Marthaler 1965a.

Methods	Trial design: 4‐armed, double‐blind, placebo‐controlled RCT Location: Switzerland Number of centres: 3 school dental clinics servicing 4 city areas of Zürich (Hongg, Industriequartier, Seebach, Wipkingen) Recruitment period: study began 1958
Participants	Inclusion criteria: not reported Exclusion criteria: non‐attenders of regular community school dental clinics (10% to 15% of sample population); severe hypoplasia; orthodontic appliance use Baseline caries: 18.9 DMFS (Gp A: 18.50; Gp B: 19.34). Baseline characteristics (DMFS, DMFT) "balanced" (DFS baseline data not reported) Age at baseline (years): range 11 to 14 years (mean 12.7) (Gp A: 12.8 years; Gp B: 12.5 years). Baseline characteristic (age) "balanced" Sex: 31 F:43 M (Gp A: 15 F:27 M; Gp B: 16 F:16 M) Any other details of important prognostic factors: background exposure to fluoride in salt (suboptimal) Number randomised: 381 (group distribution not reported) Number evaluated: 74 at 3 years (present at all assessments) (Gp A: 42; Gp B: 32) Attrition: 66% dropout (for all study groups combined) after 3 years (study duration = 3 years). Main reason for high dropout: children leaving public school on completion of last compulsory year; exclusions based on variation in toothpaste provision (51 children excluded from analysis due to non‐compliance resulting in increased losses to 81%) and presence in all follow‐up examinations; any differential group losses not assessable
Interventions	Comparison: FT versus PL Gp A (n = evaluated 42): AmF 1250 ppm F; abrasive system: IMP (Gp B in trial report)/barium sulphate (Gp D in trial report); home use/unsupervised, daily frequency assumed Gp B (n = evaluated 32): placebo; abrasive system: IMP (Gp A in trial report)/barium sulphate (Gp C in trial report); home use/unsupervised, daily frequency assumed
Outcomes	Primary: 3‐year net DFS increment ‐ (CA) cl + (DR) xr; posterior MD‐DFS; anterior MD‐DFS; BL‐DFS; O‐DFS; DMFT (at 3 years) Secondary: none assessed Assessments irrelevant to this review's scope: FT; FS; MT; compliance Follow‐up duration: 3 years
Notes	Adverse effects: not reported Funding source: GABA AG (Basel, Switzerland), manufacturer of Elmex intervention toothpaste Declarations/conflicts of interest: not reported Data handling by review authors: this study reported 2 age groups of children: 6 to 10 years (Marthaler 1965: 7 years duration)/11 to 14 years (Marthaler 1965a: 3 years duration). 4 arms distributed between 2 intervention groups (B and D in trial reports) and 2 placebo groups (A and C in trial reports). Pooled groups in analyses Other information of note: clinical (V) caries assessment by 1 examiner, diagnostic threshold = CA and NCA; state of tooth eruption included not reported. Radiographic assessment (2 postBW) by 1 examiner, diagnostic threshold = DR and ER; partial recording. Diagnostic errors not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Randomisation was carried out with the aid of the alphabetical class lists. The dentifrices were assigned to the children listed in this way, in a fixed order according to the code numbers printed on the tubes. The numbers in turn had been randomly assigned to the dentifrices A, B, C, D, E. In this way a random assignment of the dentifrices throughout the school was obtained" Comment: not enough information provided
Allocation concealment (selection bias)	Low risk	Central allocation described
Blinding (performance bias and detection bias) All outcomes	Low risk	Quotes: "... the examinations were carried out without knowledge of the dentifrice used by the children" and "Tubes and content were only distinguishable with the aid of a small mark printed on the neutral tube"  Comment: blind outcome assessment and use of placebo described
Incomplete outcome data (attrition bias) All outcomes	High risk	Overall dropout for length of follow‐up: 66.2% 245/370 (for all 4 groups) in 3 years. Dropout by group: not reported. Reasons for losses: children completing school; exclusions based on variation in toothpaste provision (51 children attending final examination were excluded from analysis due to non‐compliance) and presence in follow‐up examinations, including those unsatisfactorily radiographed (not reported by group) Comment: numbers lost are unduly high for 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 present for all examinations
Selective reporting (reporting bias)	Low risk	Outcomes reported: DFS increment ‐ (CA) cl + (DR) xr, reported at 1.5, 3, 5 and 7 years follow‐ups posterior MD‐DFS anterior MD‐DFS BL‐DFS O‐DFS DMFT FT FS MT 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: mean age: 12.8 FT, 12.5 PL DMFS: 18.5 FT, 19.34 PL DMFT: 9.93 FT, 10.25 PL Comment: initial caries appears balanced
Free of contamination/co‐intervention?	Low risk	Quote: "In order to exclude exchange of tubes at the start of the study, two tubes of dentifrices...were sent to the parents. The parents were told that upon returning the empty tubes, their child could get new dentifrice at the local school dental clinic" Comment: there is sufficient indication overall of prevention of contamination/co‐intervention