Zacherl 1981.

Methods	Trial design: 3‐armed, double‐blind, placebo‐controlled and head‐to‐head, stratified RCT Location: USA Number of centres: not reported. Central Ohio, USA Recruitment period: study began in/before 1977
Participants	Inclusion criteria: not reported Exclusion criteria: orthodontic treatment; extensive prosthetic appliance use Baseline caries: 5.82 DMFS (Gp A: 6.06 (SE 0.0.223); Gp B: 5.65 (SE 0.206); Gp C: 5.59 (SE 0.315)). Baseline characteristics (DMFS, DMFT) "balanced" Age at baseline (years): range 6 to 14 years, mean 8.9 years (Gp A: 8.95 years; Gp B: 8.93 years; Gp C: 8.93 years) Sex: 1552 F:1541 M (Gp A: 669 F:659 M; Gp B: 667 F:660 M; Gp C: 216 F:222 M) Any other details of important prognostic factors: background exposure to fluoride: none reported. Naturally fluoridated community water supply, < 0.3 ppm F Number randomised: 3093 (Gp A: 1328; Gp B: 1327; Gp C: 438) Number evaluated: 1754 at 3 years (available at final examination) (Gp A: 760; Gp B: 740; Gp C: 254) Attrition: 43% dropout after 3 years (study duration = 3 years). Reasons for attrition described: change of residence, absent on examination day, poor quality of x‐rays; no differential group losses
Interventions	Comparison: FT (2 groups) versus PL Gp A (n = 1328): SnF2 1000 ppm F; abrasive system: Ca pyrophosphate; home use/unsupervised, daily frequency assumed Gp B (n = 1327): NaF 1100 ppm F; abrasive system: silica; home use/unsupervised, daily frequency assumed Gp C (n = 438): placebo; abrasive system: Ca pyrophosphate; home use/unsupervised, daily frequency assumed
Outcomes	Primary: 3‐year DMFS increment ‐ (CA) cl + (ER) xr; DMFT (at 1, 2, 3 years) Secondary: none assessed Assessments irrelevant to this review's scope: n/a Follow‐up duration: 3 years
Notes	Adverse effects: not reported Funding source: Procter & Gamble, Cincinatti, Ohio Declarations/conflicts of interest: institutional affiliation reported only Data handling by review authors: Gps A + B versus C in analyses Other information of note: clinical (VT) caries assessment (FOTI used) by 1 examiner, diagnostic threshold = CA. Radiographic assessment (postBW) by 1 examiner, diagnostic threshold = ER. State of tooth eruption included not reported. Intra‐examiner reproducibility checks for incremental clinical and radiographic caries data in 10% sample (ICC score 0.9). Reversal rate very low and similar among groups
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Following the baseline examinations, the subjects were separated by sex, age and DMFS. Within these strata, they were assigned to a treatment regimen by random permutations of seven in a 1:3:3 ratio.."
Allocation concealment (selection bias)	Unclear risk	Quote: "Following initial assignment of subjects to treatment groups, the investigator was supplied with a file of tamper proof, sealed opaque envelopes which contained the name and identification number of each subject. Within each envelope, the treatment identity for the subject was printed" Comment: allocation concealment should be dealt with prior to not after assignment
Blinding (performance bias and detection bias) All outcomes	Low risk	Quotes: "No situations occurred during the study that required any of the envelopes to be opened. At no time during the course of the study did the examiner or the subjects know which dentifrice the subjects were assigned" and "The design used for this study is a modification of the classical double‐blind placebo controlled clinical trial. In this study, three times as many subjects were assigned to the groups constituting the primary comparison, than were assigned to the placebo group" Comment: blind outcome assessment and use of placebo described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Overall dropout for length of follow‐up: 43% in 3 years. Dropout by group: 568/1328 FT, 184/438 PL. Reasons for losses: changing of residence, poor quality radiographs, exclusion due to absence at final examination Comment: numbers lost were not unduly high for the length of follow‐up with no differential losses between groups. It is unclear if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at final examination
Selective reporting (reporting bias)	Low risk	Outcomes reported: DMFS increment ‐ (CA) cl + (ER) xr, reported at 1, 2 and 3 years follow‐ups DMFT 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 risk	Prognostic factors reported: DMFS: 6.06 (6.15) FT 1, 5.65 (5.60) FT 2, 5.59 (5.02) PL DMFT: 3.61 (3.31) FT 1, 3.49 (3.07) FT 2, 3.44 (2.77) PL Comment: initial caries appears balanced
Free of contamination/co‐intervention?	Unclear risk	Quote: "Toothbrushes and dentifrice labelled with the subject's name and unique identification number were supplied by the study's sponsor in plain white tubes...." Comment: not enough information provided

AI = aluminium; AmF = amine fluoride; ANC = active non‐cavitated caries lesions; APF = acidulated phosphate fluoride; BL = bucco and lingual; BW = bite‐wing; Ca = calcium; CaHPO₄ 2H₂O = dicalcium phosphate; CA = lesions showing loss of enamel continuity that can be recorded clinically (undermined enamel, softened floor/walls) or showing frank cavitation; CAR = caries attack rate; CIR = caries incidence rate; cl = clinical examination; CPP = casein phosphopeptide; dfs = decayed and filled primary surface; DFS = decayed and filled permanent surface; DFT = decayed and filled permanent teeth; DMFS = decayed, missing, and filled permanet surface; DMFT = decayed, missing, and filled permanent teeth; dmft/s = decayed, missing (or extracted) and filled deciduous teeth or surface; DR = radiolucency into dentine; DSTM = Dundee selectable threshold method for caries diagnosis; D₁ = enamel/non‐cavitated caries lesions; D₂ = enamel caries; D₃ = dentinal/cavitated caries lesions; D₄ = caries lesions extending into the pulp; E + U = all erupted and erupting teeth combined; ECSI = Extrapolated Carious Surface Increment Index; ER = radiolucency in enamel/enamel‐dentine junction; F = female; F = fluoride; FOTI = fiber‐optic transillumination; FT = fluoride treatment; Gp = group; ICC = intra‐class correlation coefficient; IMP = insoluble sodium metaphosphate; ITT = intention‐to‐treat; M = male; MD = mesio and distal; MFP = monofluorophosphate; n/a = not applicable; Na = sodium; NaF = sodium fluoride; NCA = non‐cavitated incipient enamel lesions clinically visible as white spots or discoloured fissures; NS = not significant; O = occlusal; OHI = oral hygiene index; postBW = posterior bite‐wing X‐ray assessment; PF = pit and fissure; PL = placebo; ppm = parts per million; RCT = randomised controlled trial; SAR = surfaces at risk; SD = standard deviation; SE = standard error; SEM = standard error of the mean; SMFP = sodium monofluorophosphate; SnF₂ = stannous fluoride; SnF₂‐HMP = stannous fluoride with sodium hexametaphosphate; TAR = teeth at risk; TMP = trimetaphosphate; VT = visual/tactile methods; xr = radiographic examination.