Liu 2012.

Methods	Trial design: parallel‐group study, 4 treatment arms (sealant, sodium fluoride varnish, silver diamine fluoride solution, placebo) Follow‐up: 24 months Study started in 2008
Participants	Location: Children were chosen from primary schools, China Inclusion criteria: ≥ 1 sound permanent first molar with deep fissures or fissures with signs of early (enamel) caries viewed as wet, with opacities and discolouration, similar to ICDAS code 2 (proportion of early caries 35% of tooth sites) (clinical examinations included DIAGNOdent readings and were done by a dentist) Age at baseline: mean age 9.1 years (range 8 to 10 years) Gender: 248 boys and 253 girls Baseline caries: baseline mean dmft scores with SD for groups: sealant 3.19 (2.68), fluoride varnish 3.58 (2.25) (information obtained from study author) Number randomly assigned: 501 children (1539 molars, on average 3 teeth per child) in 4 groups: 124 children in sealant, 124 in fluoride varnish, 125 in silver diamine fluoride solution, 128 in placebo Number evaluated: 482 at 2‐year follow‐up (121 children in sealant, 116 in fluoride varnish, 121 in silver diamine fluoride solution, 124 in placebo)
Interventions	Comparison: resin‐based fissure sealant vs fluoride varnish 4 treatment arms Group 1: light‐cured, fluoride‐releasing resin‐based sealant Clinpro Sealant (3M ESPE, St Paul, MN, USA) (applied by a dentist). No resealing Group 2: NaF – semi annual application of 5% sodium fluoride (NaF) varnish (Duraphat) (applied by a dentist) Group 3: SDF – annual application of 38% silver diamine fluoride (SDF) solution (applied by a dentist) Group 4: placebo control – annual application of water (applied by a dentist) (group 1 and group 2 were considered in this review) Co‐interventions: 90% of toothpastes on sale contained fluoride (no systemic fluoridation in the study area)
Outcomes	Sound or carious occlusal surface of molar (caries in dentine ICDAS codes 4 to 6) Each molar was assessed at 2 sites (upper molar – mesial pit/fossa and distal‐palatal groove; lower molar – occlusal fissure and buccal pit/groove). Caries incidence was reported as child level, tooth level and fissure site level Outcomes were assessed by the same blinded examiner using disposable mouth‐mirrors attached to an intra‐oral LED (light‐emitting diode) light and CPI (community periodontal index) probes Adverse events
Notes	Intra‐examiner reliability: Kappa statistic over 0.9 Sealant retention 46% Funding source: Hong Kong Research Grants Council (study authors were from the university)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "An assistant, using computer‐generated random numbers, allocated the children individually among four groups" Comment: adequate random sequence generation was provided
Allocation concealment (selection bias)	Low risk	Additional information was obtained from study author Computer‐generated random number table (consisting only of numbers 1, 2, 3 and 4) was printed out and kept by a research assistant. Group allocation of participants, i.e. group 1 to group 4, followed random numbers in the random number table. Treatment was performed immediately on‐site by a dentist not involved in examination of children according to group allocation while research assistant was present Comment: adequate allocation concealment
Blinding of outcome assessor (detection bias)	Unclear risk	Quote: "Status of the molars, including sealant retention and development of caries into dentin (ICDAS codes 4‐6), was assessed every 6 mos by the same blinded examiner" Additional information obtained from study author indicated that "The record forms with group assignment information of the children were kept away from the examiner by the recorder" Comment: Blinding of outcome assessor was intended, but it remains unclear whether outcome assessor had information on study design
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing data: 3/124 (2.4%) in sealant group, 7/124 (5.6%) in fluoride varnish group Comment: marginal drop‐out rates
Selective reporting (reporting bias)	Low risk	Outcomes reported: caries response, sealant retention Comment: Pre‐specified outcomes (in methods) were reported in pre‐specified way
Other bias	Low risk	Comparability of groups: Quote: "Proportionately more children in the sealant group than in other groups had visited a dentist or consumed snacks once a day or less (P < 0.05)". (13% of children in sealant group and 31% in fluoride varnish group consumed snacks twice or more often a day) Additional information obtained from study author revealed no statistically significant differences between groups in baseline caries risk of children Mean baseline dmft scores with SD for groups: sealant 3.19 (2.68); fluoride varnish 3.58 (2.25) Comment: We decided to grade this domain as having 'low' risk of bias, although we noted differences in dental visit history and consumption of snacks between groups at baseline because baseline caries risk scores of children were similar Co‐interventions: "No systemic fluoridation in the study area. 90% of the toothpastes on sale contained fluoride" Comment: This domain was graded as having 'low' risk of bias because no co‐interventions other than fluoridated toothpaste were included in the protocol