Daily Archives: July 4, 2015

Information Lacking on Potential Adverse Effects of Fluoride Gels

Marinho VC, Worthington HV, Walsh T, Chong LY. Fluoride gels for preventing dental caries in children and adolescents. The Cochrane database of systematic reviews. 2015 Jun 15;6:CD002280.

BACKGROUND: Topically applied fluoride gels have been widely used as a caries-preventive intervention in dental surgeries and school-based programmes for over three decades. This updates the Cochrane review of fluoride gels for preventing dental caries in children and adolescents that was first published in 2002.

OBJECTIVES: The primary objective is to determine the effectiveness and safety of fluoride gels in preventing dental caries in the child and adolescent population.The secondary objectives are to examine whether the effect of fluoride gels is influenced by the following: initial level of caries severity; background exposure to fluoride in water (or salt), toothpastes, or reported fluoride sources other than the study option(s); mode of use (self applied under supervision or operator-applied), and whether there is a differential effect between the tray and toothbrush methods of application; frequency of use (times per year) or fluoride concentration (ppm F).

SEARCH METHODS: We searched the Cochrane Oral Health Group Trials Register (to 5 November 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2014, Issue 11), MEDLINE via OVID (1946 to 5 November 2014), EMBASE via OVID (1980 to 5 November 2014), CINAHL via EBSCO (1980 to 5 November 2014), LILACS and BBO via the BIREME Virtual Health Library (1980 to 5 November 2014), ProQuest Dissertations and Theses (1861 to 5 November 2014) and Web of Science Conference Proceedings (1945 to 5 November 2014). We undertook a search for ongoing trials on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform on 5 November 2014. We placed no restrictions on language or date of publication in the search of the electronic databases. We also searched reference lists of articles and contacted selected authors and manufacturers.

SELECTION CRITERIA: Randomised or quasi-randomised controlled trials where blind outcome assessment was stated or indicated, comparing topically applied fluoride gel with placebo or no treatment in children up to 16 years. The frequency of application had to be at least once a year, and study duration at least one year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces in both permanent and primary teeth (D(M)FS and d(e/m)fs).

DATA COLLECTION AND ANALYSIS: At least two review authors independently performed study selection, data extraction and ‘Risk of bias’ assessment. We contacted study authors for additional information where required. The primary measure of effect was the prevented fraction (PF), 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. We performed random-effects meta-analyses where we could pool data. We examined potential sources of heterogeneity in random-effects metaregression analyses. We collected adverse effects information from the included trials.

MAIN RESULTS: We included 28 trials (3 of which are new trials since the original review), involving 9140 children and adolescents. Most of these trials recruited participants from schools. Most of the studies (20) were at high risk of bias, with 8 at unclear risk of bias.Twenty-five trials (8479 participants) contributed data for meta-analysis on permanent tooth surfaces: the D(M)FS pooled prevented fraction (PF) estimate was 28% (95% confidence intervals (CI) 19% to 36%; P < 0.0001; with substantial heterogeneity (P < 0.0001; I2 = 82%); moderate quality evidence). Subgroup and metaregression analyses suggested no significant association between estimates of D(M)FS prevented fractions and the prespecified trial characteristics. However, the effect of fluoride gel varied according to the type of control group used, with D(M)FS PF on average being 17% (95% CI 3% to 31%; P = 0.018) higher in non-placebo-controlled trials (the reduction in caries was 38% (95% CI 24% to 52%; P < 0.0001, 2808 participants) for the 10 trials with no treatment as control group, and 21% (95% CI 15% to 28%; P < 0.0001, 5671 participants) for the 15 placebo-controlled trials. A funnel plot of the 25 trials in the D(M)FS PF meta-analysis indicated a relationship between prevented fraction and study precision, with an apparent lack of small studies with statistically significant large effects. The d(e/m)fs pooled prevented fraction estimate for the three trials (1254 participants) that contributed data for the meta-analysis on primary teeth surfaces was 20% (95% CI 1% to 38%; P = 0.04; with no heterogeneity (P = 0.54; I2 = 0%); low quality evidence).There was limited reporting of adverse events. Only two trials reported information on acute toxicity signs and symptoms during the application of the gel (risk difference 0.01, 95% CI -0.01 to 0.02; P = 0.36; with no heterogeneity (P = 36; I2 = 0%); 490 participants; very low quality evidence). None of the trials reported information on tooth staining, mucosal irritation or allergic reaction.

AUTHORS’ CONCLUSIONS: The conclusions of this updated review remain the same as those when it was first published. There is moderate quality evidence of a large caries-inhibiting effect of fluoride gel in the permanent dentition. Information concerning the caries-preventive effect of fluoride gel on the primary dentition, which also shows a large effect, is based on low quality evidence from only three placebo-controlled trials. There is little information on adverse effects or on acceptability of treatment. Future trials should include assessment of potential adverse effects.