Marthaler 1970a.

Methods	Trial design: 4‐armed placebo‐controlled RCT (2nd phase) Location: Switzerland Number of centres: not reported. Zürich Recruitment period: study began 1966
Participants	Inclusion criteria: not reported Exclusion criteria: fixed orthodontic appliance use Baseline caries: mean 2.35 DMFS (Gp A: 2.75 DMFS; Gp B: 2.00 DMFS). Baseline characteristics (DMFS, 1st molar DMFS) "balanced" (DFS baseline data not reported) Age at baseline (years): range: 7 to 9 years; mean 8.18. Baseline characteristic (age) "balanced" Sex: not reported Any other details of important prognostic factors: background exposure to fluoride in community water supply < 0.2 ppm F; 0.3 mg daily dose of salt assumed from F domestic salt Number randomised: 128 (group distribution not reported) Number evaluated: 90 at 4 years (present for all assessments. Gp A: 23; Gp B: 20) Attrition: 30% dropout (for all study groups combined) after 4 years (study duration = 4 years). Exclusions based on: use of orthodontic bands, and presence in all follow‐up examinations; any differential group losses not assessable
Interventions	Comparison: FT versus PL Gp A (n = evaluated 23): AmF 1250 ppm F; abrasive system: IMP; home use/unsupervised, twice/3 times a day/800 times a year estimated Gp B (n = evaluated 20): placebo; abrasive system: IMP; home use/unsupervised, twice/3 times a day/800 times a year estimated
Outcomes	Primary: 2‐year net DFS increment ‐ (CA) cl + (DR) xr; 1st molar PF‐DFS; 1st molar MD‐DFS (at 2 and 4 years) Secondary: none assessed Assessments irrelevant to this review's scope: compliance Follow‐up duration: 4 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: 2 of 4 trial arms not included in the scope of this review (Gp 3: F gel + placebo paste; Gp 4: F gel + F paste). Final 4‐year results not considered due to concurrent active caries intervention delivery after 2 years (bimonthly (6 times per year) supervised brushing with 1.0% NaF solution) Other information of note: clinical (V) caries assessment by 2 examiners, diagnostic threshold = CA and NCA; state of tooth eruption included not reported. Radiographic assessment (2 postBW) by 2 examiners, diagnostic threshold = DR and ER; partial recording. "Sufficient agreement of examiners known from earlier work"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Children were paired according to their sequence in the class lists. The first and second child of each pair was allocated control and fluoride respectively when, in a table of random digits, an even digit was present. In the case of an odd random digit, the first child was allocated fluoride, and the second one control"
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Quotes: "..... the first child was allocated fluoride, and the second one control" and "Control group received exactly the same dentifrice, just without fluoride"  Comment: use of placebo described. No direct information on whether the examiners were blinded to treatment allocations, although it is probable that clinical and radiographic exams were done independently
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Overall dropout for length of follow‐up: 29.7% 38/128 in 3 years (for all 4 groups). Dropout by group: not reported. Reasons for losses: exclusions based on use of orthodontic bands and presence at all follow‐up examinations Comment: numbers lost not unduly high for length of follow‐up; any differential losses between groups not assessable. It is unclear if reasons for missing outcome data are acceptable and balanced. Caries data used in analysis pertain to participants present at all examinations
Selective reporting (reporting bias)	Low risk	Outcomes reported: DFS increment (CA) cl + (DR) xr, reported at 1 and 3 years follow‐up 1st molar PF‐DFS 1st molar MD‐DFS  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: 2.00 FT, 2.75 PL 1st molar DMFS: 0.0 FT, 0.1 PL  Comment: initial caries appears (DMFS) balanced
Free of contamination/co‐intervention?	Low risk	Quote: "... in this case however siblings were both randomly allocated to either the fluoride or control dentifrice group to prevent the exchange of different types of toothpaste within the families" Comment: there is sufficient indication overall of prevention of contamination/co‐intervention