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Fluoride varnishes for preventing dental caries in children and adolescents

  1. Valeria CC Marinho1,
  2. Helen V Worthington2,*,
  3. Tanya Walsh3,
  4. Jan E Clarkson4

Editorial Group: Cochrane Oral Health Group

Published Online: 11 JUL 2013

Assessed as up-to-date: 13 MAY 2013

DOI: 10.1002/14651858.CD002279.pub2


How to Cite

Marinho VCC, Worthington HV, Walsh T, Clarkson JE. Fluoride varnishes for preventing dental caries in children and adolescents. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD002279. DOI: 10.1002/14651858.CD002279.pub2.

Author Information

  1. 1

    Queen Mary University of London, Clinical and Diagnostic Oral Sciences, Barts and The London School of Medicine and Dentistry, London, UK

  2. 2

    School of Dentistry, The University of Manchester, Cochrane Oral Health Group, Manchester, UK

  3. 3

    School of Dentistry, The University of Manchester, Manchester, UK

  4. 4

    University of Dundee, Dental Health Services Research Unit, Dundee, Scotland, UK

*Helen V Worthington, Cochrane Oral Health Group, School of Dentistry, The University of Manchester, Coupland III Building, Oxford Road, Manchester, M13 9PL, UK. helen.worthington@manchester.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 11 JUL 2013

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Characteristics of included studies [ordered by study ID]
Arruda 2012

MethodsDesign: 2-arm parallel group RCT

Location: Tapiratiba, South Eastern Brazil

Study started: January 2006


ParticipantsNumber randomised: 379 (198/181)

Number analysed: 210 (113/97)
Age range: At baseline 9.62 ± 1.36 and 9.63 ±1.36 years

Background exposure to other fluoride: 58.4% and 59.7% of varnish and placebo groups attended a school with fluoridated water (0.7 ppm)


InterventionsComparison: FV versus PL
Group 1 (n = 113 ): 5% NaF varnish group (Cavity Shield ® = 22,600 ppm F from Omni oral pharmaceuticals), applied twice (baseline, 6 months), from single dose vials, applied by dentists in portable dental units under standard operating light illumination, with small brush, left to dry (duration NR)

Group 2 (n = 97): Placebo provided by manufacturer in identical vials, pre-numbered with the number assigned to each child

Application method identical for all children (after toothbrushing teeth were dried and varnish/placebo applied using disposable brush, then varnish was air dried)

Post-op instructions: Nil solid foods for 4 hours, nil toothbrushing till next day

Manufacturer provided both varnish and placebo


OutcomesDFS CA + NCA (ICDAS code 1 (non-cavitated lesions)) and preventive fraction assessed at baseline 6 and 12 months


NotesSociodemographic and oral health questionnaire administered to all participants, with 7 day food frequency diary

All children received oral health education, toothbrushing and caries examinations at baseline

High sugar consumption in 53.1% and 71.1% of varnish and control groups respectively (P = 0.007)

Toothbrushing at least once a day was reported by 104/113 (92%) and 80/97 (82%) of varnish and placebo groups (P = 0.04)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High risk"Children were identified by their school ID number. Randomisation was achieved on the basis of odd and even ID numbers by a coin toss.... children with odd ID numbers were assigned to one group and the IDs with even numbers were allocated to the other group"

Comment: Quasi-random. 2 cohorts enrolled, 1 in June 2006 and another in December 2006

Allocation concealment (selection bias)High riskUnclear who performed the coin toss but allocation was determined once the first participant was enrolled

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"All parents, children and examiners were blinded to group allocation and intervention status (double blind design)"

Blinding of outcome assessment (detection bias)
All outcomes
Low risk"All parents, children and examiners were blinded to group allocation and intervention status (double blind design)"

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk85/198 (43%) and 84/181 (46%) lost to follow-up because children moved to other schools. Numbers high but numbers and reason similar in each group

Selective reporting (reporting bias)Unclear riskCaries assessed at 6 and 12 months but only reported at 12 months (increment and PF)

Baseline characteristics balanced?High riskSugar consumption higher and toothbrushing less likely in placebo group

Free of contamination/co-intervention?Low riskExposure to fluoridated water similar in each group

Compliance; only 57/198 (29%) and 43/181(24%) children in varnish and placebo groups received application twice at baseline and 6 months

Borutta 1991

MethodsDesign: 4-arm RCT

Location: Erfurt, Germany

Study started: In/before 1988


ParticipantsNumber randomised: 400

Number analysed: 360 analysed at 2 years

Age range: 12-14 years

Background exposure to other fluoride: No


InterventionsComparison: FV (3 groups) + ptc versus PL + ptc
Group 1 (n = 100): Bifluorid 12®: NaF + CaF (27,100 + 29,200 ppm F), applied twice a year
Group 2 (n = 100): Bifluorid 12®: NaF + CaF (27,100 + 29,200 ppm F), applied 4 times a year
Group 3 (n = 100): Lawefluor®: NaF (22,600 ppm F), applied 4 times a year
Group 4 (n = 100): Placebo group, applied 4 times a year


Outcomes**2-year DMFS increment - (CA)cl + FOTI
Reported at 2 years follow-up: O-DMFS; MD-DMFS; BL-DMFS; DMFT(CA)


NotesBaseline characteristics (DMFS, DMFT) 'balanced'
Clinical caries assessment by 2 examiners; diagnostic threshold = CA; FOTI assessment (loss of translucency on transillumination) for approximal surfaces. State of tooth eruption included NR; inter-examiner reproducibility checked for DMFS
**Results presented separately by examiner (1 chosen by coin flip)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "The aim of this randomised...."

Comment: Not enough information

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Double blind study"

Comment: Use of placebo described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Double blind study"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall drop-out for length of follow-up: 10% in 2 years. Drop-outs by group: 10/100 FV1, 10/100 FV2, 10/100 FV3, 10/100 PL. Reasons for losses not reported, but "Groups kept at equal sizes for statistical reasons"

Comment: Numbers lost were not unduly high for the length of follow-up, and showed no differential loss between groups, but it is unclear why/how group sizes were kept equal at all times. It is also unclear if reasons for the missing data are acceptable and balanced. It is unclear to which sample caries data used in the analysis pertain to

Selective reporting (reporting bias)Low riskOutcomes reported:

DMFS increment - (CA) cl + FOTI, at 2 years follow-up; O-DMFS, MD-DMFS, BL-DMFS, DMFT (CA); drop-outs

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported in the pre-specified way

Baseline characteristics balanced?Low riskPrognostic factors reported: DMFT: 3.7(3.2) FV1, 3.7(2.8) FV2, 3.3(2.6) FV3, 3.5(2.7) PL; DMFS: 5.1(5.8) FV1, 5.1(4.5) FV2, 5.1(5.1) FV3, 5.4(5.5) PL

Comment: Initial caries appears balanced between groups

Free of contamination/co-intervention?Unclear riskTranslation of report not detailed enough to make a categorical decision regarding contamination/co-intervention

Borutta 2006

MethodsDesign: 3-arm cluster RCT. 7 clusters were randomly allocated to study groups

Location: Germany, 7 randomly selected day care centres (nurseries) in Erfurt/Thirugia where caries risk is high

Study started: 2002/2003


ParticipantsNumber randomised: 288 (84, 113, 91)

Number analysed: 200 (60, 76, 64) at 2 years
Age range: 2-4 years

Exposure to other fluoride: All children used fluoride dentifrice daily (500 ppm F) under supervision of staff


InterventionsComparison: FV versus FV versus N/T*
Group 1: 5% Na varnish (Fluoridin N5 = 22,600 ppm F) applied twice a year, total of 4 applications
Group 2: 5% NaF varnish (Duraphat® = 22,600 ppm F) applied twice a year, total of 4 applications
Group 3: No treatment

Both varnish groups combined
Both varnishes applied by dental hygienist, after lunch and dental hygiene session. Cartridge and cannula (not product) supplied by manufacturer was used to apply varnishes

All children received 6 monthly instruction including dietary advice, instruction and motivation for dental and oral hygiene. Children in varnish groups then had varnish applied


Outcomes**2-year dmfs increment - (CA)cl + FOTI
Reported at 2 years follow-up

*2-year dmft increment - (CA)cl + FOTI
Reported at 2 years follow-up. No data on numbers with increment presented


NotesBaseline characteristics (dmfs, dmft) described as balanced but large differences (baseline FV mean dmfs = 3.75, NT = 1.94). Unable to use data as no standard deviations and only 7 clusters. Caries reduction in both varnish groups was 56% to 57%


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "their allocation was random......"

Comment: Not enough information but only 7 clusters over 3 groups

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo information on blinding of participants and personnel. No placebo used so risk of bias is high

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: " This was an examiner blind, clinically controlled 2 year study..."

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskDrop-outs by group: 24/84 (29%) FV1, 76/113 (33%) FV2, 27/91 (30%) N/T. Reasons for losses not reported

Comment: Numbers lost were high for the length of follow-up (2 years), but showed no differential loss between groups. It is also unclear if reasons for the missing data are acceptable and balanced between groups

Selective reporting (reporting bias)High riskOutcomes reported: dmfs increment - (CA)cl + FOTI, at 2 years follow-up; dmft increment - (CA)cl + FOTI, at 2 years follow-up

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported in the pre-specified way. No standard deviations presented

Baseline characteristics balanced?High riskPrognostic factors reported: dmft: (1.62) FV1, (1.53) FV2, (0.92) NT; dmfs: (4.22) FV1, (3.38) FV2, (1.94) N/T

Comment: Initial caries does not appear balanced between groups

Free of contamination/co-intervention?Unclear riskTranslation of report not detailed enough to make a categorical decision regarding contamination/co-intervention

Bravo 1997

MethodsDesign: 3-arm cluster quasi-RCT (1 arm is not eligible for inclusion in this review)

Location: Granada, Spain

Study started: 1990


ParticipantsNumber randomised: Not reported by group

Number analysed: 214 analysed (in 15 schools) at 2* years (present for all examinations)

Age range: 6-8 years (mean = 7)

Background exposure to other fluoride: water (0.07 ppm F in the drinking water), data not obtained for toothpaste


InterventionsComparison: FV versus NT
Group 1 (n = 98): NaF varnish group (Duraphat® 22,600 ppm F), applied twice a year, with Q-tip, about 0.1 ml applied per tooth (1stm) or 0.4 ml per child, left to dry for 15 seconds

Group 2 (n = 116): No treatment

Post-op instructions: No hard food for 4 hours, no teeth cleaning until following day


Outcomes*2-year Net1stm DMFS increment - (CA) (E+U)
Reported at 2 and 4* years follow-ups:

1stm PF-DMFS; 1stm MD-BL-DMFS; 1st molar occlusal CIR, molar failures over time (for molars healthy and fully erupted); costs; drop-outs (no data by group)


NotesSchool-classes randomised (15) and children taken as units of analysis for caries increment analyses, molars as units for caries incidence and survival analyses; number of children by group NR
Baseline characteristics (age, gender, SES, dft, 1stmF/DM, 1stmM; 1stmDMFS) described as 'balanced' (results NR)
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold = CA; state of tooth eruption included = E+U; examiner reproducibility checks (Kappa coefficient) in 10% sample greater than 0.71 in all 1stm DFT measurements
*Only survival analysis results (molar failures over time) reported at 4 years, when results were not available for DMFS increment


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuote: "First and second year classes were assigned at random into groups"

Quote from correspondence: "The school classes allocation was not completely random since it had some restrictions: No more than 3 classes from same treatment group in the same school, and the total number of children should be at least more or less equilibrated between the groups. Thus, after the first random assignment, they were conditional"

Comment: Probably was not a randomly generated sequence

Allocation concealment (selection bias)High riskQuote: "..clusters (n = 11) not randomised at once"

Comment: The likely non-random method used for sequence generation would not allow for allocation concealment

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: ".......and a control group which had no intervention"

Comment: No placebo described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "All children received biannual exams by a dentist using standardized criteria, and who was unaware of group assignments"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall drop-out for length of follow-up (reported for individuals within clusters only): 14.4% in 2 years. Drop-outs by group (for the 2 relevant groups of the 3 in the trial) : 17/115 FV, 19/135 NT (14.8%, 14.1%). Reason for losses: 5 children were excluded from FV group only due to unerupted teeth; moved to other schools (numbers not reported by group)

Comment: Recruitment of children was correctly done before clusters (school classes) had been randomised. Numbers lost were not unduly high for the length of follow-up, and showed no differential losses between groups. However, the exclusions after allocation done in the treatment group only have the potential to introduce bias. Caries data used in analysis pertain to participants followed up for the entire study duration (and analysis done at individual level within clusters does not take clustering into account)

Selective reporting (reporting bias)Low riskOutcomes reported:

1stm DMFS increment - (CA) (E+U), at 2 and 9 years follow-ups; 1stm PF-DMFS, 1stm MD-BL-DMFS,1st molar occlusal CIR, molar failures over time (for molars healthy and fully erupted), drop-outs, costs

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way

Baseline characteristics balanced?Low riskPrognostic factors not reported by group: 1stm DMFS: 0.45 (0.99) FV, 0.74 (1.43) NT

Mean age: 7.28; gender (51% M 49% F); mean SES (class IV), mean dft 2.52 (2.90), 1stm F/DMF: 4.3%, 1stmM: 0 (not reported by group)

Comment: Initial caries appears slightly imbalanced between groups (for individual within clusters). Adjustments in analysis for this and other factors are reported though

Free of contamination/co-intervention?Unclear riskNo information provided

Chu 2002

MethodsDesign:5-arm quasi-RCT (3 arms are not eligible for inclusion in this review)

Location: Hong Kong, China

Study started: Not reported


ParticipantsNumber randomised: 146 (73, 73)

Number analysed: 123 (61, 62) at 30 months
Age range: 3-5 years with caries in upper primary anteriors, mean age at baseline 4 years

Background exposure to other fluoride: water (below 0.2 ppm), toothpaste

Other background exposures: Oral health education was provided to all participants


InterventionsComparison: FV* versus 'PL'
Group 1 (n = 73): 5% NaF varnish group (Duraphat® 22,600 ppm F), applied 4 times a year, at schools (kindergartens), to carious surfaces, with small brush, left to dry (duration NR)

Group 2 (n = 73): Water painted onto carious teeth

Post-op instructions: Not reported


OutcomesReported at 18 and 30 months follow-up:

Number of new carious tooth surfaces (upper anterior teeth); number of arrested carious tooth surfaces; percentage of arrested caries that were black; increment of non-vital teeth; drop-outs


NotesBaseline characteristics (ds, dmfs, age) balanced
Clinical (VT + fibre-optic light) caries assessment by 1 examiner, diagnostic threshold = CA "caries diagnosed at the cavitation level and explored with a sickle shaped probe". Radiographic assessment NR; state of tooth eruption NR. Intra-examiner reliability calculated. Kappa (0.95-0.98)

* A FV study group receiving 5% sodium fluoride + prior caries removal was not considered

**Additional analysis of multilevel grouped survival data with time-varying regression coefficients and bayesian analysis of clustered multiple interval-censored data (failure times) also reported for arrested caries, but not considered


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuote: "Children were sequentially allocated...first child who came for examination to the first group, second child to the second group..."

Comment: Alternation used to generate sequence

Allocation concealment (selection bias)High riskNo information provided. However, the non-random method used for allocation would not allow for allocation concealment

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Children in the fourth group had fluoride varnish applied....Only water was painted onto the carious teeth in the last group of children"

Comment: Use of 'placebo' described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuotes: "Examinations were carried out every 6 months after baseline by the same examiner without knowing the subjects treatment group assignments"; "Dentists who were not involved in the examination of the children performed the treatments"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall drop-out for length of follow-up: 15.8% in 30 months (for the 2 relevant groups of the 5 in the trial)

Drop-outs by group: 12/73 FV, 11/73 'PL'. Reasons for losses: Not reported

Comment: Numbers lost were not unduly high for the length of follow-up, and showed no differential loss between groups. It is unclear if reasons for the missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants present at final examination

Selective reporting (reporting bias)Low riskOutcomes reported at 18 and 30 months follow-ups; dmfs, arrested caries surfaces, percentage of arrested caries that were black, non-vital teeth Drop-outs 

Comment: Trial protocol not available

Baseline characteristics balanced?Low riskPrognostic factors reported: ds: 3.54 (2.34) FV, 3.76 (2.68) 'PL'

dmfs: 4.33 (3.84) FV, 4.24 (2.84) PL; mean age: 4.0 (0.8) years (all groups) 

Comment: Initial caries appears balanced between groups

Free of contamination/co-intervention?Low riskComment: No apparent unbalanced provision of additional interventions/no difference in co-interventions

No apparent contamination

Clark 1985

MethodsDesign: 3-arm parallel RCT

Location: Quebec, Canada

Study started: 1981


ParticipantsNumber randomised: 787

Number analysed: 676 analysed at 2.5* years (available at 2nd examination, present in at least 5 of 6 treatments)

Age range: 6-7 years

Background exposure to other fluoride: toothpaste + others


InterventionsComparison: FV (2 groups) + ptc versus 'PL' + ptc
Group 1 (n = 232): FV group: Fluor Protector® Difluorsilane (7000 ppm F), applied twice a year, about 0.5 ml applied per child
Group 2 (n = 280): FV group: Duraphat® NaF (22,600 ppm F), applied twice a year, about 0.5 ml applied per child

Group 3 (n = 275): Water, applied in the same manner as test groups


Outcomes2.5-year* DMFS increment - (CA) (E+U)
dfs increments
Reported at 1.5, 2.5* and 4.5 years follow-ups**: O-DMFS; MD-DMFS; BL-DMFS


NotesBaseline characteristics (dental age, DMFS) 'balanced'
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA; state of tooth eruption included = E+U/E; duplicate examination of 10% sample between examiners done (mean difference of 0.86 DMFS), "results of integrated analysis of treatment and examiner effects remained the same (significant)"
* Results closest to 3 years chosen
**Results presented separately by examiner and combined (integrated results chosen)

Prior prophylaxis with non-fluoride paste carried out in both groups nothing to eat and no brushing for 3-4 hours


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "All children examined at baseline were stratified by dental age... and group assignments were made randomly from within each of the resulting partitions"

Comment: Not enough information

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuotes: "The study was also double blind; neither the examiners nor the participants were aware of group assignments"

"Children in group 1 were treated with Fluor-Protector, children in group 2 with Durafluor and children in group 3 were treated with water"

"Clinical procedures were performed by dental hygienists"

Comment: Use of 'placebo' described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuotes: "The study was also double blind; neither the examiners nor the participants were aware of group assignments"

"Clinical procedures were performed by dental hygienists"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall drop-out for length of follow-up: 14% in 2.5 years. Drop-outs by group: 35/232 FV1, 35/280 FV2, 41/275 'PL' (15%, 12.5%, 15%). Reasons for attrition NR fully, but exclusions based on compliance with at least 5 of the 6 treatments

Comment: Numbers lost were not unduly high for the length of follow-up, and showed no differential loss between groups. It is unclear if reasons for the missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at all examinations, who had received at least 5 of the 6 treatments

Selective reporting (reporting bias)Low riskOutcomes reported:

DMFS increment (CA) (E+U) and 1st & 2nd molars dfs increment (CA) (E), at 1.5, 2.5 and 4.5 years follow-ups; O-DMFS, MD-DMFS, BL-DMFS, FS/DMFS and DS/DMFS ratios, drop-outs

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way

Baseline characteristics balanced?Low riskPrognostic factors reported: DMFS: 0.44 (FV1), 0.45 (FV2), 0.36 ('PL'); dental age: primary teeth number 16.5 permanent 4.4 (FV1); primary 16.7, permanent 5.1 (FV2); primary 17.1, permanent 4.9 ('PL')

Comment: Initial caries appears balanced between groups

Free of contamination/co-intervention?Unclear riskQuote: "...most of the children probably used a fluoride dentifrice at home, and some probably received daily fluoride supplements"

Comment: Unclear risk of co-intervention

Frostell 1991

MethodsDesign: 6-arm RCT, 2 arms included in this review

Location: Malmö, Sweden

Study started: 1977

6-arm study. Parents who consented had children randomly allocated to 1 of 4 sugar ± varnish arms. Children whose parents did NOT consent to the sugar study were quasi-randomised to either varnish (D) or no treatment (C) by alternation. We have included only arms D and C in this review.

Reasons for losses not fully reported; exclusions based on compliance with study protocol, any differential group losses not assessable


ParticipantsNumber randomised: Unclear

Number analysed: 206 (113 (D) and 93 (C)) present for all examinations

Age range: 4 years at baseline

Background exposure to other fluoride: "There were no statistically significant differences in the use of F toothpaste, tablets and mouthrinse solutions between the 6 groups"

Fluoride in water supply 0.2 ppm


InterventionsComparison: FV + ptc versus NT
Group D (n = 113): NaF group (Duraphat®) = 22,600 ppm F)

Group C (n = 93): No treatment

In D group all tooth surfaces were polished with pumice and rubber cap, and approximal surfaces were flossed, followed by a "thorough mouthrinse with water". Varnish was applied twice a year, with small brush, left to dry for 2 minutes, teeth were rinsed and any surfaces not coated were re-coated. Teeth gently sprayed with water, no hard foods or toothbrushing till following day


OutcomesCaries (CA) incidence and prevalence at 2 years (dmfs2 all caries, dmfs1 macroscopic caries only, dmft1 macroscopic caries only)


NotesBaseline characteristics: Only caries data at baseline reported - no difference between groups
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA and NCA; state of tooth eruption included = E. Radiographic assessment (4 postBW) by 1 examiner; diagnostic threshold = DR and ER. Diagnostic errors NR

Manufacturer thanked but unclear what for


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuote: "The children whose parents did not want to participate in the sugar groups were assigned randomly to one of two groups, one with and one without Duraphat"

Quote from correspondence: "Yes, every second child was treated with Duraphat"

Comment: Alternation used to generate sequence

Allocation concealment (selection bias)High riskNo information provided. However, the non-random method used for allocation would not allow for allocation concealment

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuotes: "The children were assigned to one of two groups, one with and one without Duraphat"

Comment: No placebo described.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuotes: "They were read by one and the same examiner (MP) who did not know which year the films were taken or to which group the child belonged"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall drop-out for length of follow-up: Not reported. Drop-outs by group: Not reported. Participants present at final examination: 93 FV, 113 NT Reasons for losses: Not fully reported, but quote from correspondence: "a number of the children in the FV-group (as well as a few in the NT-group) did not follow the whole procedure and were excluded"

Comment: Data on numbers randomised (at start) not available and drop-out data not obtainable - any differential group losses not assessable Caries data used in analysis pertain to participants present at all examinations, "who followed the study from the beginning to the end"

Selective reporting (reporting bias)Low riskOutcomes reported: dmfs increment - (E) (CA/NCA)cl + (DR/ER) xr and dmft, at 2 years follow-up

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way

Baseline characteristics balanced?Low riskPrognostic factors reported: dmfs: 4.36 (FV), 5.14 (NT); dmft: 3.63 (FV), 4.43 (NT)

Comment: Initial caries appears balanced between groups

Free of contamination/co-intervention?Unclear riskNo information provided

Gugwad 2011

MethodsDesign: 2-arm RCT

Location: India

Study started: 2008


ParticipantsNumber randomised: 250

Number analysed: 211
Age range: 6-7 years at baseline

Backgound exposure to fluoride: No water fluoridation, exposure to other sources of fluoride assessed and found similar in each group

Other background exposures: Oral hygiene instruction at baseline


InterventionsComparison: FV versus NT
Group 1 (n = 106): 5% NaF (Cavity Shield = 22,600 ppm F), unclear which dose used (0.25, 0.40 ml). Unclear where applied, 3 times in 1 week with small brush, left to dry for few seconds

Group 2 (n = 105): No treatment

Post-op instructions: Abstain brushing and flossing and avoid chewing on hard food, no hot drinks, no alcohol for entire day


OutcomesReported at 1 year follow-up: deft, deftp (posterior teeth), defs, defsp (posterior teeth), DMFT, DMFS (CA and NCA + xr)


NotesParticipants randomised (numbers NR)
Baseline characteristics 'balanced'

Oral hygiene instruction to both groups
Clinical (VT) caries assessment (ADA type iii) using mouth mirror and probe; diagnostic threshold = CA and NCA; = E. Radiographic assessment (2 postBW) baseline and follow-up; diagnostic threshold = DR and ER. Diagnostic errors NR
Prior prophylaxis with non-fluoride paste carried out in both groups


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote "Two hundred fifty children (6-7 years) randomized into varnish and control groups"

Quote from correspondence: "Children selected were randomly allocated to the groups (by lottery method)"

Comment: Probably random sequence

Allocation concealment (selection bias)Low riskQuote from correspondence: "Allocation concealment and triple blinding (Examiner, Subject and Interpreter) were done"

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote from correspondence: "...and triple Blinding (examiner, subject and interpreter) were done"

Comment: But no placebo varnish described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote from correspondence: "...and triple Blinding (examiner, subject and interpreter) were done"

Comment: Blind outcome assessment indicated

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall drop-out for length of follow-up: 39/250. Drop-outs by group: 21/125 FV; 18/125 Control group. Participants present at final examination: 106 FV, 105 NT. Reasons for losses: Not reported

Comment: Caries data used in analysis pertain to participants present at all examinations, "who followed the study from the beginning to the end"

Selective reporting (reporting bias)Unclear riskOutcomes reported: defs, defsp, deft, deftp, DMFS at baseline and 1 year follow-up, but no increment reported

Comment: Trial protocol not available. Increment calculated in methods but not reported

Baseline characteristics balanced?Low riskPrognostic factors reported: dmfs

Comment: Initial caries appears balanced between groups

Free of contamination/co-intervention?Low riskExposure to other sources of fluoride assessed and found similar in each group

Hardman 2007

MethodsDesign: Cluster RCT

Location: Manchester, UK

Study started: Not reported


ParticipantsNumber randomised: 2091 (1025, 1066)

Number analysed: 664 (334, 330) in 24 schools present at baseline and final 24 months follow-up

Age range: 6-8 years, mean age at baseline 7 years

Background exposure to other fluoride: 1450 ppm F toothpaste supplied prior to baseline and final, milk


InterventionsComparison: FV versus NT
Group 1 (n = 1025): NaF varnish group (Duraphat® 22,600 ppm F), applied 6 monthly, at schools, to all surfaces of the primary and first permanent molars, with small brush, and left to dry (duration NR)

Group 2 (n = 1066): No treatment

Post-op instructions: No control over drinking or eating after application


Outcomes2-year mdfs increment - (CA/NCA)cl + FOTI (E)

Reported at 2 years follow-up: Proportion of children with new 1stm DFS(CA/NCA); 3 levels of caries diagnosis small + large enamel lesions + dentine lesions


NotesBaseline characteristics (dft/DFT/age/dmft > 0 / DMFT > 0) balanced
Clinical (V/FOTI) caries assessment by 1 examiner; diagnostic threshold = CA and NCA; state of tooth eruption included = E/U; 15% sample re-examined; K statistics 0.94 and 0.89 for intra-examiner reliability at the first and last examinations


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "The children were clustered within the unit of randomisation, the school. In half the schools year 2 children were allocated to the test group and year 3 children served as the control. In the other schools year 3 were the test group and year 2 the control. Randomisation, by a statistician, was used to allocate the combination of test and control year groups using a computer generated randomisation sequence"

Comment: However recruitment was done after clusters (the schools) had been randomised (pre-recruitment drop-outs: 1177/2091 (56.1%), and might have led to the low numbers recruited, recruitment of participants with lower caries levels, and (selection bias - the knowledge of whether each cluster is an intervention or control cluster could affect the types of participants recruited)

Allocation concealment (selection bias)Low riskQuote: "Clusters (n = 24) randomised at once"

Comment: When clusters are large in numbers and are randomised at once as in this case, allocation concealment should not be an issue

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuotes: "The children and the therapists applying the varnish were not blinded"

Comment: No placebo described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuotes: "This was a single blind study as the examiner was unaware of the test or control status of the children"; "At baseline and after 26 months children were examined by one trained and calibrated examiner, who was blind to the children's allocation"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall drop-out for length of follow-up (reported for individuals within clusters only): 68% in 2 years. Drop-outs by group: 691/1025 FV, 734/1066 NT (67%, 69%). Reasons for drop-outs (FV, NT): Left during study (47, 16), left at final exam (28, 55), absent (33, 22), refused exam (2, 1), withdrawn (0, 1) "...an intention-to-treat approach applied in which data from each child present at the follow-up examination was analysed according to their randomised group"

Comment: Although no differential losses between groups were apparent and reasons for missing data are acceptable and balanced between groups, final numbers lost unduly high for the length of follow-up. Caries data used in the analysis pertain to participants present at baseline and final examinations (and analysis done at individual level within clusters does not take clustering into account)

Selective reporting (reporting bias)Low riskOutcomes reported: dfs/DFS increment (CA)cl + FOTI at 2 years follow-up; proportion of children with new 1stm DMFS

Comment: Trial protocol not available. Pre-specified outcomes reported

Baseline characteristics balanced?Low riskPrognostic factors reported: DFT: 0.15 (0.45) FV, 0.15 (0.54) NT; dft: 2.53 (2.43) FV, 2.26 (2.46) NT; Townsend score range (SES): -0.53 to 10.77 (for both groups); primary teeth caries prevalence: 67.7% FV, 60.9% NT, permanent teeth caries prevalence: 11.4% FV, 8.8% NT

Comment: Initial caries appears balanced between groups (for individuals within clusters)

Free of contamination/co-intervention?Low riskQuote: "During the study period a fluoride milk scheme was introduced. At the time of the final examination 18 of the 24 schools were offering fluoridated milk to those who consented and paid for it. This had been available for 15 months for 3 schools, between 3 and 12 months for 11 schools and the remaining 4 had just started on the scheme. Logistic regression analyses revealed no evidence of association with fluoride milk availability"

Comment: Possibility of co-intervention with fluoridated milk, but analysis for caries showed no association with the milk availability

Holm 1979

MethodsDesign: 2-arm quasi-RCT

Location: Sweden

Study started: Not reported


ParticipantsNumber randomised: 250 (125, 125)

Number analysed: 225 (112, 113) analysed at 2 years (available at final examination)

Age range: Mean and median 3 years

Background exposure to other fluoride: 0.3 ppm water fluoridation. At 5 years of age "no differences in toothbrushing frequency, regular use of fluoride tablets or use of fluoridated toothpaste"


InterventionsComparison: FV + ptc versus NT + ptc
Group 1 (n = 125): NaF varnish group (Duraphat® 22,600 ppm F), applied twice a year, with thin brush, left to dry (duration NR)

Group 2 (n = 125): No treatment

Post-op instructions: No hard food or toothbrushing until following day


Outcomes2-year defs increment - (E) (CA)cl + (DR)xr
Reported at 1 and 2 years follow-ups: O-defs; MD-defs; BL-defs; ds (NCA); proportion of children with 1 or more new defs (at CA level); drop-outs


NotesBaseline characteristics (defs) unbalanced, 1.05 in FV, 0.71 in NT
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold = CA and NCA; state of tooth eruption included = E. Radiographic assessment (if required) by 1 examiner; diagnostic threshold = DR. Diagnostic errors NR


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuote: "At baseline examination, every other child was assigned to the test group and the remainder to the control group"

Comment: Not randomised. Alternation used to allocate into groups

Allocation concealment (selection bias)High riskNo information provided. However, the non-random method used for allocation would not allow for allocation concealment

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: "Fluoride varnish was applied to the teeth of the children in the test group......No placebo treatment was performed in the control group"

Comment: No placebo described. Parents were not aware, however, that their children were taking part in any experiment and regarded the treatment as a routine part of the Public Dental Health Service given to all children

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Annual caries exam was performed by the same examiner and was single blind"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Low riskOverall drop-out for length of follow-up: 10% in 2 years. Drop-outs by group: 13/125 FV, 12/125 NT. Reason for losses: Moving out of town 13 FV, 12 NT

Comment: Numbers lost were not unduly high for the length of follow-up, were reported by group and showed no differential losses between groups. The only reason reported for missing data is acceptable and balanced between groups. Caries data pertain to participants present at final examinations

Selective reporting (reporting bias)Low riskOutcomes reported:

defs increment - (E) (CA)cl + (DR)xr, at 1 and 2 years follow-ups; O-defs, MD-defs, BL-defs, ds (NCA); proportion of children with 1 or more new defs (at CA level); drop-outs

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way

Baseline characteristics balanced?High riskPrognostic factor reported: ds (CA): 1.05 (2.34) FV, 0.71 (1.62) NT; ds (NCA) 1.16 (3.11) FV, 0.59 (1.81) NT

Mean age: 3 years (both groups)

Comment: Initial caries appears unbalanced between groups

Free of contamination/co-intervention?Unclear riskQuotes: "After each annual examination the child was given dental treatment by the Public Dental Health Service if necessary" and "...children in the test group had two more appointments with the dentist during these 2 years......."

Comment: These more frequent visits might have made both children and dentists rather more concerned about dental health cannot be totally excluded

Holm 1984

MethodsDesign: 2-arm RCT

Location: Eslöv, Sweden

Study started: 1977


ParticipantsNumber randomised: 120 (numbers by group NR)

Number analysed:109

Age range: Every child aged 5 years and 9 months at baseline registration

Background exposure to other fluoride: Water (Eslöv drinking water contained 0.4-0.9 ppm F), "From the age of 6 years the children received organized dental care and took part in a weekly fluoride rinsing program (0.025% NaF for the 1st year, thereafter 0.2% NaF)"


InterventionsComparison: FV + ptc** versus NT
Group 1 (n = NR): NaF varnish group (Duraphat® 22,600 ppm F), applied twice a year, with a pencil (probe used to press the varnish into fissure)

Group 2 (n = NR): No treatment

Post-op instructions: No hard food or toothbrushing of treated surfaces until following day

**Prior prophylaxis with non-fluoride paste carried out in FV group only


Outcomes2-year 1stm DFS (fissures only) increment - (CA) (U)
Reported at 2 years follow-up: 1stm DFT increment; proportion of children with 1 or more new 1stm DFS (at CA level), proportion of carious 1st molars


NotesBaseline characteristics (dmfs) 'balanced'
Clinical (VT) caries assessment by 1 examiner (probe had to stick into cavity); diagnostic threshold = CA; state of tooth eruption included = U; intra-examiner reproducibility checks for 1st molars (icc 0.98)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "...the children were randomly divided into a test and a control group"

Comment: Not enough information

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote from correspondence: "Were the treatments conducted blind? In the proper sense, no, since we did not use a placebo varnish"

Comment: No placebo described

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote from correspondence: "Were the treatments conducted blind? In the proper sense, no, since we did not use a placebo varnish"

Comment: No mention of blinding of assessors in the report, radiographic examinations performed independently of clinical examinations though, and additional information is ambiguous about blinding

Blind outcome assessment deemed likely but it remains unclear

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall drop-out: 25/120 (20.8%) in 2 years. Drop-outs not reported by group. Reasons for losses (numbers not reported by group): Excluded because molars had erupted at baseline examination (based on not meeting inclusion criteria, but probably after randomisation) (7), moved away (2), unwilling to participate (2)

Comment: Numbers lost were not unduly high for the length of follow-up. Differential losses are not assessable and it is unclear whether reasons for missing outcome data are balanced. Caries data used in analysis pertain to participants present after all reported losses (as above)

Selective reporting (reporting bias)Low riskOutcomes reported:

1stm DFS (fissures only) increment - (CA) (U), at 2 years follow-up; 1stm DFT increment; proportion of children with 1 or more new 1stm DFS (at CA level); proportion of carious 1st molars

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way

Baseline characteristics balanced?Low riskPrognostic factor reported: Initial DMFT/S: 0; mean age: 5.75 years (all participants); dmfs (total): 8.32 (8.32) FV, 10.8 (8.27) NT; dmfs (proximal): 3.50 (3.50) FV, 4.86 (3.67) NT

Comment: Initial caries appears balanced between groups

Free of contamination/co-intervention?Low riskQuote: "From the age of 6 years the children received organized dental care and took part in a weekly fluoride rinsing program (0.025% NaF for the 1st year, thereafter 0.2% NaF"

Comment: Exposure assumed to be similar in each group

Koch 1975

MethodsDesign: 2-arm RCT

Location: Jönköping, Sweden

Study started: 1973


ParticipantsNumber randomised: 135 (numbers by group NR)

Number analysed: 121 (60, 61) analysed at 1 year (available at final examination)

Age range: 15 years at start of study

Background exposure to other fluoride: Children in both groups exposed to local dental health programme involving mouthrinsing with 0.2% NaF solution every 2 weeks


InterventionsComparison: FV + ptc** versus NT
Group 1 (n = 60): NaF varnish group (Duraphat® 22,600 ppm F), applied twice a year, with a cotton swab, about 0.7 ml applied per child (full mouth treatment), left to dry for 2 minutes

Group 2 (n = 61): No treatment

Post-op instructions: No hard food or toothbrushing until following day

**Prior prophylaxis with non-fluoride paste carried out in FV group only


Outcomes1 year DMFS increment - (E) (CA/NCA)cl + (DR/ER)xr
Reported at 1 year follow-up: O-DMFS; MD-DMFS; BL-DMFS

Data for cavitated dentine lesions separate to initial enamel caries - clinical and radiographs combined


NotesBaseline characteristics (DMFS) balanced
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold = CA and NCA; state of tooth eruption included = E. Radiographic assessment (full-mouth BW) by 1 examiner; diagnostic threshold = DR and ER. Intra-examiner reproducibility checked for DMFS cl + xr examinations in 20% sample (mean difference of 0.2 DS)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "The children were randomly divided into a test and a control group"

Comment: Not enough information provided

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: No placebo described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuotes: "The examiner did not know whether the child belonged to the test or the control group"; "All children were examined clinically and radiographically"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall drop-out for length of follow-up: 10% (14/135) in 1 year. Drop-outs by group: Not reported. Reasons for losses: Not reported

Comment: Numbers lost were not unduly high for the length of follow-up. It is unclear if there were differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at final examinations

Selective reporting (reporting bias)Low riskOutcomes reported:

DMFS increment - (E) (CA/NCA)cl + (DR/ER)xr, at 1 year follow-up; O-DMFS, MD-DMFS, BL-DMFS

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way

Baseline characteristics balanced?Low riskPrognostic factor reported: DMFS 31.0 (10) FV, 27.4 (11) NT

Comment: Initial caries appears balanced between groups

Free of contamination/co-intervention?Low riskQuote: "During the experimental year, all the children in both the test and control groups were exposed to the local dental health program consisting of mouthrinsing with 0.2% NaF solution every fortnight"

Comment: Assumed that exposure to fluoride mouthrinse similar in both groups

Lawrence 2008

MethodsDesign: Cluster RCT- 2 arms

Location: Sioux Lookout Zone (SLZ), Northwest Ontario, Canada

Study started: 2003


ParticipantsNumber randomised: 1275 (915, 360)

Number analysed: 1160 (832, 328) (ITT numbers used) in 20 communities analysed at 2 years (present for at least 1 follow-up examination)
Age range: 5 months-5 years (mean = 2.5)

Background exposure to other fluoride: None reported

Other background exposures: OH counselling of caregivers (promoting good oral health habits/awareness)


InterventionsComparison: FV versus NT
Group 1 (n = 915): 5% NaF varnish group (Duraflor® 22,600 ppm F), applied 2 to 3 times/year, to all surfaces of the primary dentition, with small brush, and left to dry (duration NR)

Group 2 (n = 360): NT

Post-op instructions: Pamphlet distributed with post-fluoride application instructions


Outcomes2-year Net dmfs increment - (CA)cl (E/U)

Reported at 2 years follow-up:

Caries incidence; net caries increment calculated form change from sound, white spot or filled at baseline to 'clinical caries' missing due to carious extraction or stainless steel crown at follow-up. Caries reversals (white spots/early demineralised to sound) were subtracted from the caries increment creating 'net' caries increment


NotesBaseline characteristics balanced
Clinical caries assessment by 6 examiners, diagnostic threshold = CA

Kappa values for inter-examiner agreement ranged from 0.61 to 0.8 in all survey years


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "A randomisation master list based on computer generated random numbers assigned each community to a group"

Allocation concealment (selection bias)Low riskQuote: "..clusters (n = 20) randomised at once"

Comment: When clusters are large in numbers and are randomised at once as in this case, allocation concealment should not be an issue

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuotes: "The treatment consisted of FV 2 times per year with caregiver counselling while the no-treatment controls received counselling alone"

Comment: No placebo described

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuotes: "Six teams of dental hygienists and recorders were flown into the participating communities ... to carry out the oral examinations and interviews"

"Different examiners were sent to different communities each year to keep them masked to the community's treatment assignment"

"Dental hygienists applied the varnish using a standard method of application"

Comment: Blind outcome assessment is mentioned but there is apparently conflicting information about blinding since examiners appear to have been involved in giving treatment

Incomplete outcome data (attrition bias)
All outcomes
Low riskOverall drop-out for length of follow-up (reported for individuals within clusters only): 9% in 2 years. Drop-outs by group: 97/915 FV, 32/328 NT (10.6%, 9.8%). Reasons for losses (FV/NT): Relocated (38/7), lost to contact (10/14), did not attend appointment (34/7), sick (0/1), in foster care (8/0), parents unable to bring in (1/2), deceased (3/0), discontinued intervention (1/0), unco-operative (1/0). "ITT analysis was carried out for 1146 children who completed either the 12 or 24 month follow-up"

Comment: Recruitment of children was correctly done before clusters (the communities) had been randomised. Numbers lost were not unduly high for the length of follow-up, and showed no differential losses between groups. Reasons for losses are acceptable and balanced between groups. Caries data used in the analysis pertain to participants present for at least 1 follow-up exam (and analysis done at individual level within clusters takes clustering into account)

Selective reporting (reporting bias)Low riskOutcomes reported: dmfs increment (CA)cl at 2 years follow-up; caries incidence; drop-outs

Comment: Trial protocol not available. The primary outcome was reported but secondary outcomes (cost, quality of life, side effects, acceptability) will be reported subsequently

Baseline characteristics balanced?Low riskPrognostic factors reported: dmft: 7.19 (6.29) FV, 6.52 (6.16) NT

Mean age: 2.54 (1.23) FV, 2.51 (1.18) NT

dfs: 12.89 (16.02) FV, 11.80 (16.30) NT

Percentage caries-free: 27.3% FV, 31.1% NT

dt/dmft: 73.9% FV, 73.3% NT

Comment: Initial caries appears balanced between groups (for individuals within clusters)

Free of contamination/co-intervention?Low riskComment: No apparent unbalanced provision of additional interventions/no difference in co-interventions. No apparent risk of contamination

Liu 2012

MethodsDesign: RCT (4 arms - sealant, varnish, fluoride solution, placebo)- 2 included in this review

Location: Guangzhou, southern China

Study started: April 2008


ParticipantsNumber randomised: 252 children (778 first molars) (molars with ICDAS 2 included carious by Diagnodent excluded)

Number analysed: 240 children (737 first molars)
Age range: Grade 2 or 3 (mean age 9.1 years)

Background exposure to other fluoride: 90% of toothpastes on sale in area were fluoridated


InterventionsComparison: FV + OH education versus PL + OH education
Group 1 (n =124 children, 385 teeth): 5% varnish group (Duraphat® = 22,600 ppm F Colgate Palmolive Ltd, Waltrop, Germany), applied every 6 months, plus oral health education (no details reported), tooth was isolated using cotton balls and varnish applied to pit/fissures with small disposable brush, and left to dry (child instructed not to eat or drink for 30 minutes)

Group 2 (n = 128 children, 393 teeth): Placebo (water) applied annually and oral health education


Outcomes2-year new dentine caries, prevented fraction

Reported at 2 years follow-up


NotesSample size calculation reported: To detect a 10% difference in new caries it was estimated that 1478 teeth and 493 children were required across the 4 arms of the study (power 80%, α = 0.05, ICC 0.2)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "..an assistant, using computer generated random numbers, allocated the children individually among 4 groups"

Allocation concealment (selection bias)Unclear riskAllocation was done by an assistant, and treatments were applied by a dentist. Unclear how allocation was communicated to treating dentist

Blinding of participants and personnel (performance bias)
All outcomes
High riskBlinding of patients not done. Sealant application process different from varnish application process. Varnish applied every 6 months, placebo applied annually

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Status of the molars, ...was assessed every 6 months by the same blinded examiner"

Incomplete outcome data (attrition bias)
All outcomes
Low risk12/252 (5%) children excluded from analysis at 2 years (8/124 in varnish - 7 children moved from area and 1 excluded due to orthodontic treatment and 4/128 in placebo group left the area)

Selective reporting (reporting bias)Low riskPlanned outcomes of new dentinal caries and preventive fraction reported

Baseline characteristics balanced?Low riskVarnish and placebo groups similar at baseline

Free of contamination/co-intervention?Low riskNo co-intervention identified

Milsom 2011

MethodsDesign: 2-arm cluster RCT

Location: Lancashire, UK

Study started: 2006


ParticipantsNumber randomised and eligible: 2967 (1473, 1494)

Number analysed: 2604 at 3 years
Age range: 7-8 average age 8.1 years
Backgound exposure to fluoride: Toothpaste + rinse


InterventionsComparison: FV versus NT
Group 1 (n = 1473): 5% NaF varnish (Duraphat® 22,600 ppm F), applied 3 times a year over 3 years in school, with small brush, 0.1 ml applied per child

Group 2 (n = 1494): No treatment

Post-op instructions: No other fluoride treatments for 2 days


Outcomes3-year DFS, DFT increment (1stm), number with caries (DFS, DFT) CA


NotesBaseline characteristics (DFS) 'balanced'
Clinical caries assessment by 8 examiners


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "...using computer-generated random numbers, stratified by the locality of the school and the size of the school"

Allocation concealment (selection bias)Low riskQuote: "An ordered list of random group codes for all schools was produced, and only the study statistician and the trial manager had access to these codes"

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding of participants mentioned and no placebo used

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Examiners and their assistants were given a sealed envelope containing the allocation code for the school; this was opened after all the baseline examinations had been completed and the dentist made another appointment for application of the fluoride varnish in the test schools. This system ensured allocation concealment and facilitated efficient delivery of the intervention"

Incomplete outcome data (attrition bias)
All outcomes
Low riskOverall drop-out for length of follow-up (reported for individuals within clusters only): 12% in 3 years. Drop-outs by group: 197/1473 FV, 166/1494 NT (13%, 11%). Reasons for losses (FV/NT): Not explained

Comment: Numbers lost were not unduly high for the length of follow -up, and showed no differential losses between groups. Losses are acceptable and balanced between groups. Caries data used in the analysis pertain to participants present for at follow-up exam (and analysis done taking clustering into account)

Selective reporting (reporting bias)Low riskOutcomes reported: DMFS/T increment (CA)cl at 3 years follow-up; caries progression/prevalence. Drop-outs

Baseline characteristics balanced?Low riskPrognostic factors reported: initial DFS: 3 FV, 3 NT

Toothbrushing frequency, toothpaste use, participation in rinsing programme, SES are not tabulated but reported as balanced between groups

Free of contamination/co-intervention?Low riskQuote: "Participants were advised not to have fluoride treatment administered by their dentist for 2 days after application of the varnish"

Modeer 1984

MethodsDesign: 2-arm RCT

Location: Stockholm, Sweden

Study started: Not reported


ParticipantsNumber randomised: 236 (118, 118)

Number analysed: 194 (87, 107) analysed at 3 years (available at final examination)

Age range: 14 years at start of study

Background exposure to other fluoride: Water (local drinking water contained 0.24 ppm F), children in both groups exposed to dental health programme involving mouthrinsing with 0.2% NaF solution every 2 weeks (for the whole duration of the study)


InterventionsComparison: FV + ptc** versus NT
Group 1 (n = 87): 5% NaF varnish group (Duraphat® 22,600 ppm F), applied 4 times a year, with small brush, 0.3 to 0.5 ml applied per child

Group 2 (n = 107): No treatment

Post-op instructions: No eating for 4 hours after application, no toothbrushing until following day

**Prior prophylaxis with non-fluoride paste carried out in FV group only


Outcomes3-year MD-DFS increment - (E) (ER/DR)xr
Reported at 3 years follow-up: Caries progression rate


NotesBaseline characteristics (toothbrushing frequency, toothpaste use, participation in rinsing programme, SES) described as 'balanced' (values NR); initial DFS unbalanced
No clinical assessment of caries
Radiographic assessment (4 postBW) by 1 examiner; intra-examiner reproducibility checks (icc = 0.89)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The children who participated during the 3-year period were randomly divided into a fluoride varnish group and a control group"

Quote from correspondence: "I do not exactly remember. It was either by lot or using special random numbers"

Comment: Probably adequate

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuotes: "The fluoride varnish application was carried out by a specially trained dental nurse"

Comment: No placebo described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuotes: "Radiographic registrations were made without knowing the group to which the child belonged"; "The fluoride varnish application was carried out by a specially trained dental nurse"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall drop-out for length of follow-up: 18% in 3 years. Drop-outs by group: 31/118 FV, 11/118 NT. Reasons for losses (FV, NT): No co-operation (20, 0), moved out (5, 3), orthodontic treatment (6, 8)

Comment: Numbers lost were not unduly high for the length of follow-up, but there is a differential loss between groups (26.3% FV, 9.3% NT) and 1 of the reasons for missing data (no co-operation) is unbalanced (unacceptable since differential drop-out might be due to treatment). Caries data used in the analysis pertain to participants present at final examinations

Selective reporting (reporting bias)Low riskOutcomes reported:

1st & 2nd mpmMD-DFS increment - (E) (ER/DR) xr, at 3 years follow-up; caries progression rate; drop-outs

Comment: Trial protocol not available. All pre-specified outcomes were reported and were reported in the pre-specified way

Baseline characteristics balanced?High riskPrognostic factors reported: Initial DFS: 1.1 FV, 1.7 NT

Toothbrushing frequency, toothpaste use, participation in rinsing programme, SES are not tabulated but reported as balanced between groups

Comment: Initial DFS levels unbalanced

Free of contamination/co-intervention?Low riskQuote: "The children in both the fluoride varnish group and the control group participated in the routine fluoride rinsing programme which consisted of mouthrinses every 14 days with a 0.2% NaF solution during the entire experimental period"

Comment: No apparent co-intervention, exposure assumed to be similar in both groups

Salazar 2008

MethodsDesign: 2-arm parallel group RCT

Location: Rio de Janeiro, Brazil

Study started: June 2006 to July 2007


ParticipantsNumber randomised: 200

Number analysed: 148

Age range: 12-48 months

Background exposure to other fluoride: Majority of participants exposed to fluoridated water but concentration varied depending on area of residence. 84% in varnish and 75% of control group used fluoride toothpaste but not all children brushed daily and some children brushed unsupervised which may have compromised effectiveness


InterventionsComparison: FV versus PL
Group 1 (n = 71): 5% NaF varnish group (Duraphat® 22,600 ppm F), applied every 6 months (2 applications)

Group 2 (n = 77 ): Placebo applied every 6 months (2 applications)

All children had their teeth cleaned with water, then isolated with cotton rolls and dried with air prior to the application of either varnish or placebo with a microbrush

Post-op instructions: Children were instructed no to eat hard food or brush their teeth on the day of application


Outcomes1 year follow-up: New dentinal caries lesions, mean caries increment, adverse effects


NotesVisual caries diagnosis ICDAS (CA + NCA)

High caries prevalence population. Approximately 1/2 children had caries in the primary teeth and approximately 1/4 had dentinal caries

Sample size calculation reported that 85 children per group were required to show a reduction in caries from 33% to 15%, and additional 15 recruited per group to allow for anticipated loss to follow-up


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "...computerised randomisation using Excel software"

Allocation concealment (selection bias)Low riskSealed envelopes used to conceal the allocation from the researchers

Blinding of participants and personnel (performance bias)
All outcomes
Low riskChildren/caregivers/operators and outcome assessors blinded to allocated treatment

Blinding of outcome assessment (detection bias)
All outcomes
Low riskChildren/caregivers/operators and outcome assessors blinded to allocated treatment

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk200 children randomised and 29 and 23 excluded from the analysis because they did not attend the final examination. Overall loss is high but reasons given are loss of contact with family due to change of address or telephone number for both groups

Selective reporting (reporting bias)Low riskCaries outcome and adverse effects reported

Baseline characteristics balanced?Low riskBoth caries prevalence and demographic factors appear to be balanced at baseline

Free of contamination/co-intervention?Unclear riskUnclear what the actual exposure to fluoride toothpaste and fluoridated water was

Sköld 2005

MethodsDesign: 4-arm RCT

Location: Sweden (West coast)

Study started: 1998


ParticipantsNumber randomised: 854

Number analysed: 758 analysed at 3 years (present for all examinations)

Age range: 13-16 years (all subjects 13 years at start of 3-year study)

Background exposure to other fluoride: Water (in 1 of 3 trial sites only), toothpaste


InterventionsComparison: FV (3 groups) + ptc** versus NT

Group 1 (n = 190): NaF varnish (Duraphat® 22,600 ppm F), twice a year
Group 2 (n = 186): NaF varnish (Duraphat® 22,600 ppm F), 3 times a year

Group 3 (n = 201): NaF varnish (Duraphat® 22,600 ppm F), 8 times a year

Group 4 (n = 181): No treatment

Application in mobile units in schools, to all posterior approximal surfaces, with syringe, 0.3 mL (1 drop) applied, left to dry (duration NR)

Post-op instructions: Refrain from eating hard foods on that day; no brushing until next day

**Toothbrushing with non-fluoride paste carried out in FV groups only


Outcomes3-year DFS incidence - (E) (DR/ER)xr (only)
Reported at 3 years follow-up: DS; FS; caries progression


NotesBaseline characteristics (DS/FS) balanced
X-Ray caries assessment by 1 examiner; diagnostic threshold = DR and DE; state of tooth eruption included = E; for intra-examiner reliability, 10% of the radiographs read twice with an interval of 2 months (Kappa 0.90 for all scores and 0.82 for carious surfaces)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "...the adolescents were randomly allocated within each school class into 4 groups"

Comment: Not enough information given

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuotes: "Three trained dental nurses and one dental hygienist performed all the treatments..."; "...treated adolescents with fluoride....and no treatment (control)"

Comment: No placebo described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuotes: "...films were scored and analysed blindly by one of the authors"; "Three trained dental nurses and one dental hygienist performed all the treatments..."

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall drop-out for length of follow-up: 11% in 3 years. Drop-outs by group: Not reported. Reasons for losses: Moving away from the area, not attending all treatment sessions

Comment: Numbers lost overall were reported, and not unduly high for length of follow-up. Numbers randomised (at start) were not reported by group, thus drop-outs by group not obtainable. It is unclear if reasons for the missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants followed up for the entire study duration and attending all treatment sessions

Selective reporting (reporting bias)Low riskOutcomes reported:

1st and 2nd mpmDS/FS final prev and DFS incidence (CA/NCA) xr at 3 years follow-up; drop-outs

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way

Baseline characteristics balanced?Low riskPrognostic factors reported:

DS (approximal dentine): 0.15 (0.51) FV1, 0.12 (0.36) FV2, 0.13 (0.49) FV3, 0.07 (0.28) NT

FS: 0.13 (0.48) FV1, 0.10 (0.43) FV2, 0.08 (0.46) FV3, 0.13 (0.45) NT

DS (approximal enamel): 2.15 (3.37)FV1, 2.13 (3.30) FV2, 2.36 (3.86) FV3, 1.75 (2.43) NT

Comment: Initial caries appears balanced between groups

Free of contamination/co-intervention?High riskQuotes: "All participants in this study attended the dental clinics for regular check-ups and were given prophylactic treatment according to their actual caries risk. The dentists who treated them had no knowledge to which group they belonged"

"... 95% of the adolescents in all areas were treated with one F varnish at the yearly check-up, ... all of them, independent of area and caries risk revealed they brushed their teeth twice a day using an F toothpaste"

Comment: Although dentists treating the children in the yearly check-ups were unaware of group assignment, 95% of all children were treated with 1 application of fluoride varnish, an apparent contamination

Tagliaferro 2011

MethodsDesign: Quasi-randomised CCT

Location: Piracicaba, Brazil

Study started: Unclear, protocol registered in 2004, before 2008


ParticipantsNumber randomised: 219

Number analysed: 181 (109, 110)

Age range: 6-8 years

Background exposure to other fluoride: Water 0.7 ppm, toothpaste

Other background exposures: OH education


InterventionsComparison: FV versus NT
Group 1(n = 109): 5% NaF varnish (Duraphat® 22,600 ppm F), applied 6 monthly, at schools, to all surfaces of first permanent molars, with small brush, and left to dry

Group 2 (n = 110): No treatment

All participants received oral health education, and a toothbrush, floss, and fluoride toothpaste for toothbrushing prior to examinations (5 during the study)

Post-op instructions: No chewing or brushing after application, no eating of hard food till next day


OutcomesReported at 2 years follow-up: DMFS (all), DMFS (1stm), increment (CA/CA+NCA)cl (E/U)


NotesBaseline characteristics (dmft/DMFT/age) balanced. Surfaces affected: NR (dmft = 4.4/ DMFT = 0.3)
Clinical (VT) caries assessment by 1 examiner; diagnostic threshold = CA and NCA; state of tooth eruption included = E/U; 10% sample re-examined at each examination; examiner calibration (Kappa 0.90 CA/ 0.95 CA+NCA)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuote: "This study was a systematically randomized trial ...Then they were systematically allocated in each treatment group by the main researcher..."

Quote from correspondence: "At baseline examination, children were systematically allocated in each treatment group, as follows: approximately 10 children of each classroom were taken to the examiner by the dental hygienist (she did not know the risk of caries level of the children before each examination) who organized them in a queue at random. The examiner (Pardi V) performed the examination of the first child, the main research (Tagliaferro EP) recorded the data in a specific form and classified the child in high or low caries risk, according to pre-established criteria. After that, each classified children were allocated in the Control, Varnish or Sealant group in this sequence"

Comment: Alternation used to generate sequence

Allocation concealment (selection bias)High riskQuote from correspondence: "The same researcher did the allocation and applied the sealants. Also, the non-random method used for allocation would not allow for allocation concealment"

Blinding of participants and personnel (performance bias)
All outcomes
High riskNo placebo varnish described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "...the calibrated dentist was not aware of group assignments during evaluations"

Quote from correspondence: "The examiner did not see the records/documents used for recording the interventions in each child"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Low riskOverall drop-out for length of follow-up: 17% in 2 years. Drop-outs by group: 19/109 2FV, 19/110 2NT (17.4%, 17.3%). Reason for losses: Moving out and refusing final examination (NR by group)

Comment: Numbers lost were not unduly high for the length of follow-up, were reported by group, and showed no differential losses between groups. The reasons reported for missing data are acceptable (although unclear if balanced) between groups. Caries data seem to pertain to participants present at final examinations

Selective reporting (reporting bias)Low riskOutcomes reported: 1stm ODMFS increment - (CA/NCA) (E+U), at 2 years follow-up; drop-outs

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way

Baseline characteristics balanced?Low riskPrognostic factors reported: DMFT: 0.26 (0.58) FV, 0.35 (0.67) NT. dmft: 4.28 (2.54) FV, 4.53 (3.0) NT; mean age: 7.0 (0.7) years (all groups)

Comment: Initial caries appears balanced between groups

Free of contamination/co-intervention?Low riskComment: No apparent co-intervention or contamination

Tewari 1990

MethodsDesign: 4-arm RCT (2 arms included in this review)

Location: Chandigarh, India

Study started: In/before 1982


ParticipantsNumber randomised: 657

Number analysed: 618 children analysed at 2.5* years (available at 2nd examination))

Age range: 6-12 years (mean = 8.5)

Background exposure to other fluoride: Water (drinking water contained 0.3 ppm F)


InterventionsComparison: FV + ptc versus 'PL' + ptc
Group 1 (n = 331): NaF varnish group (Duraphat® 22,600 ppm F), applied twice a year, with single tufted brush, about 0.5 ml applied per child, left to dry for 4 minutes

Group 2 (n = 326): Double distilled water

Post-op instructions: No rinsing or drinking for 1 hour after application, no solids (only liquids and semisolids) until following morning


Outcomes2.5-year NetDMFS increment - (CA/NCA) (E/U)
Reported at 1.5 and 2.5 year follow-ups: ODMFS (CA/NCA) (E/U); MDDMFS (CA/NCA) (E/U); BLDMFS (CA/NCA) (E/U); DMFT (CA/NCA) (E/U)


NotesBaseline characteristics (age, DMFS, DMFT) balanced
Clinical (VT) caries assessment by 2 examiners; diagnostic threshold = NCA/CA; state of tooth eruption included = E/U; constant duplicate examination of 10% sample between same and both examiners (results NR)
*Final 4.5 years results not available (but results closest to 3 years were chosen)

Prior prophylaxis with non-fluoride paste carried out in both groups


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "...children were randomly allocated into 4 groups with the help of a computer, but were stratified according to age, sex, number of erupted permanent teeth, socio-economic status and previous caries experience"

Comment: Most likely a computer generated sequence used

Allocation concealment (selection bias)Unclear riskNo information provided

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "...teeth of children in the control group was painted with double distilled water"

Comment: Most likely participants blinded. Blind outcome assessment and use of 'placebo' described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuotes: "The study was single blind as the recorder did not know the fluoride group to which the child belonged nor the previous recording"; "...teeth of children in the control group was painted with double distilled water"

Comment: Most likely assessors and participants blinded. Blind outcome assessment and use of 'placebo' described

Incomplete outcome data (attrition bias)
All outcomes
Low riskOverall drop-out for length of follow-up: 6% in 2.5 years. Drop-outs by group: 20/331 FV, 19/326 'PL'. Reasons for losses: NR

Comment: Numbers lost were not unduly high for the length of follow-up, and showed no differential loss between groups. "Balancing of DMFT and DMFS as well as the mean age was not disturbed between the various experimental groups due to the attrition of the trial population." Caries data used in the analysis pertain to participants present at final examination

Selective reporting (reporting bias)Low riskOutcomes reported:

DMFS increment - (CA/NCA) (E/U), at 1.5 and 2.5 year follow-ups; ODMFS (CA/NCA) (E/U); MDDMFS (CA/NCA) (E/U), BLDMFS (CA/NCA) (E/U), DMFT (CA/NCA) (E/U); drop-outs

Comment: Trial protocol not available. All pre-specified outcomes (in Methods) were reported and were reported in the pre-specified way

Baseline characteristics balanced?Low riskPrognostic factors reported: DMFT: 2.0 (1.88) FV, 1.87 (1.87) PL; DMFS: 2.60 (2.43) FV, 2.38 (2.29) PL; mean age: 8.43 FV, 8.33 PL

Comment: Initial caries appears balanced between groups, because these were stratified in the randomisation process

Free of contamination/co-intervention?Low riskNo information provided

Weintraub 2006

MethodsDesign: 3-arm RCT

Location: San Francisco, USA

Study started: 2000


ParticipantsNumber randomised: 376

Number analysed: 280 analysed at 2 years (available at any examination)

Age range: 6-44 months (0.5-3.7 years; mean = 1.8 years)

Background exposure to other fluoride: Water, toothpaste

Other background exposures: OH counselling


InterventionsFV (2 groups) versus 'PL'

Group 1 (n = 124): NaF varnish (Duraphat® 22,600 ppm F), twice a year
Group 2 (n = 126): NaF varnish (Duraphat® 22,600 ppm F), once a year

Application in health centres, to all teeth surfaces, teeth dried with gauze, varnish applied with brush, 0.1 mL (1 drop) applied per arch, left to dry (duration NR)

Group 3 (n = 126): NaF varnish applied to gauze, which was then folded and the dry area used to wipe the child's teeth ensuring that no NaF varnish was applied

Pre/post-op instructions: Refrain from brushing children's teeth with F dentifrice the day of varnish treatment


Outcomes2-year dfs increment - (CA/NCA)cl (E)

Reported at 1 and 2 years follow-ups: Any caries incidence/no caries incidence(CA/NCA)

Adverse events reported


NotesBaseline characteristics (initial caries = 0, age) balanced
Clinical caries assessment by 1 examiner, diagnostic threshold = CA/NCA

Intra-examiner reliability, from repeat examinations of 21 children, yielded Kappa statistic of 0.96


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The team's biostatisticians conducted the computer generated random assignment of participants"

Allocation concealment (selection bias)Low riskQuote: "Assignment was concealed in sealed, opaque, labelled envelopes, unopened until time for treatment by the clinician"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Masking accompanying caregivers to the control group assignment was attempted. The control group's tray set-up was the same. For children in this group, fluoride varnish was placed on gauze, which was then folded. The dry area was used to wipe the child's teeth, and no fluoride varnish was applied"

Comment: Use of 'placebo' described

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuotes: "One paediatric dentist (FRG) masked to treatment groups, conducted all dental examinations"; "One dentist (BJ) who spoke English, Spanish, and Cantonese provided clinical interventions at both sites"

Comment: Blind outcome assessment

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOverall drop-out for length of follow-up: 26% in 2 years. Drop-outs by group (based on data from all children with any follow-up exam): 31/124 FV1, 39/126 FV2, 26/126 'PL'. Reasons for losses: Not reported. "For primary analysis, we used the intention-to-treat approach.... Analysis used data from all children with a 12- or 24-month follow-up exam." "Markov Chain Monte Carlo estimation was used in multiple imputation of missing data."

Comment: Numbers lost were not unduly high given the length of follow-up, and losses between FV and PL not statistically significantly different. It is unclear if reasons for the missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants at a follow-up examination

Selective reporting (reporting bias)Low riskOutcomes reported: dfs (CA)cl increment at 1 and 2 years follow-ups; dfs(NCA/CA)cl; caries incidence; drop-outs

Comment: The pre-specified primary outcome was reported in the pre-specified way but the secondary outcomes (diet, bottle use, dental utilisation) will be reported subsequently

Baseline characteristics balanced?Low riskPrognostic factors reported for all groups: Mean age 1.8 (0.6)

Comment: As regards initial caries (dfs), eligibility criteria for the trial was that all primary teeth should be caries-free without demineralisation, therefore this characteristic was balanced

Free of contamination/co-intervention?Low riskThe protocol violation caused by the provision of placebo varnish to the intervention group was accounted for in the ITT analysis

Yang 2008

MethodsDesign: Double blind 4-arm RCT - 3 arms included in this review

Location: Chongqing City, China

Study started: December 2004


ParticipantsNumber randomised: 150

Number analysed: 148

Age range: 3 years old at baseline

Gender: M 79 / F 71


InterventionsComparison: FV (2 groups) versus PL

Group 1 (n = 37): 0.5% FV (Fluor Protector = 5000 ppm) applied with cotton swab twice after teeth were dried. Children told not to eat or drink for 30 minutes. Treatment was applied every 6 months

Group 2 (n = 38): 0.1% FV (Fluor Protector = 1000 ppm) applied with cotton swab twice after teeth were dried. Children told not to eat or drink for 30 minutes. Treatment was applied every 6 months

Group 4 (n = 36): Placebo (water) applied with cotton swab twice after teeth were dried. Children told not to eat or drink for 30 minutes. Treatment was applied every 6 months

Study duration: 2 years

Unclear who applied the interventions, or where the applications took place. There was also a third intervention group (Group 3) 0.5% sodium fluoride which was excluded from the review


OutcomesPrevalence of caries (CA), dmft, dmfs, number of missing teeth


NotesTranslated by Chunjie Li (September 2012)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe authors only described that the participants were allocated randomly without mentioning the methods of randomisation

Allocation concealment (selection bias)Unclear riskNot mentioned

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blinded trial

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe outcome assessors were blinded to allocated treatment but the details of how this was done are not reported

Incomplete outcome data (attrition bias)
All outcomes
Low risk2 lost to follow-up: 1 in 0.1% fluoride varnish group and 1 in 0.5% sodium fluoride group. Both of these participants were not included in the analysis. Reason was unclear. Unlikely to have introduced a bias

Selective reporting (reporting bias)Low riskPlanned outcomes prevalence of caries, dmft, dmfs reported

Baseline characteristics balanced?Low riskPrevalence of caries, dmft, dmfs were comparable at baseline

Free of contamination/co-intervention?Unclear riskIt was unclear whether participants were exposed to other treatments during the trial

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Alves 1997Length of follow-up of less than 1 year/school year (6 months)

Autio-Gold 2001Follow-up is less than 1 year/school year

Billy-Pryga 1983Split-mouth design - sites within a participant's mouth were allocated to treatment and control groups

Bodnar 1984Non-randomised split-mouth study where only 1 first molar per child was treated and another was used as control

Demito 2011Study on patients undergoing treatment with fixed orthodontic appliances

Dülgergil 2005Additional non-fluoride-based interventions associated to fluoride varnish

Grodzka 1982No random or quasi-random allocation used. Open outcome assessment reported after contacting author

Hetzer 1973Additional non-fluoride-based intervention associated to fluoride varnish. Random or quasi-random allocation not stated or indicated. Blind outcome assessment not stated and unlikely

Heuser 1968No random or quasi-random allocation used (non-random concurrent control). Blind outcome assessment not stated and unlikely. Varnish applied once in 15 months

Hochstein 1975Medically compromised group of children selected. No random or quasi-random allocation used (non-random concurrent control). Open outcome assessment

Ivanova 1990Random or quasi-random allocation not stated or indicated. Blind outcome assessment not stated and unlikely

Ji 2007Communication between Chunjie Li and the review authors confirmed that allocation was based on the preference of clinicians and was not randomly allocated

Kolehmainen 1979Split-mouth design - sites within a participant's mouth were allocated to treatment and placebo groups

Kolehmainen 1981Split-mouth design - sites within a participant's mouth were allocated to treatment and placebo groups

Kunin 1991Random or quasi-random allocation not stated or indicated. Blind outcome assessment not stated and unlikely

Lagutina 1978Random or quasi-random allocation not stated or indicated. Blind outcome assessment not stated and unlikely

Lieser 1978No random or quasi-random allocation used (non-random concurrent control - by matching procedure). Blind outcome assessment not stated and unlikely

Lindquist 1989Fluoride-based intervention associated to control group

Maiwald 1974Random or quasi-random allocation not stated or indicated

Maiwald 1978Random or quasi-random allocation not stated or indicated. Blind outcome assessment not stated and unlikely

Mari 1988Random or quasi-random allocation not stated or indicated. Blind outcome assessment not stated and unlikely

Mari 1988aRandom or quasi-random allocation not stated or indicated (Note - 2 clusters, each assigned to 1 of the 2 groups)

Murray 1977Split-mouth design - sites within a participant's mouth were allocated to treatment and placebo groups

Pashaev 1977Split-mouth design - sites within a participant's mouth were allocated to treatment and control groups. Random or quasi-random allocation not stated. Blind outcome assessment not stated and unlikely

Petersson 1998No random or quasi-random allocation used (non-random concurrent controls - by matching procedure). Blind outcome assessment not stated and unlikely

Ramos 1995Open outcome assessment

Ramos-Gomez 2012Control group of children received varnish as required if lesions developed

Riethe 1977Split-mouth design - sites within a participant's mouth were allocated to treatment and control groups

Rodríguez Miró 1988Additional non-fluoride-based intervention associated to fluoride varnish

Ruszynska 1978Split-mouth design - sites within a participant's mouth were allocated to treatment and control groups

Salem 1979Split-mouth design - sites within a participant's mouth were allocated to treatment and control groups

Schioth 19815 tooth cleaning treatments given to varnish group only. Unclear

Schmidt 1970Split-mouth design - sites within a participant's mouth were allocated to treatment and control groups

Seppä 1982Split-mouth design - sites within a participant's mouth were allocated to treatment and control groups

Shobha 1987Random or quasi-random allocation not stated or indicated. Blind outcome assessment not stated and unlikely (Note - Main outcome data not reported in control group (and not obtainable))

Slade 2011Additional non-fluoride and fluoride-based interventions associated to fluoride varnish

Splieth 2000No random or quasi-random allocation used (non-random concurrent control). Split-mouth study

Suntsov 1991Random or quasi-random allocation not stated or indicated. Blind outcome assessment not stated and unlikely (Note - Only post-treatment effects reported)

Suwansingha 2011Non-randomised split-mouth study. Length of follow-up of less than 1 year (6 months)

Todorashko 1983Additional fluoride-based intervention associated to fluoride varnish. Random or quasi-random allocation not stated or indicated. Blind outcome assessment not stated and unlikely

Tranaeus 2001Additional fluoride-based interventions associated to fluoride varnish. Length of follow-up of less than 1 year/school year (6 months) (Note - Main outcome data not reported)

Treide 1980No mention of randomisation (German translation)

van Eck 1984No random or quasi-random allocation used (non-random concurrent control - by matching procedure)

Wacińska-Drabińska 1987Children were randomly selected for participation but not randomly allocated to treatment groups

Wegner 1976Medically compromised group of children selected. No random or quasi-random allocation used (non-random concurrent control). Blind outcome assessment not stated and unlikely

Winter 1975No random or quasi-random allocation used (non-random concurrent control). Blind outcome assessment not stated and unlikely

Wojtowicz 1986No blind outcome assessment

Xhemnica 2008Length of follow-up of less than 1 year/school year (7 months)

Zimmer 1999No random or quasi-random allocation used (non-random concurrent control). Blind outcome assessment not used

 
Characteristics of ongoing studies [ordered by study ID]
Macpherson 2012

Trial name or titleComparison of the caries-protective effect of fluoride varnish (Duraphat®) with treatment as usual in nursery school attendees receiving preventive oral health support through the Childsmile Oral Health Improvement Programme: an RCT

MethodsRandomised controlled trial, parallel assignment, double blind (subject, caregiver, investigator, outcomes assessor)

Participants3- to 4-year old children in nursery schools

Interventions- Treatment as usual (i.e. any treatment from the family dentist, plus the preventive intervention programme offered to nursery school children, including daily supervised toothbrushing, distribution of toothbrushes and toothpaste and oral health advice given at nursery school)

- Duraphat® fluoride varnish (0.25 ml per application painted on tooth surfaces up to 4 6-monthly applications) in the nursery school setting

OutcomesDental caries, 2-year follow-up

Starting dateOctober 2012

Contact informationStyephen Turner, s.turner@dundee.ac.uk

Notes

 
Comparison 1. Fluoride varnish versus placebo/no treatment

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 D(M)FS increment (prevented fraction - nearest to 3 years (13 trials))13Prevented Fraction (Random, 95% CI)0.43 [0.30, 0.57]

 2 D(M)FT increment (prevented fraction - nearest to 3 years (5 trials))5Prevented fraction (Random, 95% CI)0.44 [0.11, 0.76]

 3 d(e/m)fs increment (prevented fraction - nearest to 3 years (10 trials))103804Prevented Fraction (Random, 95% CI)0.37 [0.24, 0.51]

 4 d(e/m)fs increment (prevented fraction - 2 years (incomplete data))Other dataNo numeric data

 5 d(e/m)ft increment (prevented fraction - nearest to 3 years (2 trials))2322Prevented Fraction (Fixed, 95% CI)0.65 [0.48, 0.82]

 6 d(e/m)ft increment (prevented fraction - 2 years (incomplete data))Other dataNo numeric data

 7 Developing one or more new caries (D(M)FT, 5 trials)53253Risk Ratio (M-H, Random, 95% CI)0.75 [0.53, 1.05]

 8 Developing one or more new caries (d(e/m)ft, 5 trials)51228Risk Ratio (M-H, Random, 95% CI)0.81 [0.62, 1.06]

 
Analysis 1.4 Comparison 1 Fluoride varnish versus placebo/no treatment, Outcome 4 d(e/m)fs increment (prevented fraction - 2 years (incomplete data)).
d(e/m)fs increment (prevented fraction - 2 years (incomplete data))

StudyFV nFV meanNT nNT meanPF

Borutta 20061362.01644.8758.7

 
Analysis 1.6 Comparison 1 Fluoride varnish versus placebo/no treatment, Outcome 6 d(e/m)ft increment (prevented fraction - 2 years (incomplete data)).
d(e/m)ft increment (prevented fraction - 2 years (incomplete data))

StudyFV nFV meanNT nNT meanPF

Borutta 20061360.97642.2456.7

 
Summary of findings for the main comparison.

Fluoride varnish compared with placebo/no treatment for preventing caries in children and adolescents

Patient or population: Children and adolescents

Settings: School/clinic

Intervention: Fluoride varnish

Comparison: No treatment/placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(trials)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

No treatment/placeboFluoride varnish

Permanent tooth surfaces

D(M)FS increment PF - nearest to 3 years (14 trials)

The duration of the trials ranged from 1 to 5 years with most trials (10) being of 2 to 3 years duration
Mean increment in control group 0.171The corresponding mean increments in the intervention group is 0.10 (95% CI 0.07 to 0.12)PF = 0.43 (95% CI 0.30 to 0.57)6478
(13)
⊕⊕⊕⊝
moderate2

Mean increment in control group 2.37The corresponding mean increments in the intervention group is 1.35 (95% CI 1.02 to 1.70)PF = 0.43 (95% CI 0.30 to 0.57)6478
(13)
⊕⊕⊕⊝
moderate2

Mean increment in control group 7.72The corresponding mean increments in the intervention group is 4.40 (95% CI 3.32 to 5.40)PF = 0.43 (95% CI 0.30 to 0.57)6478
(13)
⊕⊕⊕⊝
moderate2

Deciduous tooth surfaces

d((e)/m)fs increment PF - nearest to 3 years (10 trials)

The duration of the trials ranged from 1 to 2.5 years with most trials (7) being of 2 years duration
Mean increment in control group 0.893The corresponding mean increments in the intervention group is 0.56 (95% CI 0.44 to 0.68)PF = 0.37 (95% CI 0.24 to 0.51)3804

(10 )
⊕⊕⊕⊝
moderate4

Mean increment in control group 1.65The corresponding mean increments in the intervention group is 1.04 (95% CI 0.81 to 1.25)PF = 0.37 (95% CI 0.24 to 0.51)3804

(10 )
⊕⊕⊕⊝
moderate4

Mean increment in control group 13.8The corresponding mean increments in the intervention group is 8.69 (95% CI 6.76 to 10.49)PF = 0.37 (95% CI 0.24 to 0.51)3804

(10 )
⊕⊕⊕⊝
moderate4

*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; PF: prevented fraction

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low quality: We are very uncertain about the estimate

 1 The mean increments in the control group ranged from 0.17 to 7.72, median 2.37
2 The quality of the evidence was downgraded due to considerable heterogeneity; 9 trials were at high and 4 trials at unclear risk of bias. However this body of evidence showed a consistent, large clinically important effect and we have upgraded the quality of evidence to moderate
3 The mean increments in the control group ranged from 0.89 to 13.8, median 1.65
4 The quality of the evidence was downgraded due to considerable heterogeneity; 5 trials were at high and 5 trials at unclear risk of bias. However this body of evidence showed a consistent, large clinically important effect and we have upgraded the quality of evidence to moderate
 
Table 1. Study details

StudyNT or placeboStudy duration (years)Number randomisedNumber analysedCluster RCTSettingAge (years)Varnish manufacturerF conc (ppmF)Frequency per year

Arruda 2012NT1379210NoSchool7 to 14Cavity Shield22,6002

Borutta 1991Placebo2400360NoUnclear12 to 14Lawefluorid Bifluord22,600 56,3002 & 4

Borutta 2006NT2288200YesNursery2 to 4Duraphat Fluoridin22,600 22,6002

Bravo 1997NT2265*214YesSchool6 to 8Duraphat22,6002

Chu 2002Placebo2.5146123NoSchool3 to 5Duraphat22,6004

Clark 1985Placebo5787676NoSchool6 to 7Duraphat Fluor Protector22,600 70002

Frostell 1991NT2206206NoUnclear4Duraphat22,6002

Glugwad 2011NT1250211NoUnclear6 to 7Cavity Shield22,6003 times in 1 week

Hardman 2007NT22091664YesSchool6 to 8Duraphat22,6002

Holm 1979NT2250225NoClinicMean 3Duraphat22,6002

Holm 1984NT211395NoClinic6Duraphat22,6002

Koch 1975NT1135121NoClinic15Duraphat22,6002

Lawrence 2008NT212751160yesClinic1 to 5Duroflor22,6002 to 3

Liu 2012Placebo2252240noSchoolMean 9.1Duraphat22,6002

Milsom 2011NT329672604YesSchool7 to 8Duraphat22,6003

Modeer 1984NT3236194NoClinic14Duraphat22,6004

Salazar 2008Placebo1200148NoClinic1 to 4Duraphat22,6002

Sköld 2005NT1854758NoSchool13Duraphat22,6002, 3 & 8

Tagliaferro 2011NT2219177NoSchool6 to 8Duraphat22,6002

Tewari 1990Placebo2.5766*618NoClinic6 to 12Duraphat22,6002

Weintraub 2006Placebo2376280NoClinic1 to 4Duraphat22,6001.5

Yang 2008Placebo2150111NoNursery3Fluor Protector5000 10002

 * the number randomised was unclear so estimate from other studies of 19% used
F = fluoride; NT = no treatment; RCT = randomised controlled trial
 
Table 2. Random-effects meta-regression analyses of prevented fractions: D(M)FS

ObjectiveCharacteristicNumber of trialsSlope estimate95% CISlope interpretationP value

(2)Mean baseline caries111.33%(-0.72% to 3.39%)Increase per unit increase in mean baseline caries0.18

(3)Any fluorides1011.47%(-46.42% to 69.35%)Higher PF in presence of background fluorides0.66

(3)Dentifrice use8-19.88%(-74.50% to 34.74%)Lower PF in presence of dentifrice use0.41

(3)Fluoridated water1218.37%(-12.54% to 49.28%)Higher PF in presence of water fluoridation0.22

(4)Concentration of fluoride > 5%13-26.61%(-78.30% to 25.08%)Higher PF if concentration of fluoride is > 5%0.28

(4)Length of follow-up13-12.22%(-35.71% to 11.27%)Decrease per unit increase in length of follow-up0.42

(4)Prior prophylaxis1321.66%(-11.62% to 54.94%)Higher PF in presence of prophylaxis0.18

(4)Frequency of application > twice per year13-4.85%(-24.27% to 14.57%)Lower PF if application > twice per year0.59

Time since eruption12-3.79%(-40.13% to 32.55%)Lower PF if time since eruption < 2 years0.82

Placebo or no treatment control135.42%(-32.70% to 43.54%)Increase in PF for no treatment control0.76

Design (individual versus cluster)13-29.85%(-69.49% to 9.78%)Increase in PF for individual randomisation0.13

 CI = confidence interval; D(M)FS = decayed, (missing) and filled permanent surfaces; PF = prevented fraction
 
Table 3. Random-effects meta-regression analyses of prevented fractions: d(e/m)fs

CharacteristicNumber of trialsSlope estimate95% CISlope interpretationP value

(2)Mean baseline caries8-1.00%(-4.81% to 2.80%)Decrease per unit increase in mean baseline caries0.54

(3)Any fluorides7Not estimable (Collinearity)   

(3)Dentifrice use6Not estimable (Collinearity)   

(3)Fluoridated water820.64%(-36.33% to 77.61%)Higher PF in presence of water fluoridation0.41

(4)Concentration of fluoride > 5%10-5.40%(-47.10% to 36.29%)Higher PF if concentration of fluoride is > 5%0.77

(4)Length of follow-up10-5.77%(-21.48% to 9.94%)Decrease per unit increase in length of follow-up0.28

(4)Prior prophylaxis10-8.81%(-47.72% to 30.11%)Lower PF in presence of prophylaxis0.62

(4)Frequency of application > twice per year105.09%(-19.33% to 29.51%)Lower PF if application > twice per year0.64

Placebo or no treatment control10-13.99%(-47.60% to 19.62%)Increase in PF for placebo0.37

Design (individual versus cluster)10-32.71%(-67.84% to 2.42%)Increase in PF for individual randomisation0.064

 CI = confidence interval; d(e/m)fs = decayed, (extracted/missing) and filled primary surfaces; PF = prevented fraction