent	Histology	Occlusal	In vitro	No
Other visual	Rodrigues 2009	0.92	Low	Primary	Histology	Occlusal	In vitro	No
Other visual	Rodrigues 2009a	0.93	Low	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Rodrigues 2013	0.83	High	Permanent	Histology	Occlusal	In vitro	No
ERK	Seremidi 2012	0.78	Medium	Permanent	Histology	Occlusal	In vitro	Yes
Other visual	Shi 2000	0.73	High	Permanent	Histology	Smooth	In vitro	No
ERK	Shimada 2010	0.86	High	Permanent	Histology	Occlusal	In vitro	Yes
Other visual	Sidi 1988	0.03	Low	Permanent	Radiograph	Approximal	Clinic	Yes
ICDAS	Souza 2013	0.76	High	Primary	Histology	Occlusal	In vitro	No
ICDAS	Soviero 2012	0.81	Medium	Primary	Histology	Approximal	In vitro	Yes
ERK	Sridhar 2009	0.96	Low	Permanent	Histology	Occlusal	In vitro	No
ICDAS	Teo 2014	0.72	Medium	Primary	Histology	Occlusal	Dental hospital	No
ICDAS	Tonkaboni 2018	0.42	High	Permanent	Histology	Approximal	In vitro	No
ERK	Xiao‐Hua 2016	0.74	High	Permanent	Histology	Occlusal	In vitro	No

Question	What is the diagnostic accuracy of visual classification for the detection and diagnosis of 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	Visual classification. Results of the index tests were usually recorded on an ordinal scale to indicate severity of disease. For the purposes of this review the positivity threshold was caries in enamel
Comparator test	Estimates were compared across different classification systems. 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, radiographs
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	67 studies providing 71 datasets. 6827 lesions in 19,590 tooth surfaces (35% prevalence)
Findings
Sensitivity (95% CI)	0.86 (0.80 to 0.90)	There was substantial variability in the results of the individual studies, with sensitivities that ranged from 0.16 to 1.00 and specificities from 0 to 1.00. The relatively narrow confidence intervals and confidence regions for the summary estimates are reflective of the volume of data in the analysis. The prediction region, which gives an indication of between‐study heterogeneity and the region where the true sensitivity and specificity of a future study should lie, is very broad The observed heterogeneity could not be explained by tooth surface, prevalence of dentine caries in the study samples, or choice of reference standard
Specificity (95% CI)	0.77 (0.72 to 0.82)
DOR (95% CI)	20.38 (14.33 to 28.98)
Outcome	Numbers applied to a hypothetical cohort of 1000 tooth sites or surfaces Effect per 1000 tooth sites or surfaces assessed (95% CI)		Test accuracy Certainty of the evidence
	Pre‐test probability 28%^a
True positives (tooth sites or surfaces with early enamel caries)	240 (225 to 251)		⊕⊕⊝⊝ LOW
False negatives (tooth sites or surfaces incorrectly classified as not having early enamel caries)	40 (29 to 54)
True negatives (tooth sites or surfaces without early enamel caries)	557 (516 to 592)		⊕⊕⊝⊝ LOW
False positives (tooth sites or surfaces incorrectly classified as having early enamel caries)^b	163 (128 to 204)
Limitations ‐ factors that may decrease the certainty of the evidence
Risk of bias	Only 2 studies were considered to be at low risk of bias overall. Across the 4 domains, the patient selection domain had the highest number of studies judged at high risk of bias (49 studies); we judged the index test, reference standard, and flow and timing domains to have a low proportion of studies at high risk of bias (4, 9, and 7 studies respectively). All studies avoided a case‐control design, the majority avoiding inappropriate exclusions (96%), but consecutive or random sampling was used in only 10% of studies. 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, radiographs, or a visual examination after separation of the approximal surfaces
Applicability of evidence to question	15 studies were considered to have low concern for applicability across all domains. We judged 49 studies of extracted teeth to be of high concern for applicability of the sample population, with the remaining clinical studies directly applicable to our review question. Concern regarding applicability for the index test domain was also high (46 studies). Most studies were in vitro studies (48 studies), 18 studies carried out the index test evaluations in a clinical setting, 1 study carried out the clinical assessment in a school setting. The dominance of in vitro studies also means that information on how the results of these devices are used to support diagnosis, as opposed to pure detection, is limited
Test accuracy 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 results

*Study characteristics*
Patient Sampling	Method of sampling: selected Included conditions: no cavitation Teeth: permanent molars and premolars Surface: occlusal Restorations: excluded Sealants: unclear
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Greece Setting: extracted for orthodontic purposes Number of participants/teeth/sites: 38 teeth Prevalence: enamel = 0.95, dentine = 0.39
Index tests	Category of test: visual ICDAS Sequence of test(s): visual, followed by VistaProof/DIAGNOdent then reference standard Examiner training and calibration: experienced, trained and calibrated dentists: "Two dentists with 1‐year clinical experience in the ICDAS criteria" Teeth cleaning prior to examination: calculus and debris were removed by paste and brush burr Tooth drying prior to examination: yes, 5 seconds Threshold applied: ICDAS (0): sound tooth surface, (1): first visual change in dry enamel, (2): distinct visual change in moist enamel, (3): localised enamel breakdown due to caries with no visible dentine or underlying shadow, (4): underlying dark shadow in dentine with or without localised enamel breakdown, (5): distinct cavity with visible dentine, and (6): extensive distinct cavity with visible dentine
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: following index test Training of examiner: experienced, same examiner as index test Blinding to index test: no Multiple tests: no Site selection: 3 sections Target condition: caries free, early enamel, deep enamel, outer dentine, 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	Multiple examiners reported so examiner 1's values reported
*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?			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

*Study characteristics*
Patient Sampling	Method of sampling: unclear Included conditions: unclear, "suspected to have occlusal caries" but unclear to what level Teeth: permanent molars (third molars excluded) Surface: occlusal Restorations: excluded Sealants: no
Patient characteristics and setting	Age: 18 to 25 years Sex: 87 female, 74 male Ethnicity: not reported Country: Turkey Setting: restorative clinic at dental hospital Number of participants/teeth/sites: 161 participants, 187 teeth Prevalence: enamel = 0.77, dentine = 0.52
Index tests	Category of test: visual ‐ "a slightly modified version of the system previously reported by Ekstrand 1997" Sequence of test(s): visual, radiograph, DIAGNOdent, then reference standard (visual, radiograph and DIAGNOdent used as part of reference standard) ‐ assumed that visual assessment was performed before other tests Examiner training and calibration: unclear Teeth cleaning prior to examination: calculus and plaque removed using a scaler and rubber cup ‐ no pumice used Tooth drying prior to examination: 8 seconds Threshold applied: no or slight change, opacity visible after air drying, discolouration visible after drying, opacity visible, discolouration visible, localised enamel breakdown, enamel cavitation exposing dentine
Target condition and reference standard(s)	Category: used a hybrid visual, radiograph, and a fluorescence test; to determine excavation as appropriate, decay was "removed by using rotational cutting devices" and the cavities assessed visually, i.e. excavation Sequence of index test and reference standard: following index test Training of examiner: experienced, same examiner as index test Blinding to index test: no Multiple tests: no Site selection: 3 sections Target condition: caries free, early enamel, deep enamel, outer dentine, 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 observer results used
*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)?	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?	Yes
Did all patients receive the same reference standard?	No
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		High risk

*Study characteristics*
Patient Sampling	Method of sampling: selected "from a collection extracted for periodontal or orthodontic reasons" Included conditions: "a number of sound teeth and a range of occlusal carious lesions" unclear whether this included dentine caries Teeth: primary molars Sealants: not reported Restoration: excluded Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Belgium Setting: extracted teeth Number of participants/teeth/sites: 100 teeth, 169 sites ‐ reported at the tooth level Prevalence: enamel = 0.75, dentine = 0.39
Index tests	Category of test: visual ICDAS Sequence of test(s): visual, then reference standard (photographs also assessed but not used here) Examiner training and calibration: trained and calibrated dentists Teeth cleaning prior to examination: "a batch of extracted cleaned teeth" Tooth drying prior to examination: yes ‐ not details provided Threshold applied: ICDAS criteria
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: following index test, unclear whether same examiners viewed photographs and histology results Training of examiner: unclear Blinding to index test: no Multiple tests: no Site selection: "one to four histological sections and their images were assigned to each examination site" Target condition: caries free, early enamel, deep enamel, outer dentine, dentine, deep dentine
Flow and timing	Participants with index test but no reference standard: 4 ‐ broken 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?	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)?
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?	No
Could the patient flow have introduced bias?		Low risk

*Study characteristics*
Patient Sampling	Method of sampling: whole sample was selected in schools or preschools, however those included in DTA part of paper were included due to exfoliation which can be classed as random Included conditions: no cavitation and early lesions; exclusions "teeth with restorations, hypoplastic defects, sealants or frankly cavitated lesions were excluded" Teeth: primary molars Sealants: excluded Restorations: excluded Surface: occlusal
Patient characteristics and setting	Age: 3 to 12 years Sex: not reported Ethnicity: not reported Country: Brazil Setting: "selected from preschools or schools.... and from children who sought dental treatment" Number of participants/teeth/sites: 139 participants, 763 teeth, 50 included in the review because they received a reference standard Prevalence: enamel = 0.52, dentine = 0.26
Index tests	Category of test: 2 visual tests ‐ ICDAS II, Nyvad Sequence of test(s): "performed independent evaluations of all selected occlusal sites, using the NY and ICDAS‐II (plus LAA)" randomised and 2 tests separated by 1 week Examiner training and calibration: yes, trained and calibrated Teeth cleaning prior to examination: brush and slurry Tooth drying prior to examination: 3‐in‐1 syringe Threshold applied: ICDAS ‐ 0: sound tooth, 1: first visual change in enamel, 2: distinct visual change in enamel, 3: localised enamel breakdown, 4: underlying dark shadow from dentine, 5: distinct cavity with visible dentine, 6: extensive distinct cavity with visible dentine Nyvad ‐ 0: sound, 1: active caries (intact surface), 2: active caries (surface discontinuity), 3: active caries (cavity), 4: inactive caries (intact surface), 5: inactive caries (surface discontinuity), 6: inactive caries (cavity)
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: "2 examiners blind to each other and to the clinical visual scores" 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?	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?	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

*Study characteristics*
Patient Sampling	Method of sampling: not reported ‐ donated teeth but no indication of consecutive or random sampling Included conditions: no cavitation and unclear on severity of lesions Teeth: permanent: premolars and third molars Sealants: not reported Restorations: 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: 115 teeth Prevalence: enamel = 0.96, dentine = 0.50
Index tests	Category of test: visual ‐ ICDAS Sequence of test(s): index tests prior to reference standard Examiner training and calibration: "previously trained with the e‐learning program provided by the ICDAS Foundation" Teeth cleaning prior to examination: with pumice and rotating brush, washed with distilled water Tooth drying prior to examination: wet initially, then dried with compressed air for 5 seconds Threshold applied: ICDAS codes
Target condition and reference standard(s)	Category: histology ‐ microradiography and stereomicroscopy Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: yes, microradiography used for results 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	Microradiography results reported in 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)?
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

*Study characteristics*
Patient Sampling	Method of sampling: selected from a pool of previously extracted teeth Included conditions: unclear "suspected carious lesions on their occlusal surfaces" "those with extensive cavities" were excluded Teeth: permanent third molars Sealants: not reported Restorations: excluded: "sound or restored teeth" Surface: occlusal Final data sample shows sound teeth despite the intention to exclude these
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Brazil Setting: extracted teeth Number of participants/teeth/sites: 40 teeth Prevalence: enamel = 0.73, dentine = 0.45
Index tests	Category of test: visual ‐ ICDAS Sequence of test(s): index tests (standard visual prior digital images) prior to reference standard Examiner training and calibration: calibration completed, experienced examiners "pediatric dentists with a maximum of 5 years of clinical practice" Teeth cleaning prior to examination: "cleaned with ultrasonic tips to remove calculus and debris" Tooth drying prior to examination: "examined after drying" Threshold applied: ICDAS codes
Target condition and reference standard(s)	Category: microCT: "microCT (1173, Bruker, Kontich, Belgium) with the following acquisition parameters: 70 kV, 114 μA, 7.12‐ μm pixel size, 1‐mm thick Al filter, 1 s exposure, 0.5° rotation step at 360°, and 20‐line random movements" Sequence of index test and reference standard: index test then reference standard Training of examiner: not reported Blinding to index test: unclear Multiple tests: yes, microradiography used for results Site selection: sectioned teeth Target condition: healthy, enamel, dentine "To detect any sign of caries (threshold 1), positive cases were identified by setting a cutoff point of 20% deviation from the mean gray scale level of sound enamel based on the histogram distribution of each specimen. For dentin caries (threshold 2), the cutoff point was set as the demineralized dentin tissue that should be removed from the 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: 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?	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?			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

*Study characteristics*
Patient Sampling	Method of sampling: consecutive Included conditions: no cavitation and early lesions Teeth: third molars, requiring extraction Sealants: no Restorations: excluded Surface: occlusal
Patient characteristics and setting	Age: 16 to 39 years Sex: 10 male, 16 female Ethnicity: not reported Country: Brazil Setting: dental clinic Number of participants/teeth/sites: 26 participants, 43 teeth Prevalence: enamel = 0.81, dentine = 0.07
Index tests	Category of test: visual ‐ ICDAS Sequence of test(s): index tests (visual then DIAGNOdent pen) prior to reference standard Examiner training and calibration: yes Teeth cleaning prior to examination: brush and slurry Tooth drying prior to examination: yes Threshold applied: ICDAS ‐ 0: sound tooth, 1: first visual change in enamel, 2: distinct visual change in enamel, 3: localised enamel breakdown, 4: underlying dark shadow from dentine, 5: distinct cavity with visible dentine, 6: extensive distinct cavity with visible dentine
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: healthy, 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?	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?		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

*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: index test performed in clinical setting at dental school, then teeth extracted for reference standard Number of participants/teeth/sites: 88 participants, 105 teeth Prevalence: enamel = 0.95, dentine = 0.26
Index tests	Category of test: visual ‐ ICDAS Sequence of test(s): index tests (visual, radiograph, DIAGNOdent, DIAGNOdent pen, and VistaProof) followed by reference standard Examiner training and calibration: 1 experienced examiner ‐ ICDAS training and calibration Teeth cleaning prior to examination: low‐speed handpiece with a rotating brush and water Tooth drying prior to examination: unclear Threshold applied: ICDAS thresholds, only ICDAS 0‐4 found in sample
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?	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?	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

*Study characteristics*
Patient Sampling	Method of sampling: teeth were collected from clinics and the lesions selected Included conditions: not reported, suggestion that sound sites were not selected Teeth: primary teeth Sealants: not reported Restorations: not reported Surface: occlusal and smooth/approximal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Scotland and Denmark Setting: extracted teeth Number of participants/teeth/sites: 141 teeth Prevalence: enamel = 0.72, dentine = 0.38
Index tests	Category of test: visual ‐ ICDAS II Sequence of test(s): index tests followed by reference standard, only reporting on study 1 for this review Examiner training and calibration: not reported, but known to be experienced ICDAS examiners Teeth cleaning prior to examination: yes Tooth drying prior to examination: not reported Threshold applied: ICDAS II codes
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: 2 ‐ broken during sectioning, no risk of 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
*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)?
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?	No
Could the patient flow have introduced bias?		Low risk

*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: 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: visual ‐ ICDAS Teeth not set up in a model to recreate approximal contact 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 Teeth cleaning prior to examination: yes Tooth drying prior to examination: 3‐in‐1 syringe used Threshold applied: ICDAS codes
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?			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?	No
Could the patient flow have introduced bias?		Low risk

*Study characteristics*
Patient Sampling	Same as previous study, entered to allow for data entry of permanent teeth
Patient characteristics and setting
Index tests
Target condition and reference standard(s)
Flow and timing
Comparative
Notes

*Study characteristics*
Patient Sampling	Method of sampling: "selected following examination under a stereomicroscope" Included conditions: no cavitation and early lesions, "no signs of demineralization to those with varying degrees of demineralization" Teeth: permanent molars Sealants: not reported Restorations: not reported 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: 84 teeth Prevalence: enamel = 0.63, dentine = 0.23
Index tests	Category of test: visual ‐ ERK Sequence of test(s): index tests (visual, intraoral camera, (Rydalmere NSW 2116, Australia) and operating microscope (Moller‐Wedel, Dento 300, Germany)) prior to reference standard, all index tests separated by at least 1 week Examiner training and calibration: 4 examiners all with at least 4 years' experience Teeth cleaning prior to examination: cleaned with a toothbrush Tooth drying prior to examination: air and water from the unit air‐water syringe Threshold applied: ERK criteria
Target condition and reference standard(s)	Category: histology ‐ stereomicroscope Sequence of index test and reference standard: index test then reference standard Training of examiner: 2 experienced examiners ‐ possibly same examiners as index test Blinding to index test: unclear Multiple tests: no Site selection: 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: 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	Mean value of 4 examiners results used in 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?	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?	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

*Study characteristics*
Patient Sampling	Method of sampling: selected ‐ methods not reported Included conditions: not reported Teeth: permanent premolars and molars Sealants: not reported 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: 40 molars, 40 premolars, (20 canines not assessed) Prevalence: enamel = 0.86, dentine = 0.49
Index tests	Category of test: visual ‐ other Sequence of test(s): index tests (visual, intraoral camera (Clear‐Vu, UK)) prior to reference standard, all index tests separated by at least 1 week Examiner training and calibration: 6 examiners not calibrated Teeth cleaning prior to examination: not reported Tooth drying prior to examination: not reported ‐ examiners followed their usual clinical practice Threshold applied: sound, enamel lesion, enamel cavity, dentine lesion, dentine cavity
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 assessors Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth Target condition: same system as 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	Mean 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?	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?	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

*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 noncavitated and cavitated carious lesions" Teeth: "primary molar that was in an advanced stage of root resorption" (pre and post‐exfoliation) Sealants: not reported Restorations: excluded 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: visual ‐ ICDAS ‐ before and after tooth separation Sequence of test(s): index tests (visual then radiograph) on 2 occasions but the same BW 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 Teeth cleaning prior to examination: "performed after professional prophylaxis using a low‐speed handpiece with a rotating bristle brush and pumice/water slurry. The approximal surfaces were also flossed for better surface evaluation" Tooth drying prior to examination: not reported Threshold applied: ICDAS codes
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: 0 = no caries, 1 = carious lesion limited to the outer half of the enamel, 2 = caries extending into the inner half of the enamel or outer half of the dentine, 3 = caries limited to the middle third of the dentine, and 4 = 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: "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. Data extracted for the index test prior to separation as more clinically relevant
*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?		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?	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

*Study characteristics*
Patient Sampling	Method of sampling: unclear, "obtained for research purposes" Included conditions: no cavitation and early enamel lesions Teeth: permanent premolars, first and second 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: 160 teeth, 320 sites Prevalence: enamel = 0.67, dentine = 0.37
Index tests	Category of test: visual ‐ other ‐ viewed outside of a model set‐up Sequence of test(s): index tests (visual, then magnifying aid and prism loupe) performed prior to reference standard ‐ order was randomised and assessments separated by 2 weeks, however the part of the study used in the review focusses on the 2 examiners who viewed the teeth outside of the jaw model Examiner training and calibration: 2 examiners with consensus, no training described Teeth cleaning prior to examination: not reported Tooth drying prior to examination: not reported Threshold applied: "0 = no lesion, 1 = enamel opacity with smooth surface, 2 = enamel opacity with rough surface, 3 = cavitation restricted to the enamel, 4 = cavitation extending into dentine"; "instructed to assess only lesions coronal to the cemento‐enamel junction"
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: same assessors as index test Multiple tests: no Site selection: sectioned teeth Target condition: (a) presence of caries; (b) presence of 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: 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?			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

*Study characteristics*
Patient Sampling	Occlusal surfaces
Patient characteristics and setting
Index tests
Target condition and reference standard(s)
Flow and timing
Comparative
Notes

PERMALINK

Visual or visual‐tactile examination to detect and inform the diagnosis of enamel caries

Richard Macey

Tanya Walsh

Philip Riley

Anne-Marie Glenny

Helen V Worthington

Lucy O'Malley

Janet E Clarkson

David Ricketts

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Target condition being diagnosed

1. Classification of levels of caries levels.

Treatment of caries

Index test(s)

2. Common visual scoring systems.

Clinical pathway

1.

Role of index test(s)

Alternative test(s)

Rationale

Objectives

Secondary objectives

Methods

Criteria for considering studies for this review

Types of studies

Participants

Index tests

Target conditions

Reference standards

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of methodological quality

3. QUADAS‐2 tool.

Participant selection domain

Index test domain

Reference standard domain

Flow and timing domain

Statistical analysis and data synthesis

Investigations of heterogeneity

Sensitivity analyses

Assessment of reporting bias

Summary of findings and assessment of the certainty of the evidence

Results

Results of the search

2.

4. Study characteristics.

Methodological quality of included studies

3.

4.

Participant selection

Index test

Reference standard

Flow and timing

Findings

5.

6.

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

7.

8.

9.

10.

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

Investigations of heterogeneity

Reference standard

11.

Prevalence of D₃ disease

*Study characteristics*
Patient Sampling	Method of sampling: randomised Included conditions: no cavitation and early lesions Teeth: permanent molars Sealants: excluded Restorations: excluded Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Switzerland Setting: dental hospital Number of participants/teeth/sites: 117 participants Prevalence: enamel = 0.66, dentine = 0.37
Index tests	Category of test: visual ‐ Ekstrand Sequence of test(s): index tests (visual, radiograph, DIAGNOdent pen) performed prior to reference standard Examiner training and calibration: unclear, completed by a dental professional Teeth cleaning prior to examination: yes Tooth drying prior to examination: yes Threshold applied: Ekstrand criteria
Target condition and reference standard(s)	Category: excavation where suspected of cavitation, otherwise radiographs and visual were combined Sequence of index test and reference standard: index test then reference standard Training of examiner: experienced, same examiners as index tests or aware of the results of the index test Blinding to index test: unclear Multiple tests: yes Site selection: unclear which site was investigated with which test Target condition: sound, enamel, dentinal lesions
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: 21 Time interval between tests: minimal Participants receiving both tests but excluded from results: 0
Comparative
Notes	Data used from table 2, n/a results excluded from data
*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)?	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?	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

*Study characteristics*
Patient Sampling	Method of sampling: selected ‐ "teeth extracted for orthodontic or periodontal reasons was selected" Included conditions: "healthy or present incipient caries lesions but those with large cavitated lesions or filled surfaces were excluded" Teeth: permanent premolars and molars Sealants: unclear Restorations: excluded Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Spain Setting: extracted teeth Number of participants/teeth/sites: 65 teeth Prevalence: enamel = 0.68, dentine not reported
Index tests	Category of test: visual ‐ ICDAS II Sequence of test(s): index tests performed (visual then VistaProof) prior to reference standard Examiner training and calibration: 35 teeth used for calibration Teeth cleaning prior to examination: calculus and residues were removed from the selected teeth, using a KAVO Sonic Flex Tooth drying prior to examination: triple air syringe was used to dry teeth Threshold applied: ICDAS codes
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: marked prior to index test, 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	Examiner 2 used in data extraction as this is the experienced dentist rather than a student
*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?		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

*Study characteristics*
Patient Sampling	Method of sampling: selected, "One to four easily re‐located sites within the pit and fissure system of each tooth were chosen as potential investigation sites" Included conditions: not reported Teeth: permanent premolars and molars Sealants: unclear Restorations: excluded 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: 100 teeth, 181 potential sites Prevalence: enamel = 0.76, dentine = 0.46
Index tests	Category of test: visual ‐ ICDAS Sequence of test(s): index tests performed prior to reference standard Examiner training and calibration: training provided by experienced examiner and calibration performed on 20 teeth Teeth cleaning prior to examination: cleaned carefully with a rotating brush and water Tooth drying prior to examination: dried with a 3‐in‐1 syringe Threshold applied: ICDAS codes
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: 4 experienced examiners Blinding to index test: same examiners as index test Multiple tests: 2 scales used, Downer and ERK Site selection: number of sections taken dependent on the size of lesion Target condition: sound, inner/outer enamel, inner/outer dentine
Flow and timing	Participants with index test but no reference standard: 88 missing due to "section damage on some teeth and to some not being scored by all examiners" 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)?
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?	No
Could the patient flow have introduced bias?		High risk

*Study characteristics*
Patient Sampling	Method of sampling: not clearly reported Included conditions: severity of condition unclear: "subjects with 1 or more proximal caries surfaces detected visually or radiographically were included in the study", restorations were included Teeth: permanent molars and premolars Sealants: not reported Restorations: included Surface: approximal
Patient characteristics and setting	Age: 19 to 60 years Sex: 55% male Ethnicity: not reported Country: South Korea Setting: clinical setting Number of participants/teeth/sites: 65 participants, 280 sites Prevalence: enamel = 0.61, dentine = 0.20
Index tests	Category of test: visual ‐ modified ICDAS Sequence of test(s): visual then radiograph followed by QLF, radiograph was the reference standard Examiner training and calibration: 1 trained examiner completed all index tests and reference standard Teeth cleaning prior to examination: full‐mouth scaling and polishing Tooth drying prior to examination: not reported Threshold applied: "V0: sound, V1: white or brown spot, V2: localised enamel breakdown, V3: underlying dark shadow or colour change, and V4: clinically cavitated or exposed dentine"
Target condition and reference standard(s)	Category: radiograph Sequence of index test and reference standard: reference standard prior to index test Training of examiner: not reported, but experienced Blinding to index test: no Multiple tests: no Site selection: approximal surfaces Target condition: sound, outer/inner enamel, outer/inner dentine
Flow and timing	Participants with index test but no reference standard: 15 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 the fluorescence images method as the 2 x 2 figures were not available for the software method
*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?	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?		High risk

*Study characteristics*
Patient Sampling	Method of sampling: consecutive ‐ "All 18–30‐year‐old university students" Included conditions: unclear Teeth: permanent premolars and molars Sealants: not reported Restorations: not reported Surface: approximal
Patient characteristics and setting	Age: 18 to 30 years Sex: not reported Ethnicity: not reported Country: Finland Setting: routine examination in dental clinic Number of participants/teeth/sites: 137 participants, of these 91 resulted in data, 1162 teeth, 2103 surfaces Prevalence: enamel = 0.20, dentine = 0.06 (according to radiograph results)
Index tests	Category of test: visual ‐ ICDAS Sequence of test(s): visual, radiograph, DIFOTI, all recorded clinically and viewed after the event by different clinicians but uncertain whether same examiner performed each test or whether tests could be influenced by others Examiner training and calibration: experienced examiners ‐ trained and calibrated during similar studies Teeth cleaning prior to examination: not reported Tooth drying prior to examination: not reported Threshold applied: ICDAS codes
Target condition and reference standard(s)	Category: bitewing radiograph Sequence of index test and reference standard: radiograph performed and interpreted separately to index test Training of examiner: experienced examiner in consensus Blinding to index test: yes Multiple tests: visual and radiograph performed before to index test Site selection: all surfaces Target condition: sound, initial and manifested
Flow and timing	Participants with index test but no reference standard: 0 Participants with reference standard but no index test: possibly there is a difference in numbers that received DIFOTI and other tests, 2083 versus 2103, but unclear how this was dealt with 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?	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?	Unclear
Could the patient flow have introduced bias?		Low risk

*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: visual ‐ Ekstrand Sequence of test(s): visual, then DIAGNOdent, then radiograph Examiner training and calibration: not reported Teeth cleaning prior to examination: brush, pumice and slurry Tooth drying prior to examination: 5 seconds Threshold applied: Ekstrand criteria, scores 1 & 2 enamel, 3 & 4 dentine
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)?	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?		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

*Study characteristics*
Patient Sampling	Method of sampling: "arbitrarily chosen for investigation" Included conditions: no cavitation and early lesions, "visible localized enamel surface discoloration (white, brown/black) or cavitated carious lesions involving an axial smooth enamel surface", therefore an attempt to have no sound surfaces Teeth: not reported Sealants: not reported Restorations: not reported Surface: smooth
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Japan Setting: extracted teeth Number of participants/teeth/sites: 93 teeth, 127 sites Prevalence: enamel = 0.75, dentine = 0.31
Index tests	Category of test: visual ‐ scale no specified Sequence of test(s): index tests performed (visual, SS‐OCT) prior to reference standard, "Visual examination and SS‐OCT evaluations were performed in separate sessions and after shuffling the order of appearance for each case to ensure there was no interference from the previous observations" Examiner training and calibration: 2 clinical experience of over 9 years and 2 with 3 years Teeth cleaning prior to examination: "prophylaxis paste using a brush cone attached to a low‐speed handpiece" Tooth drying prior to examination: dried Threshold applied: sound, enamel demineralization without surface breakdown, enamel breakdown due to caries, dentine caries
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: "Two examiners with sufficient experience in histopathological study of caries" Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth, through locations used for index test Target condition: sound, superficial enamel demineralization, enamel breakdown, 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
*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?	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?			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

*Study characteristics*
Patient Sampling	Method of sampling: "Twenty‐six primary teeth were selected" Included conditions: sound and early lesions, "38 investigation sites of occlusal fissures (noncavitated and cavitated) were selected" ‐ level of cavitation uncertain Teeth: primary molars, "Extracted human primary molar teeth with/without occlusal caries" Sealants: not reported Restorations: not reported Surface: occlusal
Patient characteristics and setting	Age: not reported Sex: not reported Ethnicity: not reported Country: Japan Setting: dental hospital ‐ extracted teeth Number of participants/teeth/sites: 26 teeth, 38 sites Prevalence: enamel = 0.74, dentine = 0.32
Index tests	Category of test: visual ‐ scale not specified ‐ viewed on a monitor following digital imaging Sequence of test(s): index tests performed (visual, OCT) prior to reference standard, "Visual examination and SS‐OCT evaluations were performed in separate sessions and after shuffling the order of appearance for each case to ensure there was no interference from the previous observations" Examiner training and calibration: 6 dentists, with 1 hour training session Threshold applied: sound, enamel demineralization but without cavitation, localised enamel breakdown, dentine caries
Target condition and reference standard(s)	Category: histology Sequence of index test and reference standard: index test then reference standard Training of examiner: "Two examiners with sufficient experience in histopathological study of caries" Blinding to index test: unclear Multiple tests: no Site selection: sectioned teeth, through locations used for index test Target condition: sound, superficial enamel demineralization, enamel breakdown, 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	Mean results used from 6 examiners
*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

*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: clinical setting dental hospital Number of participants/teeth/sites: 50 participants, 621 sites Prevalence: enamel = 0.41, dentine = 0.03
Index tests	Category of test: visual ‐ ICDAS, no model created to replicate approximal contact Sequence of test(s): index tests (visual, radiograph, DIAGNOdent pen) then reference standard Examiner training and calibration: trained but no calibration Teeth cleaning prior to examination: brush and slurry Tooth drying prior to examination: air dried, 5 seconds Threshold applied: ICDAS codes
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?		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?	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

*Study characteristics*
Patient Sampling	Method of sampling: randomly selected from children seeking dental treatment Included conditions: no cavitation and early lesions, frank and severe lesions excluded Teeth: primary molars (first and second), in contact with another tooth Sealants: unclear Restorations: excluded Surface: approximal
Patient characteristics and setting	Age: 4 to 12 years, mean 7.25 Sex: 32 male, 44 female Ethnicity: not reported Country: Brazil Setting: clinical setting dental hospital Number of participants/teeth/sites: 76 participants, 592 sites Prevalence: enamel = 0.81, dentine = 0.05
Index tests	Category of test: visual ‐ ICDAS Sequence of test(s): index tests (visual, radiograph, DIAGNOdent pen) then reference standard Examiner training and calibration: experienced and trained but no calibration Teeth cleaning prior to examination: "cleaned with a rotating bristle brush with pumice/water slurry and dental floss" Tooth drying prior to examination: air dried, 5 seconds Threshold applied: ICDAS codes
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?		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?	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