Background Topically‐applied fluoride varnishes have been used extensively as an operator‐applied caries‐preventive intervention for over three decades. This review updates the first Cochrane review of fluoride varnishes for preventing dental caries in children and adolescents, which was first published in 2002. Objectives To determine the effectiveness and safety of fluoride varnishes in preventing dental caries in children and adolescents, and to examine factors potentially modifying their effect. Search methods We searched the Cochrane Oral Health Group's Trials Register (to 13 May 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 4), MEDLINE via OVID (1946 to 13 May 2013), EMBASE via OVID (1980 to 13 May 2013), CINAHL via EBSCO (1980 to 13 May 2013), LILACS and BBO via the BIREME Virtual Health Library (1980 to 13 May 2013), ProQuest Dissertations and Theses (1861 to 13 May 2013), and Web of Science Conference Proceedings (1945 to 13 May 2013). A search for ongoing trials was undertaken on ClinicalTrials.gov on 13 May 2013. There were no restrictions on language or date of publication in the search of the electronic databases. Selection criteria Randomised or quasi‐randomised controlled trials with blind outcome assessment used or indicated, comparing topically‐applied fluoride varnish with placebo or no treatment in children up to 16 years during at least one year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces in both permanent (D(M)FS) and primary (d(e/m)fs) teeth. Data collection and analysis At least two review authors assessed all search results, extracted data and undertook risk of bias independently. Study authors were contacted for additional information. The primary measure of effect was the prevented fraction, that is the difference in mean caries increments between the treatment and control groups expressed as a percentage of the mean increment in the control group. The caries increments nearest to three years were used from each included study. Random‐effects meta‐analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random‐effects meta‐regression analyses. Adverse effects information was collected from the included trials. Main results Twenty‐two trials with 12,455 participants randomised (9595 used in analyses) were included. For the 13 that contributed data for the permanent tooth surfaces meta‐analysis, the pooled D(M)FS prevented fraction estimate comparing fluoride varnish with placebo or no treatment was 43% (95% confidence interval (CI) 30% to 57%; P < 0.0001). There was substantial heterogeneity, confirmed statistically (P < 0.0001; I² = 75%), however this body of evidence was assessed as of moderate quality. The pooled d(e/m)fs prevented fraction estimate was 37% (95% CI 24% to 51%; P < 0.0001) for the 10 trials that contributed data for the primary tooth surfaces meta‐analysis, also with some heterogeneity (P = 0.009; I² = 59%). Once again this body of evidence was assessed as of moderate quality. No significant association between estimates of D(M)FS or d(e/m)fs prevented fractions and the pre‐specified factors of baseline caries severity, background exposure to fluorides, application features such as prior prophylaxis, concentration of fluoride, frequency of application were found. There was also no significant association between estimates of D(M)FS or d(e/m)fs prevented fractions and the post hoc factors: whether a placebo or no treatment control was used, length of follow‐up, or whether individual or cluster randomisation was used, in the meta‐regression models. A funnel plot of the trials in the main meta‐analyses indicated no clear relationship between prevented fraction and study precision. In both methods, power is limited when few trials are included. There was little information concerning possible adverse effects or acceptability of treatment. Authors' conclusions The conclusions of this updated review remain the same as those when it was first published. The review suggests a substantial caries‐inhibiting effect of fluoride varnish in both permanent and primary teeth, however the quality of the evidence was assessed as moderate, as it included mainly high risk of bias studies, with considerable heterogeneity.

Objective To investigate basic assumptions and other methodological problems in the application of indirect comparison in systematic reviews of competing healthcare interventions.Design Survey of published systematic reviews.Inclusion criteria Systematic reviews published between 2000 and 2007 in which an indirect approach had been explicitly used.Data extraction Identified reviews were assessed for comprehensiveness of the literature search, method for indirect comparison, and whether assumptions about similarity and consistency were explicitly mentioned.Results The survey included 88 review reports. In 13 reviews, indirect comparison was informal. Results from different trials were naively compared without using a common control in six reviews. Adjusted indirect comparison was usually done using classic frequentist methods (n=49) or more complex methods (n=18). The key assumption of trial similarity was explicitly mentioned in only 40 of the 88 reviews. The consistency assumption was not explicit in most cases where direct and indirect evidence were compared or combined (18/30). Evidence from head to head comparison trials was not systematically searched for or not included in nine cases.Conclusions Identified methodological problems were an unclear understanding of underlying assumptions, inappropriate search and selection of relevant trials, use of inappropriate or flawed methods, lack of objective and validated methods to assess or improve trial similarity, and inadequate comparison or inappropriate combination of direct and indirect evidence. Adequate understanding of basic assumptions underlying indirect and mixed treatment comparison is crucial to resolve these methodological problems.Appendix 1 PubMed search strategyAppendix 2 Characteristics of identified reportsAppendix 3 Identified studiesReferences of included studies