Brudevold 1966.

Methods	Trial design: 5‐armed, double‐blind, placebo/active‐controlled and stratified RCT Location: USA Number of centres: not reported, only that the sample derived from a "large school population" Recruitment period: study commenced 1961
Participants	Inclusion criteria: not reported Exclusion criteria: not reported Baseline caries: 15.4 DFS (Gp A: 16.88 DFS (SD 12.81); Gp B: 14.03 DFS (SD 10.16); Gp C: 14.89 DFS (SD 10.19); Gp D: 15.70 DFS (SD 10.96)). Baseline characteristics (DFS, DFT, DMFS, DMFT) "balanced" Age at baseline (years): range 7 to 16 years. Baseline characteristic (dental age) "balanced" Sex: 650 F:628 M (Gp A: 168 F:167 M; Gp B: 164 F:177 M; Gp C: 150 F:129 M; Gp D: 168 F:155 M). Baseline characteristic (sex) "balanced" Any other details of important prognostic factors: data unavailable for site fluoridation status Number randomised: 2156 (numbers for relevant groups not reported) Number evaluated: 1278 at 2 years (present at all assessments. relevant groups to this review: Gp A: 335; Gp B: 341; Gp C: 279; Gp D: 323) Attrition: 25% dropout after 2 years. Reasons for attrition not reported; any differential group losses not assessable
Interventions	Comparison: FT (3 groups)a versus PL Gp A (n = evaluated 335): SnF2 1000 ppm F; Ca pyrophosphate abrasive system; home use/unsupervised, daily frequency assumed (GP 1) Gp B (n = evaluated 341): SnF2 1000 ppm F; IMP abrasive system; home use/unsupervised, daily frequency assumed (GP 4) Gp C (n = evaluated 279): APF 1000 ppm F; IMP abrasive system; home use/unsupervised, daily frequency assumed (GP 3) Gp D (n = evaluated 323): placebo; abrasive system not reported; home use/unsupervised, daily frequency assumed (GP 2)
Outcomes	Primary: 2‐year DFS increment ‐ cl + xr; DFT; DMFS; DMFT (at 2 years follow‐up) Secondary: none assessed Assessments irrelevant to this review's scope: none assessed Follow‐up duration: 2 years
Notes	Adverse effects: not reported Funding source: "supported in part by the Bristol‐Myers company, New York" manufacturers of toothpastes used by Gps B (experimental formula, Bristol‐Myers) and C (Ipana Durenamel, Bristol‐Myers) Declarations/conflicts of interest: not reported Data handling by review authors: aNaF‐secondary Ca pyrophosphate toothpaste Gp E not considered (abrasive system known to be incompatible with NaF). Adjusted mean values and SEMs used in analysis. Gps A, B and C combined versus Gp D Other information of note: clinical (VT) caries assessment by 2 examiners; diagnostic threshold = CA. Radiographic assessment (10 BW) by 1 examiner; diagnostic threshold not reported. State of tooth eruption included not reported. Diagnostic errors not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "At the initial exam, the record cards of these youngest, or master, siblings were stratified (ordered) simultaneously according to 12 characteristics....The ordered cards of the 'master' siblings were then divided into 5 dentifrice groups by superimposing the numbers 1 through 5 in random sequence. The same dentifrice was assigned automatically to the other, or "trailing", siblings in his household" Comment: not enough information provided
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding (performance bias and detection bias) All outcomes	Low risk	Quotes: "Each (of 2) examiner assessed about half of the subjects in each group, and each subject had the same dentist‐examiner throughout the study. Separate records were used for each examination, and previous records were never available to the examiner. All observations were recorded in code for subsequent transfer to machine data processing. The radiographs were read and recorded independently by a third dentist. At no time was it possible for the examiners to identify a subject with a dentifrice group" and "An independent laboratory was assigned the responsibility of coding, packaging, and shipping all dentifrices in this study... NaF dentifrice was compared to.....and a fluoride free dentifrice" 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: 24.7% in 2 years (534/2156, all 5 groups combined). Dropout by group: not reported. Reasons for losses: not reported Comment: numbers lost were not unduly high given length of follow‐up; It is unclear if there were any differential losses, and if reasons for missing outcome data are acceptable and balanced. Caries data used in the analysis pertain to participants examined after 2 years
Selective reporting (reporting bias)	Low risk	Outcomes reported: DFS increment ‐ cl + xr, reported at 2 years follow‐up DMFS DMFT DFT Comment: trial protocol not available. All pre‐specified outcomes were reported and were reported in the pre‐specified way
Baseline characteristics balanced?	Low risk	Prognostic factors reported: DFS: 16.88 (12.81) FT 1; 14.03 (10.16) FT 2; 14.89 (10.19) FT 3; 15.70 (10.96) PL DFT: 8.53 (5.49) FT 1; 7.61 (4.80) FT 2; 6.04 PL; 7.59 (5.01) FT 3; 8.07 (5.02) PL DMFT: 8.84 (5.86) FT 1; 7.87 (4.80) FT 2; 2.94 PL; 7.91 (5.34) FT 3; 8.35 (5.21) PL DMFS: 18.43 (13.91) FT 1; 15.33 (11.08) FT 2; 16.48 (12.86) FT 3; 17.09 (11.68) PL dental age: 21.12 (6.59) FT 1; 22.28 (6.47) FT 2; 20.49 (6.51) FT 3; 21.70 (6.29) PL Comment: initial caries appears balanced although adjustment for baseline imbalance was made in the analysis
Free of contamination/co‐intervention?	Low risk	Quotes: "As the study group was assembled, all siblings were noted to permit limitiation of one dentifrice code to a family" and "New shipments supplied every 8 to 10 weeks, and new toothbrushes supplied every 6 months" Comment: there is sufficient indication overall of prevention of contamination/co‐intervention