Sponsorship Bias in Clinical Trials in the Dental Application of Probiotics: A Meta-Epidemiological Study

Many experimental and clinical trials have investigated the dental application of probiotics, although the evidence concerning the effects of probiotic supplements is conflicting. We aimed to examine whether sponsorship in trials about dental applications of probiotics is associated with biased estimates of treatment effects. Overall, 13 meta-analyses involving 48 randomized controlled trials (23 with high risk of sponsorship bias, 25 with low risk) with continuous outcomes were included. Effect sizes were calculated from differences in means of first reported continuous outcomes, divided by the pooled standard deviation. For each meta-analysis, the difference in standardized mean differences between high-risk and low-risk trials was estimated by random effects meta-regression. Differences in standardized mean differences (DSMDs) were then calculated via meta-analyses in a random effects meta-analysis model. A combined DSMD of greater than zero indicated that high-risk trials showed more significant treatment effects than low-risk trials. The results show that trials with a high risk of sponsorship bias showed more significant intervention effects than did low-risk trials (combined DSMD, 0.06; 95% confidence interval, 0.3 to 0.9; p < 0.001), with low heterogeneity among meta-analyses (I2 = 0%; between-meta-analyses variance τ2 = 0.00). Based on our study, high-risk clinical trials with continuous outcomes reported more favorable intervention effects than did low-risk trials in general.