Thomas 1966.

Methods	Trial design: 3‐armed, double‐blind, placebo‐controlled, and head‐to‐head, stratified RCT Location: USA Number of centres: 1 mobile dental unit visiting 6 orphanages across South‐Eastern states, USA Recruitment period: study began 1961
Participants	Inclusion criteria: not reported Exclusion criteria: not reported Baseline caries: 10.7 DFS (Gp A: 10.66 DFS (SE 0.69); Gp B: 10.57 DFS (SE 0.57); Gp C: 10.88 DFS (SE 0.60)). Baseline characteristics (DFS, DFT, TAR) "balanced" Age at baseline (years): range 7 to 16 years, mean 12 years (Gp A: 11.56 years (SE 0.19); Gp B: 11.37 years (SE 0.19); Gp C: 11.48 years (SE 0.19)) Sex: 227 F:237 M (Gp A: 71 F:80 M; Gp B: 75 F:83 M; Gp C: 81 F:74 M) (evaluated participants only) Any other details of important prognostic factors: background exposure to fluoride: none reported. Residents of "communities with only minor concentrations of fluoride in the communal water supply", levels not reported Number randomised: 679 (Gp A: 224; Gp B: 226; Gp C: 229) Number evaluated: 464 at 2 years (present during entire study period) (Gp A: 151; Gp B: 158; Gp C: 155) Attrition: 32% dropout after 2 years (study duration = 2 years). Reasons for attrition not reported; no differential group losses
Interventions	Comparison: FT (2 groups) versus PL Gp A (n = 224): SnF2 1000 ppm F; abrasive system: IMP; institution use/supervised, twice a day Gp B (n = 226): SnF2 1000 ppm F; abrasive system: Ca pyrophosphate; institution use/supervised, twice a day Gp C (n = 229): placebo; abrasive system: IMP; institution use/supervised, twice a day
Outcomes	Primary: 2‐year DFS increment ‐ cl + xr; DFT (at 6 months, 1 year, 18 months, 2 years) Secondary: none assessed Assessments irrelevant to this review's scope: n/a Follow‐up duration: 2 years
Notes	Adverse effects: not reported Funding source: not reported Declarations/conflicts of interest: not reported Data handling by review authors: Gps A + B versus C in analyses Other information of note: clinical (VT) caries assessment by 1 examiner, diagnostic threshold not reported. Radiographic assessment (10 BW) by 1 examiner, diagnostic threshold not reported. State of tooth eruption included not reported. Check of diagnostic errors done
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The children were stratified according to age, DMF permanent teeth... before dentifrices were assigned randomly within strata. Each formulation of dentifrice was assigned 8 numbers at random. These numbers were arranged into random subsets of three; each subset contained a number for each of the three formulations. This sequence was continued across strata boundaries and repeated until all of the participating children had been allocated" Comment: still not enough information provided on the actual method of sequence generation
Allocation concealment (selection bias)	Low risk	Quote: "The list of names and dentifrice numbers was forwarded to the grantor, who provided the dentifrices in plain white wax‐lined tubes labelled with each child's name, home and cottage number... The code of dentofrice numbers... and the three formulations were placed in a sealed envelope and stored in the school safe.."
Blinding (performance bias and detection bias) All outcomes	Low risk	Quotes: "The control and experimental dentifrices were identically formulated except for SnF2 which was omitted in the control toothpaste. Both toothpastes were coloured blue" and "The participating subjects, as well as the examiner were unaware of the arrangement of numbers into dentifrice groups and the specific formulas throughout the study" 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: 32% in 2 years. Dropout by group: 73/224 FT 1, 68/226 FT 2, 74/229 PL. Reasons for losses: not reported 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 for the entire study period
Selective reporting (reporting bias)	Low risk	Outcomes reported: DFS increment ‐ cl + xr, reported at 6 months, 1, 1.5 and 2 years follow‐ups DFT 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: DFS: 10.66 FT 1, 10.57 FT 2, 10.88 PL DFT: 7.05 FT 1, 6.72 FT 2, 7.01 PL mean age: 11.56 FT 1, 11.37 FT 2, 11.48 PL TAR: 12.04 FT 1, 11.47 FT 2, 11.59 PL Comment: initial caries appears balanced between groups
Free of contamination/co‐intervention?	Low risk	Quote: "The tubes were readily identified by the child's name on the label. Thus it was easy for the housemothers to prevent the children from exchanging toothpaste during brushing" Comment: there is sufficient indication overall of prevention of contamination/co‐intervention