Heifetz 1970.

Study characteristics
Methods	Study design: 4‐arm parallel‐group quasi RCT (only 2 relevant arms used); placebo controlled Study duration: 2 years
Participants	309 children analysed at 2 years (after exclusions, present for all examinations) Participants randomised (N = 525) Age range 12‐13 years Surfaces affected: 8.2 DMFS Exposure to other fluoride: none assumed Year study began: 1966 Location: USA Setting of recruitment and treatment: school
Interventions	FG + ptc vs 'PL' + ptc (APF group = 12,300 ppm F) Self applied under supervision, with toothbrush, 5 times a year, 4 ml applied for 5 min Prior to application = tooth cleaning (supervised toothbrushing) performed with non‐F prophy paste Postop instruction = No information provided.
Outcomes	2‐year net DMFS increment ‐ (E + U) Reported at 1 and 2 year follow‐ups NetDMFT(E + U) Dropout
Declaration of interest	No information provided.
Source of funding	No information provided.
Notes	Clinical (VT) caries assessment by 2 examiners; diagnostic threshold NR; state of tooth eruption included = E + U; reversal rate approximately 4% of observed DMFS increment for all groups combined
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: “The baseline records were stratified according to the sex, age and previous caries experience ... within each stratum, the children were separated into four study groups ...” Quote from correspondence: “... after stratification, the children were systematically divided into four groups ...” Comment: Non‐random method used.
Allocation concealment (selection bias)	High risk	The non‐random method used for sequence generation would not allow for adequate allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quotes: “The controls ... then brushed with a flavoured solution as a placebo.” Comment: Use of 'placebo' described.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quotes: “The examiners did not know the groups to which any child was assigned.” “The controls ... then brushed with a flavoured solution as a placebo.” 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: 41.14% in 2 years. Dropout by group: 102/263 (38.8%) FG, 114/262 (43.5%) ‘PL’. Reasons for losses: Exclusions based on compliance and presence at all follow‐up examinations. Comment: Numbers lost unduly high for length of follow‐up, though with no differential losses between groups. It is unclear if reasons for dropout are acceptable and balanced. Caries data used in analysis pertain to participants present at all examinations.
Selective reporting (reporting bias)	Unclear risk	Outcomes reported: DMFS increment ‐ (E + U), reported at 1 and 2 year follow‐ups DMFT(E + U) 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: 8.26 FG, 8.08 ‘PL’ DMFT: 4.94 FG, 4.80 ‘PL’ Comment: Initial caries appears balanced between groups.
Free of contamination/co‐intervention?	Low risk	Quote: “To prevent children from carrying out the wrong procedure or from exchanging the material of treatment, only children in the same study group assembled and brushed at any one time.” Comment: There is sufficient indication overall of prevention of contamination/co‐intervention.