Biesbrock 2003b.

Methods	Trial design: initially 3‐armed, placebo/active‐controlled and stratified RCT (placebo‐controlled until 9 months when placebo participants re‐allocated to active intervention groups) Location: Guatemala Number of centres: 2 elementary schools, in urban 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: 9.8 DMFS (Gp A: 9.64 (SD 6.73); Gp B: 10.27 DMFS (SD 6.39); Gp C: 9.56 DMFS (SD 6.56); Gp D: 9.96 (SD 5.30)). Evaluated participants at 21 months reported. Baseline DMFS appears balanced Age at baseline (years): 9 to 12 years; mean 10.3 years (Gp A: 10.3; Gp B: 10.2; Gp C: 10.3; Gp D 10.3) Sex: 289 F:245 M (Gp A: 51 F:46 M; Gp B: 51 F:37 M; Gp C: 89 F:80 M; Gp D: 98 F:82 M) Any other details of important prognostic factors: background exposure to fluoride in community water < 0.3 ppm F Number randomised: 657 (Gp A: 219; Gp B: 218; Gp C: 220) Number evaluated: 534 at 21 months (present at final assessment. Gp A: 266 (original allocation: 169; Gp C re‐allocation: 97); Gp B: 268 (original allocation: 180; Gp C re‐allocation: 88); Gp C: participants re‐randomised after 9 months and allocated between Gps A and B) Attrition: 19.8% dropout after 21 months, reasons for dropout not reported. No differential dropout
Interventions	Comparison: FT versus FT Gp A (n = not reported): placebo ‐ NaF 500 ppm F; hydrated silica abrasive system; home use (unsupervised) with supervised brushing at school twice daily Gp B (n = not reported): placebo ‐ NaF 1450 ppm F; hydrated silica abrasive system; home use (unsupervised) with supervised brushing at school twice daily Gp C (n = 219): NaF 500 ppm F; hydrated silica abrasive system; home use (unsupervised) with supervised brushing at school twice daily Gp D (n = 218): placebo ‐ NaF 1450 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 authors are employed by Procter & Gamble 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. 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 a trained and calibrated examiner according to a modification of the Radike criteria, diagnostic threshold = CA. Weighted Kappa scores of 0.77, VT on 20 children. Sensitivity of 98%, specificity of 91% relative to expert consensus panel for radiographic interpretation
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 "Each tube was 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 18.8% with slight difference in rate (15.9% for initial placebo group and 22.8% and 17.4% 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‐up 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 assigned to the same treatment group to eliminate the potential for cross‐usage of test dentifrices" Comment: contamination not observed