Cardoso 2014.

Methods	Trial design: 3‐armed, active‐controlled and stratified RCT Location: Brazil Number of centres: 5 public primary schools in Bauru (each in a different geographical region of the city), Brazil Recruitment period: study commenced in 2010
Participants	Inclusion criteria: (from NCT01049503) ≥ 2 and ≤4 years old; absence of very large carious lesions/dentine sensitivity during the study Exclusion criteria: participation in other trials in prior 3 months; orthodontic appliance use Baseline caries: 0.947 ANC; (Gp A: 1.14; Gp B 0.84) Age at baseline (years): range 2 to 4 years; mean 3.4 (SD 0.6) (distribution of mean age between groups not reported) Sex: 167 F:148 M (distribution of sex between groups not reported) Any other details of important prognostic factors: background exposure to fluoride in community water supply (0.6 to 0.8 ppm F) Number randomised: 315 (Gp A: 104; Gp B: 211) Number evaluated: 195 at 1 year (present at final assessment. Gp A: 71; Gp B: 124) Attrition: 38% dropout after 1 year, reasons for dropout reported. No differential dropout
Interventions	Comparison: FT versus FT Gp A (n = 104): NaF 1100 ppm F (pH 7.0); abrasive system not reported; home use (unsupervised) with supervised brushing at school at least twice daily Gp B (n = 211): NaF 550 ppm F (pH 4.5 (n = 104) and 7.0 (n = 107)); abrasive system not reported; home use (unsupervised) with supervised brushing at school at least twice daily
Outcomes	Primary: 12‐month net white spot lesion increment ‐ (ANC) cl (at 1 year) Secondary: adverse effects Assessments irrelevant to this review's scope: compliance; change in fluorescence; lesion area (mm) Follow‐up duration: 1 year
Notes	Adverse effects: "There were no reports on adverse effects, but some children complained about the taste of the dentifrice" Funding source: "This study was funded by FAPESP (2008/58402‐9, 2010/11916‐8, and 2010/01944‐4)." FAPESP is São Paulo's state‐funded research foundation. "...experimental formulations, manufactured by Dental Prev Ind. Com. Ltda (Lorena, Brazil)" Declarations/conflicts of interest: "University of São Paulo has a patent request in Brazil (INPI) for 'Low‐fluoride acidic liquid dentifrice and its use'" Data handling by review authors: data entered separately for caries‐active and caries‐inactive at baseline. Both 550 ppm F arms combined in this review under Gp B Other information of note: clinical (VT) caries assessment by 2 examiners, diagnostic threshold = NCA. Kappa scores of 0.88 and 0.78 for intra‐rater reliability and 0.78 for inter‐rater reliability at baseline on 20 children and at 0.84 and 0.75 at the end of the study 0.75 inter‐rater reliability
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quotes: "was randomly reassigned into three subgroups…" and "The software Excel generated random numbers ranging from 0 to 0.99" Comment: random sequence generation stated
Allocation concealment (selection bias)	Unclear risk	No information provided
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "All formulations were NaF‐based and identical, except for the dentifrices' color. The colors' code was kept by one person not involved in the examination of the children" Comment: probably done. Participants and examiners blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "38% loss, mainly due to the fact that parents changed their children's school" Comment: overall dropout rate of 38.1% with no differential dropout. Reasons for dropout reported. Caries data used in analysis pertain to participants present at final examination
Selective reporting (reporting bias)	Low risk	Outcomes reported: progression of caries in caries inactive group (lesions/child) net increment for children in caries active group ‐ (NCA)cl, reported at 12‐month follow‐up Comment: all outcomes listed in Methods section were reported
Baseline characteristics balanced?	Unclear risk	Baseline caries unbalanced in the caries active group mean 1.55 active white spot lesions in the 550 ppm group and mean 2.61 in the 1100 ppm group Comment: some imbalance in caries in the active caries group. No other prognostic factors reported
Free of contamination/co‐intervention?	Low risk	Quotes: "Kits containing dentifrices and toothbrushes were supplied for the whole family every 3 months to guarantee the use of experimental LD by the children, facilitating compliance with study protocol" and ".. and were also asked not to use other oral hygiene products" Comment: contamination not observed