Biesbrock 2003a.

Methods	Trial design: 2/3‐armed, placebo/active‐controlled and stratified RCT (placebo‐controlled until 9 months when placebo participants re‐allocated to active groups) Location: Guatemala Number of centres: not reported. Sample comprised of elementary schoolchildren resident in an urban area of Guatemala Recruitment period: not reported
Participants	Inclusion criteria: not reported Exclusion criteria: conditions preventing thorough oral examination (e.g. orthodontic or extensive prosthetic appliances) Baseline caries: 7.71 DMFS (Gp A: 8.02 (SD 5.61); Gp B: 9.14 (SD 6.30); Gp C: 7.95 (SD 6.10); Gp D: 7.47 (SD5.67)). Evaluated participants at 21 months reported. Baseline DMFS appears balanced Age at baseline (years): range 9 to 12 years; mean 10.4 years (Gp A: 10.4 (SEM 0.07); Gp B: 10.4 (0.07); Gp C:10.4 (SEM 0.08)) Sex: 214 F:430 M (Gp A: 72 F:144 M; Gp B: 70 F:142 M; Gp C: 72 F:144 M) Any other details of important prognostic factors: background exposure to fluoride in community water < 0.3 ppm F Number randomised: 644 (Gp A: 216; Gp B: 212; Gp C: 216) Number evaluated: 494 at 21 months (Gp A: 83; Gp B: 90; Gp C: 168; Gp D: 153) Attrition: 23.3% dropout after 21 months, reasons for dropout reported. Highest dropout observed in highest fluoride concentration group
Interventions	Comparison: FT versus FT Gp A (n = not reported): placebo ‐ NaF 1100 ppm F; hydrated silica abrasive system; home use (unsupervised) with supervised brushing at school twice daily Gp B (n = not reported): placebo ‐ NaF 2800 ppm F; hydrated silica abrasive system; home use (unsupervised) with supervised brushing at school twice daily Gp C (n = 216): NaF 1100 ppm F; hydrated silica abrasive system; home use (unsupervised) with supervised brushing at school twice daily Gp D (n = 212): NaF 2800 ppm F; hydrated silica abrasive system; home use (unsupervised) with supervised brushing at school twice daily
Outcomes	Primary: 21‐month net DMFS increment ‐ (CA) cl + (DR) xr; DMFS‐O; DMFS‐BL; DMFS‐MD (at 9 and 21 months follow‐up) Secondary: none assessed Assessments irrelevant to this review's scope: none assessed Follow‐up duration: 21 months
Notes	Adverse effects: not reported Funding source: "Support for this study was provided by the Procter & Gamble Company" Declarations/conflicts of interest: 4 of 5 authors (AR Biesbrock, RW Gerlach, SA Jacobs, and RD Bartizek) are employed by Procter & Gamble. L Archila is an academic at University of Texas Health Science Center Dental School, Texas, USA Data handling by review authors: after 9 months the participants in the placebo group were randomised to the fluoride groups. The data used for analysis are for the 2 active intervention groups receiving the same fluoride concentration for the duration of the study (Gps C and D). Results reported for 3 examiners. Integrated results (VT + radiograph) reported for Examiner A used for analysis Other information of note: clinical (VT) and radiographic (DR) caries assessment by 3 trained and calibrated examiners according to a modification of the Radike criteria, diagnostic threshold = CA. Weighted Kappa scores of 0.77, 0.94, 0.96 for VT on 50 children
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "and randomly assigned…" Comment: random sequence generation not stated
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding (performance bias and detection bias) All outcomes	Low risk	Quotes: "Subject and examiner blindness to treatment were maintained throughout the study" and "Dentifrice products were labeled with the subject's name and a unique identification number" Comment: participants and examiners blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: overall dropout rate of 23.3% with slight difference in rate (20% for initial placebo group and 23% and 29% for fluoride groups). Caries data used in analysis pertain to participants present at final examination
Selective reporting (reporting bias)	Low risk	Outcomes reported: DMFS increment ‐ (CA) cl + (DR) xr, reported at 9 and 21 months follow‐ups Comment: trial protocol not available. All outcomes listed in Methods section were reported (DMFS)
Baseline characteristics balanced?	Low risk	Prognostic factors reported: age, sex, caries Comment: baseline DMFS appears balanced
Free of contamination/co‐intervention?	Unclear risk	Quote: "Siblings residing in the same household were automatically assigned to minimise risk from cross‐usage of assigned dentifrice" Comment: contamination not observed