Topical silver diamine fluoride (SDF) for preventing and managing dental caries in children and adults

Abstract

Background

Dental caries is the world's most prevalent disease. Untreated caries can cause pain and negatively impact psychosocial health, functioning, and nutrition. It is important to identify cost‐effective, easy‐to‐use agents, which can prevent or arrest caries. This review evaluates silver diamine fluoride (SDF).

Objectives

To assess the effects of silver diamine fluoride for preventing and managing caries in primary and permanent teeth (coronal and root caries) compared to any other intervention including placebo or no treatment.

Search methods

We searched CENTRAL, MEDLINE, Embase, Cochrane Oral Health's Trial Register and two clinical trials registers in June 2023.

Selection criteria

We included randomised controlled trials (RCTs), with parallel‐group or split‐mouth design, in children and adults (with or without carious lesions) that compared SDF with placebo or no treatment; different frequencies, concentrations or duration of SDF; or any other intervention.

Data collection and analysis

We used standard methodological procedures expected by Cochrane, and GRADE to assess the certainty of the evidence. We collected data for primary caries prevention (change in caries increment), arrest of carious lesions, secondary prevention of caries (lesions do not progress from initial classification), adverse effects, dental pain or sensitivity, and aesthetics at the end of study follow‐up.

Main results

We included 29 RCTs (13,036 participants; 12,020 children, 1016 older adults).

We summarise outcome data for the five most clinically relevant comparisons. All studies included high risks of bias, and some findings were imprecise (e.g. because of small sample sizes).

SDF versus placebo or no treatment (14 studies; 2695 children, 905 older adults)

Compared to placebo or no treatment, SDF may help prevent new caries in the primary dentition (1 study, 373 participants), or on the coronal surfaces of permanent dentition (1 study, 373 participants) but the evidence is very uncertain. SDF likely prevents new root caries (mean difference (MD) −0.79 surfaces, 95% confidence interval (CI) −1.40 to −0.17; 3 studies, 439 participants; moderate‐certainty evidence). SDF may help arrest caries in the primary dentition (MD 0.86 surfaces, 95% CI 0.39 to 1.33; 2 studies, 841 participants; low‐certainty evidence) and the permanent dentition (coronal: 1 study, 373 participants; root: 1 study, 158 participants) but the evidence is very uncertain. The evidence is very uncertain for secondary prevention of caries (primary dentition: 1 study, 128 participants; permanent dentition (coronal): 1 study, 663 participants), for adverse effects (5 studies, 1299 participants), and aesthetics (1 study, 43 participants).

Different approaches to SDF application (5 studies, 1808 children)

Studies compared different frequencies or intervals of application, different concentrations of SDF, and different durations of treatment. Some studies included multiple comparisons of different approaches. Because of the different approaches, we could not combine findings from these studies. Due to very low‐certainty evidence, we were unsure whether any approach to SDF application was better than another for caries arrest (4 studies, including 8 comparisons of different approaches, 1360 participants); secondary prevention of caries (1 study, 203 participants), or led to differences in adverse effects (3 studies, 1121 children) or aesthetics (1 study, 119 children).

SDF versus fluoride varnish (8 studies, 2868 children, 223 older adults)

Compared to flouride varnish, SDF may result in little or no difference to the prevention of new caries in the primary dentition (MD 0.00, 95% CI ‐0.26 to 0.26; 1 study, 434 participants; low‐certainty evidence). The evidence is very uncertain for this outcome measure in the permanent dentition (coronal: 1 study, 237 participants; root: 1 study, 100 participants; very low‐certainty evidence). Due to very low‐certainty evidence, we were unsure whether or not there were any differences between flouride varnish (applied weekly for three applications) and SDF for caries arrest and secondary prevention of caries in the primary dentition (1 study, 309 participants). Similarly, we were unsure of adverse effects (3 studies, 980 children), dental pain or sensitivity (1 study, 62 children), or aesthetics (1 study, 263 children).

SDF versus sealants and resin infiltration (2 studies, 343 children)

Very low‐certainty evidence in this comparison meant we were unsure if either treatment was better than the other for primary prevention of caries in permanent dentition (coronal: 1 study, 242 participants), or adverse effects (2 studies, 336 participants).

SDF versus atraumatic restorative treatment (ART) with glass ionomer cement (GIC) or GI material (4 studies, 610 children)

Very low‐certainty evidence in this comparison meant we were unsure if either treatment was better than the other at arresting caries in the primary dentition (1 study, 143 participants). We were also unsure whether there were any differences between treatments in adverse effects (3 studies, 482 participants), dental pain or sensitivity (1 study, 234 participants), or aesthetics (2 studies, 248 participants).

Authors' conclusions

In the primary dentition, evidence remains uncertain whether SDF prevents new caries or progression of existing caries compared to placebo or no treatment, but it may offer benefit over placebo or no treatment in caries arrest. Compared to placebo or no treatment, SDF probably also helps prevent new root caries. However, the evidence is uncertain for other caries outcome measures in this dentition and in all caries outcomes for coronal surfaces of permanent dentition.

Compared to flouride varnish, SDF may offer little or no benefit in preventing new caries in the primary dentition, but the evidence is very uncertain for other caries outcome measures in the primary dentition and for preventing new caries in the permanent dentition.

We were unable to establish whether one SDF treatment approach was better than another, or how SDF compared to other treatments, because of very low‐certainty evidence.

The impact of SDF staining of teeth was poorly reported and the evidence for adverse effects is very uncertain. Additional well‐conducted studies are needed. These should measure the impact of staining and be analysed to take account of clustering issues within participants.

Plain language summary

Is silver diamine fluoride varnish an effective treatment for preventing and managing tooth decay in children and adults?

Key messages

‐ We can't tell if silver diamine fluoride (SDF) is better than no treatment at preventing or treating tooth decay.

‐ We can't tell if SDF is better or worse than other treatments at preventing or treating tooth decay.

‐ New studies could help to find out about the unwanted effects of SDF, whether people are bothered by the staining on the teeth caused by SDF, and the best treatment approach.

What is tooth decay?

Tooth decay happens when bacteria in your mouth break down sugars from food, producing acids that damage tooth enamel (hard surfaces). This can lead to holes, or cavities, in the teeth. Tooth decay affects the crown of the tooth (the part above the gum) of baby teeth, and the crown and root of permanent teeth. If it is not prevented or treated it can cause toothache, infections and tooth loss.

How is tooth decay treated?

Treatments for tooth decay include liquids, gels (varnishes) and sealants. These treatments are painted onto the tooth to protect against bacteria. Treatment may also include fillings in larger cavities. Silver diamine fluoride (SDF) is a low‐cost liquid that can be painted on a tooth by a dentist or another trained person. It is suitable for people of all ages, including people with special health needs. However, SDF can permanently stain the treated tooth surface black or dark brown.

What did we want to find out?

We wanted to find out:

‐ if SDF was better than no treatment or other treatments at preventing new tooth decay, stopping existing tooth decay or preventing tooth decay from progressing;

‐ if there were benefits to applying SDF for different numbers of times, strengths of solution, or durations;

‐ if SDF caused unwanted effects, toothache, or if people were bothered by staining.

What did we do?

We searched for studies that compared SDF with no treatment or placebo (a dummy treatment), other treatments, or different application approaches. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?

We found 29 studies, with 12,020 children and 1016 older adults.

Main results

Compared with no treatment or placebo, we can't tell if SDF prevents new tooth decay in baby teeth or crown surfaces of permanent teeth. SDF is likely to prevent new tooth decay on root surfaces of permanent teeth. It may also completely stop existing tooth decay in baby teeth. However, we are unsure if it completely stops existing tooth decay on crown and root surfaces of permanent teeth, prevents existing tooth decay from progressing in any types of teeth, increases the risk of unwanted effects, or if people are bothered by the appearance of staining.

Studies used different combinations of treatment approaches (number of times SDF is applied and how often, the strength of solution, and duration of treatment). We can't tell if one approach is better than another at stopping or preventing further decay, unwanted effects, or bother with appearance of staining.

When SDF is compared with fluoride varnish, neither treatment may be better than the other at preventing new tooth decay in baby teeth. We are unsure about the effect on crown and root surfaces of permanent teeth. We also can't tell if either treatment is better than the other at stopping existing tooth decay or preventing further decay in baby teeth, or if there are any differences in unwanted effects, toothache, or bother with appearance of staining.

When SDF is compared with sealants, we can't tell if there are any differences between treatments in preventing new tooth decay on the crown surfaces of permanent teeth, or whether there are any differences between these treatments in unwanted effects.

When SDF is compared with fillings (with tooth decay first removed using only hand tools), we can't tell if there were any differences between treatments in stopping existing decay in baby teeth, unwanted effects, toothache, or bother with appearance of staining.

What are the limitations of the evidence?

Often we were very unsure of the evidence for the following reasons.

‐ SDF stains the teeth. Everyone in the studies would have known what treatment they were given. This might affect their usual teeth‐brushing routine. In most studies, the person checking teeth for new or existing decay would also have known this information.

‐ When we compared different approaches to SDF, the studies were too different from one another to allow us to compare them.

‐ Although we found 29 studies, most evidence was from individual (or few) studies, which were very small.

How current is this evidence?

The evidence is current to June 2023.

Summary of findings

Summary of findings 1. Silver diamine flouride (SDF) compared with placebo or no treatment for managing caries in children and adults.

Population: children and adults Settings: community or dental healthcare settings Intervention: SDF Comparison: no treatment/placebo
Outcomes	Dentition, or age group	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No. of studies (participants or teeth)	Certainty of the evidence (GRADE)	Comments
		Assumed risk No treatment/placeboa	Corresponding risk SDF
Primary caries prevention Measured as increment of new caries at end of study follow‐up: 24 to 36 months (in included studies) Lower increment values = positive outcome	Primary dentition	Mean increment in control group was 1.43 surfaces	Mean increment of surfaces in the SDF group was 1.14 lower (from 1.58 lower to 0.70 lower)		1 (373 participants)	⊕⊝⊝⊝ Very lowb
	Permanent dentition: coronal caries	Mean increment in control group was 1.06 surfaces	Mean increment of surfaces in the SDF group was 0.69 lower (from 0.97 lower to 0.41 lower)		1 (373 participants)	⊕⊝⊝⊝ Very lowb
	Permanent dentition: root caries	Mean increment in control groups ranged from 1.1 to 2.5 surfaces	Mean increment of surfaces in the SDF group was on average 0.79 lower (from 1.40 lower to 0.17 lower)		3 (439 participants)	⊕⊕⊕⊝ Moderatec
Caries arrest Measured as number of arrested carious lesions or surfaces per child at end of study follow‐up: 24 to 36 months (in included studies)	Primary dentition	Mean number of arrested surfaces ranged from 1.0 to 1.8	Mean number of arrested surfaces in the SDF group was 0.86 higher (from 0.39 higher to 1.33 higher)		2 (841 participants)	⊕⊕⊝⊝ Lowd
	Permanent dentition: coronal caries	Mean number of arrested surfaces was 0.1	Mean number of arrested surfaces in the SDF group was 0.20 higher (from 0.00 higher to 0.40 higher)		1 (373 participants)	⊕⊝⊝⊝ Very lowb
	Permanent dentition: root caries	Mean number of arrested root surfaces was 0.04	Mean number of arrested surfaces in the SDF group was 0.24 higher (from 0.12 higher to 0.36 higher)		1 (158 participants)	⊕⊝⊝⊝ Very lowe
Secondary prevention of caries See comments for measurement of this outcome at study follow‐up: 18 and 24 months (in included studies)	Primary dentition	Study population		OR 1.08 (0.52 to 2.23)	1 (1813 surfaces in 128 participants)	⊕⊝⊝⊝ Very lowf	Data in this study were reported as the rate of caries development on initially treated surfaces
		‐	‐
	Permanent dentition: coronal caries	Study population		Peto OR 44.22 (33.12 to 59.04)	1 (753 teeth, in 663 participants)	⊕⊝⊝⊝ Very lowg	Data in this study measured as the number of carious lesions not progressing at study follow‐up
		62 per 1000 teeth	750 per 1000 (692 to 800) teeth
	Permanent dentition: root caries	_	_	_	_	_	No studies measured this outcome for root surfaces
Adverse effects Measured at end of study follow‐up or any other time point as defined by study authors: 48 hours, 24 to 30 months (in included studies)	Children	1 study reported 3 adverse effects in the first 48 hours. Of these, 1 effect in SDF group was possibly related to treatment (spot on corner of lip that looked like a burn), and 2 effects in placebo group were possibly related to treatment (diarrhoea and stomach ache). 1 study reported a transient bitter taste associated with SDF, and no other adverse effects. 1 study reported no adverse effects			3 (983 participants)	⊕⊝⊝⊝ Very lowh
	Adults	1 study reported no adverse effects. 1 study reported a white discolouration of the gingiva adjacent to surfaces treated with SDF (116 surfaces) as well as redness (4 surfaces), and mild ulceration (2 surfaces). In addition, 53% participants treated with SDF reported a slight but tolerable taste sensation compared with 5% treated with a placebo, 4 participants in both groups reported a mild smell during treatment. At 12 months, study authors reported "no significant difference" in colour between surfaces of both treatment groups.			2 (316 participants)
Dental pain or sensitivity	‐	‐	‐		‐	‐	No studies measured this outcome
Aesthetics Measured at the end of study follow‐up: 30 months (in included study)	Adults	1 study reported that "only 19 (7%) [older adult participants] raised a complaint about the interventions at the 30‐mo [month] examination, and half of them complained of black stain on the treated root surfaces."i			1 (43 participants)	⊕⊝⊝⊝ Very lowj	No studies measured this outcome in children
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; OR: odds ratio; SDF: silver diamine fluoride
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^aDerived from the data reported in the control group of the included studies.
^bDowngraded by one level for risk of bias, one level for impecision owing to very small sample size, and one level for indirectness because the study area in the included study had very limited access to fluoride toothpaste (evidence may not be applicable to other areas with better access to fluoride toothpaste).
^cDowngraded by one level for risk of bias. We note that all studies in this analysis were from the same study area in which fluoride concentrations in water supplies is 0.5 ppm; we could not rule out the possibility that benefits could be greater in areas with no fluoride or lower levels of fluoride in water supplies.
^dDowngraded by one level for risk of bias, and one level for indirectness because the study area in one of the included studies had very limited access to fluoride toothpaste (evidence may not be applicable to other areas with better access to fluoride toothpaste).
^eDowngraded by one level for risk of bias. Downgraded by two levels for imprecision because the data were derived from too few participants. 
^fDowngraded by one level for risk of bias, and two levels for imprecision because the data were derived from too few participants and the confidence interval included the possibility of benefit and no benefit. We also noted that this effect estimate was inconsistent with other unadjusted data for this outcome. 
^gDowngraded by one level for risk of bias, and two levels for imprecision. Data included clustering of teeth which was not accounted for in analysis. Although the degree of clustering was minimal, we could not rule out the possibility that the CI in this effect would be wider if the clustering effect had been taken into account. 
^hDowngraded by one level for risk of bias, and two levels for imprecision. Although data were available for 983 children and 316 older adults, we judged there to be too few participants for this outcome. We also noted that the types of adverse effects were not defined in two studies and we did not know if all relevant types of adverse effects were recorded in these studies.
^jThis study included a study group (SDF + potassium iodide), which we did not include in the review. It was unclear to which intervention group(s) the 19 participants belonged.
ⁱDowngraded by one level for risk of bias and two levels for imprecision because data were available from only one very small study.

Summary of findings 2. Different approaches to silver diamine fluoride (SDF) application for managing caries in children and adults.

Population: children and adults Settings: community or dental healthcare settings Intervention and comparison: SDF given at different frequencies or intervals of application, different concentrations, and for different durations
Outcomes	Impact	Certainty of the evidence (GRADE)	Comments
	‐	‐	No studies reported data for this outcome
Caries arrest Measured as number of arrested carious lesions or carious surfaces at end of study follow‐up: 12 months to 30 months (in included studies)	In 1 study (45 children), 4 applications of 38% SDF at 1‐monthly intervals resulted in fewer surfaces with active caries compared with 2 applications at 6‐monthly intervals (MD 1.04 surfaces, 95% CI 0.23 to 1.85), and 3 applications of 38% SDF at 3‐monthly intervals resulted in fewer surfaces with active caries than 2 applications at six‐monthly intervals (MD 0.82 surfaces, 95% CI 0.00 to 1.64). In 1 study (203 children), caries arrest was higher when SDF treatment was given in 3 applications at 12‐monthly intervals than in 3 applications at weekly intervals (MD 0.80 surfaces, 95% 0.15 to 1.45). In 1 study (799 children), there was little or difference in caries arrest when applications were compared at 6‐monthly intervals with 12‐monthly intervals at a concentration of 38% SDF (MD −0.29 surfaces, 95% CI −0.98 to 0.40) or 12% SDF (MD −0.26 surfaces, 95% CI −0.83 to 0.31). There was greater benefit when 38% SDF was used than 12% SDF when applied at 6‐monthly intervals (MD 0.64 surfaces, 95% CI 0.03 to 1.25), but little or no difference between concentrations when applied at 12‐monthly intervals (MD 0.61 surfaces, 95% CI −0.05 to 1.27). In 1 study (313 children), there was little or no difference when 38% SDF was compared with 12% SDF, both given in a single application (MD 0.60 surfaces, 95% CI −0.23 to 1.43).	⊕⊝⊝⊝ Very lowa
Secondary prevention of caries Measured as number of surfaces with carious lesions not progressing at study follow‐up: 30 months (in included study)	In 1 study (203 children), there was little or no difference in secondary prevention of caries when SDF treatment was given in 3 applications at 12‐monthly intervals than in 3 applications at weekly intervals (MD −0.10 lesions, 95% CI −0.61 to 0.41)	⊕⊝⊝⊝ Very lowb
Adverse effects Measured at end of study follow‐up: 24 to 30 months (in included studies)	1 study (203 children) reported that black or brown staining on treated lesions was commonly found in both groups, with little or no difference according to whether SDF treatment was given in 3 applications at 12‐monthly intervals than in 3 applications at weekly intervals (OR 1.43, 95% CI 0.81 to 2.52). This study reported that no major adverse health effects were found during the study period. 1 study (799 children), reported that "apart from black staining on the arrested lesions", there were no other adverse effects. 1 study (119 children) reported that all except 1 of the arrested carious lesions treated with SDF were stained black, with no other adverse effects.	⊕⊝⊝⊝ Very lowc
Dental pain or sensitivity	‐	‐	No studies reported data for this outcome
Aesthetics Measured at the end of study follow‐up: 24 months (in included study)	1 study (119 children) reported that 45% parents were satisfied with child's dental appearance (data not reported by study group)	⊕⊝⊝⊝ Very lowd
CI: confidence interval; MD: mean difference; OR: odds ratio; SDF: silver diamine fluoride
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded by one level for risk of bias and two levels for inconsistency (related to differences in study designs, which precluded meta‐analysis).
^bDowngraded by one level for risk of bias, and two levels for imprecision (because the data were derived from few participants and the CI included the possibility of benefit and no benefit for both treatments).
^cDowngraded by one level for risk of bias and two levels for imprecision. We judged there to be too few participants for this outcome. We also noted that the types of other adverse effects were not defined in the studies and did not know if all relevant types of adverse effects were recorded by study authors.
^dDowngraded by one level for risk of bias and two levels for imprecision (because data derived from few participants).

Summary of findings 3. Silver diamine fluoride (SDF) compared with fluoride varnish (FV) for managing caries in children and adults.

Population: children and adults Settings: community or dental healthcare settings Intervention: SDF Comparison: FV
Outcomes	Dentition, or age group	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No. of studies (participants)	Certainty of the evidence (GRADE)	Comments
		Assumed risk with FVa	Corresponding risk with SDF
Primary caries prevention Measured as increment of new caries or number of children with new caries at the end of study follow‐up: 24 to 36 months (in included studies) Lower increment = better outcome	Primary dentition	Mean increment in control group was 0.4 surfaces	The mean increment of surfaces in the SDF group was the same as the FV group (0.4 surfaces) with a CI from 0.26 lower to 0.26 higher	_	1 (434 participants)	⊕⊕⊝⊝ Lowb
	Permanent dentition: coronal caries	Study population		OR 0.95 (0.44 to 2.05)	1 (237 participants)	⊕⊝⊝⊝ Very lowc
		129 per 1000	124 per 1000 (61 to 233)
	Permanent dentition: root caries	Mean increment in control group was 0.9 surfaces	The mean increment of surfaces in the SDF group was 0.20 lower (from 0.91 lower to 0.51 higher)		1 (100 participants)	⊕⊝⊝⊝ Very lowc
Caries arrest Measured as number of surfaces with carious lesions arrested at the end of study follow‐up: 30 months (in included study)	Primary dentition	Mean number of arrested surfaces was 1.9	The mean number of arrested surfaces in the SDF group was 0.13 lower (from 0.87 lower to 0.61 higher)		1 (309 participants)	⊕⊝⊝⊝ Very lowc	In this study, FV was given at non‐standard weekly intervals (in 3 applications)
	Permanent dentition: coronal caries	_	_	_	_	_	No studies reported data in this dentition type
	Permanent dentition: root caries	_	_	_	_	_	No studies reported data in this dentition type
Secondary prevention of caries Measured as number of surfaces with carious lesions per child not progressing at the end of study follow‐up: 30 months (in included study)	Primary dentition	Mean number of surfaces without progression was 1.2	The mean number of surfaces without progression in the SDF group was 0.04 higher (from 0.30 lower to 0.38 higher)		1 (309 participants)	⊕⊝⊝⊝ Very lowc	In this study, FV was given at non‐standard weekly intervals (in 3 applications)
	Permanent dentition: coronal caries	_	_	_	_	_	No studies reported data in this dentition type
	Permanent dentition: root caries	_	_	_	_	_	No studies reported data in this dentition type
Adverse effects Measured at end of study follow‐up: 24 hours, and 24 to 30 months (in included studies)	Children	In 1 study, black or brown staining on treated lesions was more common after SDF (OR 3.19, 95% CI 1.95 to 5.23), with no other adverse effects. 1 study reported complaints of a transient bitter taste with SDF use (with no associated data), and no other adverse effects. 1 study reported that there were no short‐term (within the first 24 hours), or long‐term adverse effects (at 12 months), which included gum irritation, swelling or bleaching.			3 (980 participants)	⊕⊝⊝⊝ Very lowd	No studies reported this outcome in adults
Dental pain or sensitivity Measured at end of study follow‐up: 12 months (in included study)	Children	Study population		OR 0.36 (0.10 to 1.34)	1 (62 participants)	⊕⊝⊝⊝ Very lowc	No studies reported this outcome in adults
		290 per 1000	128 per 1000 (39 to 353)
Aesthetics Measured at the end of study follow‐up: 12 months (in included study)	Children	Study population		OR 0.68 (0.41 to 1.11)	1 (263 participants)	⊕⊝⊝⊝ Very lowc	No studies reported this outcome in adults
		770 per 1000	578 per 1000 (578 to 788)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; FV: fluoride varnish; OR: odds ratio; SDF: silver diamine fluoride
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^aDerived from the data reported in the FV groups of the included studies.
^bDowngraded by one level for risk of bias, and one level for imprecision because the CI included the possibility of benefit and no benefit for both treatments.
^cDowngraded by one level for risk of bias, and two levels for imprecision because the CI included the possibility of benefit and no benefit for both treatments and evidence was derived from few participants.
^dDowngraded by one level for risk of bias, and two levels for imprecision because we judged there to be too few participants for this outcome. We also noted that types of other adverse effects were not defined and we did not know if data for all relevant types of adverse effects were collected in these studies.

Summary of findings 4. Silver diamine flouride (SDF) compared with sealants and resin infiltration for managing caries in children and adults.

Population: children and adults Settings: community and dental care settings Intervention: SDF Comparison: sealants or resin infiltration
Outcomes	Dentition, or age group	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of studies (participants)	Certainty of the evidence (GRADE)	Comments
		Assumed risk with sealants	Corresponding risk with SDF
Primary caries prevention Measured as increment of new caries at end of study follow‐up: 24 months (in included study)	Primary dentition	_	_	_	_	_	No studies reported data in this dentition type
	Permanent dentition: coronal caries	Study population		OR 1.76 (0.74 to 4.20)	1 (242 participants)	⊕⊕⊝⊝ Very lowb
		74 per 1000a	124 per 1000 (56 to 252)
	Permanent dentition: root caries	_	_	_	_	_	No studies reported data in this dentition type
Caries arrest Measured as number of surfaces with carious lesions arrested at the end of study follow‐up	Primary and permanent dentition (coronal and root)	_	_	_	_	_	No studies reported data in either dentition type
Secondary prevention of caries Measured as number of surfaces with carious lesions per child not progressing at the end of study follow‐up	Primary and permanent dentition (coronal and root)	_	_	_	_	_	No studies reported data in either dentition type
Adverse effects Measured at end of study follow‐up: 24 months (in included studies)	Children	In 1 study, people complained about a transient bitter taste associated with SDF (with no associated data), with no other adverse effects. In another study, there were no adverse effects.			2 (336 participants)	⊕⊝⊝⊝ Very lowc	No studies reported this outcome for adults
Dental pain or sensitivity Measured at end of study follow‐up	Children and adults	_			_	_	No studies reported data for this outcome
Aesthetics Measured at end of study follow‐up	Children and adults	_			_	_	No studies reported data for this outcome
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; OR: odds ratio; SDF: silver diamine fluoride
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^aAssumed risk derived from data reported in the included studies for the comparison group.
^bDowngraded by one level for risk of bias, and two levels because the evidence was from few participants and the CI included the possibility of benefit for both treatments.
^cDowngraded by one level for risk of bias, and two levels for imprecision because we judged there to be too few participants for this outcome. We also noted that adverse effects were not defined in these studies and we could not be certain that relevant adverse effects were collected in these studies.

Summary of findings 5. Silver diamine fluoride (SDF) compared with atraumatic restorative treatments (ART) for managing caries in children and adults.

Population: children and adults Settings: community or dental healthcare settings Intervention: SDF Comparison: ART (using hand tools to remove caries), followed by application of either GIC or high‐fluoride‐releasing glass ionomer material
Outcomes	Dentition, or age group	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No. of studies (participants)	Certainty of the evidence (GRADE)	Comments
		Assumed risk ARTa	Corresponding risk SDF
Primary caries prevention Measured as increment of new caries at end of study follow‐up	Primary dentition, and permanent dentition (coronal and root caries)	‐	‐	‐	‐	‐	No studies reported this outcome
Caries arrest Measured as odds of children having caries arrest (or lesions covered by GIC) at the end of study follow‐up: 24 months (in included study)	Primary dentition			OR 1.13 (0.52 to 2.45)b	1 (143 participants)	⊕⊝⊝⊝ Very lowc
	Permanent dentition (coronal and root caries)	‐	‐	‐	‐	‐	No studies reported this outcome in this dentition type
Secondary prevention of caries Measured as number of carious lesions not progressing at study follow‐up	Primary dentition, and permanent dentition (coronal and root caries)	‐	‐	‐	‐		No studies reported this outcome
Adverse effects Measured at end of study follow‐up or any other time point as defined by study authors: 3 months, 48 hours, and 24 months (in included studies)	Children	In 1 study, 115 of 118 children had black stains on teeth treated with SDF; there were no other adverse effects or allergic reactions. In 1 study, the rate of adverse effects reported by caregiver and person who applied treatment 2 days after treatment was 14.7% in SDF group and 9.1% in ART group. Effects in SDF group included burning, pain or sensitivity in teeth during treatment or within 2 days of treatment, mouth injury, spot or pigmentation of skin or mouth. Effects in ART group included nausea, bad taste, and pain or sensitivity in teeth during treatment or within 2 days of tretatment. In 1 study, all except 1 of arrested carious lesions treated with SDF were black, and 82% of those treated with ART and GIC were yellow or brown; there were no other adverse effects.			3 (482 participants)	⊕⊝⊝⊝ Very lowd	No studies reported this outcome in adults
Dental pain or sensitivity Measured at end of study follow‐up: 3 months (in included study)	Children	Study population		OR 0.16 (0.02 to 1.32)	1 (234 participants)	⊕⊝⊝⊝ Very lowc	No studies reported this outcome in adults
		52 per 1000	9 per 1000 (1 to 67)
Aesthetics Measured at the end of study follow‐up, or as reported by study authors: 24 months, and 48 hours after treatment (in included studies)	Children	1 study reported that 45% of parents were satisfied with appearance of their child's teeth; data not reported by study group. 1 study reported that 1 of 34 caregivers in SDF group were "annoyed with teeth appearance", with none in the ART group.		‐	2 (248 participants)	⊕⊝⊝⊝ Very lowd	No studies reported this outcome in adults
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ART: atraumatic restorative treatment; CI: confidence interval; GIC: glass ionomer cement; OR: odds ratio; SDF: silver diamine fluoride
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^aDerived from the data reported in the comparison group of the included studies.
^bEffect estimate from the study report adjusted for clustering.
^cWe downgraded by one level for risk of bias and two levels for imprecision because the evidence was from very few participants and the CI included the possibility of benefit and no benefit for both treatments.
^dWe downgraded by one level for risk of bias and two levels for imprecision because we judged there to be too few participants for this outcome.

Background

Description of the condition

Dental caries is the world's most prevalent disease (Kassebaum 2015; Marcenes 2013), and can be painful and debilitating. If left untreated, dental caries may lead to dental infections or abscesses. In very rare circumstances, it may also lead to life‐threatening complications such as sepsis (Pine 2006). Caries can develop on the crown of the tooth (coronal caries), or may also develop on the root of the tooth (root caries) in adults. Caries not only affects a person's oral health but can also affect their ability to function physically and socially. Untreated caries may negatively impact oral health‐related quality of life. For children, this may have long‐term effects on learning, for those who lose time in school because of untreated caries (Jackson 2011), and who may have lower levels of performance when attending school (Blumenshine 2008; Detty 2014; Farber 2004; PR Newswire July 2015; Seirawan 2012). In a UK‐based study including children who were waiting for extractions under general anaesthetic, two thirds of children reported pain, a quarter missed school days and more than a third had sleepless nights (Goodwin 2015). Caries is associated with lower levels of nutrition (Rego 2020), which may be caused by restriction in eating, as well as with poorer growth and development, social function and psychosocial vulnerability (CMS 2013; Finlayson 2007; Mattheus 2010; Quiñonez 2001). Additionally, untreated caries may have negative consequences for employment and well‐being in adults (Gil‐Montoya 2015; Hagman 2021; Halasa‐Rappel 2019). Given the widespread nature of caries globally (WHO 2022), it is critical that interventions can be delivered in diverse settings by available personnel. Scoping reviews indicate that cost‐effective preventive agents that can be applied by families or community health workers are available but underused (Niederman 2015). In order to better implement such interventions, it is first necessary to establish their effectiveness.

Description of the intervention

The most effective, simplest, and least expensive caries preventive agents may be silver nitrate, which kills the causative bacteria, and fluoride, which renders the teeth less soluble to bacterial acids (Niederman 2015). The creation of a silver nitrate fluoride construct – silver diamine fluoride (SDF) – combines these two preventive agents (Rosenblatt 2009). SDF is also known as 'diammine' silver fluoride, silver fluoride and silver ammonium fluoride. In this review, we have used a single 'm' in the spelling of diamine as this is commonly used by dental health professionals. SDF is a topical medication, a mostly colourless and odourless liquid, which is applied to the tooth surface to treat and prevent dental caries and to treat dentinal hypersensitivity. It may be applied once or with repeated applications; different concentrations of SDF are available.

The specific interest in SDF centres around its five presumed attributes (Thibodeau 1978): control of pain and infection; ease and simplicity of use (paint on); affordability of material (pennies per application); minimal requirement for personnel time and training (one minute, once per year); and that it is non‐invasive. In this sense, SDF is sometimes referred to as a potential agent to disrupt the traditional approaches to caries prevention and control (Christensen 2009).

The main adverse effect of SDF is that it causes a black staining to the carious tooth lesion after application, and this staining is permanent. It will also stain skin, clothing or work surfaces if protection is not used during application. It is also known to have a bitter metallic taste which may last for a few minutes after application.

How the intervention might work

Multiple modes of action have been proposed for SDF (Zhao 2018). This may, in part, be explained by the multiple biological organisms, subcellular targets, and mechanisms that have been examined. SDF is thought to arrest and prevent decay progression by killing the causative bacteria, inhibiting the growth of bacteria and formation of cariogenic biofilms, promoting the remineralisation of hydroxyapatite in enamel and dentine, and inhibiting the degradation of the organic matrix of the dentine (Zhao 2018).

Why it is important to do this review

Although SDF is approved for use to treat hypersensitivity in many countries, it is often used off‐label for arresting caries (Gao 2021). For example, the United States Food and Drug Administration (FDA) approved the use of SDF in the USA in 2014 as a treatment of dentinal hypersensitivity in adults at least 21 years of age. In 2016, the FDA approved a commercially available SDF product (Advantage Arrest) as a 'breakthrough therapy' for the arrest of caries in children and adults, meaning it has the potential to address a currently unmet medical need. Although used for the treatment of cavitated lesions particularly in children, SDF is not FDA‐labeled and is currently used off‐label (ADA 2023).

Earlier systematic reviews indicated that some randomised controlled trials show that SDF may be used to halt the progression of caries (Gao 2016a; Rosenblatt 2009). The expanding availability of SDF, as well as an increase in available clinical trials data, suggest the need for an updated systematic review to examine the effectiveness of SDF for the arrest and prevention of caries.

Objectives

To assess the effects of silver diamine fluoride for preventing and managing caries in primary and permanent teeth (coronal and root caries) compared to any other intervention including placebo or no treatment.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) of parallel‐group and split‐mouth design that compared the use of silver diamine fluoride (SDF) with any other intervention, placebo or no treatment, in people with any type of carious lesions or without carious lesions. We considered any length in follow‐up period for inclusion.

We included cluster‐RCTs if studies allocated more than one cluster to each study group; we excluded cluster‐RCTs with one cluster per study group because these clusters are unable to measure variability. We excluded quasi‐randomised trials in which participants were allocated to groups using a method that is not truly random, such as date of birth or hospital record number.

Types of participants

We included children, adolescents and adults with any type of carious lesions or without carious lesions in anterior or posterior primary or permanent teeth, or both.

Types of interventions

We included topical application of SDF at any frequency of application, concentration of solution, or duration of treatment in anterior or posterior primary or permanent teeth with any type of carious lesions or without caries, and performed with or without caries excavation, compared with any other intervention including placebo or no treatment, or the same intervention given at a different frequency, concentration, or duration of treatment.

In this review, we grouped included interventions into the following five main comparison groups.

• Comparison 1: SDF versus placebo or no treatment

• Comparison 2: Different approaches to SDF application

• Comparison 3: SDF versus other topical treatments

• Comparison 4: SDF versus sealants and resin infiltration

• Comparison 5: SDF versus restorative treatments

Types of outcome measures

In order to meet the review objectives, we included only studies that measured caries prevention or arrest.

Primary outcomes

• Primary caries prevention, as measured by change from baseline in the number of decayed, missing, or filled surfaces or teeth in the permanent dentition, and decayed, missing, or filled surfaces or teeth in the primary dentition

• Caries arrest indicated by change in caries from active to arrested (inactive), measured by visual changes in enamel and dentine or any other ways that may be used for caries arrest evaluation. A sound restoration may be considered as 'arrested caries' (Kidd 2010).

• Secondary prevention of caries indicated when initial lesions (e.g. lesions classed as International Caries Detection and Assessment System (ICDAS) 3 to 4) remain active but do not progress from initial classification.

Secondary outcomes

• Adverse effects (e.g. allergic reactions, taste disturbances, tooth staining around lesions, decreased bond strength for direct restorations, or other effects as described by study authors that are likely to be related to the treatment).

• Dental pain or sensitivity (e.g. pain and postoperative sensitivity) may be measured by a visual analogue scale (VAS). Assessed by a practitioner or participant self‐report.

• Aesthetics (satisfaction or bother with appearance of teeth, e.g. acceptability of colour changes in carious lesions). Assessed by participant, parent or clinician using any methods reported by study authors.

For both primary and secondary outcomes, we collected outcome data at the final study follow‐up.

Search methods for identification of studies

Electronic searches

We conducted systematic searches in the following databases for RCTs and controlled clinical trials (the latter being considered in the search strategy in order to ensure high search sensitivity).

• Cochrane Oral Health’s Trials Register (searched 13 July 2022) (Appendix 1);

• Cochrane Central Register of Controlled Trials (CENTRAL; 2023, Issue 6) in the Cochrane Library (searched 26 June 2023) (Appendix 2);

• MEDLINE Ovid (1946 to 26 June 2023) (Appendix 3);

• Embase Ovid (1980 to 26 June 2023) (Appendix 4).

There were no language, publication year or publication status restrictions, although abstracts were not included.

We modelled subject strategies on the search strategy designed for MEDLINE Ovid. Where appropriate, we combined search terms with subject strategy adaptations of the highly sensitive search strategies designed by Cochrane for identifying RCTs and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions, version 6.3 (Lefebvre 2022)).

Searching other resources

We searched the following trial registries for ongoing studies.

• US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 13 July 2022) (Appendix 5);

• World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch; searched 13 July 2022) (Appendix 6).

We searched the reference lists of included studies and relevant systematic reviews for further studies. We checked that none of the included studies in this review were retracted due to error or fraud using Retraction Watch (https://retractionwatch.com/).

We did not perform a separate search for adverse effects of interventions used; we considered adverse effects described in included studies only.

Data collection and analysis

Selection of studies

For data collection and analysis, two review authors, independently and in duplicate, screened the identified titles and abstracts for possible inclusion in the review. We obtained full‐text copies of all potential eligible articles, which we further evaluated for final inclusion. If necessary, a third review author was available to resolve any disagreements in study selection.

Data extraction and management

Review authors, independently and in duplicate, extracted data into a data extraction form. If necessary, a third review author was available to resolve any disagreements.

For each study, we extracted the following information.

• Publication details (setting/year)

• Methodology

• Type of participants

• Type of intervention

• Control

• Outcomes

• Study dates, study duration and time points of study follow‐up

• Sample size

• Funding sources/conflicts of interest

Assessment of risk of bias in included studies

Two review authors, independently and in duplicate, assessed the risk of bias for studies that contributed outcome data to the review by using the RoB 1 tool (Higgins 2011a). If necessary, a third review author was available to resolve any disagreements in risk of bias assessments.

We assessed each included study for risk of bias in seven key domains.

• Sequence generation (selection bias)

• Allocation concealment (selection bias)

• Blinding of participants and personnel (performance bias)

• Blinding of outcome assessment (detection bias)

• Incomplete outcome data (attrition bias)

• Selective reporting (reporting bias)

• Other bias

For cluster‐RCTs, we also considered recruitment bias, baseline imbalance between clusters, loss of clusters, incorrect analysis, and comparability with individually randomised trials (Higgins 2011a); we reported our judgements related to these additional biases under the domain of 'other bias'.

We also made an overall judgement of risk of bias for each study. We assessed studies to have an overall low risk of bias when any plausible bias across all seven domains was unlikely to have altered the results. We assessed studies to have an overall unclear risk of bias when any plausible bias across one or more of the key domains raised some doubt that it may have altered the results. We assessed studies to have an overall high risk of bias when we believed any plausible bias across one or more of the key domains may seriously alter the results reported in that study.

Measures of treatment effect

If studies used the same measurement scales and unit (teeth, surfaces, participant), we used mean values and standard deviations (SDs) to calculate mean differences (MDs) with 95% confidence intervals (CIs). For studies with different measurement scales or units, we planned to use standardised mean differences (SMDs) with 95% CIs. For dichotomous data, we calculated odds ratios (ORs) with 95% CIs. For rare events or non‐events, we used Peto OR, which has been observed to be less biased and more powerful than other statistical methods.

We expected that caries event data may be reported either as continuous data (e.g. mean number of arrested carious surfaces per person), or dichotomous data (e.g. number of teeth/surfaces/lesions/people with arrested caries) and we calculated measures of treatment effect according to the type of data reported by study authors.

Unit of analysis issues

We anticipated that the trials might randomise participants or teeth to the interventions. The number of observations in the analysis should match the number of 'units' that were randomised. We followed guidance in the Cochrane Handbook for Systematic Reviews of Interventions, Section 6.2 (Higgins 2023a), in order to avoid unit of analysis errors.

To manage split‐mouth study designs, we planned to use methods as described in Rajendra 2017. However, the review included only one split‐mouth study, and we were unable to use the data from this study report (Braga 2009).

We anticipated that many of the studies would present dichotomous data ignoring the clustering of teeth, sites or lesions within participants. Therefore, for studies with clustering of teeth, we prioritised adjusted data from study reports. We used the generic inverse variance approach when adding adjusted data to RevMan 2024. Where studies used multiple regression and did not specify the total number of observations in the model, we obtained an indicative sample size (number of lesions and participants) from other information in the study report such as the study flow diagram. We included unadjusted data in the review if these were the only available data in a study report. We did not adjust the sample size or inflate the standard error for studies that did not adjust for clustering owing to uncertainty of an appropriate intraclass correlation coefficient for the approximate estimations. However, we did note whether data included adjustment for clustering throughout the review. Also, see Sensitivity analysis.

Dealing with missing data

We contacted authors of the selected studies where there was unclear methodology, missing or unclear information or missing data. Unless otherwise stated, we included only the available data from the publications in the analyses. When studies reported incomplete outcome data, we followed the methods suggested by Section 6.5.2 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2023a).

Assessment of heterogeneity

We assessed clinical heterogeneity by examining the type of participants, interventions and outcomes of each study. We assessed statistical heterogeneity by visual inspection of the point estimates and CIs in forest plots; lack of overlap of CIs may indicate heterogeneity. We also assessed statistical heterogeneity using Cochran's test for heterogeneity and the I² statistic (Higgins 2003). For interpretation of statistical heterogeneity, we used the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2023b). For the Cochran's test for heterogeneity, we considered heterogeneity to be evident if P values were less than 0.1. We interpreted the I² statistic as follows:

• 0% to 40% might not be important;

• 30% to 60% may represent moderate heterogeneity;

• 50% to 90% may represent substantial heterogeneity;

• 75% to 100% considerable heterogeneity.

Assessment of reporting biases

If there had been more than 10 studies included in any meta‐analysis, we would have assessed the risk of reporting bias by testing for asymmetry in a funnel plot. If reporting biases had been identified, we would have carried out analysis as outlined by Egger 1997 for continuous outcomes, and Rũcker 2008 for dichotomous outcomes. However, there were too few studies in any of the meta‐analyses to investigate this.

Data synthesis

We conducted meta‐analysis using RevMan 2024 for studies with similar comparisons that reported the same outcome measures.

We analysed and reported data separately for the five main comparison groups in this review (see Types of interventions). These comparison groups included more than one type of comparative treatment, and we only pooled data from studies where interventions and comparative treatments were clinically appropriate. Therefore, within these main comparison groups, we separately analysed and reported data according to the comparative treatment. For example, in the comparison group 'SDF versus other topical treatments', we separately reported data for SDF versus fluoride varnish and SDF versus chlorhexidine.

For the primary outcomes, we analysed data separately according to the type of dentition (primary or permanent), and according to the location of caries for permanent dentition (coronal or root). For the secondary outcomes, we analysed the data separately according to the age of participants (children or adults). We used data reported at the end of study follow‐up in each study.

For multi‐arm studies, in which SDF (of equivalent frequency, concentration and duration) was used in more than one study group but which included an additional treatment in one study group (e.g. SDF versus SDF plus oral health education versus placebo), we only included in the analysis the SDF study arm without additional treatment (e.g. SDF versus placebo).

We combined data from more than one study using random‐effects models. If studies reported unadjusted data as ORs with 95% CIs, we added these data to analyses using the generic inverse variance method.

Subgroup analysis and investigation of heterogeneity

We considered conducting subgroup analysis for any outcome with an estimated I² statistic of 40% to 60%. However, prior to any subgroup analyses, we considered both magnitude and direction of effects, and strength of the evidence for heterogeneity, using the CIs for the I² statistic.

We had planned to conduct subgroup analysis for study design (parallel study designs vs split‐mouth study designs) and by predominant age group in the study; however, this was not possible due to the small number of studies in all meta‐analyses.

Sensitivity analysis

We planned to conduct sensitivity analysis to evaluate the impact of including studies in which the clustering of teeth had not been taken into account. However, we found that outcomes often included data from only a single study, or meta‐analysis could only include studies with unadjusted data. Therefore, we did not conduct this planned sensitivity analysis. In this case, we excluded studies from pooled analysis of dichotomous data where clustering of teeth had not been taken into account.

We also planned to assess the impact of including studies at overall high or unclear risk of bias but because we judged all studies to include high or unclear risks of bias, this sensitivity analysis was not feasible. In addition, we planned to assess the impact of any approach taken to manage split‐mouth studies (as described in Rajendra 2017), by calculating effect sizes with different intracluster correlation coefficients. However, we did not include data from split‐mouth studies in this review.

Summary of findings and assessment of the certainty of the evidence

We used the GRADE approach to assess the certainty of the body of evidence associated with the primary and secondary outcomes in this review. In the event that data were available for an outcome with both MDs and ORs, we prioritised the data using MDs. If data did not include adjustment to account for the clustering of teeth within participants, we only included these data in the summary of findings tables if we judged that the degree of clustering was minimal. For completeness, we reported all data in the Effects of interventions, but we did not use the GRADE approach to assess certainty of these additional data, and we did not include these data in summary of findings tables.

The GRADE approach assesses the certainty of a body of evidence based on the extent to which we can be confident that an estimate of effect or association reflects the outcome being assessed. Evaluation of the certainty of a body of evidence considers five GRADE domains: within‐study risk of bias; directness of the evidence (indirectness); heterogeneity of the data (inconsistency); precision of the effect estimates (imprecision); and risk of publication bias. The certainty of the evidence could be high, moderate, low or very low, being downgraded by one or two levels depending on the presence and extent of concerns in each of the five GRADE domains. We explained reasons for downgrading the certainty of the evidence for each outcome, and we used these judgements when drawing conclusions in the review.

We constructed summary of findings tables for each of the five main comparisons in this review. Because some of the main comparisons included more than one treatment comparison, we only constructed summary of findings tables for the treatment comparisons that we judged to be most clinically relevant. Therefore, we constructed summary of findings tables for the following comparisons in this review, using the GRADE profiler software (GRADEpro GDT).

• Comparison 1: SDF versus placebo or no treatment

• Comparison 2: Different approaches to SDF application

• Comparison 3: SDF versus other topical treatments (SDF compared with fluoride varnish)

• Comparison 4: SDF versus sealants and resin infiltration

• Comparison 5: SDF versus restorative treatments (SDF compared with atraumatic restorative treatment (ART) with glass ionomer cement (GIC) or glass ionomer material)

For the primary outcomes (primary caries prevention, caries arrest, secondary prevention of caries), we reported the data separately according to dentition type. For the secondary outcomes (adverse effects, dental pain or sensitivity, aesthetics), we reported the data separately according to whether data were derived from children or adults.

Results

Description of studies

See Characteristics of included studies, Characteristics of excluded studies, Characteristics of studies awaiting classification, and Characteristics of ongoing studies.

Results of the search

We identified 7322 records from database searches, and two additional records from other sources. After the removal of duplicates, we screened 3267 records. We excluded 3134 records which were clearly irrelevant from screening of the titles and abstracts. We sourced the full‐text of 133 records which we assessed for eligibility. From these full‐text records, we excluded 19 studies (with 22 references; see Excluded studies). We found 29 eligible studies (with 63 references) and 18 ongoing studies (with 22 references). We also found 16 studies (with 26 references) that are awaiting classification. See Figure 1.

1.

Study flow diagram

Included studies

We included 29 RCTs that recruited a total of 13,036 participants (12,020 children and 1016 adults); see Characteristics of included studies tables. One study was a cluster‐RCT (Ruff 2022), and one study used a split‐mouth design (Braga 2009).

Here, we describe the main study characteristics according to the five principal comparisons in this review. We did not include a summary of water fluoridation, use of fluoridated toothpaste, caries risk and socioeconomic status, which were inconsistently reported across studies. See Appendix 7 for an overall summary of dentition, and treated surfaces and lesions, a description of interventions, and criteria for caries diagnosis and assessment.

We contacted two study authors to request additional information (Azouru 2022; Sirivichayakul 2023). We included additional data supplied by Sirivichayakul 2023 in the review, but at the time of publication of this review, we had received no reply from Azouru 2022.

Ten studies were multi‐arm studies (Braga 2009; Duangthip 2018; Fung 2018; Li 2017; Liu 2012; Mattos‐Silveira 2015; Tan 2010; Yee 2009; Zhang 2013; Zhi 2012). Of these, six included interventions in more than one main comparison group (Duangthip 2018; Li 2017; Liu 2012; Mattos‐Silveira 2015; Tan 2010; Yee 2009); other multi‐arm studies had multiple interventions that were relevant to the same main comparison.

Comparison 1. SDF versus placebo or no treatment

• Type of studies. We included 14 RCTs. These were conducted in Brazil (Mattos‐Silveira 2015), China (Jiang 2022; Li 2017; Liu 2012; Tan 2010; Zhang 2013), Cuba (Llodra 2005), Iraq (Fahmi 2019), Mexico (Torres‐Arellano 2012), Nepal (Yee 2009), Sweden (Ericson 2023), Thailand (Sirivichayakul 2023), Turkey (Seberol 2013), and the USA (Milgrom 2018). We note that those studies conducted in Hong Kong, China, had water supplies with 0.5 ppm fluoride (Jiang 2022; Li 2017; Tan 2010; Zhang 2013). Four studies reported that study areas were non‐fluoridated or had very low natural levels of fluoride in water supplies (Liu 2012; Llodra 2005; Sirivichayakul 2023; Yee 2009), and the remaining studies reported no information about fluoride levels in water supplies.

• Types of participants. Studies included 3600 randomised participants. The smallest study included 40 participants (Fahmi 2019), and the largest included 976 participants (Yee 2009). Four studies included 905 older adults recruited from nursing homes (Ericson 2023; Tan 2010), or community centres for older adults who lived independently in their own home and could participate in community centre‐led activities (Li 2017; Zhang 2013). The age in the study inclusion criteria of these four studies ranged from 56 to 89 years. We noted that the mean age was 87.7 years (Ericson 2023), 78.8 years (Tan 2010), and 72.5 years (Zhang 2013), and was not reported in Li 2017. All older adult participants had at least one exposed root surface, and study evaluation was in root caries. The remaining studies included 2695 children, with age ranges from two to 10 years old. Seven studies applied treatment to only primary dentition (Fahmi 2019; Jiang 2022; Mattos‐Silveira 2015; Milgrom 2018; Seberol 2013; Sirivichayakul 2023; Yee 2009), and in one study treatment was applied only to permanent dentition (Liu 2012). Llodra 2005 and Torres‐Arellano 2012 applied treatment to both primary and permanent dentition. Regular use of fluoride toothpaste was often not reported in studies. Sirivichayakul 2023 reported that more than 90% of participants used a fluoride toothpaste, and Yee 2009 reported that 66% of participants used a fluoride toothpaste. Liu 2012 stated that 90% of toothpaste in the study area included fluoride. However, in Llodra 2005, study authors note that there was limited availability of fluoride toothpaste in the study area.

• Types of interventions and comparison. The concentration of SDF in all studies was 38%, and one multi‐arm study also included an application of 12% (Yee 2009). In most studies, SDF was used in a single application (Ericson 2023; Jiang 2022; Mattos‐Silveira 2015; Milgrom 2018; Seberol 2013; Yee 2009). In other studies, it was given at six‐monthly intervals (Fahmi 2019; Llodra 2005; Sirivichayakul 2023; Torres‐Arellano 2012), or 12‐monthly intervals (Li 2017; Liu 2012; Tan 2010; Zhang 2013). In studies with more than one application, the number of applications in each study was determined by the length of the study follow‐up; we noted that some studies also applied interventions at the final follow‐up, although this final application was unlikely to impact outcome data. Although we included Jiang 2022 in this main comparison group, we note that all participants also received atraumatic restorative treatment (ART) on all cavitated lesions at a 10‐week follow‐up appointment. In Ericson 2023, we noted that all participants received regular routine oral healthcare (approximately four dentist visits and two dental hygienist visits) during the 12‐month study follow‐up by unblinded dentists and dental hygienists, which may have included fluoride varnish applications and other treatments; we could not be certain whether additional treatments were evenly allocated. In five studies, participants in both intervention and comparison groups received oral health instruction (Tan 2010; Zhang 2013), fluoride toothpaste and a toothbrush (Yee 2009), oral hygiene instruction and fluoride toothpaste (Li 2017), or all of these (Sirivichayakul 2023). Li 2017 included one study group in which participants were given SDF alone and another group in which participants were given SDF and potassium iodine; we did not include the SDF + potassium iodine study arm in this review. Similarly, we did not include data for a study arm in Zhang 2013, in which SDF was given in combination with oral health education, or a study arm in Yee 2009 in which tannic acid (a reducing agent) was added to the SDF. Of the studies conducted in children, four studies carried out treatments in kindergartens or primary schools (Jiang 2022; Llodra 2005; Sirivichayakul 2023; Torres‐Arellano 2012; Yee 2009), or in dental schools in the other studies involving children.

• Outcomes. Data were available from at least one study for all of our primary outcomes. We used outcome data reported at the longest follow‐up time point. Studies reported their longest follow‐up at 21 days (Milgrom 2018), 6 months (Fahmi 2019), 12 months (Ericson 2023; Mattos‐Silveira 2015), 18 months (Seberol 2013; Sirivichayakul 2023), 24 months (Jiang 2022; Liu 2012; Torres‐Arellano 2012; Yee 2009; Zhang 2013), 30 months (Li 2017), and 36 months (Llodra 2005; Tan 2010). Although Jiang 2022 reported data for decayed, missing or filled teeth in the primary dentition at the end of follow‐up, the purpose of the trial was to assess the success of ART after earlier application of SDF to cavitated lesions; therefore, data were not comparable to other measures of prevention, and we did not include data for this study in the review. Because the time point of study follow‐up in Milgrom 2018 was very short (21 days), we did not include caries data for this study in any meta‐analyses. In addition, we did not include outcome data for Seberol 2013 in the review as we could not determine a clear definition of secondary caries, and we could not determine the number of lesions for which caries arrest data were available. For Yee 2009, we reported data separately for the two concentrations of SDF. We also reported data separately for the two types of dentition in Llodra 2005 and Torres‐Arellano 2012.

• Funding. Studies were supported by government grants (Liu 2012; Llodra 2005; Milgrom 2018; Sirivichayakul 2023; Li 2017; Tan 2010), research grants (Mattos‐Silveira 2015), or were self‐funded (Fahmi 2019). Ericson 2023 and Yee 2009 included funding from multiple sources including from university, government or research grants. The remaining studies did not report funding sources or the source was unclear.

Comparison 2. Different approaches to SDF application

• Type of studies. We included five RCTs. These were conducted in China (Duangthip 2018; Fung 2018; Zhi 2012), India (Daga 2020), and Nepal (Yee 2009). We note that those studies conducted in Hong Kong, China, had water supplies with 0.5 ppm fluoride (Duangthip 2018; Fung 2018), and that two studies had very low natural levels of fluoride in water supplies (Yee 2009; Zhi 2012). Daga 2020 did not report information about fluoride levels in water supplies.

• Types of participants. Studies included 1808 children and no adult participants. The smallest study included 48 participants (Daga 2020), and the largest included 888 participants (Fung 2018). Children's ages ranged from three to nine years, and all treatment was applied to primary dentition. Studies reported the percentage of participants using fluoride toothpaste as more than 50% (Fung 2018), more than 65% (Zhi 2012), 66% (Yee 2009), and more than 80% Duangthip 2018). Daga 2020 did not report this information.

• Types of interventions. All studies applied treatment in the children's kindergarten or primary school.

  • In Daga 2020, the number and frequency of applications of 38% SDF differed in each of three study arms: four applications at one‐monthly intervals versus three applications at three‐monthly intervals versus two applications at six‐monthly intervals. Participants in both groups received an oral health talk before application as well as regular reinforcement from teachers.

  • Duangthip 2018 applied three applications of 30% SDF, at 12‐monthly intervals versus weekly intervals. Although oral health instruction is not explicitly described in this study, we note that participants were recruited from kindergartens that were part of an oral health promotion programme, and we assumed that all children received some oral health instruction.

  • Fung 2018 compared both the concentration of SDF and the intervals of application in four study arms: 12% or 38% SDF applied at 12‐monthly intervals (three applications) versus six‐monthly intervals (six applications).

  • Yee 2009 compared different concentrations of SDF: 38% versus 12% SDF, both given in a single application. We did not include in the review a study arm in Yee 2009 in which tannic acid (a reducing agent) was given with SDF application. Participants in both groups received a toothbrush and fluoride toothpaste.

  • Zhi 2012 compared different frequencies and intervals of SDF application: 12‐monthly intervals versus six‐monthly intervals.

• Outcomes: data were available for at least one of the primary outcomes for each of the above comparisons. The final time points in studies were 12 months (Daga 2020), 24 months (Yee 2009; Zhi 2012), and 30 months (Duangthip 2018; Fung 2018). For studies with multiple study arms that were relevant to this comparison, we included available data from all study arms. Because each study was different in terms of concentrations, frequency of applications, and duration of treatment, we did not pool any of the data in this comparison.

• Funding. Studies were supported by government grants (Fung 2018), universities (Duangthip 2018; Zhi 2012), or were self‐funded (Daga 2020). Yee 2009 included funding from multiple sources (as described above).

Comparison 3. SDF versus other topical treatments

• Type of studies. We included eight studies. They were conducted in China (Duangthip 2018; Gao 2019; Liu 2012; Tan 2010; Zheng 2023), Egypt (Rehim 2021), and Thailand (Mabangkhru 2020; Sirivichayakul 2023). We note that those studies conducted in Hong Kong, China, had water supplies with 0.5 ppm fluoride (Duangthip 2018; Gao 2019; Tan 2010; Zheng 2023). In Mabangkhru 2020, concentration of fluoride in water supplies was 0.3 ppm. In Sirivichayakul 2023, concentrations were less than 0.03 ppm, and Liu 2012 described the study area as non‐fluoridated. Rehim 2021 did not report information about fluoride levels in water supplies.

• Types of participants. Studies included 3091 participants. The smallest study included 62 participants (Rehim 2021), and the largest included 1070 participants (Gao 2019). One study included 223 older adults with a mean age of 78.8 years (Tan 2010); older adult participants had at least five exposed root surfaces. The remaining studies included 2868 children, ranging in age from 1 to 9 years old. Liu 2012 applied treatment to permanent dentition; in the other four studies, application was to primary dentition. In two studies, more than 90% of participants used fluoride toothpaste (Mabangkhru 2020; Sirivichayakul 2023), and more than 80% of participants used fluoride toothpaste in Duangthip 2018. Liu 2012 stated that 90% of toothpaste in the study area included fluoride. The remaining studies reported no information about this.

• Types of interventions. Six studies applied treatments in the children's kindergarten or primary school (Duangthip 2018; Gao 2019; Jiang 2022; Liu 2012; Sirivichayakul 2023; Zheng 2023). The other studies involving children applied treatment in a dental school. In older adults, treatment was applied in residential and nursing homes (Tan 2010). In Tan 2010, participants in both intervention and comparison groups received oral health instruction, and this was supplemented with a toothbrush and fluoride toothpaste in Sirivichayakul 2023. Although oral health instruction is not explicitly described in Duangthip 2018, we note that participants were recruited from kindergartens that were part of an oral health promotion programme, and we assumed that all children received some oral health instruction. The remaining studies reported no additional information regarding oral health instruction.

  • Seven studies compared SDF with flouride varnish (Duangthip 2018; Liu 2012; Mabangkhru 2020; Rehim 2021; Sirivichayakul 2023; Tan 2010; Zheng 2023). Concentration of SDF was 30% in Duangthip 2018 and 38% in the other studies. Participants were treated with a single application of SDF (Zheng 2023), at weekly intervals for three applications (Duangthip 2018), applications at six‐monthly intervals (Mabangkhru 2020; Rehim 2021; Sirivichayakul 2023), or 12‐monthly intervals (Duangthip 2018; Liu 2012; Tan 2010). In three studies, flouride varnish was applied every six months (Liu 2012; Mabangkhru 2020; Sirivichayakul 2023), and in two studies, it was applied every three months (Rehim 2021; Tan 2010). Zheng 2023 applied flouride varnish in a single application. However, Duangthip 2018 applied flouride varnish at weekly intervals for three applications.

  • One study compared 38% SDF applied at 12‐monthly intervals with chlorhexidine varnish applied at three‐monthly intervals (Tan 2010).

  • One study compared 38% SDF with silver nitrate plus flouride varnish, both given at six‐monthly intervals (Gao 2019).

• Outcomes: data were available for at least one of the primary outcomes for each comparison. The final time points in studies were at 12 months (Mabangkhru 2020; Rehim 2021; Zheng 2023), 18 months (Gao 2019; Sirivichayakul 2023), 24 months Liu 2012; Zhi 2012), 30 months (Duangthip 2018), and 36 months (Tan 2010). We were unable to use the clinical data from Rehim 2021 for caries arrest, because study authors reported this outcome within a composite measure (defined by the study authors as 'failure' and including caries arrest, abscess, pain, infection, and swelling); therefore, we could not determine which data were specifically caries arrest in this study.

• Funding. Studies were supported by government grants (Gao 2019; Liu 2012; Tan 2010; Sirivichayakul 2023), universities (Duangthip 2018; Mabangkhru 2020; Zheng 2023), or were self‐funded (Rehim 2021).

Comparison 4. SDF versus sealants and resin infiltration

• Type of studies. We included three studies, which were conducted in China (Liu 2012), and Brazil (Braga 2009; Mattos‐Silveira 2015). In Liu 2012, local water supplies were not fluoridated; the other studies did not report information about fluoride levels.

• Types of participants. Studies included 412 children, and no adult participants. The smallest study included 22 participants (Braga 2009), and the largest included 249 participants (Liu 2012). Where reported, the mean ages of children ranged from 6.7 years to 9.1 years, and treatment was applied in primary dentition in Mattos‐Silveira 2015 and Braga 2009, and permanent dentition in Liu 2012. Liu 2012 stated that 90% of toothpaste in the study area included fluoride, and Braga 2009 reported that all children had used fluoride toothpaste; Mattos‐Silveira 2015 reported no information about this.

• Types of interventions. In Liu 2012, treatment was either SDF (at 12‐monthly intervals) or resin sealant; this was applied at the children's primary school. In Mattos‐Silveira 2015, a single application of SDF was compared with resin infiltration, with treatment carried out at a Dental School. In Braga 2009, 10% SDF (2 applications with a week's interval, and study duration of 30 months) was compared with GIC or with a cross‐brushing programme, and participants in both groups also received oral hygiene instruction; we did not include the group in which a cross‐brushing programme was used because of insufficient detail in the study report.

• Outcomes: data were available for at least one of the primary outcomes in Liu 2012 and Mattos‐Silveira 2015, and final time points in these studies were reported at 24 months. We did not report outcome data for Braga 2009 in this review because the study authors did not account for the split‐mouth study design by reporting 'paired data'.

• Funding. Studies were supported by government grants (Braga 2009; Liu 2012), and research grants (Mattos‐Silveira 2015).

Comparison 5. SDF versus restorative treatments

• Type of studies. We included seven studies, which were conducted in China (Zhi 2012), Brazil (Vollú 2019), India (Mendiratta 2021), Nigeria (Azouru 2022), Saudi Arabia (Abdellatif 2021), and the USA (Cleary 2022; Ruff 2022). Zhi 2012 stated that the study area received non‐fluoridated water, but the other studies did not report fluoride levels in water supplies.

• Types of participants. Studies included 5571 children and no adult participants. The smallest study included 68 participants (Vollú 2019), and the largest included 4718 participants (Ruff 2022). The children ranged in age from 2 to 10 years at baseline in all studies except Mendiratta 2021; in this study, all participants had intellectual disabilities and had a mean age of 15.2 years to 17.6 years (in the two study groups). In Abdellatif 2021, all children had 'negative behaviours' according to a behaviour rating scale. Ruff 2022 applied treatment to both primary and permanent dentition and the remaining studies to primary dentition. Mendiratta 2021 reported that more than 90% of participants used a fluoride toothpaste, and Zhi 2012 reported that more than 65% of participants used a fluoride toothpaste. In Cleary 2022, fluoride toothpaste use was more than 57% amongst participants. The other studies did not report this information.

• Types of interventions. Three studies applied treatment in the children's kindergarten or primary school (Azouru 2022; Ruff 2022; Zhi 2012). The remaining studies applied treatment in a dental school.

  • Four studies compared SDF with ART:

    • Abdellatif 2021 treated participants with either two applications of 38% SDF at six‐monthly intervals or ART (carious and unsupported enamel removed with a dental hatchet, carious dentine removed using small excavator) and application of glass ionomer cement (GIC). In both groups, caregivers were provided with oral hygiene instruction.

    • Azouru 2022 treated participants with either a single application of 38% SDF or ART (excavation of carious lesion with disposable plastic excavator) and GIC.

    • Vollú 2019 treated participants with either a single application of 30% SDF or ART (selective removal of caries using an excavator) and GIC. In both groups, children and their caregivers were provided with oral hygiene instruction.

    • Zhi 2012 treated participants with either 38% SDF or ART sealed with a low viscosity, high fluoride‐releasing glass ionomer material. In this study, two groups had SDF, which was applied in 12‐monthly intervals or six‐monthly intervals; the total number of applications was not specified, and we could not be certain whether the final application was given at the final follow‐up appointment. In the study group of glass ionomer material, application was repeated at 12‐monthly intervals. Although we have included this study in this comparison, we note that participants in both groups had the superficial soft decayed tissues of the decayed tooth removed before application of study treatments.

  • Mendiratta 2021 treated participants with 38% SDF (single application) or with ART and GIC plus flouride varnish. In both groups, caregivers were provided with oral hygiene instruction.

  • Ruff 2022 treated participants with either flouride varnish on all teeth and 38% SDF to all asymptomatic cavitated lesions (single application) or with flouride varnish, glass ionomer sealants to all pits and fissures of bicuspids and molars, and ART on all frank asymptomatic cavitated lesions.

  • Cleary 2022 treated participants with either 38% SDF at six‐monthly intervals (baseline and six months) or with restorative treatment (level of caries removal and type of material used was selected on a case‐by‐case basis. Although ART was not excluded in this trial, all dentists used other more invasive restorative techniques). All participants also received dietary advice, toothbrushing instruction, and bi‐annual flouride varnish application.

• Outcomes. Data were available for at least one of the primary outcomes in all studies. The final time points in studies were three months (Azouru 2022), six months (Mendiratta 2021), 12 months (Abdellatif 2021; Cleary 2022; Vollú 2019), and 24 months (Ruff 2022; Zhi 2012). Although Ruff 2022 reported data for primary prevention, we did not include these data in the review as they measured the effectiveness of flouride varnish application rather than SDF.

• Funding. Studies were supported by universities (Abdellatif 2021; Zhi 2012), research grants (Cleary 2022; Ruff 2022), or by both government and research grants (Vollú 2019). Azouru 2022 received no study funding, and Mendiratta 2021 did not report sources of funding.

Excluded studies

We excluded 19 studies (Characteristics of excluded studies). Two studies were not randomised (Lo 1998; Lo 2001), and five were quasi‐randomised (Chu 2002; dos Santos 2012; Mohammed 2022; Monse 2012; Thakur 2022). The randomisation process was unclear in two studies; we contacted study authors of these two studies but received no reply (Bijella 1991; Vasconcelos 2011). Five studies had no caries outcomes (Garrastazu 2019; Salem 2022; Shah 2013; Sing‐In 2019; Verma 2022), and one study was designed as a cluster‐randomised trial with only one cluster per group (Turton 2021). One study compared SDF + GIC versus ART + GIC; however, the GIC application/postrestoration instructions varied between groups (Satyarup 2022). The use of SDF in Hernandez 2013 was part of an intervention to restore the tooth, which did not comply with the objectives of this review. Two studies applied potassium iodide (KI) with SDF, and we excluded these studies because we could not be certain of the impact of KI on dental caries (Hamdi 2022; Mani Prakash 2022).

Ongoing studies

We found 18 ongoing studies (Characteristics of ongoing studies). Two studies are comparing SDF with a placebo, with an estimated enrolment of 851 children (CTRI/2020/11/029210; Duangthip 2022). Duangthip 2022 is a three‐arm study that also compares flouride varnish with SDF or placebo. Three studies are comparing SDF given at different intervals, frequency or concentrations with an estimated enrolment of 711 children (CTRI/2020/02/023420; Janakiram 2021; NCT04054635). Seven studies are comparing SDF with other topical treatments; six with flouride varnish in an estimated enrolment of 1402 participants, of whom 60 participants were adults aged 60 years or older (CTRI/2022/04/042177; Gao 2020; NCT03770286; NCT04213573; NCT04432415; NCT05008718), and one is comparing SDF with nano silver in an estimated 350 children (NCT05255913). Three studies are comparing SDF to restorative treatments ‐ ART in an estimated 180 children (CTRI/2020/07/026614), and 220 adults aged 18 to 65 years (Varughese 2022), and ART plus SDF in an estimated 50 children (NCT05188846). Two other studies use GIC, but we are uncertain whether this includes ART; CTRI/2021/05/033876 has an estimated enrolment of 100 children, and Ruff 2018, which uses flouride varnish as well as SDF or GIC, has an estimated enrolment of 3960 children. One study is comparing SDF with the Hall Technique in an estimated 72 children aged four to six years (NCT04737057).

Studies awaiting classification

Sixteen studies are awaiting classification (Characteristics of studies awaiting classification).

We found eight studies that were described as completed on clinical trials registers. We will include them in the review when the results have been published. One study compared SDF with placebo and included 831 children (NCT03649659). Another study compared SDF with placebo, as well as SDF at different frequencies and intervals, and application of Tiefenfluorid, in 420 children (ISRCTN17005348). Four studies compared SDF with other topical treatments, which were flouride varnish in approximately 240 children (NCT04514094; NCT05761041), and nano silver fluoride in approximately 296 children (CTRI/2021/04/032480; ISRCTN14037606). One study compared SDF with restorative treatment (ART or with ultra conservative treatment) in 135 children (NCT05314660). A final study with 192 children compared SDF with cross‐brushing technique alongside oral hygiene instruction (NCT01508611).

In addition, we found eight studies that were published only as abstracts and included insufficient information for us to warrant including the studies in the review; again, we await publication of the full study results before including in the review. Of these, one study compared SDF with a placebo in 533 older adults (Lo 2015), and one study compared SDF with a placebo, with the addition of flouride varnish in both groups, in 41 children (Jaradat 2018). One study compared SDF that was applied for a different length of time (application lasting between 3 and 180 seconds; Yan 2022). Three studies compared SDF with other topical treatments, which were flouride varnish in 450 children (Jirattanasopha 2021; Salamoon 2021; Zhang 2020). Zhang 2020 also applied povidone iodine alongside flouride varnish. Two studies compared SDF with restorative treatment in 962 children (Chan 2020; Nelson 2020).

Risk of bias in included studies

We assessed no studies to be at low risk of bias in all domains, and only one study to have no high risks of bias (Fung 2018). We judged only one domain to be unclear in Fung 2018. Therefore, we judged all studies in this review, except Fung 2018, to have an overall high risk of bias. This judgement was mainly due to the SDF staining preventing blinding of the participants and outcome assessors (Figure 2; Figure 3).

2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study. Blank spaces in the risk of bias summary indicate that risk of bias assessment was not conducted in these studies (because the studies contributed no outcome data to the review)

We did not assess risk of bias in Braga 2009 and Seberol 2013 because these studies contributed no outcome data to the review. Therefore, the figures contain blank spaces for these studies.

Allocation

Random sequence generation

We assessed the risk of bias for random sequence generation to be unclear in three studies because the information published in the study reports was insufficient (Daga 2020; Fahmi 2019; Torres‐Arellano 2012). We assessed the remaining studies to be at low risk of bias for random sequence generation.

Allocation concealment

Ten studies did not describe methods to conceal allocation, and we judged risk of bias for allocation concealment to be unclear (Azouru 2022; Cleary 2022; Daga 2020; Fahmi 2019; Milgrom 2018; Tan 2010; Torres‐Arellano 2012; Yee 2009; Zhang 2013; Zhi 2012). Risk of selection bias (allocation concealment) was low in the remaining studies.

Blinding

Performance bias: blinding of participants and personnel

Due to staining caused by SDF treatment, we considered blinding of participants to be impossible in almost all studies, which we assessed as at high risk of bias for this domain. For those studies in which SDF was applied in both treatment groups, blinding may be possible. We judged Fung 2018 to be at low risk of performance bias because this study actively disguised variation between groups (the number of applications and concentrations) by using a placebo, and the treatment was applied in coded containers. Performance bias was also low in Yee 2009 for the different concentrations of SDF (although high risk when SDF was compared with no treatment). Daga 2020 and Zhi 2012, which include comparisons of SDF with SDF, made no attempts to blind participants and personnel to treatment frequencies and concentration, and we judged these studies to be at high risk of performance bias. We also judged Duangthip 2018 to have a high risk of performance bias because, although they attempted to disguise the different frequencies of SDF applications with the use of a placebo, staining of teeth could influence tooth‐brushing behaviour.

Detection bias: blinding of outcome assessors

In most studies, we also considered that blinding of outcome assessors was impossible because of staining from SDF treatment, and we assessed these studies to be at high risk of detection bias. As above, we assessed Fung 2018 as being at low risk of detection bias; study authors clearly state that outcome assessment was conducted by an examiner who was blinded to treatment allocation. We also judged Duangthip 2018, Yee 2009 and Zhi 2012 to be at low risk of detection bias for their comparisons of SDF with SDF because study authors clearly reported methods to ensure outcome assessors were blinded to treatment allocation. However, when comparing SDF to another treatment in these studies, detection bias was high risk because of staining. Whilst blinding of outcome assessors was also possible in Daga 2020 (the three study groups looked at different numbers of applications and different timings of SDF), study authors did not describe any methods of blinding outcome assessors to participant allocation; therefore, we judged the risk of detection bias to be unclear.

Incomplete outcome data

We assessed three studies as having high risk of attrition bias; two of these had high levels of participant loss (Abdellatif 2021; Ruff 2022), and one had different rates of attrition in the two study groups (Li 2017). Li 2017 noted that “the retention rate of [older adult participants] who had more root caries lesions was lower...so the study results might be biased towards the [older adults] who were more concerned about their oral health.” We assessed risk of attrition bias to be unclear in five studies because we could not be certain whether the imbalance between groups or reasons for losses were likely to impact the results (Mattos‐Silveira 2015; Mendiratta 2021; Torres‐Arellano 2012; Vollú 2019; Zheng 2023). We assessed the remaining studies as having low risk of attrition bias.

Selective reporting

Eight studies had published protocols or were prospectively registered with a clinical trials register, and we judged these studies to be at low risk of selective reporting bias because data in study reports were consistent with outcomes in these prospective records (Azouru 2022; Cleary 2022; Ericson 2023; Mabangkhru 2020; Mattos‐Silveira 2015; Ruff 2022; Sirivichayakul 2023; Zheng 2023). Although seven other studies were also registered with clinical trials registers, registration was retrospective; we judged risk of bias in these studies to be unclear because we could not use these retrospective documents to effectively assess risk of selective reporting (Duangthip 2018; Fung 2018; Gao 2019; Jiang 2022; Li 2017; Liu 2012; Vollú 2019). We judged two studies to be at high risk of selective reporting bias because of inconsistencies between the methods section of the report and the reported outcome data in the results (Abdellatif 2021; Rehim 2021), and the remaining studies to be unclear because protocols or clinical trials registration were not reported.

Other potential sources of bias

In Ruff 2022, we assessed additional biases relevant to the cluster‐RCT design. Overall, we judged other risks of bias for this study to be low. Although Ruff 2022 did not clearly report whether there were loss of clusters or baseline imbalances between clusters, we found no evidence of recruitment bias at the cluster level and the reported analyses were correctly adjusted for clustering. Because of the specific intervention designs in this study, we did not assess its comparability to other non‐clustered study designs included in this review.

We detected no other potential sources of bias in the remaining studies.

Effects of interventions

See: Table 1; Table 2; Table 3; Table 4; Table 5

Comparison 1: Silver diamine fluoride (SDF) versus placebo or no treatment

See Table 1. In this comparison, no studies reported data for dental pain or sensitivity.

Primary caries prevention

Primary dentition

• Llodra 2005 reported the primary prevention of caries in the primary dentition at 36 months, with evidence indicating a greater benefit after treatment with SDF (mean difference (MD) −1.14 surfaces, 95% confidence interval (CI) −1.58 to −0.70; 1 study, 373 participants; very low‐certainty evidence; Analysis 1.1). In this analysis, we used data for decayed surfaces because data for decayed, missing and filled surfaces were not reported. We downgraded the certainty of evidence by one level for risk of bias, one level for imprecision owing to the very small sample size from which the evidence is derived, and one level for indirectness because the study area had very limited access to fluoride toothpaste (and therefore may not be applicable to other areas).

• Another study reported the rate of caries development on sound approximal surfaces at 18 months, and we used data supplied from the study authors that were adjusted for clustering of teeth within participants (Sirivichayakul 2023). In this analysis, there was no evidence that SDF was better than a placebo for primary caries prevention (odds ratio (OR) 1.12, 95% CI 0.46 to 2.73; 1372 surfaces, 128 participants; Analysis 1.2).

1.1. Analysis.

Comparison 1: Comparison 1: SDF versus placebo/no treatment, Outcome 1: Primary caries prevention (at end of study follow‐up)

1.2. Analysis.

Comparison 1: Comparison 1: SDF versus placebo/no treatment, Outcome 2: Primary caries prevention (at end of study follow‐up)

Permanent dentition (coronal caries)

• Llodra 2005 also showed a benefit for SDF in the permanent dentition (MD −0.69 surfaces, 95% CI −0.97 to −0.41; 1 study, 373 participants; very low‐certainty evidence; Analysis 1.1). In this analysis, we used data for decayed and filled surfaces; data were also reported for decayed surfaces and filled surfaces (not reported here). We downgraded the certainty of the evidence by one level for risk of bias, one level for imprecision owing to the very small sample size from which the evidence is derived, and one level for indirectness because the study area had very limited access to fluoride toothpaste in the study area (and therefore the evidence may not be applicable to other areas).

• Another study reported the odds of people developing coronal caries in the permanent dentition at 24 months (Liu 2012), and, similarly, data indicated that there was a benefit for SDF over placebo (OR 0.44, 95% CI 0.21 to 0.93; 1 study, 245 participants; Analysis 1.2); we used data as reported by study authors, which were adjusted for clustering of surfaces.

Permanent dentition (root caries)

• Three studies provided data for the primary prevention of root caries (Li 2017; Tan 2010; Zhang 2013), indicating a benefit for SDF (MD −0.79, 95% CI −1.40 to −0.17; I² = 67%; 3 studies, 439 participants; moderate‐certainty evidence; Analysis 1.1); these data were measured at 24 to 36 months. We downgraded the certainty of the evidence by one level because we judged all three studies to have an overall high risk of bias. We also note that all studies in this analysis were from the same study area in which levels of fluoride in the water supplies are at 0.5 ppm fluoride; we could not rule out the possibility that benefits could be greater in areas with no fluoride or lower levels of fluoride in water supplies.

• Ericson 2023 reported increments of new caries, but we could not be certain whether these data represented primary prevention or secondary prevention, or both. For completeness, we included a calculated effect estimate (using frequency data in the study report) in Appendix 8.

Caries arrest

Primary dentition

• Two studies provided data for caries arrest in the primary dentition (Llodra 2005; Yee 2009); data were collected for canines and molars in Llodra 2005, and for anterior and posterior teeth in Yee 2009. These studies showed a benefit for SDF in arresting caries (MD 0.86 surfaces, 95% CI 0.39 to 1.33; 2 studies, 841 participants; I² = 0%; low‐certainty evidence; Analysis 1.3); these data were measured at 24 and 36 months, and included data separately for different concentrations of SDF in Yee 2009 (12% and 38%). We downgraded the certainty of the evidence by one level for risk of bias, and one level for indirectness because one included study had limited access to fluoride toothpaste in the study area (and therefore the evidence may not be applicable to other areas). We did not include the short study by Milgrom 2018 in this analysis, which showed a benefit of SDF at 21 days (MD 3.00 lesions, 95% CI 1.96 to 4.04; 1 study, 64 participants; data not shown).

• The benefit of SDF was also supported by data from Fahmi 2019, in which the number of children with arrested carious lesions was measured at six months (OR 30.86, 95% CI 3.35 to 283.82; 1 study, 38 participants; Analysis 1.4).

1.3. Analysis.

Comparison 1: Comparison 1: SDF versus placebo/no treatment, Outcome 3: Caries arrest (at end of study follow‐up)

1.4. Analysis.

Comparison 1: Comparison 1: SDF versus placebo/no treatment, Outcome 4: Caries arrest (at end of study follow‐up)

Permanent dentition (coronal caries)

• Llodra 2005 also showed a benefit for arresting caries in the first permanent molars at 36 months (MD 0.20 surfaces, 95% CI 0.00 to 0.40; 1 study, 373 participants; very low‐certainty evidence; Analysis 1.3). We downgraded the certainty of the evidence by one level for risk of bias, one level for imprecision owing to the very small sample size from which the evidence is derived, and one level for indirectness because the study area had very limited access to fluoride toothpaste (and therefore may not be applicable to other areas).

Permanent dentition (root caries)

• Zhang 2013 showed a benefit for SDF arresting caries on the root surfaces at 24 months (MD 0.24 surfaces, 95% CI 0.12 to 0.36; 1 study, 158 participants; very low‐certainty evidence; Analysis 1.3). We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision because the data were from few participants.

• The benefit of SDF for the arrest of root caries was also supported by Li 2017, who reported the number of root surfaces with arrested caries at 30 months. However, we noted that these data were reported without adjustment for clustering of teeth within participants, and although the degree of clustering may be minimal in these data, we could not rule out the possibility that the effect estimate (using data that have been adjusted for clustering of surfaces within participants) includes a CI that is too precise. For completeness, we included these data in Analysis 1.4 (OR 11.00, 95% CI 2.83 to 42.76; 1 study, 60 lesions, 43 participants).

Secondary prevention of caries

Primary dentition

Three studies reported data for this outcome in the primary dentition. Mattos‐Silveira 2015 reported the number of lesions not progressing at 24 months, and Torres‐Arellano 2012 reported the number of teeth for which lesions were not progressing at 24 months. We prioritised data from Sirivichayakul 2023 in the review, which were supplied by the study authors, and adjusted for clustering of teeth within participants; however, we note that these data are for rate of development rather than rate of prevention of secondary caries. We did not pool data in the other studies, which were not adjusted for clustering.

• In Sirivichayakul 2023, there was no evidence that SDF was better than a placebo in terms of the rate of caries development on initially treated surfaces (OR 1.08, 95% CI 0.52 to 2.23; 1 study, 1813 surfaces, 128 participants; very low‐certainty evidence; Analysis 1.5). We downgraded the certainty of the evidence by one level for risk of bias and two levels for imprecision because the data were derived from few participants and the CI included the possibility of benefit and no benefit. We also noted inconsistencies across the different data for this outcome.

• In Torres‐Arellano 2012, data indicated a benefit for SDF in reducing the progression of caries (Peto OR 41.82, 95% CI 30.91 to 56.58; 1 study, 677 teeth, 663 participants; Analysis 1.6). We note that the degree of clustering of teeth within participants was minimal in this study, however, the effect estimate (using data that have not been adjusted for clustering of teeth within participants) may include the possibility that the CI is too precise.

• In Mattos‐Silveira 2015, there was no benefit for SDF in the number of carious lesions that did not progress (OR 1.97, 95% CI 0.46 to 8.51; 1 study, 176 lesions, 72 participants; Analysis 1.7); the degree of clustering in this study was large, and the effect estimate (using data that have not been adjusted for clustering within participants) may include the possibility that the CI is too precise.

1.5. Analysis.

Comparison 1: Comparison 1: SDF versus placebo/no treatment, Outcome 5: Secondary prevention of caries (at end of study follow‐up; analysed with OR)

1.6. Analysis.

Comparison 1: Comparison 1: SDF versus placebo/no treatment, Outcome 6: Secondary prevention of caries (at end of study follow‐up; analysed using Peto OR)

1.7. Analysis.

Comparison 1: Comparison 1: SDF versus placebo/no treatment, Outcome 7: Secondary prevention of caries (at end of study follow‐up; analysed with OR)

Permanent dentition (coronal caries)

• Torres‐Arellano 2012 also reported the secondary prevention of coronal caries in the permanent dentition. Again, although these data did not include adjustment of clustering of teeth, we judged the degree of clustering of teeth within participants to be minimal. This study showed a benefit in favour of SDF in this dentition (Peto OR 44.22, 95% CI 33.12 to 59.04; 1 study, 753 teeth, 663 participants; very low‐certainty evidence; Analysis 1.6). We downgraded the evidence by one level for risk of bias, and two levels for imprecision as we could not rule out the possibility that the CI in this effect estimate (using data that were not adjusted for clustering of teeth within participants) would be wider if the clustering effect had been taken into account.

Root caries

• Ericson 2023 reported increments of new caries, but we could not be certain whether these data represented primary caries prevention or secondary prevention of caries, or both. For completeness, we included these data in Appendix 8.

Adverse effects

Three studies reported adverse effects in children (Liu 2012; Milgrom 2018; Torres‐Arellano 2012), and two studies reported adverse effects in adults (Ericson 2023; Li 2017). We judged the certainty of the evidence to be very low for both children and adults. We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision in both sets of results. Data were available for 983 children and 316 adults, and we judged there to be too few participants for this outcome. We also noted that the types of adverse effects (or events) were not always defined in studies, and we did not know if all relevant types of adverse effects were recorded in these studies.

Children

• Milgrom 2018 reported that three participants had adverse effects within 48 hours of treatment. In the SDF group of this study, 1/30 participants had a spot on the corner of the lip that looked like a possible burn. In addition, 3/30 participants in the SDF group had other adverse events that study authors expected were probably not related to treatment (one each of: flu‐like symptoms; redness around the mouth; nausea and stomach ache). In the placebo group of this study, 2/35 participants had adverse effects that were possibly related to treatment (one each of: diarrhoea; stomach ache). Study authors reported two other adverse events that they judged unrelated or probably not related to the treatment (one with diarrhoea, and another with "sporadic hurting tooth").

• Liu 2012 reported that "The only complaint received was a transient bitter taste associated with SDF"; no data were reported for the number of participants who complained of the bitter taste. This study reported that there were no other adverse effects.

• Torres‐Arellano 2012 reported that there were no adverse effects.

Adults

• Li 2017 reported that there were no adverse effects.

• Ericson 2023 reported a whitish discolouration of the gingiva adjacent to surfaces treated with SDF (116 surfaces), as well as redness (four surfaces), and mild ulceration (two surfaces). Of the participants treated with SDF, 53% reported a slight but tolerable taste sensation compared with 5% treated with a placebo. Four participants in both groups reported a mild smell during treatment. At 12 months, study authors reported "no significant difference" in colour between surfaces of both treatment groups.

Aesthetics

One study reported data for satisfaction with the appearance of teeth (Li 2017).

This study reported data for aesthetics in adult participants, stating that "only 19 (7%) [older adult participants] raised a complaint about the interventions at the 30‐mo [month] examination, and half of them complained of black stain on the treated root surfaces." This study included a study group (SDF + potassium iodide), which we did not include in this review. It was unclear from the statement in the published report to which intervention groups these participants belonged. The study concluded that "it seems that application of SDF solution could be generally accepted by [older adults]". We judged the certainty of the evidence to be very low; we downgraded by one level for risk of bias and two levels for imprecision because data were available from only one very small study.

No studies with children reported data for this outcome.

Comparison 2: Different approaches to SDF application

See Table 2. This comparison included data only in the primary dentition. Because the number of applications, intervals between applications, concentrations of SDF and the duration of treatment differed in each study, we did not pool any data in this comparison. Wherever possible, we prioritised the reporting of data according to the interval of application (with six‐monthly intervals as the comparator).

In this comparison, no studies reported data for the following outcomes: primary caries prevention, and dental pain or sensitivity.

Caries arrest

Four studies reported mean data for this outcome (Daga 2020; Duangthip 2018; Fung 2018; Yee 2009). In Daga 2020, we used data for the mean number of surfaces with active (rather than arrested) caries at the end of study follow‐up. Unpooled data are presented in Analysis 2.1. We judged the certainty of the evidence to be very low; we downgraded by one level for risk of bias and two levels for inconsistency (related to differences in study designs, which precluded meta‐analysis).

2.1. Analysis.

Comparison 2: Comparison 2: Different approaches to SDF application, Outcome 1: Caries arrest (at end of study follow‐up)

• Four applications of 38% SDF at one‐monthly intervals resulted in fewer surfaces with active caries compared with two applications of 38% SDF in six‐monthly intervals (MD 1.04 surfaces, 95% CI 0.23 to 1.85; 1 study, 30 participants; Daga 2020).

• Three applications of 38% SDF at three‐monthly intervals resulted in fewer surfaces with active caries than two applications of 38% SDF in six‐monthly intervals (MD 0.82 surfaces, 95% CI 0.00 to 1.64; 1 study, 29 participants; Daga 2020).

• There were more surfaces with caries arrest lesions (in lesions classed as ICDAS 5 or 6 at baseline) at 24 months when treatment was given in three applications at 12‐monthly intervals compared with weekly applications (three applications over a two‐week period) (MD 0.80 surfaces, 95% 0.15 to 1.45; 1 study, 203 participants; Duangthip 2018).

• There was little or no difference between groups in the mean number of tooth surfaces with arrested lesions when 38% SDF was given as either three applications in 12‐monthly intervals or six applications in six‐monthly intervals (MD −0.29 surfaces, 95% CI −0.98 to 0.40; 1 study, 398 participants; Fung 2018).

• There was little or no difference between groups in the mean number of tooth surfaces with arrested lesions when 12% SDF was given as either three applications in 12‐monthly intervals or six applications in six‐monthly intervals (MD −0.26 surfaces, 95% CI −0.83 to 0.31; 1 study, 401 participants; Fung 2018).

• There was greater benefit when 38% SDF was used than 12% SDF, with six applications given at six‐monthly intervals in both groups (MD 0.64 surfaces, 95% CI 0.03 to 1.25; 1 study, 399 participants; Fung 2018).

• There was little or no difference in the mean number of tooth surfaces with arrested lesions when 38% SDF was compared with 12% SDF, with three applications given at 12‐monthly intervals in both groups (MD 0.61 surfaces, 95% CI −0.05 to 1.27; 1 study, 400 participants; Fung 2018).

• There was little or no difference in the mean number of arrested cavitated surfaces when 38% SDF was compared with 12% SDF, with interventions given in a single application (MD 0.60 surfaces, 95% CI −0.23 to 1.43; 1 study; 313 participants; Yee 2009).

Three studies reported additional data for this outcome, measured as the number of arrested lesions at 30 months (Duangthip 2018; Fung 2018), and 24 months (Zhi 2012). For Duangthip 2018 and Fung 2018, we present unpooled data in Analysis 2.2; these data were not adjusted for clustering of teeth and, therefore, the effect estimates may include a CI that is too precise.

2.2. Analysis.

Comparison 2: Comparison 2: Different approaches to SDF application, Outcome 2: Caries arrest (at end of study follow‐up)

• There were more arrested caries lesions (in lesions classed as ICDAS 5 or 6 at baseline) at 30 months when participants were given treatment in three applications at 12‐monthly intervals compared with weekly applications (three applications over a two‐week period) (OR 1.86, 95% CI 1.38 to 2.50; 1 study, 744 caries lesions, 203 participants; Duangthip 2018). We note that study authors also reported the results of multi‐level survival analysis (not reported here) and stated that the effect of clustering for caries arrest in this analysis was significant.

• There was little or no difference in the rate of caries arrest at the surface level when six applications of 12% SDF at 12‐monthly intervals was compared with three applications of 12% SDF at six‐monthly intervals (OR 1.15, 95% CI 0.96 to 1.37; 1 study, 1914 surfaces, 401 participants; Fung 2018).

• Six applications of 38% SDF at 12‐monthly intervals led to a higher rate of surface‐level caries arrest when compared with three applications of 38% SDF at six‐monthly intervals (OR 1.54, 95% CI 1.26 to 1.88; 1 study, 1876 surfaces, 398 participants; Fung 2018).

• A higher concentration of 38% SDF led to a higher rate of surface‐level caries arrest when compared with a lower concentration of 12% when treatment was given at six‐monthly intervals for six applications (OR 2.20, 95% CI 1.81 to 2.69; 1 study, 1892 surfaces, 399 participants; Fung 2018).

• A higher concentration of 38% SDF led to a higher rate of surface‐level caries arrest when compared with a lower concentration of 12% when treatment was given at 12‐monthly intervals for three applications (OR 1.64, 95% CI 1.36 to 1.98; 1 study, 1898 surfaces, 400 participants; Fung 2018).

• Zhi 2012 reported the odds of caries arrest with five applications of 38% SDF at six‐monthly intervals, leading to more surfaces with arrested caries when compared with three applications of 38% SDF at 12‐monthly intervals (OR 2.55, 95% CI 1.40 to 4.64; 1 study, 379 lesions, 119 participants; data not shown); here, we present an OR adjusted for clustering by the study authors.

Secondary prevention of caries

There was very low‐certainty evidence from Duangthip 2018 that neither applications of SDF at 12‐monthly intervals (three applications) or weekly applications of SDF (three applications over a 2‐week period) were better than the other regarding the mean number of surfaces with moderate lesions (ICDAS 3 or 4) that did not progress to cavitated lesions (ICDAS 5 or 6) at 30 months (MD −0.10 lesions, 95% CI −0.61 to 0.41; 1 study, 203 participants; very low‐certainty evidence; Analysis 2.3). We downgraded the certainty of the evidence by one level for serious risk of bias, and two levels for imprecision because the data were derived from few participants and the CI included the possibility of benefit and no benefit for both durations.

2.3. Analysis.

Comparison 2: Comparison 2: Different approaches to SDF application, Outcome 3: Secondary prevention of caries (at end of study follow‐up)

Duangthip 2018 also reported the odds of people having secondary prevention of caries, again with little or no difference between treatment approaches (OR 0.69, 95% CI 0.40 to 1.20; 1 study, 203 participants; Analysis 2.4). Here, we report an effect estimate from the study report analysed with adjustment for the clustering effect.

2.4. Analysis.

Comparison 2: Comparison 2: Different approaches to SDF application, Outcome 4: Secondary prevention of caries (end of study follow‐up)

Adverse effects

Three studies reported adverse effects in children (Duangthip 2018; Fung 2018; Zhi 2012). We downgraded the evidence by three levels to very low certainty ‐ one level for risk of bias and two levels for imprecision. Although data were available for 1121 participants, we judged there to be too few participants for this outcome. We also noted that the types of other adverse effects were not defined in the studies, and we did not know if all relevant types of adverse effects were recorded by study authors.

• Duangthip 2018 reported that black or dark brown staining on the treated lesions was commonly found in both SDF groups, with little or no difference between different durations of treatment (OR 1.43, 95% CI 0.81 to 2.52; 1 study, 203 participants; very low‐certainty evidence; Analysis 2.5). This study reported that no major adverse health effects were found during the 30‐month study period.

• Fung 2018 reported that "apart from the black staining on the arrested lesions, the present study did not find any major long‐term or permanent adverse effects"; no data were reported for the number of people with black staining.

• Zhi 2012 reported that all except one of the arrested carious lesions treated with SDF were black at the end of study follow‐up. Zhi 2012 reported no other adverse side effects on the treated teeth and soft tissues.

2.5. Analysis.

Comparison 2: Comparison 2: Different approaches to SDF application, Outcome 5: Adverse effects

Aesthetics

Zhi 2012 reported parents' satisfaction with their child’s dental appearance, with approximately 45% of the parents satisfied with the appearance of their child’s teeth at the 24‐month evaluation. Study authors did not report data by study group and noted that the difference in parental satisfaction between study groups was not statistically significant (Chi² test, P > 0.05). We downgraded the evidence by three levels to very low‐certainty ‐ one level for risk of bias, and two levels for imprecision because the data were derived from few participants.

Comparison 3: SDF versus other topical treatments

SDF versus fluoride varnish

See Table 3.

Primary caries prevention

Primary dentition

• Zheng 2023 reported the mean increment of new carious surfaces in the primary dentition at 12 months, with little or no difference between treatments (MD 0.00 surfaces, 95% CI −0.26 to 0.26; 1 study, 434 participants; low‐certainty evidence; Analysis 3.1). We downgraded the certainty of the evidence by one level for risk of bias, and one level for imprecision because the CI included the possibility of benefit and no benefit for both treatments.

• Sirivichayakul 2023 reported the caries development rate on approximal surfaces that were sound at baseline. Although study authors provided data adjusted for the clustering of surfaces within participants for this multi‐arm study (SDF, flouride varnish, and placebo), we were unable to use the adjusted data here as study authors had used the placebo as the reference treatment in their adjusted analysis. For completeness, we included unadjusted data in Analysis 3.2 but note that this effect estimate (using data that have not been adjusted for clustering) includes the possibility that the CI is too precise (OR 1.99, 95% CI 1.49 to 2.65; 1 study, 1357 surfaces, 126 participants).

3.1. Analysis.

Comparison 3: Comparison 3: SDF versus other topical treatments (FV), Outcome 1: Primary caries prevention (at end of study follow‐up)

3.2. Analysis.

Comparison 3: Comparison 3: SDF versus other topical treatments (FV), Outcome 2: Primary caries prevention (at end of study follow‐up)

Permanent dentition (coronal caries)

• Liu 2012 reported the number of children with new caries in the permanent dentition at 24 months, with neither intervention better at preventing carious lesions in the permanent teeth than the other (OR 0.95, 95% CI 0.44 to 2.05; 1 study, 237 participants; very low‐certainty evidence; Analysis 3.2). Data were reported per child and therefore included no analysis issues with clustering of teeth. We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision because the CI included the possibility of benefit and no benefit for both treatments and the evidence was derived from few participants.

Permanent dentition (root caries)

• Tan 2010 reported the primary prevention of root caries in the permanent dentition at 36 months, with neither intervention better at preventing root carious lesions than the other (MD −0.20 surfaces, 95% CI −0.91 to 0.51; 1 study, 100 participants; very low‐certainty evidence; Analysis 3.1). We downgraded the certainty of the evidence by one level for risk of bias and two levels for imprecision because the CI included the possibility of benefit and no benefit for both treatments and the evidence was derived from very few participants.

Caries arrest

Primary dentition

• Duangthip 2018 reported the mean number of coronal surfaces (with lesions classed as ICDAS 5 or 6 at baseline) with caries arrest, with neither intervention better than the other at arresting coronal caries at 30 months (MD −0.13 surfaces, 95% CI −0.87 to 0.61; 1 study, 309 participants; very low‐certainty evidence; Analysis 3.3). In this analysis, we included data for two intervention groups in which SDF was given for different time periods (24 months and 2 weeks) compared with flouride varnish. We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision because the CI included the possibility of benefit and no benefit for both treatments. We also note that the application of flouride varnish in this study comparison was given at non‐standard intervals (three applications at weekly intervals).

• Duangthip 2018 and Mabangkhru 2020 reported the number of arrested carious lesions. We did not pool data, which included both adjusted and unadjusted data, and noted that a pooled effect estimate would have included substantial levels of statistical heterogeneity (I² = 87%). In Mabangkhru 2020, the odds of arrest of carious lesions at baseline were greater (from initial cavitated lesions) after application of SDF than flouride varnish (OR 2.04, 95% CI 1.41 to 2.96; 1 study, 1908 lesions, 263 participants; Analysis 3.4); we used data reported by study authors, which were adjusted for clustering of surfaces. In Duangthip 2018, we used data that were not adjusted for clustering, but note that study authors also report a multi‐level survival analysis for caries arrest and state that the effect of clustering for caries arrest rate in this analysis was significant; therefore, this effect estimate (using unadjusted data) is likely to include the possibility that the CI is too precise. For completeness, we include these data in Analysis 3.4, comparing arrested carious lesions (lesions classed as ICDAS 5 or 6 at baseline) for three applications of SDF at weekly intervals with three application of flouride varnish at weekly intervals (OR 0.96, 95% CI 0.72 to 1.28; 1 study, 851 surfaces, 208 participants), and three applications of SDF at 12‐monthly intervals with three applications of flouride varnish at weekly intervals (OR 1.78, 95% CI 1.35 to 2.35; 1 study, 861 surfaces, 207 participants); again, we note the non‐standard intervals for flouride varnish applications in this evidence.

3.3. Analysis.

Comparison 3: Comparison 3: SDF versus other topical treatments (FV), Outcome 3: Caries arrest (at end of study follow‐up)

3.4. Analysis.

Comparison 3: Comparison 3: SDF versus other topical treatments (FV), Outcome 4: Caries arrest (at end of study follow‐up)

Permanent dentition (coronal and root caries)

• No studies reported this outcome in this dentition.

Secondary prevention of caries

Primary dentition

• Duangthip 2018 reported the mean number of surfaces with moderate lesions (ICDAS 3 or 4 at baseline) that did not progress to cavitated lesions (ICDAS 5 or 6) at 30 months, with neither intervention better than the other (MD 0.04 surfaces, 95% CI −0.30 to 0.38; 1 study, 309 participants; very low‐certainty evidence; Analysis 3.5). In this analysis, we included data for two intervention groups in which SDF was given for different time periods (24 months and two weeks) compared with flouride varnish. We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision because the CI included the possibility of benefit and no benefit for both interventions and evidence is derived from few participants. We also note the non‐standard intervals for flouride varnish applications in this evidence.

• Duangthip 2018 also reported the odds of secondary prevention of caries (lesions at ICDAS 3 and 4 at baseline that did not progress) at 30 months. We used adjusted data reported by study authors comparing three applications of SDF at 12‐monthly intervals with non‐standard weekly intervals (three applications) (OR 1.37, 95% CI 0.77 to 2.43; 1 study, 403 lesions, 207 participants; Analysis 3.6). Study authors also reported the number of lesions (ICDAS 3 and 4) that did not progress for weekly‐intervals of SDF application (three applications) and non‐standard weekly applications of flouride varnish (three applications); study authors did not report adjusted odds ratio for this comparison group, and we have not included these data here.

• Rather than reporting the number of lesions that do not progress from initial classification, Sirivichayakul 2023 reported the caries development rate on initial carious approximal surfaces. As for primary prevention data in this study, we could not use adjusted data provided by study authors for this comparison. For completeness, we included unadjusted data in Analysis 3.7 but note that this effect estimate (which includes data that have not been adjusted for clustering of surfaces within participants) includes the possibility that the CI is too precise (OR 1.39, 95% CI 0.93 to 2.08; 1 study, 424 surfaces, 126 participants).

3.5. Analysis.

Comparison 3: Comparison 3: SDF versus other topical treatments (FV), Outcome 5: Secondary prevention of caries (at end of study follow‐up)

3.6. Analysis.

Comparison 3: Comparison 3: SDF versus other topical treatments (FV), Outcome 6: Secondary prevention of caries (at end of study follow‐up)

3.7. Analysis.

Comparison 3: Comparison 3: SDF versus other topical treatments (FV), Outcome 7: Secondary prevention of caries (at end of study follow‐up)

Permanent dentition (coronal and root caries)

• No studies reported this outcome in this dentition.

Adverse effects

Three studies (980 participants) reported adverse effects (Duangthip 2018; Liu 2012; Zheng 2023). We assessed the certainty of this evidence to be very low; we downgraded by one level for risk of bias, and two levels for imprecision because we judged there to be too few participants for this outcome. We also noted that the types of adverse effects were not always defined, and we did not know if all relevant types of adverse effects were collected in these studies.

• Duangthip 2018 reported that black or dark brown staining on the treated lesions was more commonly found in the two SDF groups (OR 3.19, 95% CI 1.95 to 5.23; 1 study, 309 participants; Analysis 3.8). Duangthip 2018 also reported that no major adverse health effects were found during the 30‐month study period.

• In Liu 2012, study authors stated that there were complaints about the transient bitter taste associated with SDF (with no associated data), but that no other adverse effects were observed.

• Zheng 2023 reported that there were no short‐term adverse effects (within the first 24 hours), and no long‐term adverse effects (at 12 months). Examples of adverse effects that were measured in Zheng 2023 included gum irritation, swelling or bleaching.

3.8. Analysis.

Comparison 3: Comparison 3: SDF versus other topical treatments (FV), Outcome 8: Adverse effects

Dental pain or sensitivity

Only Rehim 2021 reported pain, which was measured at 12 months, with no evidence of a difference between treatments in the number of participants who had pain (OR 0.36, 95% CI 0.10 to 1.34; 1 study, 62 participants; very low‐certainty evidence; Analysis 3.9). We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision because we judged the sample size to be too small for this outcome and the CI included the possibility of benefit and harm in both treatments.

3.9. Analysis.

Comparison 3: Comparison 3: SDF versus other topical treatments (FV), Outcome 9: Pain (at end of study follow‐up)

Aesthetics

Mabangkhru 2020 measured parental satisfaction with children’s dental appearance at baseline and the 12‐month follow‐up. Regardless of the intervention, there was little or no difference in parental satisfaction with their child’s dental appearance at 12 months (OR 0.68, 95% CI 0.41 to 1.11; 1 study, 263 participants; very low‐certainty evidence; Analysis 3.10). We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision because we judged the sample size to be too small for this outcome and the CI included the possibility of benefit and harm in both treatments.

3.10. Analysis.

Comparison 3: Comparison 3: SDF versus other topical treatments (FV), Outcome 10: Aesthetics (end of study follow‐up)

SDF versus chlorhexidine varnish

In this comparison, no studies reported data for coronal caries. No studies reported data for the following outcomes: caries arrest, secondary prevention of caries, adverse effects, dental pain or sensitivity, and aesthetics.

Primary caries prevention

Tan 2010 reported the primary prevention of root caries in the permanent dentition, with neither intervention better than the other at preventing new carious lesions at 36 months (MD −0.40 surfaces, 95% CI −0.95 to 0.15; 1 study, 99 participants; very low‐certainty evidence; Analysis 4.1). We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision because the evidence is derived from few participants and the CI includes the possibility of benefit for both treatments.

4.1. Analysis.

Comparison 4: Comparison 3: SDF versus other topical treatments (chlorhexidine varnish), Outcome 1: Primary caries prevention (at end of study follow‐up)

SDF versus silver nitrate + flouride varnish

In this comparison, no studies reported data for root caries. No studies reported data for the following outcomes: primary caries prevention, secondary prevention of caries, dental pain or sensitivity, and aesthetics.

Caries arrest

• Gao 2019 reported coronal caries arrest in the primary dentition at 18 months, with neither intervention better than the other at arresting carious lesions in the primary dentition (MD −0.10 surfaces, 95% CI −0.51 to 0.31; 1 study, 1070 participants; low‐certainty evidence; Analysis 5.1). We downgraded the certainty of the evidence by one level for risk of bias, and one level for imprecision because the CI includes the possibility of benefit and no benefit for both treatments.

• This evidence was also supported by data for the rate of caries arrest in children at 18 months (Gao 2019). We used data from the published study report, which were adjusted for clustering (OR 1.17, 95% CI 0.98 to 1.40; 1 study, 1070 participants; Analysis 5.2).

5.1. Analysis.

Comparison 5: Comparison 3: SDF versus other topical treatments (silver nitrate + FV), Outcome 1: Caries arrest (at end of study follow‐up)

5.2. Analysis.

Comparison 5: Comparison 3: SDF versus other topical treatments (silver nitrate + FV), Outcome 2: Caries arrest (at end of study follow‐up)

Adverse effects

Gao 2019 noted that "arrested lesions were stained black", but this was reported with no associated data. Study investigators observed no other adverse effects, and also reported that there were no reports from parents of systemic disease. We judged the certainty of this evidence to be very low; we downgraded by one level for risk of bias and two levels for imprecision. Although this study included more than 1000 participants, we judged there to be too few participants for this outcome. We also noted that the types of other adverse effects were not defined, and we did not know if all relevant types of adverse effects were collected in this study.

Comparison 4: SDF versus sealants and resin infiltration

See Table 4. In this comparison, no studies reported data for root caries. No studies reported data for the following outcomes: caries arrest, dental pain or sensitivity, and aesthetics.

Primary caries prevention

Primary dentition

No studies reported this outcome in this dentition.

Permanent dentition (coronal caries)

Liu 2012 reported the number of children with new caries at 18 months, with neither intervention better than the other at primary caries prevention (OR 1.76, 95% CI 0.74 to 4.20; 1 study, 242 participants; very low‐certainty evidence; Analysis 6.1). The data were reported by child and therefore included no issues with clustering. We downgraded the certainty of the evidence by one level for risk of bias, and two levels because the evidence was from few participants and the CI included the possibility of benefit for both treatments.

6.1. Analysis.

Comparison 6: Comparison 4: SDF versus sealants and resin infiltration, Outcome 1: Primary caries prevention (at end of study follow‐up)

Secondary prevention of caries

Primary dentition

Mattos‐Silveira 2015 reported data for the number of lesions on surfaces with progression of caries at 24 months, and we used these data to calculate the number of lesions prevented from secondary progression of coronal caries. However, the original data were reported without adjustment for clustering of teeth, and therefore we could not be certain whether the effect estimate includes the possibility that the CI is too precise. For completeness, we included these data in Analysis 6.2 (OR 2.76, 95% CI 0.67 to 11.43; 1 study, 166 lesions, 75 participants); because of the clustering issues, we did not include these data in the summary of findings table for this comparison.

6.2. Analysis.

Comparison 6: Comparison 4: SDF versus sealants and resin infiltration, Outcome 2: Secondary prevention of caries (at end of study follow‐up)

Permanent dentition (coronal caries)

No studies reported this outcome in this dentition.

Adverse effects

Apart from a complaint received about a transient bitter taste associated with SDF, no adverse side effects were observed for 242 participants in Liu 2012. Mattos‐Silveira 2015 stated that no adverse events had been reported for all 94 participants; these were not defined, and we assumed included adverse effects of treatment. We judged the certainty of the evidence for this outcome to be very low; we downgraded by one level for risk of bias, and two levels for imprecision because we judged there to be too few participants for this outcome. Because adverse effects and events were not defined in these studies, we could not be certain that relevant adverse effects were collected in these studies.

Comparison 5. SDF versus restorative treatments

SDF versus atraumatic restorative treatment (ART) with glass ionomer cement (GIC) or glass ionomer material

See Table 5. In this comparison, no studies reported data for permanent dentition. No studies reported data for the following outcomes: primary caries prevention, or secondary prevention of caries.

Caries arrest

Four studies reported data for caries arrest (Abdellatif 2021; Azouru 2022; Vollú 2019; Zhi 2012). For each study, we describe the definition of caries arrest in the ART group alongside the data.

• Zhi 2012 reported caries arrest at 24 months, defining arrest in the ART group as lesions that were totally covered by GIC at study follow‐up. We report the odds of caries arrest from the study report (using analysis adjusted for clustering) for GIC compared with 12‐monthly applications of SDF (OR 1.13, 95% CI 0.52 to 2.45; 1 study, 403 lesions, 122 participants; very low‐certainty evidence; Analysis 7.1). Although the study authors report caries arrest rate for all groups (including six‐monthly applications of SDF), adjusted data comparing GIC with six‐monthly applications of SDF were not reported in this multi‐arm study. We downgraded the certainty of the evidence by one level for risk of bias and two levels for imprecision because the evidence was from few participants and the CI included the possibility of benefit and no benefit for both treatments.

• Abdellatif 2021 considered caries to be arrested in the ART group if the cavity was sealed with the restoration at the 12‐month follow‐up. Data did not account for clustering of teeth within participants. For completeness, we included these data in Analysis 7.2 (OR 5.06, 95% CI 0.58 to 44.30; 1 study, 167 lesions, 53 participants); we note that participants in this study were exclusively children with 'negative behaviours' according to a behaviour rating scale.

• Azouru 2022 reported the number of children with caries arrest at three months. We used data in the ART group for success (defined as when signs of restorative failure were absent). In this study, we compared SDF with ART and found that more children experienced caries arrest at three months after treatment with SDF than with ART (OR 18.03, 95% CI 7.34 to 44.28; 1 study, 234 participants; Analysis 7.2); these data did not include clustering issues.

• Vollú 2019 reported the proportion of treated teeth with arrested lesions. In this study, arrest in the ART group was defined as when the restoration was present with apparent dentine or the dentine was exposed but inactive in the ART group. Again, these data did not account for clustering issues, and we include these data for completeness (OR 0.37, 95% CI 0.07 to 1.85; 1 study, 107 participants; Analysis 7.2). Because these data were not adjusted for clustering, the effect estimates include the possibility that the CI is too precise.

7.1. Analysis.

Comparison 7: Comparison 5: SDF versus restorative treatments (SDF versus ART (with GIC or glass ionomer material)), Outcome 1: Caries arrest (at end of study follow‐up)

7.2. Analysis.

Comparison 7: Comparison 5: SDF versus restorative treatments (SDF versus ART (with GIC or glass ionomer material)), Outcome 2: Caries arrest (at end of study follow‐up)

Adverse effects

Three studies reported adverse effects (Azouru 2022; Vollú 2019; Zhi 2012). We judged the certainty of the evidence for this outcome to be very low; we downgraded by one level for risk of bias, and two levels for imprecision because we judged there to be too few participants (482 participants) for this outcome.

• Azouru 2022 reported that 115 of 118 participants had black stains on teeth treated with SDF at the final study follow‐up (three months); this study reported that there were no other adverse effects or allergic reactions to treatments in either group.

• Vollú 2019 reported that two days after treatment all main caregivers were contacted by telephone, and data were compiled for both the operator (person who gave treatment to the child) and the caregiver. Overall, the adverse effect rate per child was 14.7% in the SDF group and 9.1% in the ART group (OR 1.85, 95% CI 0.40 to 8.44; 1 study, 67 participants; data not shown). In the SDF group, adverse effects included burning, pain or sensitivity in teeth, mouth injury, spot or pigmentation of the skin or mouth; in the ART group, adverse effects included nausea, bad taste, and pain or sensitivity in teeth.

• Zhi 2012 reported that all except one of the arrested carious lesions treated with SDF were black at the end of study follow‐up, and 82% of those treated by GIC were yellow/brown; for these data, study authors reported the results of a Chi² test, with P < 0.001. Zhi 2012 reported no other adverse side effects on the treated teeth and soft tissues.

Dental pain or sensitivity

Azouru 2022 reported the number of children with tooth sensitivity at three months after treatment, with neither treatment worse than the other (OR 0.16, 95% CI 0.02 to 1.32; 1 study, 234 participants; Analysis 7.3). We downgraded the certainty of the evidence for this outcome by three levels to very low. We downgraded by one level for risk of bias, and two levels for imprecision because these data were derived from few participants and the CI indicated benefit or no benefit for both treatments.

7.3. Analysis.

Comparison 7: Comparison 5: SDF versus restorative treatments (SDF versus ART (with GIC or glass ionomer material)), Outcome 3: Dental pain or sensitivity (number of people with tooth sensitivity; end of study follow‐up)

Aesthetics

Zhi 2012 reported parents' satisfaction with their child’s dental appearance, with approximately 45% of the parents satisfied with the appearance of their child’s teeth at the 24‐month evaluation. Study authors in Zhi 2012 did not report data by study group and noted that the difference in parental satisfaction between study groups was not statistically significant (Chi² test, P > 0.05). Vollú 2019 reported the number of caregivers who were "annoyed with teeth appearance" as measured two days after treatment; one caregiver in the SDF group (of 34 children) expressed this opinion, with none from the ART group. We judged the certainty of the evidence for aesthetics to be very low; we downgraded by one level for risk of bias, and two levels for imprecision because the sample size (248 participants) included too few participants.

SDF versus GIC + flouride varnish

In this comparison, no studies reported data for the permanent dentition. No studies reported data for the following outcomes: primary caries prevention, secondary prevention of caries, dental pain or sensitivity, and aesthetics.

Caries arrest

Mendiratta 2021 reported arrest of coronal caries at six months, with neither intervention better than the other at arresting caries in the primary dentition (OR 1.89, 95% CI 0.61 to 5.87; 1 study, 182 lesions, 69 participants; very low‐certainty evidence; Analysis 8.1). Data were not adjusted for clustering and the effect estimate includes the possibility that the CI is too precise. In this study, interventions in both groups were given exclusively to people with intellectual disabilities. We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision because the evidence was from very few participants and the CI included the possibility of benefit and no benefit for both treatments.

8.1. Analysis.

Comparison 8: Comparison 5: SDF versus restorative treatments (GIC+FV), Outcome 1: Caries arrest (at end of study follow‐up)

Adverse effects

At the six‐month follow‐up, teeth were assessed for arrest in enamel and dentine caries and parents were asked if any harm was noticed due to the use of SDF (Mendiratta 2021). However, the results of this were not reported in the study report, and we could not determine whether there were any associated harms with either treatment.

SDF plus flouride varnish versus sealants plus flouride varnish (with or without restorations)

In this comparison, data were available for mixed dentition, including coronal caries only; no studies in this comparison reported data for root caries. No studies reported data for the following outcomes: primary caries prevention, secondary prevention of caries, dental pain or sensitivity, and aesthetics.

Caries arrest

Ruff 2022 reported the mean proportion of children with all caries arrested at 24 months, with SDF plus flouride varnish better than sealant plus flouride varnish (with or without restoration) at arresting caries in the mixed dentition (MD 0.11, 95% CI −0.01 to 0.22; 1 study, 413 participants; low‐certainty evidence; data not shown). We downgraded the certainty of the evidence by one level for risk of bias in the included study, and one level for imprecision because the data were available from few participants.

Ruff 2022 also reported this outcome as the number of children with arrested caries at 24 months, and these data indicated no evidence of a difference in effect according to treatments (OR 1.49, 95% CI 0.91 to 2.43; Analysis 9.1); we used imputed data for 874 participants from the study report. These data were adjusted for the clustering of schools at randomisation.

9.1. Analysis.

Comparison 9: Comparison 5: SDF versus restorative treatments (SDF + FV versus sealants + FV (+/‐ restorations)), Outcome 1: Caries arrest (at end of study follow‐up)

Adverse effects

Ruff 2022 reported that there were no adverse events during the study period; adverse events were not defined by the study authors, and we assumed that this included adverse effects. We downgraded the certainty of the evidence to very low. We downgraded by one level for risk of bias and two levels for imprecision. Although we assumed that the data were available for 1398 participants, we judged there to be too few participants for this outcome. Because adverse events were not defined in this study, we could not be certain that data for relevant adverse effects were collected.

SDF versus restoration

In this comparison, no studies reported data for root caries. No studies reported data for the following outcomes: primary caries prevention, and secondary prevention of caries.

Caries arrest

Cleary 2022 reported arrest of coronal caries in the primary dentition at 12 months; in the restoration group, this was defined when the restoration appeared to be satisfactory. In this study, findings indicated that more children had arrested caries lesions after restoration than with SDF (OR 0.03, 0.01 to 0.10; 1 study, 98 participants; very low‐certainty evidence; Analysis 10.1); data included no issues with clustering of the teeth. We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision because the evidence was from very few participants.

10.1. Analysis.

Comparison 10: Comparison 5: SDF versus restorative treatments (SDF + FV versus restoration + FV), Outcome 1: Caries arrest (at end of study follow‐up)

Adverse effects

Cleary 2022 reported that there were no unanticipated adverse events; adverse events were not defined, and we assumed they included adverse effects. We judged the certainty of the evidence for this outcome to be very low; we downgraded by one level for risk of bias, and two levels for imprecision because we judged that there to be too few participants for this outcome. Because adverse events were not defined in this small study, we could not be certain that relevant adverse effects were collected by study investigators.

Dental pain or sensitivity

Cleary 2022 reported children's pain in the study tooth at 12 months, and the findings were imprecise (OR 9.14, 95% CI 0.49 to 172.21; 1 study, 69 participants; very low‐certainty evidence; Analysis 10.2). We downgraded the certainty of the evidence by one level for risk of bias, and two levels for imprecision because the sample size included too few participants.

10.2. Analysis.

Comparison 10: Comparison 5: SDF versus restorative treatments (SDF + FV versus restoration + FV), Outcome 2: Pain (at end of study follow‐up)

Aesthetics

Cleary 2022 reported from both the parents' and child's point of view, "At 6 and 12 mo [months] there were no significant differences (P > 0.05) in parental acceptability, satisfaction, and preference between treatments. The majority of parents stated that they had no concerns with their child’s tooth appearance after treatment, were not dissatisfied with the tooth colour, did not believe that their child was concerned with the tooth appearance, and were willing to have another tooth treated with the same treatment modality as the study tooth... At 12 mo, children in the RT [restoration] arm versus the SDF arm felt happier with how their teeth looked (P = 0.047), and their dental visit hurt less (P = 0.049). No significant differences (P > 0.05) were noted in any prior visits, with the majority of children stating that they were happy with how their tooth looked, that their tooth felt great, and that their visit was easy and did not hurt". This information was reported with no associated data. We downgraded the evidence to very low‐certainty; we downgraded by one level for risk of bias, and two levels for imprecision because the sample size included too few participants.

Discussion

See Table 1; Table 2; Table 3; Table 4; Table 5.

Summary of main results

We included 29 studies with 13,036 participants, of which 12,020 were children and 1016 were older adults. We also identified 16 completed studies with 4514 participants for which we await publication of the full study reports, and 18 ongoing studies with an estimated recruitment of nearly 8000 participants.

We grouped the findings into five main comparisons. We report below the evidence from the most relevant clinical treatment comparisons within these main comparison groups.

• Comparison 1: SDF versus placebo or no treatment. Compared to placebo or no treatment, we found very low‐certainty evidence for SDF in primary caries prevention (i.e. reducing the number of tooth surfaces with new caries) in primary dentition and on the coronal surfaces of permanent dentition. Although moderate‐certainty evidence indicated a benefit for SDF compared to placebo or no treatment in primary caries prevention on root surfaces, we noted that this evidence was derived from three study areas that had concentrations of fluoride in water supplies of 0.5 ppm. In addition, SDF may increase the arrest of existing caries in primary dentition (low‐certainty evidence), but we were unsure of the findings for caries arrest on the coronal and root surfaces of permanent dentition (very low‐certainty evidence). We were also very unsure whether there were any benefits for SDF compared to placebo or no treatment for secondary prevention of caries (preventing the progression of existing caries), adverse effects and aesthetics (bother with the appearance of staining on teeth) because we judged evidence these outcomes to be very low‐certainty. In this comparison, no studies reported data for dental pain or sensitivity, or for secondary prevention of caries on root surfaces.

• Comparison 2:Different approaches to SDF application. We found five studies that compared different approaches to SDF treatment. Some of these studies included more than two study arms, and the differences between approaches in all studies were so varied that it was not feasible to combine any of the findings in meta‐analysis. These studies reported findings for caries arrest, secondary prevention of caries, adverse effects, and aesthetics. We could not be sure of any differences between approaches because we judged the certainty of the evidence for these treatment comparisons to be very low. In this comparison, no studies reported data for primary caries prevention, or dental pain or sensitivity.

• Comparison 3: SDF versus other topical treatments. We considered the evidence for SDF compared with fluoride varnish to represent the most clinically relevant treatment comparison amongst the available evidence for other topical treatments. We found low‐certainty evidence that neither SDF nor flouride varnish was better than the other at primary caries prevention in primary dentition, but we were unsure of any effects on the coronal or root surfaces of the permanent dentition because of very low‐certainty evidence. Similarly, we found very low‐certainty evidence for caries arrest or secondary prevention of caries in the primary dentition, adverse effects, dental pain or sensitivity, and aesthetics. Therefore, we were unsure whether either treatment was better than the other for these outcome measures.

• Comparison 4: SDF versus sealants and resin infiltration. We found very low‐certainty evidence for this comparison. Therefore, we were unsure whether there were any differences between treatments in primary prevention of caries on the coronal surfaces of permanent dentition, or in adverse effects. In this comparison, no studies reported data for caries arrest, dental pain or sensitivity, or aesthetics. We did not include available data for secondary prevention of caries in the summary of findings table because these data were not adjusted for clustering.

• Comparison 5: SDF versus restorative treatments. We prioritised the evidence for SDF compared with ART (using GIC or glass ionomer material) in our summary of findings table. The evidence for all outcomes in this comparison was very low‐certainty. Therefore, we could not be sure whether either treatment was better than the other at caries arrest in the primary dentition or whether there were any differences between these treatments in adverse effects, dental pain or sensitivity, or aesthetics. In this comparison, no studies reported data for primary caries prevention or secondary prevention of caries.

Overall completeness and applicability of evidence

We included 13,036 participants in the review, both children and older adults, with primary and permanent teeth. The children were recruited from dental clinics or their schools or kindergartens, and the older adults were recruited from care homes and community centres for older adults. There were no studies involving adults aged 18 to 65 years; therefore, we could not establish applicability in this age group, nor whether adults living in marginalised groups with limited access to dental care could benefit from SDF. Studies often omitted information about the socioeconomic status of participants, or the fluoridation status of local water supplies, and we were unable to further examine our data in terms of these important variables. We note that almost a third of studies in this review were conducted in Hong Kong and thus were particularly applicable to the population, relative extent of disease, healthcare and dental healthcare setting, and levels of fluoride in water supplies in this geographic region (Duangthip 2018; Fung 2018; Gao 2019; Jiang 2022; Li 2017; Liu 2012; Tan 2010; Zhang 2013; Zheng 2023).

We found evidence from enough studies to summarise the results according to five main comparison groups, with most evidence comparing SDF with no treatment or a placebo. Although data comparing SDF with no treatment or placebo were reported differently across these studies, findings were largely comparable and provided an adequate evidence base to determine that SDF is likely more effective than no treatment in managing dental caries in children and adults. Other main comparisons in this review included fewer studies, and there were often differences between studies ‐ particularly when comparing different approaches to SDF application, or comparing SDF with restorative treatments ‐ meaning that the findings for these comparisons may still be incomplete.

Sustainability of the intervention

Promoting oral health and disease prevention is the most impactful route to environmental sustainability in dentistry. This review evaluates interventions for caries prevention and management. Following Cochrane Oral Health policy (https://oralhealth.cochrane.org/about-us/sustainability), we conducted a brief search for healthcare sustainability science research for SDF using the search strategy in Appendix 9 (MEDLINE Ovid; 1946 to 15 May 2024); one person (SL) screened the results of this search. We found no sustainability science research for this intervention. We note that SDF can be delivered in community settings, such as schools or residential homes for older people, and it therefore has the potential to reduce individual travel to appointments in dental settings. It is a low‐cost product, which is easy to apply with minimal application time. However, it is likely that people will need repeat applications, and therefore there are no sustained benefits from SDF. We are currently unaware of other sustainability implications for SDF and, from this brief search, we cannot rule out any potential environmental harms associated with the chemical components of SDF. We encourage users to explore other resources on this topic to understand, learn and promote sustainable actions in their practice.

Certainty of the evidence

The certainty of most evidence in this review was very low.

When assessing risk of bias, we noted that most studies were unable to blind participants to treatment allocation because of the likely staining on tooth surfaces caused by SDF. Similarly, staining would be obvious to outcome assessors. Thus, most studies were at high risk of performance and detection bias. Because all studies included high or unclear risks of bias in at least one domain, we judged all studies to have overall high or unclear risk of bias; subsequently, we downgraded the certainty of the evidence for all outcomes because of risk of bias.

We noted that effect estimates were often imprecise, with CIs that included both benefit or no benefit and evidence derived from studies with small or very small sample sizes; additionally, we downgraded some of the evidence for imprecision. We also noted that some data were not adjusted for clustering of teeth within participants. Although we found the degree of clustering in one study to be minimal, and we included these unadjusted data in the summary of findings tables because unadjusted data were unavailable, we also downgraded for imprecision. In this case, because we used data that were not adjusted for clustering of teeth within participants, the CI in the effect estimate includes the possibility that the CI may be too precise.

Some findings within the same comparison were inconsistent with one another, and we chose not to pool these data and downgraded the certainty of this evidence for inconsistency. It is likely that inconsistencies related to differences in study approaches for applying SDF treatment; however, because of too few studies with comparable study designs, we could not explore this further.

We noted that one study, providing evidence for SDF compared to placebo or no treatment, was conducted in an area in which access to fluoride toothpaste was limited. We downgraded the certainty of the evidence from this study for indirectness because it is unlikely that this evidence would be applicable to other settings with better access to fluoride toothpaste. Although we did not downgrade other evidence for indirectness, we note that a third of included studies were conducted from the study centre in Hong Kong and similarities may not always be applicable to other settings (see Overall completeness and applicability of evidence). We did not assess publication bias in this review because we had too few studies for each comparison to do so effectively. Whilst we did not downgrade for this reason, we note that we could not rule out the possibility of publication bias.

Potential biases in the review process

We conducted this review following the Cochrane Methodological Expectations for Cochrane Intervention Reviews (MECIR). We have transparently reported any changes to the methods since the protocol was published (Differences between protocol and review). In particular, we made a post‐hoc decision to group studies together according to the main type of comparison. Whilst most studies fit easily into one of these five main comparisons, Ruff 2022 could have been included either within Comparison 4: SDF versus sealants or Comparison 5: SDF versus restorative treatments, because both comparative treatments may have been used in this study. However, because of the differences in treatment approaches in this study, we did not pool this study with other studies in its main comparison group, and we do not expect that this introduced bias to the reporting of our results of these comparisons. In addition, we did not select studies based on the frequency, concentration or duration of the intervention or comparison. Hence, we included Duangthip 2018, which was eligible for this review, in a comparison group for SDF versus fluoride varnish, but note that this study used a non‐standard application approach for fluoride varnish (three applications at weekly intervals). We highlighted this information alongside each relevant result from this study.

The clustering of teeth, surfaces or lesions in the participants was an issue with much of the dichotomous data in this review. We planned to use sensitivity analysis to assess the impact of using unadjusted data within a meta‐analysis. However, only a small number of studies took clustering into account and presented adjusted odds ratios. Excluding unadjusted data in a sensitivity analysis was not feasible as meta‐analyses often included few studies with only unadjusted data, or available data from only single studies. Therefore, we decided to prioritise reporting of adjusted data whenever possible in this review. When only unadjusted data were available, we included these data in the review in order to present the most comprehensive set of data. However, if we judged the degree of clustering to be large in unadjusted data, we did not judge the certainty of the evidence for outcomes using these data, and we did not include these data in the Summary of findings table, Abstract or Plain language summary; we believed the risk of the CIs in these effect estimates being too precise was very large. In addition, we prioritised continuous data in the Summary of findings tables as these data did not include unit of analysis issues and were likely to provide more sensitive data.

We found that some studies reported additional caries data and this allowed us to evaluate the impact of SDF on secondary prevention of caries (when initial caries do not progress from initial classification). We made a post hoc decision to include this additional outcome in the review in order to provide a more complete picture of effect.

We did not specify a minimum time point for reporting caries outcome measures in the review. Despite this, we did not report caries arrest data for Milgrom 2018, which were reported at only 21 days after treatment. For this study, we expected that it would be almost impossible to make reproducible decisions of caries arrest detection after such a short time frame. However, we acknowledge that this principle could apply to other studies with short follow‐up times in this review. In particular, we included caries arrest data for Azouru 2022 at three months (primary dentition), and Fahmi 2019 (primary dentition) and Mendiratta 2021 (coronal surfaces of permanent dentition) at six months. These follow‐up times may also be too short for diagnostic accuracy and reproducibility of visual detection of caries arrest (also bearing in mind the staining caused by SDF) for these dentition types. We are confident that the decision to include these studies in the review does not impact our overall conclusions as this evidence is very low certainty. We will reconsider specifying appropriate follow‐up time points according to caries outcome measure and dentition type in future updates.

We downgraded all the evidence owing to risk of bias. Blinding is difficult or not possible to achieve in many oral health‐related studies, and we expect our judgements in this review are consistent with other similar Cochrane reviews.

In our review criteria, we included split‐mouth study designs. Although we included one study with this design, we did not use the data because the study had not analysed data in a way that was suitable for our review (Braga 2009). This study design may not be appropriate when evaluating the effects of SDF owing to the potential for a spill‐over effect. We will reconsider these eligibility criteria in any future updates.

Agreements and disagreements with other studies or reviews

Other reviews comparing SDF with a placebo or no treatment for arresting root caries in older adults reached similar conclusions to our review, indicating a benefit in arresting active caries on root surfaces with SDF treatment (Grandjean 2021; Oliveira 2018; Subbiah 2018).

We are also aware of reviews that compare SDF with no treatment or other treatments in the primary dentition (Chibinski 2017; Contreras 2017; Duangthip 2015; Gao 2016a; Gao 2016b; Jabin 2020; Oliveira 2019; Santamaria 2020; Schmoeckel 2020). Duangthip 2015 compared different interventions and concluded that "There is limited evidence to support the effectiveness of SDF applications or daily toothbrushing with fluoride toothpaste in arresting or slowing down the progression of active dentin caries in primary teeth in preschool children". Chibinski 2017 compared SDF with a placebo or other treatments and concluded that "The use of SDF is 89% more effective in controlling/arresting caries than treatments or placebos", and Jabin 2020, comparing a similar variety of treatment to our review, concluded that "The cumulative results of the studies showed that 38% SDF application is efficacious and safe for the control of dental caries in primary teeth. Its advantages over different other techniques or placebo have been demonstrated.” These reviews often included quasi‐randomised or non‐randomised studies, and risk of bias judgements that are often not comparable to our own (for example, they did not always take into account the likely high risk of performance and detection bias). We also noted in some of these reviews that issues with clustering of teeth within individually randomised participants were not taken into account. Comparison of these systematic reviews with our own are not meaningful – they may include CIs that are too precise and indicate a higher level of certainty in the evidence, which we believe is not warranted.

We note that SDF is recommended for use by some professional bodies. Whilst we agreed with the likely effectiveness of SDF when compared to no treatment in caries arrest, we did not find high‐certainty evidence in our review to support any guidance statements that SDF was preferable to fluoride varnish (as stated in ADA 2021, BPSD Patient Information Leaflet on Silver Diamine Fluoride, and within the current supporting document for AAPD 2023). We anticipate that differences in interpretation may be due to the evidence used in guideline development ‐ for example, inclusion of other study designs, or reviews that have not accounted for high risks of performance and detection bias or the effect of clustering. We note that an earlier systematic review and guideline document for the American Academy of Pediatric Dentistry (AAPD) assessed the quality of the evidence for SDF to be low, and the quality of some comparisons to be very low (Crystal 2017); this was more comparable to our own findings.

We identified one review comparing SDF with ART for the arrest of caries in the primary teeth and first permanent molars and included the same studies as we have included (Wakhloo 2021). This review had similar conclusions to our systematic review, "The current SR [systematic review] points to the lack of solid evidence comparing SDF with ART for arresting active caries in primary teeth, especially in the first permanent molars". Whilst our judgements during risk of bias assessment differ from Wakhloo 2021, we similarly found the evidence was insufficient to draw confident conclusions about the effectiveness of one treatment over another.

Authors' conclusions

Implications for practice.

We are unable confidently to conclude whether or not silver diamine fluoride (SDF) is better than any other treatment for preventing or managing coronal caries in children and adults.

Although we found that SDF may offer benefit in preventing new caries in the primary dentition compared to placebo or no treatment, the evidence was very uncertain. We found that SDF is more likely to prevent new root caries than placebo or no treatment. We also found that SDF may offer benefit in caries arrest in the primary dentition when compared to placebo or no treatment. The evidence for other caries outcome measures across dentition types when compared to placebo or no treatment was very uncertain. Although we found that SDF may result in little or no difference to the prevention of new caries in the primary dentition when compared to fluoride varnish, the results across other caries outcomes (and in other dentition types) was very uncertain.

We noted concerns related to risk of bias in studies, as well as imprecision from small sample sizes and confidence intervals that include the possibility of benefit for either treatment option; this indicates that the evidence may be insufficient and not generalisable to all settings to draw meaningful conclusions about the effectiveness of SDF.

Although it is known that SDF causes black staining on the areas of teeth that are directly treated with SDF, this was not always reported in studies and few studies measured whether participants, or the parents or caregivers of children, were bothered by the appearance of staining on teeth.

Implications for research.

This is not a static topic area for research. We are aware of a large number of ongoing studies, or recently completed and not‐yet published studies, comparing SDF with other treatments. Timely publication of these studies is encouraged, as evidence from these studies should help to establish whether SDF offers any important benefits over other existing treatments. Whilst the evidence for SDF remains uncertain, we are committed to incorporating new studies in regular updates of this Cochrane review.

Ongoing and future studies must conform to CONSORT guidelines. Randomised controlled trials (RCTs) should evaluate the effectiveness of SDF in children and adults (to include root caries), and an ideal trial would compare SDF with no treatment and with fluoride varnish. Study investigators should follow appropriate clinical guidance for application (e.g. dose and frequency) of any comparative interventions. As well as caries outcome measures, studies should comprehensively report adverse effects, pain, and whether people are satisfied with the appearance of teeth (aesthetics) that may be stained black after SDF application. Clustering of lesions, surfaces or teeth within participants must be taken into account when analysing the data from studies; the inclusion of a statistician on the trial team is vital.

We encourage the producers of clinical guidelines for SDF to consider the findings of this review when preparing their recommendations. Currently, this Cochrane review provides the most up‐to‐date evidence for SDF, using robust methods to identify only RCTs, with an assessment of the certainty of the evidence using the GRADE approach. Given our commitment to keeping this review updated, production of other non‐Cochrane systematic reviews that duplicate this work would introduce research waste.

History

Protocol first published: Issue 7, 2017

Appendices

Appendix 1. Cochrane Oral Health Trials Register search strategy

Cochrane Oral Health’s Trials Register is available via the Cochrane Register of Studies.

1 MESH DESCRIPTOR Tooth Demineralization EXPLODE ALL AND INREGISTER

2 (teeth NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND INREGISTER

3 (tooth NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND INREGISTER

4 (dental NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND INREGISTER

5 (enamel NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND INREGISTER

6 (dentin NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND INREGISTER

7 (root* NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND INREGISTER

8 MESH DESCRIPTOR Dental Plaque AND INREGISTER

9 ((dental or tooth or teeth) and plaque) AND INREGISTER

10 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9

11 (silver NEAR3 fluorid*) AND INREGISTER

12 ("silver diamine" or "diamine silver" or "silver diammine" or "diammine silver") AND INREGISTER

13 ((silver NEAR3 nitrate) or (silver NEAR3 protein*) or (nano NEAR3 silver)) AND INREGISTER

14 ((ammonical or ammoniacal) NEAR2 silver) AND INREGISTER

15 (SDF or AgF or AgNO3 or Ag‐nano) AND INREGISTER

16 ("Advantage Arrest" or "Howe?s Solution" or "Riva Star" or Cariestop or Ancarie or "Salfluoraide di Walter" or (Cariostatic adj4 Inodon) or Saforide or Flurophat or Fagamin or Bioride) AND INREGISTER

17 #11 or #12 or #13 or #14 or #15 or #16

18 #10 and #17

Appendix 2. Cochrane Central Register of Controlled Clinical Trials (CENTRAL) search strategy

1 MESH DESCRIPTOR Tooth Demineralization EXPLODE ALL AND CENTRAL:TARGET

2 (teeth NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND CENTRAL:TARGET

3 (tooth NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND CENTRAL:TARGET

4 (dental NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND CENTRAL:TARGET

5 (enamel NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND CENTRAL:TARGET

6 (dentin NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND CENTRAL:TARGET

7 (root* NEAR5 (cavit* or caries or carious or decay* or lesion* or deminerali* or reminerali*)) AND CENTRAL:TARGET

8 MESH DESCRIPTOR Dental Plaque AND CENTRAL:TARGET

9 ((dental or tooth or teeth) and plaque) AND CENTRAL:TARGET

10 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 AND CENTRAL:TARGET

11 (silver NEAR3 fluorid*) AND CENTRAL:TARGET

12 ("silver diamine" or "diamine silver" or "silver diammine" or "diammine silver") AND CENTRAL:TARGET

13 ((silver NEAR3 nitrate) or (silver NEAR3 protein*) or (nano NEAR3 silver)) AND CENTRAL:TARGET

14 ((ammonical or ammoniacal) NEAR2 silver) AND CENTRAL:TARGET

15 (SDF or AgF or AgNO3 or Ag‐nano) AND CENTRAL:TARGET

16 ("Advantage Arrest" or "Howe?s Solution" or "Riva Star" or Cariestop or Ancarie or "Salfluoraide di Walter" or (Cariostatic adj4 Inodon) or Saforide or Flurophat or Fagamin or Bioride) AND CENTRAL:TARGET

17 #11 or #12 or #13 or #14 or #15 or #16 AND CENTRAL:TARGET

18 #10 and #17 AND CENTRAL:TARGET

Appendix 3. MEDLINE Ovid search strategy

1. exp Tooth demineralization/
2. (teeth adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.
3. (tooth adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.
4. (dental adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.
5. (enamel adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.
6. (dentin adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.
7. (root adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.
8. Dental plaque/
9. ((dental or tooth or teeth) and plaque).mp.
10. or/1‐9
11. (silver adj3 fluorid$).mp.
12. ("silver diamine" or "diamine silver" or "silver diammine" or "diammine silver").mp.
13. ((silver adj nitrate) or (silver adj3 protein$) or (nano adj3 silver)).mp.
14. ((ammonical or ammoniacal) adj2 silver).mp.
15. (SDF or AgF or AgNO3 or Ag‐nano).ti,ab.
16. ("Advantage Arrest" or "Howe?s Solution" or "Riva Star" or Cariestop or Ancarie or "Salfluoraide di Walter" or (Cariostatic adj4 Inodon) or Saforide or Flurophat or Fagamin or Bioride).mp.
17. or/11‐16
18. 10 and 17

The above subject search was linked with the highly sensitive search strategy designed by Cochrane for identifying randomised controlled trials and controlled clinical trials in MEDLINE (as described in Lefebvre 2022, box 3c).

1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
3. randomized.ab.
4. placebo.ab.
5. drug therapy.fs.
6. randomly.ab.
7. trial.ab.
8. groups.ab.
9. or/1‐8
10. exp animals/ not humans.sh.
11. 9 not 10

Appendix 4. Embase Ovid search strategy

1. exp Dental caries/

2. (teeth adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.

3. (tooth adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.

4. (dental adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.

5. (enamel adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.

6. (dentin adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.

7. (root$ adj5 (cavit$ or caries or carious or decay$ or lesion$ or deminerali$ or reminerali$)).mp.

8. Dental plaque/

9. ((dental or tooth or teeth) and plaque).mp.

10. or/1‐9

11. (silver adj3 fluorid$).mp.

12. ("silver diamine" or "diamine silver" or "silver diammine" or "diammine silver").mp.

13. ((silver adj nitrate) or (silver adj3 protein$) or (nano adj3 silver)).mp.

14. ((ammonical or ammoniacal) adj2 silver).mp.

15. (SDF or AgF or AgNO3 or Ag‐nano).ti,ab.

16. ("Advantage Arrest" or "Howe?s Solution" or "Riva Star" or Cariestop or Ancarie or "Salfluoraide di Walter" or (Cariostatic adj4 Inodon) or Saforide or Flurophat or Fagamin or Bioride).mp.

17. or/11‐16

18. 10 and 17

The above subject search was linked with the highly sensitive search strategy designed by Cochrane for identifying randomised controlled trials and controlled clinical trials in Embase (as described in Lefebvre 2022, box 3e).

1. Randomized controlled trial/

2. Controlled clinical study/

3. random$.ti,ab.

4. randomization/

5. intermethod comparison/

6. placebo.ti,ab.

7. (compare or compared or comparison).ti.

8. ((evaluated or evaluate or evaluating or assessed or assess) and (compare or compared or comparing or comparison)).ab.

9. (open adj label).ti,ab.

10. ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab.

11. double blind procedure/

12. parallel group$1.ti,ab.

13. (crossover or cross over).ti,ab.

14. ((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab.

15. (assigned or allocated).ti,ab.

16. (controlled adj7 (study or design or trial)).ti,ab.

17. (volunteer or volunteers).ti,ab.

18. human experiment/

19. trial.ti.

20. or/1‐19

21. random$ adj sampl$ adj7 ("cross section$" or questionnaire$1 or survey$ or database$1)).ti,ab. not (comparative study/ or controlled study/ or randomi?ed controlled.ti,ab. or randomly assigned.ti,ab.)

22. Cross‐sectional study/ not (randomized controlled trial/ or controlled clinical study/ or controlled study/ or randomi?ed controlled.ti,ab. or control group$1.ti,ab.)

23. (((case adj control$) and random$) not randomi?ed controlled).ti,ab.

24. (Systematic review not (trial or study)).ti.

25. (nonrandom$ not random$).ti,ab.

26. "Random field$".ti,ab.

27. (random cluster adj3 sampl$).ti,ab.

28. (review.ab. and review.pt.) not trial.ti.

29. "we searched".ab. and (review.ti. or review.pt.)

30. "update review".ab.

31. (databases adj4 searched).ab.

32. (rat or rats or mouse or mice or swine or porcine or murine or sheep or lambs or pigs or piglets or rabbit or rabbits or cat or cats or dog or dogs or cattle or bovine or monkey or monkeys or trout or marmoset$1).ti. and animal experiment/

33. Animal experiment/ not (human experiment/ or human/)

34. or/21‐33

35. 20 not 34

Appendix 5. US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) search strategy

silver and fluoride

Appendix 6. World Health Organization International Clinical Trials Registry Platform search strategy

silver and fluoride

Appendix 7. Summary of treated dentition, interventions, and caries diagnosis and assessment

Study ID	Teeth/surfaces/lesions treated	How interventions are used	Caries diagnosis
Abdellatif 2021	Anterior and posterior primary asymptomatic teeth with active single‐surface lesions (ICDAS 4,5 or 6)	38% SDF (Advantage Arrest, Elevate Oral Care LLC, West Palm Beach, Florida, USA) or ART applied to primary asymptomatic teeth with active single‐surface lesions, either occlusal surfaces in primary molars or labial surfaces in anterior teeth. No attempt was made to remove decayed tissue from the affected teeth for the SDF group, but carious dentine removed for ART and restored by GIC.	Diagnosis through clinical evaluation visual and tactile evaluation. If the lesion was smooth, hard on gently probing with a ball probe, it was considered arrested; If the lesion was rough, soft and easily penetrated on gently probing, considered active. For the ICDAS II evaluation, each lesion was compared to its original baseline ICDAS score to identify whether it has been arrested or progressed. A lesion was considered progressed if its ICDAS score changed to a higher score. A tooth that became symptomatic or was replaced by another restoration, endodontically treated or extracted was considered a failure.
Azouru 2022	Primary teeth with dental caries (ICDAS 5 or 6)	38% SDF (Tedequim SRLB) or ART (excavation of carious lesion and application of GIC.	Diagnosis using ICDAS II criteria (visual tactile examination with aid of WHO probe and mouth mirror, and ICDAS II criteria to classify active and arrested caries).
Braga 2009	Erupting first molars with active enamel (non‐cavitated) occlusal caries	10% SDF (Cariostatic Inodon, Porto Allegre, Brazil) or GIC applied to occlusal surface with enamel caries. The cross brushing was done on the occlusal surfaces. It is unclear if parents were told which occlusal surface to brush with for this third group in this split‐mouth trial.	Adapted from Carvalho 1992, evaluating the activity of enamel lesions. Dental caries were recorded as: 0 = entire sound surface; 1 = surface presenting only arrested lesion(s) (shiny white spot lesions) or with different degrees of brownish discolouration without any opacities around it; 2 = unique surface associating presence of arrested and active lesion(s); 3 = surfaces presenting only active lesions or sites (opaque enamel with a dull‐whitish surface); and 4 = enamel with loss of continuity of the surface.
Cleary 2022	At least one active/soft carious lesion into dentine in a primary tooth (molar, canine or incisor), scored 5 or 6 by ICDAS criteria.	38% SDF (Advantage Arrest, Elevate Oral Care LLC, West Palm Beach, Florida, USA) applied or restoration undertaken to single randomly selected tooth with carious lesions with at least one‐third of the crown remaining, no pulpal exposure, anticipated exfoliation greater than 12 months, and no spontaneous or elicited pain or signs of periapical infection.	Lesions were assessed by severity (ICDAS score), dentine colour (yellow, brown, black), periapical radiograph depth (outer, middle, or inner third of dentine), and dentine texture (soft, hard). For lesion and restoration assessment, teeth were cleaned with a toothbrush, dried with air, and assessed visually without magnification by using light and an explorer. Soft dentine was defined as any explorer penetration with light force (Chu 2002).
Daga 2020	Primary molars with active caries	38% SDF (Fagamin, Tedequim SRL, Argentina) applied to primary molars. Teeth that were grossly decayed, with more than one third of the crown missing, teeth symptomatic of pulpal involvement, non‐vital teeth, any presence of a sinus or an abscess, and premature hypermobility were excluded.	Active caries was recorded when the probe, applied with light force could penetrate dentine (Chu 2002). Caries was recorded as arrested when the dentine could not be penetrated (Zhi 2012).
Duangthip 2018	At least one untreated active caries lesion (ICDAS codes 3–6) in primary anterior or posterior teeth	30% SDF (Cariestop, Biodinâmica, Brazil) or FV solutions applied to each carious tooth surface	Clinical examination using a ball‐end CPI probe and a disposable dental mirror attached to a handle with an intraoral LED light. Saliva, food debris and plaque obscuring visual inspection of tooth surfaces were removed, but the teeth were not dried. Caries activity (arrested/active), extent of caries lesion (ICDAS codes 3 to 6) and colour of lesion (yellow, light brown, hard brown, or black) recorded. For cavitated dentine lesions (ICDAS 5 or 6), visual inspection and tactile detection using a 0.5 mm ball‐ended CPI probe were used for assessing caries activity. If a wall or floor of the lesion was soft and easily penetrated by the probe using light force, then it was diagnosed as active. A lesion with all surfaces being hard and smooth was diagnosed as arrested caries. For a moderate caries lesion with no visible dentine (ICDAS 3 or 4) at baseline, it was classified as arrested caries at follow‐up examinations if the lesion did not progress to become a cavitated lesion with visible dentine (ICDAS 5 or 6)
Ericson 2023	Exposed root surfaces on teeth 15, 14, 13, 23, 24 or 25, of older adults aged ≥ 70 years	38% SDF (Advantage Arrest Silver Diamine Fluoride 38%, Advantage Arrest, LCC, Redmond, USA) or placebo applied to affected root surfaces. Initial plaque removal in both groups	Described as a transition between categories according to Nyvad and modified by Zhang 2013. Status classified as new caries or caries progression, no change, or caries regression/inactivation. Change score was calculated by a summation of scores for the individual participant.
Fahmi 2019	Active caries lesions with exposed dentine (level 3) in primary teeth	One drop of 38% SDF (Saforide Seiyaku Kasei Co. Ltd, Osaka, Japan) or placebo solution applied to each lesion.	Active caries lesions with exposed dentine (level 3) selected, but no further diagnostic criteria reported.
Fung 2018	All carious tooth surfaces in primary anterior and posterior teeth were treated.	Solutions of 12% SDF (Cariestop, Biodinâmica, Brazil) or 30% SDF (Saforide Seiyaku Kasei Co. Ltd, Osaka, Japan) applied to each carious lesion	"At tooth level size of lesion was classified as small (less than half of mesial or distal surface or less than one‐third of the buccal, lingual or occlusal surface) or large. For lesion activity a caries lesion was diagnosed as arrested if its surface was smooth and hard on probing. A lesion was recorded as active if it was soft on probing. A lesion that was later restored or in a tooth later extracted due to caries was categorised as not arrested because the lesion had led to surgical intervention."
Gao 2019	Primary anterior and posterior teeth with at least 1 untreated active dentine carious lesion. Teeth considered nonvital (pulp exposure, abscess/fistula, or generalised tooth discolouration related to tooth nonvitality) were excluded.	38% SDF (Saforide Seiyaku Kasei Co. Ltd, Osaka, Japan) or AgNO3+FV solutions applied to each carious lesion.	“A carious lesion was recorded as active if softness was detected upon probing with a light force. If the lesion was hard upon probing, it was classified as arrested. Only the carious lesions detected in the baseline examination were included for evaluation in the follow‐up examinations.”
Jiang 2022	Cavitated dentine carious lesions in primary dentition	38% SDF (Saforide, Toyo Seiyaku Kasei Co, Osaka, Japan) or placebo applied to affected carious lesions. After 10 weeks, ART restorations were placed on all cavitated lesions	Number of dmft recorded according to the WHO criteria. Status of caries lesion (active/arrested), cavity class (I to IV), and cavity size (large‐small) recorded according to Lo 2017.
Li 2017	Permanant teeth with exposed root surfaces not indicated for extraction	38% SDF (Saforide Seiyaku Kasei Co. Ltd, Osaka, Japan) or placebo applied to all exposed tooth root surfaces	Status of the mesial, distal, buccal, and lingual root surfaces of each included tooth was classified according to ICDAS. Both noncavitated (code 1) and cavitated (code 2) root caries lesions were included. A caries lesion was recorded as: ‐ active when dentine could be easily penetrated with a ball‐ended probe with light force. ‐ Inactive when the lesion surface was hard and smooth. Colour of the arrested root caries lesion was classified into one of four types according to PANTONE colour plates: yellow, light brown, dark brown and black.
Liu 2012	At least one sound permanent first molar with deep fissures or fissures with signs of early (enamel) caries viewed as wet, with opacities and discolouration, similar to ICDAS code 2	38% SDF (Saforide Seiyaku Kasei Co. Ltd, Osaka, Japan) or FV solution/sealant was applied to the first permanent molar (i.e. those with early caries)	“Each included molar was assessed at 2 sites (upper molar ‐ mesial pit/fossa and distal‐palatal groove; lower molar ‐ occlusal fissure and buccal pit/groove). The recorded status included fissure morphology (deep/shallow), sign of early caries (yes/ no), and DIAGNOdent reading” “Status of the molars, including sealant retention and development of caries into dentine (ICDAS codes 4‐6), was assessed every 6 mos by the same blinded examiner using disposable mouth‐mirrors attached to an intra‐oral LED light and CPI probes. Sites with sealant fully retained were regarded as sound”
Llodra 2005	Active caries in primary canines and posterior teeth; erupted permanent first molar teeth	38% SDF (Fluoroplat Laboratories Naf, Buenos Aires, Argentina) applied to decayed surfaces of primary teeth and the occlusal surfaces of any first permanent molars that had erupted	Primary teeth: ‐ data were gathered for the surfaces of canines and molars only. Permanent teeth: ‐ data were gathered for first molars only. Each surface was classified as: ‐ healthy, ‐ with active caries (presence of cavity with soft floor/walls), ‐ inactive caries (cavity with hard floor/walls), filled, ‐ absent (for primary teeth, only those extracted for caries were considered absent)
Mabangkhru 2020	All active cavitated surfaces with dentine caries in primary anterior and posterior teeth	38% SDF (Topamine DentaLife, Australia) and FV applied to active carious tooth surfaces	"The carious lesion activity was evaluated by visual‐tactile inspection using a WHO CPI periodontal probe without radiograph examination. A soft tooth surface, when gently drawing the probe, was diagnosed as an active lesion. A smooth and hard tooth surface that could not be penetrated easily was classified as an arrested lesion."
Mattos‐Silveira 2015	All caries lesions clinically into enamel sited on an approximal surface of primary molars	30% SDF (Cariestop, Biodinâmica, Brazil) and sealant applied to affected tooth surface	Progression classified according to ICDAS criteria. Highest score found per surface was recorded. Two definitions of progression were considered: a) Progression to any score (transition from scores 1 to 2 was not considered in this outcome); b) Progression to scores that involve dentine: progression from any score to scores 5 or 6
Mendiratta 2021	Permanent posterior teeth and their surfaces with caries	38% SDF (Fagamin, Tedequim SRL, Argentina) and GIC applied to affected tooth surface. FV was applied to sound surfaces of treated teeth in GIV group.	Nyvad criteria for caries assessment, using trained and calibrated examiners. The caries assessment at 6 months was based on changes in Nyvad score. Conversion 2 and 3 (active caries) to 5 and 6 (inactive caries) in SDF group considered arrest of caries. Whereas in GIC group conversion of 2 and 3 (active caries) to only score 7 (restoration) was considered as arrest of caries. Any treated surface in either group showing active lesion or dislodged restoration (partial/complete) at 6 months follow‐up was considered as caries increment and failure of treatment.
Milgrom 2018	Untreated cavitated active caries lesions in primary teeth	38% SDF (Advantage Arrest, Elevate Oral Care LLC, West Palm Beach, Florida USA) or placebo applied to affected tooth surface	Caries arrest was defined according to Nyvad lesion: change from code 3 to 6 (“Enamel/dentine cavity easily visible with the naked eye; surface of cavity may be shiny and feels hard on probing with gentle pressure”)
Rehim 2021	Carious surfaces in primary teeth were treated with SDF, all teeth surfaces were treated with FV	SDF (concentration and manufacturer not reported) applied to affected tooth surface FV varnish painted on all teeth surfaces	Tactile examination at baseline and each recall visit. Treated lesions were assessed for dentine colour and hardness using gentle pressure with probe. No other caries diagnostic criteria are reported.
Ruff 2022	SDF group: Carious tooth surfaces were treated with SDF, SDF also brushed on all pits and fissures of bicuspids and molars. GI sealants applied at all pits and fissures of bicuspids and molars. Placement of atraumatic restorations on all frank lesions. FV was applied to all teeth in both groups. Treatment in both primary and permanent teeth.	SDF (concentration and manufacturer not reported) applied to affected tooth surface, and all pits and fissures of bicuspids and molars. GI sealant applied at all pits and fissures of bicuspids and molars. Placement of atraumatic restorations on all frank lesions. FV was applied to all teeth in both groups.	ICDAS II criteria used. Individual surfaces assessed as being intact or sound (ICDAS codes 0‐4, sealed, restored, decayed (ICDAS 5‐6), or arrested. Primary outcomes: proportion of children with arrested caries lesions (arrest) and proportion of children with no cumulative incidence of decayed teeth from previously sound (prevention). Arrest failure was recorded if tooth presented at baseline with untreated caries, received treatment at baseline with either treatment. If tooth exfoliated prior to 2 year follow‐up that was coded as arrested after baseline treatment, that tooth was discounted from the analysis; this was coded as arrested. Caries prevention compared the cumulative incidence of caries in each treatment group. Children with new caries included those who presented at follow‐up with either (i) untreated carious lesions or (2) presence of a filling not present at baseline.
Salem 2022	Asymptomatic enamel and dentine caries in primary molars	38% SDF (manufacturer not reported) applied before cementation of crown with GIC in Hall technique or Hall technique without SDF. An additional study group included use of diode laser before cementation of crown in Hall technique	Assessed as clinical and radiographic success and failure. Clinical success: crowns were acceptable clinically; no signs or symptoms of any pulpal disease. Minor clinical failure: crown fracture or perforation; reversible pulpitis with no need for intervention. Major clinical failure: an abscess or irreversible pulpitis that needs pulpotomy or extraction; crown loss and the tooth is non‐restorable. Radiographic success: no evidence or radicular radiolucency; no internal or external root resorption. Radiographic failure: periapical or furcation radiolucency; external or internal root resorption; widening in the periodontal ligament space.
Seberol 2013	Primary anterior teeth with enamel or dentine caries were included	38% SDF (Fagamin, Tedequim SRL, Argentina) or placebo applied to affected tooth surface	In addition to the ICDAS II scores, evaluation was made by giving a “0” to the caries‐free teeth, “1” to the teeth with active caries and a “2” to the teeth with inactive caries. According to ICDAS II, in the classification of caries observed on flat surfaces and free flat surfaces, the soft caries tissue on the teeth with the value of code 5 and above was removed from the tooth surface with the help of excavator.
Sirivichayakul 2023	Distal surfaces of the canine or first molar, or the mesial surfaces of the first or second molars showing clinically sound and radiographically sound or initial carious lesion. Initial approximal carious lesions were defined as radiolucency confined to the enamel or outer third of dentine	38% SDF (Topamine, Dentalife, Australia) or FV or placebo	Clinical examination using WHO CPI periodontal probes with an LED dental mouth mirror. The tooth or surface status was recorded as sound dmf/dmfs based on WHO criteria. Bitewing radiographic images were assessed; caries development was determined when the recruited approximal surface had a carious lesion at the moderate stage or extensive stages according to ICDAS.
Tan 2010	At least 5 teeth with exposed sound root surfaces (permanent dentition)	38% SDF (Saforide Seiyaku Kasei Co. Ltd, Osaka, Japan), FV and chlorhexidine varnish applied to exposed root surfaces	Active root caries was recorded when a lesion on the root surface could be easily penetrated by a sharp sickle‐shaped probe with light force (Banting 2001). A lesion involving more than one root surface was recorded as a single surface lesion if the width of the extension was less than one‐third of the extended surface.
Torres‐Arellano 2012	Incipient caries lesions, primary posterior teeth and permanent molars	38% SDF (Fluoroplat Laboratories Naf, Buenos Aires, Argentina) or placebo applied to affected tooth surface	Incipient diagnosis in primary molars: Grade 2 or 3 ICDAS Incipient diagnosis in permanent molars: Grade 2 or 3 ICDAS Progression of the incipient lesion: > 3 in ICDAS Arrest: teeth with dark colour and hard surface
Vollú 2019	Untreated cavitated active caries lesion involving only the occlusal surface of a primary molar	30% SDF (Cariestop, Biodinâmica, Brazil) and ART applied to occlusal surface of included teeth	Inactive/active status defined according to ICDAS or when there was spontaneous pain or signs of pulpal involvement
Yee 2009	Carious surfaces of the primary teeth	12% SDF (PROBEM Laboratório de Produtor Farmacêuticos Odontológicos LTDA, São Paulo, Brazil) or 38% (Bee Brand Medical Dental Company Ltd, Osaka, Japan) applied to all carious surfaces	Sound surfaces ‐ not soft to the touch with a sharp sickle probe, but they may be discoloured Initial caries ‐ localised enamel breakdown (microcavity) in opaque or discoloured enamel Arrested cavitated caries ‐ as d2, but the wall and floor of the cavity were hard and could not be penetrated by the sharp sickle probe Filled surface with no decay ‐ a permanent restoration is present, and there is no caries anywhere on the surface. Non‐vital tooth ‐ abscessed/pulpally involved teeth with abnormal colouring Missing due to caries ‐ teeth extracted due to caries Included in this category were teeth having more than two‐thirds of the crown destroyed by caries and the root remaining
Zhang 2013	At least 5 teeth with exposed root surfaces (permanent dentition)	38% SDF (Saforide Seiyaku Kasei Co. Ltd, Osaka, Japan) or placebo applied to exposed root surfaces	The traditional visual‐tactile diagnosis for root caries was employed to make a diagnosis (Banting 2001). Active caries was recorded if soft dentine was detectable when a light force was applied with the tip of the explorer; typically the root surface was rough and light brown in colour (Fejerskov 1991). Inactive caries was recorded if no soft dentine was detected when a light force was applied with the tip of the explorer; the root surface was typically smooth and dark brown or black in colour.
Zheng 2023	Upper anterior teeth in primary dentition	38% SDF (Advantage ARrest, Elevate Oral Care) or FV applied to each tooth surface (sound or decayed) of the 6 upper anterior teeth	Caries incidence evaluated using dfmt index and the tooth status of the 6 upper anterior teeth under investigation, using WHO criteria
Zhi 2012	Children who had primary anterior and posterior teeth with active dentine caries “To avoid over clustering, up to 3 decayed teeth in one child” – however, there is a higher ratio of participants to lesions.	Superficial soft decayed tissues of the selected decayed primary tooth were removed by hand instruments. 38% SDF (Saforide Seiyaku Kasei Co. Ltd, Osaka, Japan) or GIC applied to the cavities	Status of the dentine caries lesions was assessed by visual inspection and aided by tactile detection using a sharp probe. Cavities with yellowish/brown rough wall/floor, which could be easily penetrated by the probe using a light force, were diagnosed as active. Those with smooth hard surfaces that could not be penetrated were classified as arrested. The treated caries lesions were classified as either active or arrested according to the diagnostic criteria used at baseline. Lesions in Group 3 that were totally covered by the glass ionomer material were classified as arrested.
AgNO3: silver nitrate; ART: Atraumatic Restorative Treatment; CPI: Community Periodontal Index; dmfs: decayed, missing and filled surfaces; dmft: decayed, missing and filled teeth; FV: fluoride varnish; GI: glass ionomer; GIC: glass ionomer cement; ICDAS: International Caries Detection and Assessment System; LED: light‐emitting diode; SDF: silver diamine fluoride; WHO: World Health Organization

Appendix 8. Data not used in analyses (Ericson 2023)

Caries prevention (primary prevention or secondary prevention, or both) on root surfaces of permanent teeth; at end of study follow‐up (12 months)
Study ID	Mean (SDF)	SD (SDF)	Total participants (SDF)	Mean (placebo)	SD (SDF)	Total participants (placebo)	Effect estimate
Ericson 2023	0.1	0.65	138	0	0.56	135	MD 0.10, 95% CI −0.04 to 0.24
CI: confidence interval; MD: mean difference; SD: standard deviation; SDF: silver diamine fluoride

Appendix 9. Sustainability of intervention: search strategy

MEDLINE (via Ovid; 1946 to 15 May 2024)

1. (silver adj3 fluorid$).mp.

2. ("silver diamine" or "diamine silver" or "silver diammine" or "diammine silver").mp.

3. ((silver adj nitrate) or (silver adj3 protein$) or (nano adj3 silver)).mp.

4. ((ammonical or ammoniacal) adj2 silver).mp.

5. (SDF or AgF or AgNO3 or Ag‐nano).ti,ab.

6. ("Advantage Arrest" or "Howe?s Solution" or "Riva Star" or Cariestop or Ancarie or "Salfluoraide di Walter" or (Cariostatic adj4 Inodon) or Saforide or Flurophat or Fagamin or Bioride).mp.

7. or/1‐6

8. exp Sustainable Development/

9. Environmental Monitoring/

10. Carbon Footprint/

11. "Conservation of Natural Resources"/

12. Waste Management/

13. Air Pollution/

14. Climate Change/

15. (life cycle adj3 (assess* or analys*)).mp.

16. "cradle to grave".mp.

17. sustainab*.mp.

18. (environment* adj3 impact).mp.

19. carbon footprint.mp.

20. sustainable development.mp.

21. waste management.mp.

22. climate change.mp.

23. circular economy.mp.

24. or/8‐23

25. 7 and 24

Data and analyses

Comparison 1. Comparison 1: SDF versus placebo/no treatment.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Primary caries prevention (at end of study follow‐up)	4		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.1.1 Primary dentition	1	373	Mean Difference (IV, Random, 95% CI)	‐1.14 [‐1.58, ‐0.70]
1.1.2 Permanent dentition ‐ coronal caries	1	373	Mean Difference (IV, Random, 95% CI)	‐0.69 [‐0.97, ‐0.41]
1.1.3 Permanent dentition ‐ root caries	3	439	Mean Difference (IV, Random, 95% CI)	‐0.79 [‐1.40, ‐0.17]
1.2 Primary caries prevention (at end of study follow‐up)	2		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
1.2.1 Primary dentition	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
1.2.2 Permanent dentition ‐ coronal caries	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
1.3 Caries arrest (at end of study follow‐up)	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.3.1 Primary dentition	2	841	Mean Difference (IV, Random, 95% CI)	0.86 [0.39, 1.33]
1.3.2 Permanent dentition ‐ coronal caries	1	373	Mean Difference (IV, Random, 95% CI)	0.20 [0.00, 0.40]
1.3.3 Permanent dentition ‐ root caries	1	158	Mean Difference (IV, Random, 95% CI)	0.24 [0.12, 0.36]
1.4 Caries arrest (at end of study follow‐up)	2		Odds Ratio (M‐H, Random, 95% CI)	Totals not selected
1.4.1 Primary dentition	1		Odds Ratio (M‐H, Random, 95% CI)	Totals not selected
1.4.2 Permanent dentition ‐ root caries	1		Odds Ratio (M‐H, Random, 95% CI)	Totals not selected
1.5 Secondary prevention of caries (at end of study follow‐up; analysed with OR)	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
1.5.1 Primary dentition	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
1.6 Secondary prevention of caries (at end of study follow‐up; analysed using Peto OR)	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected
1.6.1 Primary dentition	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected
1.6.2 Permanent dentition ‐ coronal caries	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Totals not selected
1.7 Secondary prevention of caries (at end of study follow‐up; analysed with OR)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.7.1 Primary dentition	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 2. Comparison 2: Different approaches to SDF application.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Caries arrest (at end of study follow‐up)	4		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.1.1 Primary dentition	4		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.2 Caries arrest (at end of study follow‐up)	2		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
2.2.1 Primary dentition	2		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
2.3 Secondary prevention of caries (at end of study follow‐up)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.3.1 Primary dentition	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.4 Secondary prevention of caries (end of study follow‐up)	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
2.4.1 Primary dentition	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
2.5 Adverse effects	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 3. Comparison 3: SDF versus other topical treatments (FV).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Primary caries prevention (at end of study follow‐up)	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.1.1 Primary dentition	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.1.2 Permanent dentition ‐ root caries	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
3.2 Primary caries prevention (at end of study follow‐up)	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.2.1 Primary dentition	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.2.2 Permanent dentition ‐ coronal caries	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.3 Caries arrest (at end of study follow‐up)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
3.3.1 Primary dentition	1	309	Mean Difference (IV, Fixed, 95% CI)	‐0.13 [‐0.87, 0.61]
3.4 Caries arrest (at end of study follow‐up)	2		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
3.5 Secondary prevention of caries (at end of study follow‐up)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
3.5.1 Primary dentition	1	309	Mean Difference (IV, Fixed, 95% CI)	0.04 [‐0.30, 0.38]
3.6 Secondary prevention of caries (at end of study follow‐up)	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
3.7 Secondary prevention of caries (at end of study follow‐up)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.7.1 Primary dentition	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.8 Adverse effects	1	309	Odds Ratio (M‐H, Fixed, 95% CI)	3.19 [1.95, 5.23]
3.9 Pain (at end of study follow‐up)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
3.10 Aesthetics (end of study follow‐up)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 4. Comparison 3: SDF versus other topical treatments (chlorhexidine varnish).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Primary caries prevention (at end of study follow‐up)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
4.1.1 Permanent dentition ‐ root caries	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 5. Comparison 3: SDF versus other topical treatments (silver nitrate + FV).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Caries arrest (at end of study follow‐up)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
5.1.1 Primary dentition	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
5.2 Caries arrest (at end of study follow‐up)	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
5.2.1 Primary dentition	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected

Comparison 6. Comparison 4: SDF versus sealants and resin infiltration.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Primary caries prevention (at end of study follow‐up)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
6.1.1 Permanent dentition ‐ coronal caries	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
6.2 Secondary prevention of caries (at end of study follow‐up)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
6.2.1 Primary dentition ‐ coronal caries	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 7. Comparison 5: SDF versus restorative treatments (SDF versus ART (with GIC or glass ionomer material)).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Caries arrest (at end of study follow‐up)	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
7.1.1 Primary dentition	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
7.2 Caries arrest (at end of study follow‐up)	3		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
7.3 Dental pain or sensitivity (number of people with tooth sensitivity; end of study follow‐up)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 8. Comparison 5: SDF versus restorative treatments (GIC+FV).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
8.1 Caries arrest (at end of study follow‐up)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 9. Comparison 5: SDF versus restorative treatments (SDF + FV versus sealants + FV (+/‐ restorations)).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
9.1 Caries arrest (at end of study follow‐up)	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected
9.1.1 Primary and permanent coronal caries	1		Odds Ratio (IV, Fixed, 95% CI)	Totals not selected

Comparison 10. Comparison 5: SDF versus restorative treatments (SDF + FV versus restoration + FV).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
10.1 Caries arrest (at end of study follow‐up)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.1.1 Primary dentition	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.2 Pain (at end of study follow‐up)	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Abdellatif 2021.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 12 months' duration
Participants	90 children aged from 3 to 8 years, with negative and definitely negative behaviour according to Frankl’s behaviour rating scale, with ≥ 1 primary asymptomatic tooth with active single‐surface lesions on occlusal (posterior teeth) or labial (anterior teeth) surfaces, ICDAS codes 4, 5 or 6. In University Paediatric outpatient clinic, Saudi Arabia Exclusion criteria: children with systemic diseases or syndromes, having silver allergy, oral ulceration or teeth with proximal or multi‐surfaces caries, pulp pathology or anomalies in structure SES: not reported Sex: G1 42.5% male; G2 38.5% male Age: baseline data not reported by group. All children aged between 3 and 8 years of age Baseline caries: G1 75.2% ICDAS 5 or 6; G2 97.4%. More severe caries (ICDAS 5 and 6) in the ART group than the SDF group, but distribution in the cohort with 12 months follow‐up fairly similar Fluoridation status: not reported Use of fluoride toothpaste: not reported Number randomised: 90 children (G1 45; G2 45) Number evaluated at 12 months: 53 children (G1 27; G2 26)
Interventions	Comparison 5: SDF versus restorative treatment G1: 38% SDF at 6‐monthly intervals (baseline and then at 6 months). 1 drop of SDF (Advantage Arrest, Elevate Oral Care) was placed into a disposable dish, SDF was applied with a microsponge directly to the affected tooth surface(s), allowed to soak in for 2 minutes then air‐dried. G2: ART. Carious and unsupported enamel was removed with a dental hatchet, carious dentine was removed using a small excavator, the cavity was cleaned and dried, cavity walls and floor were conditioned for 10 s then washed and dried. Finally, the cavity was restored using chemically cured GIC (Fuji IX, GC America Inc. IL, USA), and a protection varnish was applied on the GIC surface to prevent gain or loss of water.
Outcomes	Outcomes included in the review: caries arrest and secondary prevention (evaluated by ICDAS II visual and tactile assessment of lesions; for secondary prevention, we used data defined by study authors as '"active caries lesion" at follow‐up) Note: total working time per tooth per treatment, pain and sensitivity to percussion, gingival staining and abscess formation were also evaluated. Results for pain were not reported.
Notes	Funding: Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast‐track Research Funding Program Declarations of interest: no statement reported Study dates: not reported Baseline demographics reported for the 79 children who were allocated intervention and who attended appointment to receive treatment. Analysis not by ITT
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block randomisation using coin toss for each block of size 2
Allocation concealment (selection bias)	Low risk	Quote: "Allocation sequence was concealed from the operator in sequentially numbered, opaque, sealed envelopes." Quote: "The random allocation of treatment was carried out by an independent clinical coordinator"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not possible due to the nature of the interventions being evaluated
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not possible due to the nature of the interventions being evaluated
Incomplete outcome data (attrition bias) All outcomes	High risk	Overall attrition of 36% (32/90 children) at 6 months and 41% (37/90) at 12 months. Loss was reasonably balanced between groups. Reasons for loss included loss to follow‐up (13 participants in G1 and G2) or loss of teeth due to tooth exfoliation (9 teeth in G1) or tooth endodontically treated or extracted (8 teeth in G2). We judged this to be high risk because reasons for loss are not comparable between groups and overall rate of attrition is very high.
Selective reporting (reporting bias)	High risk	No clinical trial registry number provided, and no published protocol referenced, so we were unable to confirm whether all measured outcomes were reported. However, pain and sensitivity were stated as outcomes stated in the Methods section but were not reported in the Results section of the report.
Other bias	Low risk	We identified no other sources of bias

Azouru 2022.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 3 months
Participants	240 children aged 3 to 10 years, with dental caries ICDAS 5 or 6, parent/guardian consent. Recruited from primary schools in Lagos, Southwest Nigeria Exclusion criteria: children with symptomatic carious tooth (toothache or sensitivity), mobile carious tooth, with dental caries IDCAS 0 to 4; exposed to fluoride from other sources apart from dentifrice; allergic to silver or heavy metals; amelogenesis or dentinogenesis imperfecta, oral ulceration, stomatitis, swelling or abscess; co‐operation challenge, obvious learning disability, systemic disease like asthma, epilepsy, leukaemia, kidney disease; parents or guardian could not understand consent documentation SES: not reported Sex: G1 53.3% male, G2 50% male Age: baseline data not reported. All children are between 3 and 10 years of age Baseline caries: G1 mean (SD) 1.87 (± 0.9) dmft; G2 mean (SD) 1.75 (± 0.9) dmft Fluoridation status: not reported Use of fluoride toothpaste: not reported Number randomised: G1 120 children; G2 120 children Number evaluated at 3 months: G1 118 children; G2 116 children
Interventions	Comparison 5: SDF versus restorative treatment G1: 38% SDF (Tedequim SRL); single application G2: carious lesion of affected tooth was excavated with disposable plastic excavator; tooth cleaned, dried and isolated with cotton rolls; conventional GIC (PrevestDenPro) was used to seal the surface
Outcomes	Outcomes included in the review: caries arrest (using ICDAS II criteria, visual tactile examination with aid of WHO probe and mouth mirror using ICDAS II criteria to classify active and arrested caries), dental pain (toothache) and sensitivity; adverse effects (stain, nausea, vomiting, silver allergy, oral soft tissue ulceration, rashes, other)
Notes	Funding: study received no funding Declarations of interest: study authors report no conflicts of interest Study dates: October 2019 to March 2020 Sample size allowed for 10% attrition, with minimum sample of 107 in each group Note: we attempted to contact the study authors (email 14 July 2023) to establish if clustering had been accounted for in their analysis; we received no reply.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Initial random sampling of schools using computer‐generated numbers, then simple random sampling of classes within schools, then allocation of sample population using simple randomisation.
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding is not described and we assumed no attempts were made to blind participants to treatment. It is not possible to blind personnel to treatment
Blinding of outcome assessment (detection bias) All outcomes	High risk	Because of the staining on teeth caused by SDF, it is not possible to blind outcome assessors to treatment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Small loss of participants at 3 months, due to tooth exfoliation, relatively balanced between groups
Selective reporting (reporting bias)	Low risk	Prospective clinical trials registration in April 2019 (PACTR 201908699150281). Primary outcome reported in the full study report is consistent with the clinical trials register
Other bias	Low risk	We identified no other sources of bias

Braga 2009.

Study characteristics
Methods	RCT, split‐mouth study design 3 arms 30 months' duration
Participants	22 children (66 molars), 5 to 7 years of age with at least 3 erupting permanent first molars. Dental School University of Sao Paulo, Brazil SES: not reported Sex: not reported Age: baseline age not reported by group. All children between 5 and 7 years of age Baseline caries: erupting first molars, with active enamel caries lesions Fluoridation status: not reported Use of fluoride toothpaste: "All children have used fluoridated toothpaste"; no additional details in the study report Number randomised: 22 children (3 teeth randomly allocated to groups) Number evaluated at 30 months: G1 18 teeth; G2 20 teeth; G3 20 teeth
Interventions	Comparison 4: SDF versus sealants and infiltration G1: SDF group; applied twice with an interval of 1 week G2: cross tooth‐brushing technique G3: sealing with GIC Evaluated 3, 6, 12, 18 and 30 months' follow‐up The cross brushing was done on the occlusal surface. It is unclear how parents were told which occlusal surfaces to brush. Due to the lack of clarity, we considered only the comparison between G1 and G3.
Outcomes	We did not include any outcome data in the review because the data in the study report did not account for the split‐mouth study design. Outcomes reported by study authors included: caries arrest (in lesions with active caries at baseline; diagnosis by visual (Carvalho criteria)/tactile and assessment of bitewing radiographic images)
Notes	Funding: Conselho National de Desenvolvimiento Cientifico e Tecnologico, Brazil Study dates: 2002 to 2005 Statistical unit: the surface. Unable to use data as should be paired analysis with equal n values. No SDs given and inappropriate statistical test used Pilot study, 18 to 20 participants in each group We did not assess risk of bias in this study because we did not include any outcome data in the review

Cleary 2022.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 12 months' duration
Participants	98 children, aged between 2 and 10 years with at least 1 active/soft caries lesion into dentine in a primary tooth scored as ICDAS 5 or 6. Only 1 randomly selected tooth per child was included. Caries lesions were on teeth with at least 1‐third of the crown remaining, no pulpal exposure, anticipated exfoliation > 12 months, and no spontaneous or elicited pain or signs of periapical infection. In Mott children's Health Centre and University of Michigan School of Dentistry Exclusion criteria: children who were wards of the state, or had hereditary enamel/dentine developmental defects, known allergy to heavy metals or restorative materials, or medical conditions that would prevent treatment in the dental clinics SES: not reported Sex: G1 47% male; G2 62% male Age, mean (SD): G1 4.7 (± 1.9) years; G2 4.9 (± 1.7) years Baseline caries, mean (SD): G1 5.6 (± 3.7) dmft + DMFT; G2 7.2 (± 3.8) dmft + DMFT Fluoridation status: not reported Use of fluoride toothpaste: G1 71%; G2 57% Number randomised: 98 children (G1 56; G2 42) Number evaluated at 12 months: 69 children (G1 40; G2 29)
Interventions	Comparison 5: SDF versus restorative treatments (SDF + FV versus restorative treatment + FV) G1: the carious lesion was treated with 38% SDF (Advantage Arrest; Elevate Oral Care) at 6‐monthly intervals (baseline and 6 months). The selected tooth was isolated and dried, and SDF was applied on the entire carious dentine. Excess was blotted dry to prevent unnecessary swallowing. G2: local anaesthesia and behaviour guidance as needed. The study tooth received restorative treatment, with level of caries removal and type of material used selected per current restorative treatment guidelines. Study authors state that, although ART was an option for restorative treatment, this less invasive option was not used in any participants. Bi‐annual FV applications were given to all participants, as well as dietary advice and toothbrushing instruction.
Outcomes	Outcomes included in the review: caries arrest (clinical and radiographic classification of minor and major failures at participant level. We used data for "no failure" to indicate caries arrest for SDF and restorative group). Pain and signs or symptoms of irreversible pulpitis, parental acceptance and satisfaction with study treatment were also evaluated.
Notes	Funding: study supported by a grant from Delta Dental Plan of Wisconsin and the Renaissance Health Service Corporation of Michigan Declarations of interest: M. Fontana (study author) is a scientific advisory consultant for the Delta Dental Plans Association. The study authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of the article. Study dates: recruitment from 2016 to 2019; last follow‐up assessment in September 2020 Simple imputation for missing data using carry forward method for multiple time points and simulation‐based imputation for 12‐month visit
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "...participants were randomly allocated (1:1) to 1 of 2 treatment groups in blocks of 4 per a random number generator. The study statistician stratified randomization by site." Comment: stratified randomisation using fixed block size
Allocation concealment (selection bias)	Unclear risk	Quote: "Envelopes provided by the statistician with the randomized treatment order were prepared by the study manager and located at each clinical site for use." Comment: insufficient information, use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not possible due to the nature of the interventions being evaluated
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not possible due to the nature of the interventions being evaluated
Incomplete outcome data (attrition bias) All outcomes	Low risk	Overall attrition of 18% (18/98 children) at 6 months and 29% (29/98 children) at 12 months, comparable across groups. Reasons for loss to follow‐up provided and reasonably similar in each group
Selective reporting (reporting bias)	Low risk	Prospective clinical trials registration (NCT02601833). Outcomes in study report that are relevant to this review are also described in clinical trials registration documents.
Other bias	Low risk	We identified no other sources of bias

Daga 2020.

Study characteristics
Methods	RCT, parallel‐group design 3 arms 12 months' duration
Participants	48 children, aged 5 to 8 years, who had active caries affecting the primary molars. Recruited from a primary school outside Mangalore, India SES: children from low socioeconomic strata Sex: not reported Age: baseline data not reported by group. Study included children between 5 to 8 years of age. Baseline caries, mean active caries surfaces: G1 2.56; G2 2.25; G3 2.12 Fluoridation status: not reported Use of fluoride toothpaste: not reported Number randomised: 48 children (unclear how many in each group) Number evaluated at 12 months: G1 16 children; G2 15 children; G3 14 children
Interventions	Comparison 2: different number of applications; different timings of SDF application G1. 38% SDF (Fagamin, Tedequim SRL Argentina), 1‐monthly intervals (baseline, end of month 1, end of month 2, and end of month 3); 4 applications G2. 38% SDF (Fagamin, Tedequim SRL Argentina), 3‐monthly intervals (baseline, end of month 3, end of month 6); 3 applications G3. 38% SDF (Fagamin, Tedequim SRL Argentina), 6‐monthly intervals (baseline, end of month 6); 2 applications
Outcomes	Outcomes included in the review: caries arrest (person‐level, mean active caries surfaces; recorded as arrested when dentine could be be penetrated using tactile assessment; 12 months)
Notes	Funding: self‐funded Study dates: not reported Sample size: calculation not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "randomly allocated" Comment: method not stated
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias) All outcomes	High risk	Different frequency of application according to group. No attempts to blind participants and personnel to group allocation
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Minimal loss to follow‐up at 12 months (3/48), and losses were similar across groups
Selective reporting (reporting bias)	Unclear risk	Study authors do not report whether study was registered in a clinical trials register or whether a protocol was published. It is not feasible to effectively assess risk of selective reporting bias without these documents.
Other bias	Low risk	We identified no other sources of bias

Duangthip 2018.

Study characteristics
Methods	RCT, parallel‐group design 3 arms 30 months' duration
Participants	371 children (2526 tooth surfaces) with at least 1 anterior or posterior primary tooth with untreated active dentine caries, not involving pulp (ICDAS codes 3 to 6). From 16 kindergartens in Hong Kong, China SES: high caries‐risk children: at least 55% in low family monthly income Sex: not reported by group. Overall, 60% were boys Age, mean (SD): 41 (± 4) months Caries at baseline, mean (SD): 3.7 (± 3.5) dmft, 5.6 (± 6.8) dmfs score Fluoridation status: fluoridated area (0.5 ppm) Use of fluoride toothpaste: > 80% using fluoridated toothpaste Number randomised: G1 124 children; G2 122 children; G3 125 children Number evaluated at 30 months: G1 101 children; G2 102 children; G3 106 children
Interventions	Comparison 2: different timing of applications. Comparison 3: SDF versus other topical treatments (FV) G1. 30% SDF (Cariestop, Biodinamica, Brazil); 3 applications at 12‐monthly intervals: baseline, 12 and 24 months (n = 124 children; 880 caries lesions) G2. 30% SDF (Cariestop, Biodinamic, Brazil); 3 applications at weekly intervals: baseline, 1 and 2 weeks (n = 122 children; 799 caries lesions)* G3. 5% sodium FV (Duraphat, Colgate Palmolive, USA); 3 applications at weekly intervals: baseline, 1 and 2 weeks (n = 125 children; 847 caries lesions)* *Placebo (water) applied in G2 and G3 at 12 month follow‐ups. Unclear if water applied to G1 at 1 and 2 weeks to mimic procedures from G2 and G3
Outcomes	Outcomes included in the review: caries arrest and secondary prevention of caries (using ICDAS system, visual and tactile examination; 18 months); adverse events
Notes	Funding: University of Hong Kong Study dates: not reported Sample size calculation: 90 children needed in each group Data included from publications Duangthip 2016 and Duangthip 2018. Duangthip 2018 used as primary reference.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: computer‐stratified randomisation Quote: "randomization process was carried out confidentially by a research assistant who held the random allocation list and prepared the materials according to the child’s assigned group"
Allocation concealment (selection bias)	Low risk	Randomisation list was concealed from all treatment providers and examiner, children, teacher and parents
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "a dentist who was not involved in the examination of the children applied the fluoride agents according to the child's group allocation." Comment: a placebo was used to mimic SDF applications for G1. Staining may influence brushing practice and result in potential bias when comparing SDF to varnish.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The examiner did not know the subjects’ group allocation." Comment: detection bias would be low risk for SDF vs SDF comparison, but high risk for other SDF vs FV owing to staining.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Loss to follow‐up similar in all 3 groups (G1 19% dropout; G2 16% dropout; G3 15% dropout)
Selective reporting (reporting bias)	Unclear risk	Retrospectively registered with a clinical trials register (NCT02426619). It is not feasible to use retrospectively written documents to effectively assess risk of selective reporting bias. Study authors do not report whether a study protocol was published.
Other bias	Low risk	We identified no other sources of bias

Ericson 2023.

Study characteristics
Methods	RCT, parallel design 2 arms 12 months
Participants	356 older adults living in nursing homes in Scania Region of Sweden, aged ≥ 70 years, with ≥ 1 exposed root surface on teeth 15, 14, 13, 23, 24, or 25. Exclusion criteria: people with ≥ 4 caries lesions requiring restoration (because people with higher caries activity were outside the therapeutic limit of the intervention and at higher risk to losing several teeth due to caries on non‐target surfaces); not cognitively capable of understanding the purpose of the study and the meaning of informed consent. SES: not reported Sex: not reported Age, mean (SD): 87.7 (± 6.3) years Baseline caries: 20.4 (± 5.7) existing teeth, 2.9 (± 3.4) decayed teeth Fluoridation status: not reported Use of fluoride toothpaste: not reported Number randomised: G1 174 adults (495 surfaces); G2 182 adults (594 surfaces) Number evaluated at 12 months: G1 135 adults (339 surfaces); G2 138 adults (345 surfaces)
Interventions	Comparison 1: SDF versus placebo/no treatment G1: plaque removal, cleaned root surfaces of included teeth were dried with cotton gauze and dry filled with cotton rolls. 38% SDF (Advantage Arrest Silver Diamine Fluoride 38%, Advantage Arrest, LCC, Redmond, USA) applied to root surfaces; single application G2: plaque removal, cleaned root surfaces of included teeth were dried with cotton gauze and dry filled with cotton rolls. Placebo (tap water) applied to root surfaces Both groups: all participants received regularly routine oral healthcare during the study period, including professional tooth cleaning, FV application, and dietary advice and OHI. G1 had 4.1 (± 1.3) dental hygienist visits and 2.1 (± 1.3) dentist visits; G2 had 4.0 (± 1.5) dental hygienist visits and 2.0 (± 1.3) dentist visits.
Outcomes	Outcomes included in the review: primary caries prevention and secondary prevention of caries (change in root caries score according to modified Nyvad criteria (new caries or caries progression +1; no change 0; caries regression or inactivation −1). Mean score per participant (e.g. if participants had 2 surfaces with progression and 2 inactive surfaces, this would be recorded as no change; method of assessment was not reported; 12 months); adverse effects
Notes	Funding: supported by grants from Odontologisk Forskning Region Skåne and Faculty of Odontology, Malmő University Declarations of interest: study authors declared no conflicts of interest Study dates (recruitment): January 2017 to October 2018
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation
Allocation concealment (selection bias)	Low risk	Allocation sequence stored at a separate location and not managed by the person applying treatments. Participant assigned to group by opening a sequentially numbered, opaque, sealed envelope.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Dental hygienists aware of allocation. Although participants were blinded to treatment, black staining on teeth treated with SDF could influence oral hygiene behaviour. In addition, we note that participants had access to other dental treatments throughout the study period and, although number of dental visits were comparable, we could not be certain whether treatments during these visits were comparable. Personnel conducting additional dental healthcare checks and treatment were aware of group allocation.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Although outcome assessors were blinded to allocation, we expected that staining on teeth would mean that they would be aware of allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Most losses owing to death, which is expected in this age group. Losses were relatively balanced between groups and other types of losses (discontinuation of treatment) were few.
Selective reporting (reporting bias)	Low risk	Prospective clinical trials registration (EudraCT Number: 2015‐005300‐29). Outcome on clinical trials register is caries incidence rather than change in caries, but as this is comparable, we have judged this to be low risk of selective reporting bias
Other bias	Low risk	We identified no other sources of bias

Fahmi 2019.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 6 months' duration
Participants	40 primary school children aged 5 to 7 years with at least one active caries lesion with exposed dentine (level 3 ‐ but scoring system not specified); healthy medical history. In Iraq (setting not reported but "participants were private paediatric dental clinic patients"); the study authors' listed affiliations are universities Exclusion: sensitivity to SDF or other heavy‐metal ions; gingival ulceration; tooth abscess SES: not reported Sex: not reported Age, mean: 45% participants were 5 years; 55% participants were 7 years (not reported by group) Baseline caries: not reported by group, but inclusion criterion was score of 3 Fluoridation status: not reported Use of fluoride toothpaste: not reported Number randomised: G1 20 children; G2 20 children Number evaluated at 6 months: G1 19 children ; G2 19 children
Interventions	Comparison 1: SDF versus placebo G1: 1 drop of 38% SDF applied for each lesion and left for 2 mins; study reports application at 6‐monthly intervals. We note that study follow‐up is at 6 months G2: placebo as above
Outcomes	Outcomes included in the review: caries arrest (participant level); no details reported of definition or method of assessment
Notes	Funding: "self‐funding" Declaration of interests: "The authors have no conflict of interest" Study dates: February 2018 to October 2018 Sample size: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "They were divided into two groups, 19 children randomly treated with placebo (liquid A), and 19 treated with (liquid B) SDF" Comment: insufficient information on the method of randomisation
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not possible due to the nature of the interventions being evaluated
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not possible due to the nature of the interventions being evaluated
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only 1 participant per group lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	No details of any trial registration so not possible to determine whether there were outcomes that were measured but not reported
Other bias	Low risk	We identified no other sources of bias

Fung 2018.

Study characteristics
Methods	RCT, parallel‐group design 4 arms 30 months' duration
Participants	888 healthy children, 3 to 4 years old with at least 1 soft carious lesion at the dentine level (anterior and posterior primary teeth). Recruitment from 37 kindergartens in Hong Kong, China SES: monthly family income < HKD 10,000: G1 37%; G2 37%; G3 38%; G4 41%. Monthly income HKD 10,000 to HKD 20,000: G1 37%; G2 31%; G3 35%; G4 31%. Monthly income > HKD 20,000: G1 26%; G2 32%; G3 27%; G4 28% Sex: G1 60% male, G2 59% male, G3 60% male, G4 55% male Age, mean: 3.8 years Baseline caries, mean: 3.84 dmft; 5.15 dmfs Fluoridation status: fluoridated area (0.5 ppm) Use of fluoride toothpaste: > 50% reported use of fluoridated toothpaste Number randomised: G1 222 children (1051 surfaces); G2 222 children (1072 surfaces); G3 222 children (1073 surfaces); G4 222 children (1024 surfaces) Number evaluated at 30 months: G1 198 children (927 surfaces); G2 203 children (987 surfaces); G3 202 children (971 surfaces); G4 196 children (905 surfaces)
Interventions	Comparison 2: different frequency of SDF applications; different concentrations of SDF G1. 12% SDF (Cariostop, Biodinamica Quimica) applied every 12 months (n = 222 children, 1051 surfaces) G2. 12% SDF( Cariostop, Biodinamica Quimica) applied every 6 months (n = 222 children, 1072 surfaces) G3. 38% SDF (Saforide, Toyo Seiyaku Casei) applied every 12 months (n = 222 children, 1073 surfaces) G4. 38% SDF (Saforide, Toyo Seiyaku Casei) applied every 6 months (n = 222 children, 1024 surfaces) Note: placebo given in G1 and G3 for 6‐monthly applications
Outcomes	Outcomes included in the review: caries arrest (surface‐ and participant‐level; diagnosed at the cavitation level using visual and tactile assessment; a caries lesion was diagnosed as arrested if its surface was smooth and hard on probing; 30 months); adverse effects
Notes	Funding: Research Grants Council of Hong Kong Study dates: recruitment September 2009 to November 2010; last follow‐up examination in May 2013 Sample size calculation: minimum of 565 caries lesions in 188 children/group needed. 222 children/group recruited
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A list of random allocation numbers was generated by computer using a stratified randomization method based on the aforementioned disease severity level with a block size of 8"
Allocation concealment (selection bias)	Low risk	Quote: “After screening at baseline, a dental assistant enrolled the participant children. Before randomisation the children were put into strata (see above)...The assistant who performed the random allocation of study children also prepared the treatment materials. The bottles were wrapped in aluminium foil and coded.”
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "An independent dentist who was blind to the children’s group allocation applied SDF or placebo on the caries lesion. For groups 1 and 3, normal saline was applied as placebo at the semiannual visits to blind the study children." Participants were blinded to the solutions.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: “Follow‐up examinations were performed every 6 mo [months] by the same trained examiner who was blinded to the treatment group allocation.” Comment: as SDF was in all study groups, staining was not considered a problem.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Loss was reasonably balanced between groups (ranging from 9% to 12%), with reason given for all losses as "moving to another kindergarten"
Selective reporting (reporting bias)	Unclear risk	The trial protocol was retrospectively registered (NCT02385474). It is not feasible to use retrospective documents to assess risk of selective reporting bias.
Other bias	Low risk	We identified no other sources of bias

Gao 2019.

Study characteristics
Methods	Non‐inferiority RCT, parallel‐group design 2 arms 18 months' duration
Participants	1070 schoolchildren, 3 to 4 years old healthy children with at least 1 untreated active dentine carious lesion (anterior and posterior primary teeth). Children recruited from kindergartens in Hong Kong, China SES: monthly income ≤ HKD 20,000: G1 57%; G2 59%. Monthly income HKD 20,001 to 40,000: G1 34%; G2 29%. Monthly income > HKD 40,000: G1 10%; G2 12% SES: mother's education level (higher education): G1 68%; G2 66% Sex: G1 55%; G2 55% male Age, range: 3 to 4 years Caries at baseline, mean (SD): 5.96 (± 6.11) dmft in G1; 5.87 (± 6.26) dmft in G2 Fluoridation status: fluoridated area (0.5 ppm) Use of fluoride toothpaste: number of children using fluoridated toothpaste not reported, but used to inform multilevel logistic regression of confounding factors on caries arrest Number randomised: G1 535 children; G2 535 children Number evaluated at 18 months: G1 476 children; G2 484 children. ITT ‐ G1 535 children, G2 535 children
Interventions	Comparison 3: SDF versus other topical treatments (AgNO3 + FV) G1: 38% SDF (Saforide, Toyo Seiyaku Kasei Co) applied every 6 months, followed by a placebo varnish (Vaseline; Unilever); applications at baseline, 6, 12, and 18 months (n = 535 children) G2: 25% AgNO3 (Gordon Labs)+ 5% NaF (Duraphat Varnish; Colgate Palmolive) applied every 6 months (n = 535)
Outcomes	Outcomes included in the review: caries arrest (surface‐level; tactile assessment; 18 months); adverse effects
Notes	Funding: General Research Fund of the University Grant Council Hong Kong Study dates: March 2013 to March 2016 (taken from clinical trials register) Sample size calculation: minimum of 856 children were required in total, 1070 were recruited ITT ‐ last observation carried forward used for imputing missing data; adjusted OR given
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A stratified block randomisation ‐ computer‐generated randomisation
Allocation concealment (selection bias)	Low risk	An independent assistant conducted the random allocation procedure.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "The examiner, study children, and their caretakers were blinded to the treatment allocation. Treatment was provided by an independent operator after the clinical examination." Comment: however, the staining of the teeth by SDF would have made blinding unlikely.
Blinding of outcome assessment (detection bias) All outcomes	High risk	The examiner was blinded; however, the staining of the teeth by SDF would have made blinding unlikely.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The dropout rate after 18 months was 11.0 % in G1 and 9.5% in G2. Reasons for follow‐up were explained. ITT analysis was performed.
Selective reporting (reporting bias)	Unclear risk	Retrospective clinical trials registration (NCT02385474; registered part‐way through the study). It was not feasible to effectively assess risk of selective reporting bias from these documents.
Other bias	Low risk	We identified no other sources of bias

Jiang 2022.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 24 months' duration
Participants	194 preschool children from 9 kindergartens in Hong Kong, generally healthy, with ≥ 1 cavitated dentine caries lesion Exclusion criteria: children with serious systemic disease or condition; uncooperative during examination or treatments; teeth with signs of pulpal pathology (e.g. having an abscess) SES (parents not completed secondary school/completed secondary school/tertiary non‐degree course/university degree programme/missing information): G1 30/123/28/17/4; G2 26/105/29/21/5 Sex, male: G1 57.4%; G2 62.4% Age: not reported Baseline caries, mean (SD): G1 4.6 (± 3.6) dmft; G2 4.6 (± 3.3) dmft Fluoridation status: not reported (it is known from other studies in Hong Kong, that this is a fluoridated area with 0.5 ppm) Use of fluoride toothpaste: not reported Number randomised: G1 101 children; G2 93 children Number evaluated at 24 months: G1 88 children; G2 84 children
Interventions	Comparison 1: SDF versus placebo/no treatment G1: SDF (Saforide, Toyo Seiyaku Kasei Co, Osaka, Japan); single application G2: placebo (tonic water) All groups: 10 weeks after application of SDF or placebo, ART restorations were placed on all cavitated caries lesions following standard practice.
Outcomes	Outcomes included in the review: none Note: we did not include outcome data from this study in the review. The study aimed to evaluate the success of restorations (ART) given after SDF or control treatment rather than the prevention of caries or caries arrest. In addition, we judged that data for parental satisfaction more closely related to the treatment with ART.
Notes	Funding: not reported Declarations of interest: study authors declare no conflicts of interest Study dates: October 2017 to March 2020
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block randomisation, generated list of random numbers managed by independent statistician who was not involved in the trial
Allocation concealment (selection bias)	Low risk	Quote: "Dental assistants followed the random‐number list to dip dental micro‐applicators in either SDF or tonic water, and then passed the micro‐applicators to the dentists, so as to achieve the allocation concealment"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Dentists were blinded to treatment allocation (dental assistants followed random number lists and passed applicators pre‐dipped in allocated solution to the dentist). Although participants were blinded to allocation, treatment was likely apparent owing to staining caused by SDF
Blinding of outcome assessment (detection bias) All outcomes	High risk	Because of the staining caused by SDF, it is likely that outcome assessors would be aware of allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Participant loss was 13/101 in the SDF group and 9/93 in the control group. Losses were mostly owing to children moving schools and no longer contactable.
Selective reporting (reporting bias)	Unclear risk	Retrospective clinical trials registration (NCT03657862) and no protocol. It was not feasible to use the clinical trials details to assess risk of selective reporting bias
Other bias	Low risk	We identified no other sources of bias

Li 2017.

Study characteristics
Methods	RCT, parallel‐group design 3 arms 30 months' duration
Participants	323 older adults, aged 56 to 85 years, with at least 5 teeth with exposed root surfaces and not indicated for extraction. For caries arrest, 83 older adults (157 root caries lesions) were identified. Participants were living in the community and had self‐care abilities for normal daily activities, recruited from social centres for older people, located in different districts of Hong Kong, China. SES: not reported Sex: not reported by group. Overall, 22% were men and 78% were women Age: not reported by group. Overall, mean (SD) 72.1 (± 6.3) years Caries level at baseline: mean of 41.2 exposed sound root surfaces and mean DFS root score of 1.1 Fluoridation status: fluoridated area (0.5 ppm) Use of fluoride toothpaste: all participants received 1450 ppm fluoride toothpaste Number randomised: For prevention ‐ G1 107 adults; G2 108 adults; G3 108 adults For arrest ‐ G1 31 adults (55 surfaces); G2 30 adults (62 surfaces); G3 22 adults (40 surfaces) Number evaluated at 30 months: For prevention‐ G1 95 adults; G2 82 adults; G3 80 adults For arrest ‐ G1 27 adults (40 surfaces); G2 24 adults (40 surfaces); G3 16 adults (20 surfaces)
Interventions	Comparison 1: SDF versus placebo G1. 38% SDF (Saforide, Tyo Seiyaku Kasei Co. Ltd, Osaka, Japan) applied every 12 months (at baseline, 12 months, 24 months) G2. 38% SDF (Saforide, Tyo Seiyaku Kasei Co. Ltd, Osaka, Japan) + KI applied every 12 months (at baseline, 12 months, 24 months) G3. Placebo control, soda water with a bitter flavour (to mimic the bitter metallic taste of SDF) applied every 12 months Individualised OHI, and provision of fluoride toothpaste (1450 ppm) were given to all study participants at each examination. Note: we did not include data for G2 in analysis
Outcomes	Outcomes included in the review: primary prevention of caries (new root caries experience, status evaluated using ICDAS, visual and tactile assessment; surface‐level; 30 months); caries arrest (arrest of root caries; surface‐level; 30 months), adverse effects (reported as harmful effects, or injury to teeth or gums), aesthetics (reported as complaints of staining)
Notes	Funding: Hong Kong Research Grants Council Study dates: April 2012 to March 2015 Sample size: a minimum of 80 participants in each group required, with aim to recruit 100 participants in each group. 323 participants recruited in total; 83 participants were recruited for caries arrest assessment. Note: there are two references for this study. The prevention data is provided in 2017 paper, and the arrest data in the 2016 paper
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "randomly allocated to three groups using block randomization. A list was produced with a block size of 6 which contained 90 different combinations."
Allocation concealment (selection bias)	Low risk	Quote: “A dental surgery assistant carried out the subject allocation according to the combinations randomly generated by computer.”
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Both the examiner and the subjects were blinded to group assignment." Comment: however, staining may influence brushing behaviour
Blinding of outcome assessment (detection bias) All outcomes	High risk	Although study states that “both the examiner and the subjects were blinded to group assignment", it is not possible to blind outcome assessors because of staining associated with SDF
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote (primary prevention participants): "After 30 mo [months], 257 (80%) subjects remained in the study. The subject dropout rate of the SDF group was lower than that of the other 2 groups (11% vs. 25%; χ2 test, P = 0.014)" Quote (caries arrest participants): “The drop‐out rates of subjects and caries lesions in the three groups were not significantly different (χ2 test, p > 0.05).” Participant dropout proportion at 30 mon months] was 27.3%, 12.9% and 20% in control, SDF and SDF+KI groups. Quote: “the retention rate of [older adult participants] who had more root caries lesions was lower...so the study results might be biased towards the [older adults] who were more concerned about their oral health.”
Selective reporting (reporting bias)	Unclear risk	The protocol registration reports that the primary outcome measure is the number of new tooth root caries lesions; fully reported in Li 2017. The number of arrested caries is reported in Li 2016 (secondary ref to Li 2017). However, we note that clinical trials registration was completed retrospectively (NCT02360124) and it is not feasible to use these documents to effectively assess risk of selective reporting bias.
Other bias	Low risk	We identified no other sources of bias.

Liu 2012.

Study characteristics
Methods	RCT, parallel‐group design 4 arms 24 months' duration
Participants	501 school children, grades 2 to 3, with at least 1 sound permanent first molar with deep fissures or fissures with signs of early (enamel) caries viewed as wet, with opacities and discolouration, similar to ICDAS code 2. Recruited from 4 primary schools in Guangzhou, China SES: not reported Sex: G1 55% male; G2 45% male; G3 44% male; G4 54% male Age, mean: 9.1 years Baseline caries: not reported Fluoridation status: non‐fluoridated water Use of fluoride toothpaste: approximately 90% of toothpastes on sale contained fluoride Number randomised: G1 125 children (390 teeth); G2 124 children (371 teeth); G3 124 children (385 teeth); G4 128 children (393 teeth) Number evaluated at 24 months: G1 121 children (378 teeth); G2 121 children (367 teeth); G3 116 children (358 teeth); G4 124 children (379 teeth)
Interventions	Comparison 1: SDF versus placebo. Comparison 3: SDF versus other topical treatments. Comparison 4: SDF versus sealants G1. 38% SDF (Saforide, Toyo Siyaku Kasei Co. Ltd, Osaka, Japan) applied every 12 months (n = 125 children, 390 teeth) G2. Resin sealant (Clinpro Sealant, 3M ESPE, St Paul, Minnesota, USA) (n = 124 children, 371 teeth) G3. 2.5% NaF varnish (Duraphat Colgate Palmolive Ltd, Waltrop, Germany) applied every 6 months (n = 124 children, 385 teeth) G4. Placebo (water) every 12 months (n = 128 children, 393 teeth)
Outcomes	Outcomes included in the review: primary caries prevention (prevention of dentine caries in permanent first molars; visual and tactile assessment; site‐, tooth‐ and participant‐level data available; 24 months); adverse effects
Notes	Funding: Hong Kong Research Grants Council Study dates: December 2007 to December 2010 (information taken from clinical trials register) Sample size: minimum of 950 teeth were required, 501 children and 1539 teeth recruited ORs taking clustering into account available in study report
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “An assistant, using computer‐generated random numbers, allocated the children individually among four groups.”
Allocation concealment (selection bias)	Low risk	Cochrane (Dental sealants review) additional information obtained from the author says Low and justifies: We used information obtained in another Cochrane Review to support this judgement (Kashbour 2020): “computer generated random number table (only consisting of numbers 1, 2, 3, and 4) was printed out and kept by a research assistant. The group allocation of the subject, i.e. group 1 to group 4 followed the random numbers in the random number table. The treatment was performed immediately on site by a dentist not involved in the examination of the children according to the group allocation while the research assistant was present.”
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Water was used as a placebo and applied at the same interval as the SDF solution. Thus, blinding may have been effective for the comparison between SDF and placebo. However, blinding for the comparisons: SDF versus NaF varnish and SDF versus sealant was probably not achieved."
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: “Follow‐up examinations were conducted every 6 months by a masked examiner.” Comment: however, due to the likelihood of staining from SDF, blinding may not be feasible.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The flowchart shows that participant loss to follow‐up was 1.6%, 2.4%, 5.6% and 3.1% in SDF, sealant, NaF varnish and placebo groups, respectively. Loss to follow‐up of teeth was 1.5%, 1.1%, 6.2% and 3.6% in SDF, sealant, NaF varnish and control groups, respectively. Although there is an imbalance between groups, rates of loss are low and reasons for withdrawal seem to be unrelated to the outcome (moved from school or absent on day of examination).
Selective reporting (reporting bias)	Unclear risk	Study is retrospectively registered in a clinical trials register (NCT01446107). It is not feasible to effectively assess risk of reporting bias using retrospective documents.
Other bias	Low risk	We identified no other sources of bias

Llodra 2005.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 36 months' duration
Participants	425 school children. Santiago de Cuba, Cuba. Active caries in primary canines and posterior teeth; erupted permanent first molar teeth SES: not reported Sex: not reported Age, mean (SD): 6.29 (± 0.48) years Baseline caries, mean (SD): G1 3.6 (± 0.2) dmfs; G2 3.5 (± 0.3) dmfs Fluoride toothpaste: non‐fluoridated water (0.09 ppm) Use of fluoride toothpaste: extremely limited availability of fluoride toothpastes ("during term time, mouthrinses every 2 wks [weeks] with 0.2% sodium fluoride") Number randomised: G1 225 children; G2 227 children Number evaluated at 36 months: G1 180 children; G2 193 children
Interventions	Comparison 1: SDF versus no treatment G1. 38% SDF (Flouroplat Laboratories Naf, Buenos Aires, Argentina) applied every 6 months (n = 225 children) G2. No treatment (n = 227 children)
Outcomes	Outcomes included in the review: primary prevention of caries (reported as new dental caries on first molars, dmft; surface level); caries arrest (arrest of coronal caries on primary teeth; surface level). Caries diagnosis by visual and tactile assessment; 36 months Note: study also reported loss of tooth vitality
Notes	Funding: local government of the Balearic Islands Study dates: February 2000 to March 2003 Sample size: undertaken but not fully reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Information from study author: “For every 10 children we had a new random sequence (from random tables) with 5 children being test and 5 controls). This was done to get similar samples in both groups. The reason for not having exactly the same number of children was because this strategy was started in the schools more than once (i.e. primary school children or secondary).”
Allocation concealment (selection bias)	Low risk	Quote: “The schoolchildren were assigned on an individual random basis to the SDF or control group by a third researcher ensuring that the examiners were blinded to the group of each child.”
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding not feasible due to nature of the comparison
Blinding of outcome assessment (detection bias) All outcomes	High risk	Due to the nature of the different techniques and the potential staining of SDF‐treated teeth, blinding was not possible. However, the study authors report that "Examiners were blinded to the group of each child. … It could be argued that black stains, much more frequent in the SDF group, compromised the blinded nature of the analysis. However, numerous black stains also appeared in the control group, making it impossible for the examiner to know the group of the child on this basis."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: “The entire study period was completed by 373 schoolchildren (82%). Forty‐five children (20%) were lost to the follow‐up in the SDF group and 34 (15%) in the control group." Comment: although the reason for loss was not reported, we judged attrition to be relatively low and reasonably balanced between groups
Selective reporting (reporting bias)	Unclear risk	Study authors do not report details of a protocol or clinical trials registration. It is not feasible to effectively assess risk of selective reporting bias without these documents.
Other bias	Low risk	We identified no other sources of bias.

Mabangkhru 2020.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 12 months' duration
Participants	302 healthy children (2249 lesions), aged 1 to 3 years, with at least 1 cavitated lesion on anterior or posterior teeth. Children registered with 19 public development centres/child care centres, Fang District, Chaing Mai Province, Thailand SES: family income (> 10,000 Baht): G1 36 %; G2 50%. Mother education (college/university): G1 11%; G2 11% Sex: G1 60% male; G2 54% male Age, mean (SD): 36.8 (± 6.4) months Baseline caries, mean (SD) 5.3 (± 3.6) dmft; 9.2 (± 9.0) dmfs Fluoridation status: water fluoride concentration: ≤ 0.3 ppm Use of fluoride toothpaste: > 90% used fluoride toothpaste Number randomised: G1 153 children, 1111 surfaces; G2 149 children, 1138 surfaces Number evaluated at 12 months: G1 130 children, 957 surfaces; G2 133 children, 951 surfaces
Interventions	Comparison 3: SDF versus other topical treatments G1. 38% SDF (Topamine DentaLife, Australia) applied every 6 months (n = 153 children, 1111 surfaces) G2. 5% NaF varnish (Duraphat, Colgate Palmolive) applied every 6 months (n = 149 children, 1138 surfaces)
Outcomes	Outcomes included in the review: caries arrest (lesion‐level; smooth and hard surface that could be easily penetrated; 12 months); aesthetics (parental satisfaction with children's dental appearance) Note: study authors reported data adjusted for clustering
Notes	Funding: Mahidol University Faculty of Dentistry Grant Study dates: recruitment started in June 2018 (end date is not reported; information taken from clinical trials register) Sample size: a minimum of 343 dentine carious tooth surfaces were required/group; 302 children with 2249 active dentine carious tooth surfaces recruited The majority of the children were on milk feeding (81.1%) and brushed their teeth at least once a day (90.6%) with fluoride toothpaste (91.4%).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "stratified block randomization method with two strata of the severity of caries experience in a block size of 4."
Allocation concealment (selection bias)	Low risk	Quote: "allocation list was kept in opaque sealed envelopes and arranged sequentially by a dental assistant who was not involved in the study. Each envelope was opened after completing the oral exam and before application of the fluoride treatment"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: “Topical applications of...were carried out by 2 dental nurses who were not included in the screening and assessing of the lesion activity” Comment: staining may influence brushing behaviour.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Although examiner was blinded to the group assignment, staining of lesions in SDF group is considered a problem.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The dropout rate was 15% in the SDF group and 10.7% in the NaF group. In most cases, the reason for loss was because participants had moved. We judged loss to be relatively low and reasonably balanced between groups.
Selective reporting (reporting bias)	Low risk	Review primary outcomes (caries arrest) were reported in prospective clinical trials registration (TCTR20180624001).
Other bias	Low risk	We identified no other sources of bias

Mattos‐Silveira 2015.

Study characteristics
Methods	RCT, parallel‐group design 3 arms 12 months' duration
Participants	141 school children, 3 to 10 years, with at least 1 active initial caries lesion on approximal surface of the primary molars. Children were attending dental school clinic in São Paulo, Brazil SES: not stated in translation Sex: 48% male Age, mean (SD): 6.56 (± 1.69) years Baseline caries: not stated in translation Fluoridation status: not stated in translation Use of fluoride toothpaste: not stated in translation Number randomised: G1 47 children (108 surfaces); G2 47 children (112 surfaces), G3 47 children (96 surfaces) Number evaluated at 12 months: G1 40 children (94 surfaces), G2 32 children (82 surfaces), G3 35 children (72 surfaces)
Interventions	Comparison 1: SDF versus placebo. Comparison 4: SDF versus sealants G1. 30% SDF; single application (n = 47 children) G2. Placebo (n = 47 children) G3. Caries resin infiltration (n = 47 children) All groups received instruction about flossing.
Outcomes	Outcomes included in the review: secondary prevention of caries (coronal caries; visual and tactile examination according to ICDAS criteria; surface level; 12 months) Note: this study reported data for discomfort during the procedure. We did not include this as data for the pain outcome because this 'discomfort' was transient and associated only with the procedure
Notes	Funding: Pro‐Reitoria de Pesquisa da USP, FAPESP, CNPQ and CAPES (abbreviations not defined in study report) Declarations of interest: study authors declare no conflicts of interest Study dates: January 2012 to October 2018 Sample size calculation: study authors reached a final sample size of 504 surfaces (on average, 168 surfaces per group). Only the control group had, at baseline, the minimum number of surfaces as per the calculated sample size required to achieve 80% power (112 surfaces). Data from publication and translation from original report
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The individuals will be randomly allocated to each group according to a sequence obtained in appropriate statistical software"
Allocation concealment (selection bias)	Low risk	Quote: "The generated sequence will be distributed in opaque and sealed envelopes, which will be opened by the operators only at the moment of the interventions."
Blinding of participants and personnel (performance bias) All outcomes	High risk	Due to the nature of the comparison, blinding not feasible
Blinding of outcome assessment (detection bias) All outcomes	High risk	Examiners were not aware of the intervention. However, due to the staining associated with SDF, full blinding not feasible
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "At 12 months loss to follow‐up was almost similar in the three groups: 14.9%, 17.0% and 12.8% in the SDF, resin infiltration and toothbrushing groups respectively. However, at 24 months, missing outcome data was not balanced in numbers across groups: loss to follow‐up was 14.9%, 25.5% and 31.9% in the SDF, resin infiltration and toothbrushing groups respectively. Reasons for loss to follow‐up were similar in the three groups but we don’t know whether, at baseline, children analysed were similar to children randomised."
Selective reporting (reporting bias)	Low risk	Primary review outcomes (secondary prevention) are reported in clinical trials registration documents (NCT01477385; registered shortly after start of study recruitment)
Other bias	Low risk	We identified no other sources of bias

Mendiratta 2021.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 6 months' duration
Participants	82 high‐caries‐risk intellectually disabled individuals with up to 3 active enamel or dentinal caries lesions in permanent posterior teeth (Nyvad Score 2 or 3), in 5 special institutions for intellectually disabled individuals in Rohtak, Haryana, India Exclusion criteria: people who had teeth with presence of an abscess or sinus, obvious discolouration, premature hypermobility, already restored, dislodged restoration, secondary caries, arrested caries, with reduced mouth opening and a large tongue, or pulpal involvement SES: upper class: G1 = 3 (7.3%); G2 = 0 (0%) upper middle: G1 = 6 (14.6%); G2 = 10 (24.4%) lower middle: G1 = 12 (29.3%); G2 = 11 (26.8%) upper lower: G1 = 18 (43.9%); G2 = 16 (39%) lower: G1 = 2 (4.9%); G2 = 4 (9.8%) Sex: G1 80.5% male; G2 78% male Age, mean (SD): G1 15.2 (± 4.3) years; G2 17.6 (± 5.5) years Baseline caries: not reported by group, but inclusion criterion was Nyvad score of 2 or 3 Fluoridation status: not reported Use of fluoride toothpaste: > 90% brushed with fluoride dentifrice daily Number randomised: G1 41 people (91 teeth); G2 41 people (91 teeth) Number evaluated at 6 months: G1 41 people (91 teeth); G2 41 people (91 teeth)
Interventions	Comparison 5: SDF versus restorative treatment (GIC + FV) G1: visible debris removed from enroled teeth and air dried before 38% SDF (44,800 ppm) applied to all surfaces (both carious and sound) of the enroled carious teeth for 1 minute with a microbrush; single application G2: carious lesion of enroled teeth excavated with spoon excavator and then restored with high fluoride‐releasing, high‐viscosity GIC, and then 5% FV (22,600 ppm) on the sound surfaces of those enroled teeth with a microbrush No food or drink for 30 minutes after application in both groups
Outcomes	Outcomes included in the review: caries arrest (tooth level; 6 months); adverse effects G1 defined change in Nyvad score of 2 or 3 (active caries) to score of 5 or 6 (inactive caries) G2 defined change in Nyvad score of 2 or 3 (active caries) to score of 7 (restoration) Note: any treated surface in either group showing active lesion or dislodged restoration (partial/complete) at 6‐month follow‐up was considered as caries increment and failure of treatment
Notes	Funding: not reported Conflicts of interest: "no conflicts of interest" Study dates: April 2019 to November 2019 Sample size: 120 carious teeth per group needed. Therefore, 41 people per group randomised on the assumption that each person would have 3 active lesions; calculated based on anticipated 12‐month caries arrest rate of 38% SDF and GIC (reported in the literature as 81% and 65% respectively); absolute difference of 16% in caries arrest rate (obtained from the literature) considered clinically significant between groups; 5% significance and 80% power We used the hazard ratio presented in Table 3 of the study report, assuming the negative sign indicates the value stated is ln(OR)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The study participants after recruitment were initially divided into two groups based on number of decayed teeth with a cut off of 3; the assessment sheets were numbered sequentially in both the groups and participants from each group were further categorized into two treatment arms, that is, SDF and GIC using online random number generation software"
Allocation concealment (selection bias)	Low risk	Quote: "participants from each group were further categorized into two treatment arms, that is, SDF and GIC using online random number generation software by another investigator to ensure allocation concealment"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not possible due to the nature of the interventions being evaluated
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not possible due to the nature of the interventions being evaluated
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All data reported despite the study stating that 10/41 in G1 and 3/41 in G2 were lost to follow‐up. ITT appears to have been carried out but this is not stated in the study report so assumptions cannot be checked.
Selective reporting (reporting bias)	Unclear risk	Study not registered and protocol not available so unable to check if all outcomes measured were also reported
Other bias	Low risk	We identified no other sources of bias

Milgrom 2018.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 21 days' duration
Participants	66 healthy preschool children, aged 24 to 72 months, with ≥ 1 untreated cavitated active caries lesion with dentine exposed. Recruited from 3 Head Start programmes in Oregon, USA. SES: not reported Sex, male: G1 55%; G2 49% Age, mean (SD): 4.8 (± 0.6) years Baseline caries: not reported Fluoridation status: not reported Use of fluoride toothpaste: not reported Number randomised: G1 30 children; G2 36 children Number evaluated at 21 days: G1 29 children; G2 35 children
Interventions	Comparison 1: SDF versus placebo G1. 38% SDF (Advantage Arrest, Elevate Oral Care LLC, West Palm Beach, Florida, USA); single application (n = 30 children) G2. Placebo (n = 36 children)
Outcomes	The study reported caries arrest (coronal teeth/surfaces; visual and tactile examination), adverse effects, and changes in microbial species. We did not use caries arrest data in the review because the follow‐up time for this outcome was within 21 days of treatment.
Notes	Funding: NIDCR grant T32‐DE007306 and funds from Advantage Dental Services, LLC, and the NIH National Center for Advancing Translational Sciences through the University of Washington’s CTSA Study dates: February 2016 to May 2016 Sample size: 79 to 100 participants per group. Due to a delay in initiating the study only 66 participants were enroled
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "computer‐generated randomization schedule with stratification by Head Start program and randomly permuted blocks of sizes 2 and 4"
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: ''The dental providers who applied the treatments, participants, and examiners were blinded. Blinding was maintained by dispensing the test and comparator liquids from similar bottles. The test and placebo bottles were assigned codes A, B, C or D with 2 codes for test and 2 codes for placebo. Four bottles were used to strengthen the blinding of treatment, and were otherwise identical" Comment: however, staining associated with SDF may influence brushing behaviour
Blinding of outcome assessment (detection bias) All outcomes	High risk	Examiners were blinded to allocation. However, due to the staining associated with SDF, blinding not feasible.
Incomplete outcome data (attrition bias) All outcomes	Low risk	97% completed follow‐up (1 missing in each group)
Selective reporting (reporting bias)	Unclear risk	Study authors do not report a protocol or clinical trials registration. It is not feasible to effectively assess risk of selective reporting bias without these documents.
Other bias	Low risk	We identified no other sources of bias

Rehim 2021.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 12 months' duration
Participants	62 children (255 carious primary teeth), recruited from the outpatient clinic of Pediatric Dentistry and Dental Public Health Department, Faculty of Dentistry, Cairo University. Children were aged 1 to 6 years. Children had carious primary teeth and were considered to be "high caries risk patients", "uncooperative children" and those experiencing a "financial barrier in accessing dental care" Exclusion criteria: children with spontaneous pain from caries; tooth mobility; pulpal infection SES: high‐caries‐risk children with financial barriers to dental care Sex: G1 65% male; G2 45% male Age range: 1 to 6 years Caries at baseline: not reported Fluoridation status: not reported Use of fluoride toothpaste: children and parents in both groups were advised to brush with fluoride paste following treatment Number randomised: G1 31 children; G2 31 children Number evaluated at 12 months: G1 31 children; G2 31 children
Interventions	Comparison 3: SDF versus other topical treatments G1: 38% SDF applied every 6 months G2: 5% sodium fluoride varnish applied every 3 months Evaluated at baseline, 1, 3, 6, 9 and 12 months Caries assessed via visual tactile examination
Outcomes	Outcomes included in the review: dental pain or sensitivity (number of people with pain; 12 months) Note: although caries arrest is mentioned no data are presented for this (failure includes abscess, pain, infection, swelling). New caries data in study report are not cumulative, and are presented as independent data; therefore, we were unable to use these data.
Notes	Funding: self‐funded Conflicts of interest: none Study dates: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation sequence was computer‐generated
Allocation concealment (selection bias)	Low risk	Sealed opaque envelopes were used to conceal allocation
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding is not possible
Blinding of outcome assessment (detection bias) All outcomes	High risk	It is reported in the study that the outcome assessor was blinded however, SDF was used only in the experimental arm and not in the control meaning that staining is likely to have compromised blinding substantially.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Although some participants were lost to follow‐up at interim time points, all were included in analysis at end of follow‐up
Selective reporting (reporting bias)	High risk	The specified outcome data reported in the paper do not match the trials registry which stated that patient/parent reported discolouration was to be the primary outcome measure. This is not reported in the publication and no results have been posted on the trials registry. All data regarding the clinical outcomes appears fully reported.
Other bias	Low risk	We identified no other sources of bias

Ruff 2022.

Study characteristics
Methods	Cluster‐RCT (by schools) (CariedAway) 2 arms 24 months' duration
Participants	4718 children Inclusion criteria: 2‐stage enrolment. First, eligible primary schools in New York City with overall student population of 80% or higher receiving free or reduced cost lunch and at least 50% of enroled students reporting Hispanic or Latino or Latina ethnicity and/or Black race. Secondly, only children in kindergarten through to grade 3 were included in the analysis, as health data could only be collected on children still enroled at the end of the study. Exclusion criteria: children were excluded if they did not speak English or were enroled in special education classes. SES: low SES due to the selection criteria for schools Sex: G1 49% male; G2 46% male Age, mean (SD): G1 6.6 (± 1.2) years; G2 6.6 (± 1.3) years Baseline caries: untreated decay G1 29% children; G2 31%. Decayed teeth, mean (SD): G1 0.7 (± 1.4), G2 0.7 (± 1.7) Fluoridation status: not reported Use of fluoride toothpaste: not reported Number randomised: G1 2348 children; G2 2370 children Number evaluated at 24 months: G1 611 children; G2 787 children
Interventions	Comparison 5: SDF versus restorative treatment (SDF+ FV versus GIC sealant + restorative treatment + FV) G1: 5% FV applied to all teeth. Asymptomatic cavitated lesions were treated with 38% SDF, SDF also brushed on all pits and fissures of bicuspids and molars G2: 5% FV applied to all teeth. GIC sealants applied to all pits and fissures of bicuspids and molars and placement to atraumatic restorations on all frank asymptomatic cavitated lesions. Treatments were provided in a single application after the baseline exam, and followed up for 24 months
Outcomes	Outcomes included in the review: primary caries prevention (proportion of children with no cumulative incidence of decayed teeth from previously sound dentition; 24 months); caries arrest (proportion of children with all caries arrested, and proportion with arrested caries; visual and tactile assessment; 24 months); adverse effects Note: due to the selected outcomes, there were no clustering issues
Notes	Funding: Award PSC‐1609‐36824 from the Patient Centred Outcomes Research Institute Declarations and conflicts of interest: Dr Neiderman (study author) reported receiving donation of toothpaste, toothbrushes and FV from Colgate, and donation of glass ionomer from GC America. No other disclosures were reported Study dates: start date February 2019; anticipated completion date June 2023 The trial was designed with a noninferiority margin predetermined to be 10% as the maximum clinically relevant difference Published report of interim results
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Consenting schools were listed in ascending order of population size and block randomized in blocks of 4 schools using 1:1 allocation ratio. Allocation sequences were created using a random number generator."
Allocation concealment (selection bias)	Low risk	Quote: "Allocation was performed at the school level and concealed from the participants within each school."
Blinding of participants and personnel (performance bias) All outcomes	High risk	The staining of the SDF made it possible for the patients to determine their group assignment. Clinicians were not blinded due to the nature of the interventions.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Due to the nature of the outcomes blinding of outcome assessment was not possible
Incomplete outcome data (attrition bias) All outcomes	High risk	Although some losses were explained by study authors, we judged rates of attrition in this study to be high in both groups.
Selective reporting (reporting bias)	Low risk	Prospectively published protocol. All outcomes are fully reported.
Other bias	Low risk	We identified no issues with recruitment bias. Loss of clusters and baseline imbalance of clusters were not reported. Study investigators accounted for the effect of clustering within their analysis. We could not evaluate comparability of this study's findings with other RCTs because of differences in intervention design; we reported data separately for this study.

Seberol 2013.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 18 months' duration
Participants	114 children, aged 2 to 7 years, with caries in anterior teeth (1331 teeth). Teeth with enamel or dentine caries were included. Children recruited from the Pediatric Department, Ankara University Faculty of Dentistry, Turkey. SES: not mentioned in translation Sex: 58% male Age: 2 to 7 years Baseline caries, mean (SD): G1 28.5 (± 11.4) dmfs; G2 30.6 (± 9.6) Fluoridation status: unclear Use of fluoride toothpaste: unclear Number randomised: G1 65 children; G2 49 children Number evaluated at 18 months: G1 65 children; G2 49 children
Interventions	Comparison 1: SDF versus placebo G1. 38% SDF (Fagamin, Tedequin SRL, Córdoba, Argentina); single application (n = 65 children) G2. Placebo (saline solution); single application (n = 49 children)
Outcomes	We did not include any outcome data in the review because we could not determine a clear definition of secondary caries, and we could not determine the number of lesions for which caries arrest data were available
Notes	Funding: not reported Study dates: not reported Sample size: minimum of 30 children per group. Information taken from translation of thesis; additional information may be present in original document We did not assess risk of bias in this study because we did not include any outcome data in the review

Sirivichayakul 2023.

Study characteristics
Methods	RCT, parallel‐group design 3 arms 18 months
Participants	190 children from 6 public schools in Thailand, aged 4 to 6 years, able to co‐operate with clinical examination, with ≥ 1 quadrant showing sound contact surfaces of posterior teeth. At the tooth surface level, distal surfaces of the canine or first molar, or the mesial surfaces of the first or second molars showing clinically sound and radiographically sound or initial carious lesion. Initial approximal carious lesions defined as radiolucency confined to the enamel or outer third of dentine (RA1 to RA3 according to ICDAS or ICCMS) Exclusion criteria: history of allergy to fluoride, silver, or colophony agent, had undergone topical fluoride application in previous 6 months, resistant to bite‐wing radiography SES, monthly family income, < 10,000 Thai Bhat/10,000 to 20,000 Thai Bhat/>20,000 Thai Bhat: G1 16/31/17; G2 11/39/12; G3 11/36/17 Sex, male: G1 53.1%; G2 45.2%; G3 51.6% Age, mean (SD): G1 58.7 (± 10.6) months; G2 60.1 (± 10.8) months; G3 61.4 (± 9.8) months Baseline caries, mean (SD): G1 5.5 (± 4.2) dmft, 11.3 (± 12.1) dmfs; G2 5.4 (± 4.8) dmft, 11.4 (± 12.6) dmfs; G3 5.1 (± 4.0) dmft, 10.9 (± 10.5) dmfs Fluoridation status: fluoride concentration in drinking water < 0.03 ppm Use of fluoridated toothpaste: G1 95.3%; G2 91.9%; G3 95.3% Number randomised: G1 64 children (909 approximal surfaces); G2: 62 children (872 approximal surfaces); G3: 64 children (904 approximal surfaces) Number evaluated at 18 months: all participants (and surfaces) as randomised, in ITT analysis
Interventions	Comparison 1: SDF versus placebo/no treatment. Comparison 3: SDF versus other topical treatments G1: 38% SDF (Topamine, Dentalife, Australia), ≤ 1 drop (25 μL), applied at six‐monthly intervals G2: 5% NaF varnish (Duraphat, Colgate Palmolive, USA), ≤ 0.25 mL, applied at six‐monthly intervals G3: placebo (water) All groups: all participants practised teeth cleaning with research team, were given dietary advice and received set of oral health care packages (including toothbrushes, fluoride toothpaste, dental floss, and leaflets on OHE). Treatment was applied in schools by trained dentists.
Outcomes	Outcomes included in the review: primary caries prevention (caries development on sound surfaces); secondary caries prevention (caries development on initially treatment surfaces). Based on radiographic examination; 18 months Note: we emailed the study authors who provided adjusted analyses for sound caries and existing caries
Notes	Funding: Young Researcher Development Program from the National Research Council of Thailand Declarations of interest: study authors declare no competing interests Study dates: March 2019 to October 2020
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Stratified block randomisation in blocks of 6, generated using Excel
Allocation concealment (selection bias)	Low risk	Allocation was managed by an assistant who was not otherwise involved in the trial, handing out sealed envelopes, which were arranged sequentially and opened immediately before the intervention
Blinding of participants and personnel (performance bias) All outcomes	High risk	Although participants and parents were blinded to treatment allocation, we expected that staining would be apparent in the SDF group which could influence toothbrushing behaviour
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcome assessor was blinded to allocation. However, we expected that staining would be apparent on teeth treated with SDF
Incomplete outcome data (attrition bias) All outcomes	Low risk	Participant dropout was owing to moving schools, and relatively balanced between groups. Data reported as ITT
Selective reporting (reporting bias)	Low risk	Study registered in March 2019, shortly after first participant recruitment (TCTR20190315003). Outcomes reported in the published study report are consistent with those in the trials register
Other bias	Low risk	We identified no other sources of bias

Tan 2010.

Study characteristics
Methods	RCT, parallel‐group design 3 arms 36 months' duration
Participants	306 older adults with at least 5 teeth with exposed roots. Recruited from 21 residential and nursing homes, Hong Kong, China SES: not reported Sex: 24% male Age, mean (SD): 78.8 (± 6.2) years Baseline caries, mean DFS: 2.2 (mean number of teeth (SD): 14.0 (± 6.3) Fluoridation status: fluoridated area (0.5 ppm) Use of fluoride toothpaste: not reported Number randomised: G1 72 adults; G2 71 adults; G3 80 adults; G4 83 adults Number evaluated at 36 months: G1 51 adults; G2 48 adults; G3 49 adults; G4 55 adults
Interventions	Comparison 1: SDF versus placebo. Comparison 3: SDF versus other topical treatments (FV; chlorhexidine) G1. 38% SDF every 12 months (n = 72 adults) G2. 1% chlorhexidine varnish every 3 months through study (n = 71 adults) G3. 5% NaF varnish every 3 months through study (n = 80 adults) G4. Placebo (n = 83 adults) All groups received OHI
Outcomes	Outcomes included in the review: primary caries prevention (development of new caries on the exposed sound root surfaces of the participant; mean number of root surfaces with new active caries or restorations was recorded (person level); visual and tactile examination; 36 months)
Notes	Funding: Hong Kong Research Grant Council Study dates: December 2002 to August 2003 Sample size: a minimum of 50 participants in each group required
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A research assistant conducted the random assignment of participants by drawing numbers from a bag. Randomization was conducted at the participant level; thus, participants in the four study groups were evenly distributed among the 21 institutions"
Allocation concealment (selection bias)	Unclear risk	Not enough information to determine the risk
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Blinding was attempted by applying water to the teeth of one of the intervention groups but this would not allow complete blinding and the lack of blinding could influence the toothbrushing behavior of the elderly and/or the care provided to them by personnel in the institutions thus affecting the outcome." Comment: application of the non‐SDF interventions differs and staining associated with SDF may influence brushing behaviour
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote:"Follow‐up examinations were carried out annually by the same independent examiner, who did not know the participant’s group assignment.” “In the follow‐up examinations, examiner blindness was maintained, since the examination took place before the application of agents by another dentist" Comment: however, staining associated with SDF prevents full blinding of outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: “The intention‐to‐treat approach was used.” Comment: at 3 years, the dropout rates were: control 33.7%; CHX 32.4%; NaF 38.8% and SDF 29.2%. Reasons for dropout were given and a comparison of baseline characteristics of subjects randomised and analysed was provided
Selective reporting (reporting bias)	Unclear risk	Study authors do not provide details for a published protocol or clinical trials registration. It is not feasible to effectively assess selective reporting bias without these documents
Other bias	Low risk	We identified no other sources of bias

Torres‐Arellano 2012.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 24 months' duration
Participants	663 school children, aged 6 to 10 years with incipient caries lesions, primary and permanent molars diagnosed with ICDAS 2 to 3 (1430 teeth). Recruited from Schools Independencia and Defensores, Colona Mattamorros, Mexico SES: not reported in translation Sex (male): G1 46% male; G2 52% male Age, median: G1 8.05 years; G2 7.79 years Baseline caries: unclear from translation Fluoridation status: unclear from translation Use of fluoride toothpaste: unclear from translation Number randomised: G1 322 children; G2 341 children (not clearly reported) Number evaluated at 24 months: G1 322 children, 346 primary molars, 407 permanent molars; G2 341 children, 331 primary molars, 346 permanent molars.
Interventions	Comparison 1: SDF versus placebo G1. 38% SDF (Fluroplat, Laboratories NAF, Buenos Aires, Argentina) every 6 months (n = 322 children, 753 teeth) (translation 753 states discrepancy with graphic and written part) G2. Placebo (distilled water) every 6 months (n = 341 children, 677 teeth)
Outcomes	Outcomes included in the review: secondary prevention of caries (number of teeth for which lesions were not progressing; visual and tactile examination; 24 months); adverse effects Note: data reported separately for both primary and permanent teeth
Notes	Funding: not reported Study dates: not reported Sample size: unclear Thesis. Information extracted from a translation. Further detail may be available in the original document Number in Table on page 57 of the study report is incorrect; the number of permanent teeth in the placebo group was 346 not 486.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were assigned to each of the two groups (FDP [SDF] or placebo) in a totally random manner, assigning each subject an identification number."
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias) All outcomes	High risk	The application of SDF and placebo were performed by a different collaborator. However, staining associated with SDF may influence brushing behaviour
Blinding of outcome assessment (detection bias) All outcomes	High risk	Blinded examiner may be influenced by the change in colour of the lesion
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No losses reported, and data are reported for all randomised participants. However, given the size of the study (663 participants) and duration (24 months), we expected that numbers initially recruited were not reported and, therefore, we could not be certain of attrition rates.
Selective reporting (reporting bias)	Unclear risk	Study protocol or clinical trials registration not reported. It is not feasible to effectively assess risk of selective reporting bias without these documents.
Other bias	Low risk	We identified no other sources of bias

Vollú 2019.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 12 months' duration
Participants	68 children, aged 2 to 5 years, with active dentine caries lesions on the occlusal surface of primary molars (118 molars). Recruited at Pediatric Dental Clinic of Federal University of Rio de Janeiro, Brazil SES: 84% from low‐income families Sex, male: G1 61.8%; G2 60.6% Age, mean (SD): 3.62 (± 1.07) years Baseline caries, mean (SD): 6.72 (± 3.73) dmft Fluoridation status: not reported Use of fluoride toothpaste: > 80% used fluoride toothpaste (> 1000 ppm) Number randomised: G1 34 children, 65 teeth; G2 34 children, 53 teeth Number evaluated at 12 months: G1 31 children, 61 teeth; G2 26 children, 45 teeth
Interventions	Comparison 5: SDF versus restorative treatments G1. 30% SDF, single application G2. ART and GIC
Outcomes	Outcomes included in the review: caries arrest (coronal caries; tooth‐level; visual and tactile evaluation with occlusal dentine surfaces classified as active or inactive according to ICDAS criteria; 12 months); adverse effects; aesthetics (number of caregivers who were "annoyed with teeth appearance") Other outcomes reported by study authors (not included in the review): time required for treatment; anxiety; OHRQoL Note: data corrected for clustering using Bootstrap method
Notes	Funding: financial support from FAPERJ Study dates: June 2016 to August 2017 Sample size: a minimum of 49 children/teeth per group required Changes to protocol: "it was not possible to reach the number of children who met the eligibility criteria within the planned recruitment interval, we chose to analyze all the eligible teeth of each child."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "block randomization of four, through the generation of a random numbers table in the Excel program"
Allocation concealment (selection bias)	Low risk	Quote: "Allocation concealment was achieved with sequentially numbered, opaque, sealed envelopes containing the treatment allocation cards, which were prepared before the trial."
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Blinding of either patient or operator during the treatment was not possible due to the difference between the materials."
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "in the follow‐up assessments, the examiner was blind". Comment: however, due to the nature of the interventions, blinding to treatment type not feasible.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Attrition imbalanced by 12 months (loss of 9% in G1, and 24% in G2). Reasons for not completing follow‐up were not explained.
Selective reporting (reporting bias)	Unclear risk	Retrospective clinical trials registration (NCT03063307). It is not feasible to effectively assess risk of selective reporting bias from retrospectively published protocols
Other bias	Low risk	We identified no other sources of bias

Yee 2009.

Study characteristics
Methods	RCT, parallel‐group design 4 arms 24 months' duration
Participants	976 kindergarten and primary school children, aged 3 to 9 years, with primary teeth with caries. Recruited through kindergarten or schools in Katmandu, Nepal SES: collected but not reported Sex: not reported Age, mean (SD): 5.2 (± 1.2) years Baseline caries, mean (SD): 4.6 (± 4.3) dmft Fluoridation status: low fluoride (0.03 ppm) Use of fluoride toothpaste: 66% of the children reported brushing once a day with fluoride toothpaste; similarly distributed across groups Number randomised: G1 249 children; G2 243 children; G3 243 children; G4 241 children Number evaluated at 24 months: G1 156 children; G2 157 children; G3 156 children; G4 155 children
Interventions	Comparison 1: SDF versus no treatment. Comparison 2: different concentrations of SDF G1. 38% SDF (Bee Brand Medical Dental Company Ltd, Osaka, Japan) with a reducing agent (tannic acid); single application G2. 38% SDF (Bee Brand Medical Dental Company Ltd, Osaka, Japan) without a reducing agent; single application G3. 12% SDF (PROBEM, Laboratorio de Produtos Farmacêuticos e Odontológicos LTDA, São Paulo, Brazil); single application G4. No treatment‐control group
Outcomes	Outcomes included in the review: caries arrest (surface level; visual and tactile examination; 24 months) Other outcomes reported by study authors (not included in the review): tooth vitality, tooth loss
Notes	Funding: The United Mission to Nepal Oral Health Programme and by the WHO Collaborating Centre for Oral Health Care; Planning and Future Scenarios, Radboud University, Nijimen Medical Centre, College of Dental Sciences Study dates: May 2005 to August 2005 Sample size: a minimum of 160 children in each group required
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The SPSS statistical program (version 10.0) was used for random allocation of the children to one of the treatment groups"
Allocation concealment (selection bias)	Unclear risk	Unclear method for allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Staining associated with SDF may influence brushing behaviour. This only applies to the comparisons between SDF
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "follow‐up examinations were carried out at 6, 12, and 24 mos [months] by the dental therapist (DL), blind to the children’s treatment group assignment" Comment: risk of detection bias is low for SDF vs SDF comparisons. However, staining by the SDF would make this high risk of bias for the comparisons with no treatment control
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "The numbers of children who were examined at 6, 12, and 24 mos [months] were 908, 768, and 634, respectively, resulting in dropout rates of 7%, 21%, and 35%. The dropout rates in the four groups did not differ statistically significantly (X2 test, p > 0.05)" Comment: the large proportion of dropouts from the study (35%) at 24 months was due to a school closing and to the mobility of the parents.
Selective reporting (reporting bias)	Unclear risk	Published protocol or clinical trials registration not reported. It is not feasible to effectively assess risk of selective reporting bias without these documents.
Other bias	Low risk	We identified no other sources of bias

Zhang 2013.

Study characteristics
Methods	RCT, parallel‐group design 3 arms 24 months' duration
Participants	266 older adults, aged 60 to 89 years, with at least 5 teeth with exposed root surfaces. Recruited from 11 community centres in Hong Kong, China SES: not reported Sex, male: 25.6% Age, mean (SD): 72.5 (± 5.7) years Baseline caries, DFSroot (SD): 1.97 (± 0.15) Fluoridation status: fluoridated area (0.5 ppm) Use of fluoridated toothpaste: "asked to brush their teeth twice a day and to use fluoridated toothpaste" Number randomised: G1 98 adults; G2 84 adults; G3 81 adults Number evaluated at 24 months: G1 83 adults; G2 69 adults; G3 75 adults
Interventions	Comparison 1: SDF versus placebo G1. 38% SDF every 12 months (n = 98) G2. 38% SDF every 12 months + OHE every 6 months (n = 84) G3. Placebo every 12 months (n=81) All 3 groups received OHI Note: we did not include G2 data in the review
Outcomes	Outcomes included in the review: primary caries prevention (preventing new active caries developing on the exposed sound root surfaces (DFSroot increment); 24 months); caries arrest on root surface (24 months). Visual and tactile evaluation; person‐level analysis
Notes	Funding: not reported Study dates: not reported Sample size: approximately 60 participants per group required
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “subjects were randomly assigned to one of the following 3 groups according to a random list generated by a computer”
Allocation concealment (selection bias)	Unclear risk	The method of concealment is not described in the publication.
Blinding of participants and personnel (performance bias) All outcomes	High risk	The participants were unaware as to what intervention group they were assigned to. Personnel were not blinded. However, staining associated with SDF may influence brushing behaviour
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "the examiner did not know the group the subjects were assigned to when conducting the clinical examination.” Comment: however, staining associated with SDF prevents blinding of outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "A total of 227 subjects finished the 24‐month follow‐up with an overall 15% drop‐out." Quote: “...reasons for dropout are similar and probably unrelated to the outcome.”
Selective reporting (reporting bias)	Unclear risk	Published protocol or clinical trials registration not reported. It is not feasible to effectively assess risk of selective reporting bias without these documents.
Other bias	Low risk	We identified no other sources of bias

Zheng 2023.

Study characteristics
Methods	RCT, parallel‐group design 2 arms 12 months' duration
Participants	688 children aged 3 to 4 years old, generally healthy, with or without caries experience. 9 kindergartens in Hong Kong Exclusion criteria: children with significant systemic diseases; taking regular medication such as methylphenidate SES: not reported Sex, male: G1 50%; G2 51% Age: not reported Baseline caries, mean (SD): 0.8 (± 2) dmft; G2 0.7 (± 2.1) dmft Fluoridation status: fluoride concentration in water 0.5 ppm Use of fluoridated toothpaste: not reported Number randomised: G1 344 children; G2 344 children Number evaluated at 12 months: G1 225 children; G2 209 children
Interventions	Comparison 3: SDF versus other topical treatments G1: 38% SDF (Advantage Arrest, Elevate Oral Care), applied to each tooth surface (sound or decayed) of the 6 upper anterior teeth; single application G2: 5% NaF varnish (Duraphat Varnish, Colgate‐Palmolive), applied to each tooth surface (sound or decayed) of the 6 upper anterior teeth; single application
Outcomes	Outcomes included in the review: primary caries prevention (caries incidence based on the number of decayed surfaces developed (sound to decayed surfaces) in the 6 upper anterior teeth; 12 months); adverse events (including gum irritation, swelling or bleaching) Other outcomes reported by study authors (not included in the review): parent satisfaction with treatment
Notes	Funding: General Research Fund of the University Grant Council, Hong Kong Declarations of interest: study authors declare no conflicts of interest Study dates: September 2020 to April 2022
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block randomisation in blocks of 8, generated and managed by an independent researcher
Allocation concealment (selection bias)	Low risk	Numbers were sealed in opaque envelopes.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Although participants were blinded to treatment allocation, staining caused by SDF would be apparent and may influence toothbrushing behaviour.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Although outcome assessors were blinded to treatment allocation, staining caused by SDF would be apparent .
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Large number of losses at 12 months. Most are lost because of refusal of school to follow‐up (with the trial conducted during the COVID‐19 pandemic). Other losses were because of parents' refusal (G1 17 losses; G2 28 losses) and we could not determine whether this difference may have been related to treatment or may have impacted results.
Selective reporting (reporting bias)	Low risk	Prospective clinical trials registration (NCT04399369). Outcomes in the published study report and consistent with those in the trials register
Other bias	Low risk	We identified no other sources of bias.

Zhi 2012.

Study characteristics
Methods	RCT, parallel group design 3 arms 24 months duration
Participants	212 children, aged 3 to 4 years, with primary teeth with active dentine caries not involving the pulp (599 teeth/719 active dentine caries lesions). Recruited from kindergarten in Guangzhou, Guangdong, China SES: not reported Sex: G1 51% males; G2 63% males; G3 54% males Age, mean (SD): 3.8 (± 0.6) years Baseline caries, mean (SD): 5.1 (± 4.0) dmf Fluoridation status: non‐fluoridated area Use of fluoride toothpaste: > 65% used fluoride toothpaste Number randomised: G1 71 children, 218 lesions; G2 69 children, 239 lesions; G3 72 children, 262 lesions Number evaluated at 24 months: G1 60 children, 174 lesions; G2 59 children, 205 lesions; G3 62 children, 229 lesions
Interventions	Comparison 2: different frequency and timings of SDF applications. Comparison 5: SDF versus restorative treatments (GIC) G1. 38% SDF (Saforide, Seiyaku Kasei Co Ltd, Osaka, Japan) every 12 months (n = 71 children, 218 lesions) G2. 38% SDF (Saforide, Seiyaku Kasei Co Ltd, Osaka, Japan) every 6 months (n = 69 children, 239 lesions) G3. Low viscosity high fluoride‐releasing glass ionomer material (Fuji VII, GC Corporation, Tokyo, Japan) every 12 months (n = 72 children, 262 lesions)
Outcomes	Outcomes included in the review: caries arrest (lesion level; visual and tactile examination; 24 months); adverse events; aesthetics (parents' satisfaction with their child's dental appearance) Note: study authors reported data with GEE OR, which takes account of clustering
Notes	Funding: University of Hong Kong Study dates: 2007 to 2009 Sample size: 200 lesions in each group required. "Assuming, on average, each child had 4 caries lesions, 50 children were needed in each group."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “...based on computer‐generated random numbers by an assistant. To avoid over clustering, up to 3 decayed teeth in one child, selected using computer‐generated random numbers, were included in this study.“
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias) All outcomes	High risk	There is no information on blinding of participants and personnel, but, staining associated with SDF may influence brushing behaviour. Because different frequencies of SDF were given, allocation to SDF treatment groups would have been known.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: “Follow‐up examinations at 6‐month intervals were carried out by a single examiner who was not involved in the provision of treatments and did not know the children’s group assignment.” Comment: Staining associated with SDF prevents blind outcome assessment of SDF vs FV comparison (high risk), but for SDF vs SDF comparison, low risk of detection bias.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "After 24 months, 181 (85%) children remained in the study, 60, 59 and 62 children in Groups 1–3, respectively. The drop‐out rates among the three groups were similar (x2 test, p > 0.05)"
Selective reporting (reporting bias)	Unclear risk	We could not source details of clinical trials registration with Hong Kong Clinical Trials Register to determine whether registration was prospective and whether reported outcomes were prospectively specified
Other bias	Low risk	We identified no other sources of bias

AgNO₃: silver nitrate; ART: Atraumatic Restorative Treatment; CHX: chlorhexidine (varnish); CTSA: Clinical and Translational Science Award; dmf(s/t): decayed, filled, missing (surfaces/teeth) in primary dentition; DMFT: decayed, missing and filled permanent teeth; DFS: decayed and filled surface; FAPERJ: (not defined by study authors); FV: fluoride varnish; G: group; GEE: Generalized Estimating Equations; GIC: glass ionomer cement; HKD: Hong Kong Dollar; ICCMS: International Caries Classification and Management System; ICDAS: International Caries Detection and Assessment System; ln(OR): log of the odds ratio; ITT: intention‐to‐treat; KI: potassium iodide; mon: months; min: minutes; NaF: sodium fluoride; NIDCR: National Institute of Dental and Craniofacial Research; NIH: National Institutes of Health; OHE: oral health education; OHI: oral hygiene instruction; OHRQOL: oral health‐related quality of life; OR: odds ratio; RA: radiolucency; RCT: randomised controlled trial; SD: standard deviation; SDF: silver diamine fluoride; SES: socioeconomic status; WHO: World Health Organization

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Bijella 1991	We excluded this study because it did not appear to be randomised. We emailed the study authors for clarity but, at the time of publication of this review, we received no reply.
Chu 2002	We excluded this study because it used a quasi‐randomised method to allocate participants to groups.
dos Santos 2012	In the published report, this study was described as a cluster‐RCT (with primary schools allocated to groups), with further randomisation on an individual participant level. However, in the PhD Thesis related to this study, it states that "After the initial exams, children who met inclusion criteria were allocated to the IRT and SDF groups according to their shift at school. Thus, children attending the morning shift received one treatment and children attending the afternoon shift received the other treatment." Therefore, we excluded this because it is a quasi‐randomised trial
Garrastazu 2019	This study compared SDF with chlorhexidine gel and measured outcomes for Streptococcus mutans count. We excluded this study because it did not measure caries prevention or arrest, and therefore the study was not designed to meet the review objective.
Hamdi 2022	This study compared TCS with SDF plus KI and with CPP‐ACP. We excluded this study because the intervention group (SDF) included an additional treatment (KI). The effect of KI with SDF is not known, and it is not the objective of this review to determine the effectiveness of SDF plus KI.
Hernandez 2013	We excluded this study because SDF was used as part of restoration (not as a single treatment), and therefore does not meet the objectives of this review.
Lo 1998	We excluded this study because it was not a RCT.
Lo 2001	We excluded this study because it was not a RCT.
Mani Prakash 2022	We excluded this study because the intervention group (SDF) included an additional treatment (KI). The effect of KI with SDF is not known, and it is not the objective of this review to determine the effectiveness of SDF plus KI.
Mohammed 2022	We excluded this study because it used a quasi‐randomised method to allocate participants to groups.
Monse 2012	We excluded this study because it used a quasi‐randomised method to allocate participants to groups.
Salem 2022	This study compared SDF plus Hall technique with Hall technique or with laser diode and Hall technique. We excluded this study because it did not measure caries prevention or arrest, and therefore the study was not designed to meet the review objective.
Satyarup 2022	This study compared SDF + GIC with ART + GIC but GIC application/post‐restoration instructions vary between groups. We excluded this study because we could not be certain of the effect of GIC on the intervention groups.
Shah 2013	This study measured outcomes for plaque and Streptococcus mutans. We excluded this study because it did not measure caries prevention or arrest, and therefore the study was not designed to meet the review objective.
Sing‐In 2019	This study only measured outcomes related to OHRQoL. We excluded this study because it did not measure caries prevention or arrest, and therefore the study was not designed to meet the review objective.
Thakur 2022	We noted the following detail in the study report: "When multiple teeth falling in inclusion criteria are present in a single patient, the next tooth was allotted to the successive group." We excluded this study because we determined that it used a quasi‐randomised method for allocation.
Turton 2021	We excluded this cluster‐RCT because the study included only 1 cluster per group
Vasconcelos 2011	We excluded this study because we judged that a quasi‐randomised method was used to allocate participants to groups. We contacted the study authors but, at the time of publication of this review, we received no reply.
Verma 2022	The study only measured Streptococcus mutans count and plaque score. We excluded this study because it did not measure caries prevention or arrest, and therefore the study was not designed to meet the review objective.

CPP‐ACP: casein phosphopeptide amorphous calcium phosphate; IRT: interim restorative treatment; KI: potassium iodide; OHRQoL: oral health‐related quality of life; RCT: randomised controlled trial; SDF: silver diamine fluoride; TCS: tricalcium silicate

Characteristics of studies awaiting classification [ordered by study ID]

Chan 2020.

Methods	RCT
Participants	Number of randomised participants: 412 Inclusion criteria: children aged 3 to 4 years old, from 23 kindergartens, with cavitated dentine caries lesions in their primary teeth
Interventions	SDF vs ART
Outcomes	Caries arrest, active caries, discomfort, success of ART restoration
Notes	Study is published only as abstract with insufficient information to warrant inclusion in the review; described as an interim report with more findings still to be reported. We await publication of the full study report before inclusion in the review.

CTRI/2021/04/032480.

Methods	RCT
Participants	Anticipated recruitment: 196 Inclusion criteria: 3 to 4 years, active carious lesion
Interventions	38% SDF varnish vs 5% nano silver fluoride
Outcomes	Caries arrest
Notes	Completed but without published results. We await publication of full results before inclusion in the review.

ISRCTN14037606.

Methods	RCT, split‐mouth, 2 arms 3 months
Participants	Estimated number of participants: 100 Inclusion criteria: children, untreated cavitated active caries lesion with dentin exposed based on the ICDAS II
Interventions	SDF vs nano silver fluoride
Outcomes	Caries arrest, discomfort
Notes	Study is listed as completed on the clinical trials register, with no results posted. We await publication of the full study report before inclusion in the review.

ISRCTN17005348.

Methods	RCT, parallel design, 6 arms 12 months
Participants	Number of randomised participants: 420 Inclusion criteria: children aged 1 to 6 years, with ≥ 1 active caries damage
Interventions	SDF (2 applications, 6‐monthly intervals), SDF (4 applications, weekly intervals, Tiefenfluorid (2 applications, 6‐monthly intervals), Tiefenfluorid (4 applications, weekly intervals), placebo (2 applications, 6‐monthly intervals), placebo (4 applications, weekly intervals)
Outcomes	Change in caries, pain, abscess history, number of newly extracted or otherwise treated teeth, parent and child satisfaction, child's feelings during treatment, direct costs, side effects
Notes	Study is listed as completed on the clinical trials register, with no results posted. We await publication of the full study report before inclusion in the review.

Jaradat 2018.

Methods	RCT, parallel design, 2 arms 12 months duration
Participants	Number of randomised participants: 41 Inclusion criteria: adults aged 21 to 64 years
Interventions	SDF + 5% NaF varnish (single application) vs placebo + 5% NaF varnish (single application)
Outcomes	Assessment of radiographic change in dental cavity
Notes	Results are posted on the clinical trials register. However, we were unable to determine if the reported data were comparable to the review outcomes. We contacted the study authors to request further information but received no reply. We await publication of the full study report.

Jirattanasopha 2021.

Methods	RCT
Participants	Number of randomised participants: 290 Inclusion criteria: children aged 1 to 3 years, with ≥ 1 enamel carious surface
Interventions	SDF vs FV
Outcomes	Caries arrest (18 months)
Notes	Study published only as an abstract with insufficient information to warrant inclusion in the review. Although there are some similarities with Mabangkhru 2020, we judged this to be a different study. We await publication of the full study report before inclusion in the review.

Lo 2015.

Methods	RCT
Participants	Number of randomised participants: 533 older adults Inclusion criteria: community‐dwelling older adults who were generally healthy, with ≥ 5 teeth with exposed root surfaces
Interventions	SDF vs placebo
Outcomes	Root caries increment (24 months)
Notes	Study published only as abstracts with insufficient information to warrant inclusion in the review. We await publication of the full study report before inclusion in the review.

NCT01508611.

Methods	RCT
Participants	Number of randomised participants: 192 Inclusion criteria: children aged 4 to 7 years, "not special children", children with ≥ 1 occlusal surface with initial caries lesion (ICDAS 1, 2, 3)
Interventions	SDF vs cross‐toothbrushing technique and OHI
Outcomes	Caries progression, cost, participant satisfaction and discomfort, duration
Notes	Information in clinical trials register indicates that enrolment is complete. We await publication of full study report before inclusion in the review.

NCT03649659.

Methods	RCT, parallel design, 2 arms 8 months
Participants	Number of randomised participants: 831 Inclusion criteria: age 12 to 71 months at baseline with at least 1 SDF‐target tooth, parental consent
Interventions	SDF vs placebo
Outcomes	Caries arrest (proportion and change in proportion), toothache
Notes	Study is listed as completed in clinical trials register with no results posted. We await publication of the full study report before inclusion in the review

NCT04514094.

Methods	RCT, parallel design, 2 arms
Participants	Anticipated recruitment: 100 Inclusion criteria: 2‐ to 5‐year‐olds with primary dentition
Interventions	SDF vs FV
Outcomes	New caries; caries arrest
Notes	Completed but without published results. We await publication of full results before inclusion in the review

NCT05314660.

Methods	RCT, parallel design, 3 arms
Participants	Total number of participants: 135 Inclusion criteria: children aged 3 to 5 years, having ≥ 1 carious dentine lesion
Interventions	38% SDF versus ART versus UCT
Outcomes	Caries arrest
Notes	Completed but without published results. We await publication of full results before inclusion in the review

NCT05761041.

Methods	RCT, parallel design, 2 arms 6 months
Participants	Number of randomised participants: 140 Inclusion criteria: children aged ≤ 4 years old, ≥ 1 active carious lesion on primary tooth
Interventions	SDF vs 5% NaF varnish plus motivational interviewing
Outcomes	Caries arrest, new caries, parental satisfaction with treatment
Notes	According to the clinical trials register, recruitment is complete, with no results posted. We await publication of the full study report before inclusion in the review.

Nelson 2020.

Methods	RCT, parallel‐group design, 2 arms
Participants	Anticipated number of participants: 550 Inclusion criteria: older adult tenants of 22 housing facilities for adults of low income in Northeast Ohio, aged ≥ 62 years
Interventions	SDF vs ART + FV
Outcomes	Caries arrest, participant‐reported outcomes (tooth pain and hypersensitivity), new caries, oral health‐related quality of life. Measured at 6 and 12 months
Notes	According to the clinical trials register, this study is completed but without published results. We await publication of full results before inclusion in the review.

Salamoon 2021.

Methods	RCT
Participants	Number of randomised participants: 62 Inclusion criteria: children with carious primary teeth
Interventions	SDF vs FV
Outcomes	Discolouration, failure (no definition of failure)
Notes	Study is published only in an abstract with insufficient information to warrant inclusion in the review. We await publication of the full study report before inclusion in the review

Yan 2022.

Methods	RCT, parallel design, 9 arms
Participants	Anticipated number of participants: 414 Inclusion criteria: children attending kindergarten, aged 3 to 5 years, generally healthy, with untreated caries that extend into the dentine, parental consent
Interventions	SDF applied for a different length of time (3, 5, 10, 15, 30, 45, 60, 120, 180 seconds)
Outcomes	Active and arrested caries (measured at 6 months)
Notes	According to the clinical trials register, this study is completed but without published results. We await publication of full results before inclusion in the review.

Zhang 2020.

Methods	RCT, parallel design, 2 arms
Participants	Number of randomised participants: 98 Inclusion criteria: people aged > 60 years of age, with ≥ 1 root surface with active caries lesion, at least 6 natural teeth, basic self‐care and communication ability
Interventions	SDF vs PVP‐I plus NaF
Outcomes	Caries arrest (24 months)
Notes	Study is only published as abstracts with insufficient information to warrant inclusion in the review. We await publication of the full study report before inclusion in the review.

ART: Atraumatic Restorative Treatment; FV: fluoride varnish; ICDAS: International Caries Detection and Assessment System; NaF: sodium fluoride; OHI: oral hygiene instruction; PVP: povidone iodine; RCT: randomised controlled trial; SDF: silver diamine fluoride; UCT: ultra conservative treatment

Characteristics of ongoing studies [ordered by study ID]

CTRI/2020/02/023420.

Study name	Effect of fluoride paint in arresting decay among children of age 24‐72 months in Mangaluru Taluk
Methods	RCT
Participants	Anticipated recruitment: 150 Inclusion criteria: children aged 24 to 72 months, with ≥ 1 soft carious lesion
Interventions	SDF at concentrations of 12% vs 30% vs 38%
Outcomes	Caries arrest, caries progression
Starting date	20 February 2020
Contact information	Praveen S Jodalli; praveenjodalli@gmail.com
Notes

CTRI/2020/07/026614.

Study name	Comparison of two types treatment of decayed teeth in primary school children with limited access to dental care
Methods	RCT, parallel design
Participants	Anticipated recruitment: 180 Inclusion criteria: children aged 6 to 12 years
Interventions	SDF vs ART
Outcomes	Intact restoration, no secondary caries, loss of restoration, discolouration, pain and infection of tooth
Starting date	28 August 2020
Contact information	Dr Dharmashree Satyarup; dharmashree_s@yahoo.com
Notes

CTRI/2020/11/029210.

Study name	Assessing benefits of treatment of dental caries using 38% silver diamine fluoride and placebo among primary school children in Hyderabad city: a randomized controlled trial
Methods	RCT, parallel design
Participants	Anticipated recruitment: 60 Inclusion criteria: children with at least 1 untreated cavitated active caries lesion based on Nyvad criteria. Written consent from parents
Interventions	38% SDF vs placebo
Outcomes	Caries arrest (measured at 21 days)
Starting date	20 November 2020
Contact information	Dr Srilatha; phdpani@gmail.com
Notes

CTRI/2021/05/033876.

Study name	Comparitive effectiveness of SDF and GC IX for caries prevention in children
Methods	RCT, parallel design
Participants	Anticipated recruitment: 100 Inclusion criteria: preschool children aged 3 to 5 years within initial dentinal caries in primary molars (ICDAS score 4 and 5)
Interventions	38% SDF vs GIC
Outcomes	Clinical and radiographic assessment of primary molars; chairside time and participant co‐operation with treatment
Starting date	4 June 2021
Contact information	Dr Anil Gupta; anilgupta_in@yahoo.co.in
Notes

CTRI/2022/04/042177.

Study name	Topical fluorides to arrest dental caries among Anganwadi children in Jaipur ‐ a randomized controlled trial
Methods	RCT, parallel design
Participants	Anticipated recruitment: 360 Inclusion criteria: children aged 3 to 5 years with cavitated lesions
Interventions	38% SDF vs fluoride varnish (NaF) application
Outcomes	Caries arrest
Starting date	27 April 2022
Contact information	Dr Abhishek Sharma; drabhi712@gmail.com
Notes

Duangthip 2022.

Study name	Effectiveness of silver diamine fluoride for preventing occlusal caries in the primary teeth of preschool children: protocol for a randomized controlled trial
Methods	3‐arm, parallel‐design, double‐blind, RCT
Participants	Anticipated recruitment: 791 Inclusion criteria: preschool children
Interventions	3 arms: SDF vs FV vs placebo control
Outcomes	New caries development
Starting date	1 September 2020
Contact information	Edward Lo; edward‐lo@hku.hk
Notes

Gao 2020.

Study name	Preventing early childhood caries with silver diamine fluoride
Methods	RCT
Participants	Anticipated recruitment: 730 Inclusion criteria: children aged 3 to 4 years who are generally healthy, with parental consent
Interventions	38% SDF vs 5% NaF
Outcomes	Caries prevention (30 months)
Starting date	Not reported
Contact information	Dr Chun‐Hung Chu, The University of Hong Kong
Notes

Janakiram 2021.

Study name	Effectiveness of silver diammine fluoride applications for dental caries cessation in tribal preschool children in India: study protocol for a randomized controlled trial
Methods	RCT, parallel design
Participants	Anticipated recruitment: 480 Inclusion criteria: arresting active coronal dentinal carious lesions on primary teeth amongst tribal preschool children aged 2 to 6 years
Interventions	38% SDF application on an annual (baseline) vs bi‐annual (baseline and 6 months) vs four times a year (baseline, 2nd, 4th, and 8th week)
Outcomes	Arresting active coronal dentinal carious lesions
Starting date	April 2021
Contact information	Chandrashekar Janakiram; chandrashekarj@aims.amrita.edu
Notes	CTRI/2020/03/024265

NCT03770286.

Study name	Treatment of interproximal cavities on primary molar teeth with silver diamine fluoride
Methods	RCT, parallel design, 3 arms
Participants	Anticipated recruitment: 60 Inclusion criteria: children aged 3 to 12 years, ASA status I and II, behaviour 3 or 4 on Frankl scale, radiographic decay within enamel or extending to the dentine‐enamel junction based on ICCMS categories 1, 2 and 3 ("Initial stages"), target interproximal lesion does not have existing restoration, recurrent decay, or adjacent teeth with existing restorations
Interventions	SDF with Super Floss vs SDF without Super Floss vs FV
Outcomes	Interproximal caries zone of radiolucency (6 and 12 months)
Starting date	22 January 2019
Contact information	Stephanie Shimizu; sshimizu@chla.usc.edu
Notes

NCT04054635.

Study name	A clinical trial of silver diamine fluoride to arrest early childhood caries in young children
Methods	RCT, parallel design
Participants	Anticipated recruitment: 81 Inclusion criteria: children < 72 months of age with ECC with active lesions, ≥ 1 primary tooth with caries that is eligible to receive SDF
Interventions	SDF (2 applications, 4‐monthly intervals) vs SDF (2 applications, 6‐monthly intervals) vs SDF (2 applications, 1‐monthly intervals)
Outcomes	Caries arrest (10 months, 14 months, 26 months)
Starting date	First posted on clinical trials register on 13 August 2019, current status is active (not recruiting)
Contact information	Robert J Schroth, University of Manitoba
Notes

NCT04213573.

Study name	Efficacy of silver diamine fluoride and its parental perception
Methods	RCT
Participants	Anticipated recruitment: 60 Inclusion criteria: healthy children without any systemic disease, ≥ 1 carious dentine lesion in their primary teeth
Interventions	SDF vs FV with calcium and phosphate
Outcomes	Caries arrest, parental perception of staining on children's teeth
Starting date	Trial is currently suspended due to the coronavirus pandemic
Contact information	Asmaa Mohammed Khammas, University of Baghdad
Notes

NCT04432415.

Study name	Comparison of silver diamine fluoride and sodium fluoride varnish to prevent and arrest root caries in older adults
Methods	RCT
Participants	Anticipated recruitment: 60 Inclusion criteria: adults aged ≥ 60 years of age
Interventions	SDF vs FV
Outcomes	New root caries, caries arrest
Starting date	September 2017
Contact information	Aida Borges‐Yañez; Universidad Nacional Autonoma de Mexico
Notes	Recruitment status: suspended (coronavirus pandemic) First posted: 16 June 2020 Last update posted: 16 June 2020

NCT04737057.

Study name	Clinical efficiency and child's behavior of hall versus SDF techniques in the management of carious primary molar
Methods	RCT
Participants	Anticipated recruitment: 72 Inclusion criteria: children aged 4 to 6 years, caries in primary molars within enamel/dentine without pulp disease
Interventions	SDF vs Hall technique
Outcomes	Caries arrest
Starting date	May 2021
Contact information	Gihan Abo el Neil, Ahmed Alkhadem, Egypt
Notes

NCT05008718.

Study name	Silver diamine fluoride: a randomized controlled trial on its effectiveness as a caries arresting agent
Methods	RCT
Participants	Anticipated recruitment: 132 Inclusion criteria: 6 to 8 years old, at least one active carious lesion on a primary tooth
Interventions	SDF vs FV
Outcomes	Caries arrest
Starting date	August 2021
Contact information	Budi Aslinie Md Sabri; budiaslinie@uitm.edu.my
Notes

NCT05188846.

Study name	Caries arresting in primary molar teeth using SDF vs ART
Methods	RCT
Participants	Anticipated recruitment: 50 Inclusion criteria: 4 to 6 years
Interventions	SDF vs SDF + ART
Outcomes	Caries arrest
Starting date	25 January 2022
Contact information	Ola Adel; olaadel@dentistry.cu.edu.eg
Notes

NCT05255913.

Study name	Effectiveness of nano‐silver fluoride and silver diamine fluoride for arresting early childhood caries
Methods	RCT
Participants	Anticipated recruitment: 360 Inclusion criteria: 2 to 4 years old; at least 1 active carious lesion on a primary tooth
Interventions	SDF vs nano silver
Outcomes	Caries arrest
Starting date	March 2022
Contact information	Maryam Quritum; maryamquritum@gmail.com
Notes

Ruff 2018.

Study name	Comparative effectiveness of treatments to prevent dental caries given to rural children in school‐based settings
Methods	RCT
Participants	Anticipated recruitment: 3960 Inclusion criteria: any primary school with a previously employed caries prevention program operating in rural areas and located in a health professional shortage area. Within participating schools, all children (with informed consent) are eligible to participate
Interventions	SDF + FV vs glass ionomer sealant + FV
Outcomes	Caries arrest, caries prevention
Starting date	Not reported
Contact information	Richard Niederman; rniederman@nyu.edu Ryan R Ruff; ryan.ruff@nyu.edu
Notes

Varughese 2022.

Study name	Effectiveness of 38% silver diamine fluoride application along with atraumatic restorative treatment for arresting caries in permanent teeth when compared to atraumatic restorative treatment in adults ‐ study protocol for a randomized controlled trial
Methods	RCT
Participants	Anticipated recruitment: 220 Inclusion criteria: adults 18 to 65 years of age, with cavitated lesion
Interventions	38% SDF application vs ART
Outcomes	Caries arrest
Starting date	Not reported
Contact information	Anju Varughese; ann.wez0306@gmail.com
Notes	CTRI/2021/12/038816

ART: Atraumatic Restorative Treatment; ASA: American Society of Anesthestiologists; ECC: early childhood caries; FV: fluoride varnish; GIC: glass ionomer cement; ICCMS: International Caries Classification and Management System; ICDAS: International Caries Detection and Assessment System; NaF: sodium fluoride; NaF: sodium fluoride; RCT: randomised controlled trial; SDF: silver diamine fluoride

Differences between protocol and review

Review authors: the following additional review authors were involved in the review ‐ Helen Worthington, Sharon Lewis, Anne‐Marie Glenny, Shulamite Huang, Lucy O'Malley, Philip Riley, Tanya Walsh. The following authors (who contributed to the protocol) were not involved in review production ‐ Anjana Rajendra, Branca Heloisa Oliveira, Ryan R Ruff, John Radford, Nassar Seifo, Richard Niederman.

Title: we amended the title to include prevention as well as management of dental caries.

Background: we updated the background of the review to improve the readability and explanations of the condition, the intervention, and how it might work.

Types of studies: we provided more detail. In particular, we noted that we included cluster RCTs (except when they included only one cluster per study group as these studies are unable to measure variability) and that we excluded quasi‐randomised trials.

Types of interventions: because we found that there were a wide range of comparison treatments in this review, we separated the reporting of studies according to five distinct comparisons (SDF vs placebo or no treatment; different approaches to SDF application; SDF vs other topical treatments; SDF vs sealants and resin infiltration; SDF vs restorative treatments).

Types of outcome measures:

• we noted in this section that assessment of caries (prevention, arrest or progression) was essential for inclusion in the review; this was in order to meet our specific review objectives;

• we added another outcome to the review (secondary prevention of caries). We found that this was often reported in studies instead of, or in addition to, caries arrest, and we considered that it was important and relevant to collect these data;

• previously, we stated that we collected data on adverse events. We have changed the term for this outcome to adverse effects because it was our intention to collect data on adverse effects that were likely to be caused by the treatment rather than unrelated adverse events;

• we added more detail to make a clearer distinction between adverse effects (which may include the number of people with staining on teeth) and aesthetics (which may include the number of people who are bothered by the appearance of staining on teeth);

• we added a time point of follow‐up for all outcome data (final study follow‐up).

Search methods for identification of studies:

• we had planned to search only for recent months of the Embase database (because Embase records are available through the Cochrane Central Registered of Controlled Trials). However, to ensure completeness and reduce the risk of missing earlier trials, we searched all years of Embase and used Cochrane's validated Embase filter to limit the search to RCTs. We also used the validated Cochrane RCT filter for MEDLINE.

• we planned to handsearch conference proceedings from the International Association for Dental Research and the American Dental Association conferences. However, because at the time of the search, RCTs from these sources were available through the Cochrane Oral Health Group's trial register, we did not undertake this handsearch.

Assessment of risk of bias in included studies: we provided additional methods to describe the additional consideration for risk of bias for cluster‐randomised trials. We based these other risk of bias considerations on information in Chapter 16.3.2 of Higgins 2011b.

Unit of analysis issues: the review included a large number of studies that reported only data that did not account for clustering of teeth within participants, and, wherever possible, we did not include unadjusted data in Summary of findings tables, Abstract or Plain language summary, because these data may have included confidence intervals that are too precise.

Data synthesis: because data were available for different types of dentition, we analysed and reported these data separately throughout the review. We also analysed and reported data separately for the five main comparison groups (as specified in Types of interventions), as well as the individual types of interventions and comparative treatments in these comparison groups.

Sensitivity analysis: we did not conduct any sensitivity analyses in this review. Planned sensitivity analyses were not practical because the criteria (risk of bias and clustering issues) were too common to provide any meaningful results from sensitivity analysis.

Summary of findings tables and assessment of the certainty of the evidence: we assessed the certainty of the body of evidence in the review using the GRADE approach for all outcomes. In addition, we prepared summary of findings tables for the five comparison groups in the review. Because comparison groups included more than one comparative treatment (e.g. silver diamine fluoride (SDF) vs other topical treatments includes SDF versus fluoride varnish as well as SDF versus chlorhexidine), we prioritised preparation of one summary of findings table for one comparative treatment for each of the main comparison groups. Judgements for which data to prioritise for summary of findings tables were based on which comparative treatments we believed to be most clinically relevant. We also prioritised reporting of continuous data (mean caries data), which was more sensitive than dichotomous data, and we did not include any data with serious issues related to clustering of teeth within participants.

Contributions of authors

• Co‐ordinating the review: HW, SL

• Screening of studies: HW, SL, AMG, PR, LO'M, AVK

• Risk of bias assessments: HW, SL, AMG, PR, LO'M, TW, AVK

• Data extraction: HW, SL, AMG, PR, LO'M, TW, AVK, SH

• Analysis of data: HW, SL, AMG, TW

• Interpretation of data: HW, SL, AMG, TW, JC

• Writing the review: HW, SL, AMG, TW, JC

• Providing general advice and approving the final draft of the review: AVK, NI, JC, MW

Sources of support

Internal sources

• The University of Manchester, UK

  Support to Cochrane Oral Health

• MAHSC, UK

  Cochrane Oral Health is supported by the Manchester Academic Health Sciences Centre (MAHSC) and the NIHR Manchester Biomedical Research Centre

External sources

• The University of Pennsylvania, USA

  Funding acknowledgement: the work of Cochrane Oral Health (COH) is supported by a collaborative research agreement between The University of Manchester and The University of Pennsylvania. The research collaboration sees the creation of a Cochrane Oral Health Collaborating Center at the University of Pennsylvania School of Dental Medicine, Center for Integrative Global Oral Health, which will work alongside COH (Manchester).
Disclaimer: the views and opinions expressed therein are those of the authors and do not necessarily reflect those of either The University of Pennsylvania or The University of Manchester.

• National Institute for Health and Care Research (NIHR), UK

  This review was supported by the NIHR via Cochrane Infrastructure funding to Cochrane Oral Health until 31 March 2023. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

• Cochrane Oral Health Global Alliance, Other

  Cochrane Oral Health reviews have previosuly been supported by Global Alliance member organisations (British Association of Oral Surgeons, UK; British Orthodontic Society, UK; British Society of Paediatric Dentistry, UK; British Society of Periodontology, UK; Canadian Dental Hygienists Association, Canada; National Center for Dental Hygiene Research & Practice, USA; Mayo Clinic, USA; New York University College of Dentistry, USA; and Royal College of Surgeons of Edinburgh, UK) providing funding for the editorial process (prior to March 2023).

Declarations of interest

• HW reports being Emeritus Co‐ordinating Editor for Cochrane Oral Health; she has had no role in the editorial process for this review.

• SL is a former Deputy Co‐ordinating Editor of the Cochrane Bone, Joint and Muscle Trauma group; she has had no role in the editorial process for this review.

• AMG reports being Joint Co‐ordinating Editor for Cochrane Oral Health; she has had no role in the editorial process for this review.

• SH reports conducting an economic evaluation that included one of the included studies in this review. SH was not involved in the data extraction, or assessment of risk of bias and certainty of the evidence involving this study.

• NI reports being a Professor of Paediatric Dentistry and Honorary Consultant in Paediatric Dentistry. NI has declared that they have no conflict of interest.

• LO'M reports being a former Methods Editor with Cochrane Oral Health; she has had no role in the editorial process for this review

• PR reports being Deputy Co‐ordinating Editor for Cochrane Oral Health; he has had no role in the editorial process for this review.

• TW reports being a principal investigator for an unrestricted research grant from Colgate‐Palmolive; paid to The University of Manchester, where TW is wholly employed. Colgate‐Palmolive does not manufacture silver diamine fluoride. TW reports being a former Statistical Editor for Cochrane Oral Health; she has had no role in the editorial process for this review.

• MW reports being an author on some studies that were eligible for inclusion in the work. These studies did not involve funding from a commercial sponsor and, in this review, MW was not involved in the data extraction, or assessment of risk of bias and the certainty of the evidence involving these studies. MW reports being a former Editor for Cochrane Oral Health; she has had no role in the editorial process for this review.

• JC reports having an editorial role for Cochrane Oral Health (Joint Co‐ordinating Editor); she has had no role in the editorial process for this review.

• AVK reports being a Dentistry Clinical Professor. AVK has declared she has no conflicts of interest.

These authors should be considered joint last author

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