Influence of blinding on treatment effect size estimate in randomized controlled trials of oral health interventions.

BACKGROUND: Recent methodologic evidence suggests that lack of blinding in randomized trials can result in under- or overestimation of the treatment effect size. The objective of this study is to quantify the extent of bias associated with blinding in randomized controlled trials of oral health interventions. METHODS: We selected all oral health meta-analyses that included a minimum of five randomized controlled trials. We extracted data, in duplicate, related to nine blinding-related criteria, namely: patient blinding, assessor blinding, care-provider blinding, investigator blinding, statistician blinding, blinding of both patients and assessors, study described as "double blind", blinding of patients, assessors, and care providers concurrently, and the appropriateness of blinding. We quantified the impact of bias associated with blinding on the magnitude of effect size using a two-level meta-meta-analytic approach with a random effects model to allow for intra- and inter-meta-analysis heterogeneity. RESULTS: We identified 540 randomized controlled trials, included in 64 meta-analyses, analyzing data from 137,957 patients. We identified significantly larger treatment effect size estimates in trials that had inadequate patient blinding (difference in treatment effect size = 0.12; 95% CI: 0.00 to 0.23), lack of blinding of both patients and assessors (difference = 0.19; 95% CI: 0.06 to 0.32), and lack of blinding of patients, assessors, and care-providers concurrently (difference = 0.14; 95% CI: 0.03 to 0.25). In contrast, assessor blinding (difference = 0.06; 95% CI: -0.06 to 0.18), caregiver blinding (difference = 0.02; 95% CI: -0.04 to 0.09), principal-investigator blinding (difference = - 0.02; 95% CI: -0.10 to 0.06), describing a trial as "double-blind" (difference = 0.09; 95% CI: -0.05 to 0.22), and lack of an appropriate method of blinding (difference = 0.06; 95% CI: -0.06 to 0.18) were not associated with over- or underestimated treatment effect size. CONCLUSIONS: We found significant differences in treatment effect size estimates between oral health trials based on lack of patient and assessor blinding. Treatment effect size estimates were 0.19 and 0.14 larger in trials with lack of blinding of both patients and assessors and blinding of patients, assessors, and care-providers concurrently. No significant differences were identified in other blinding criteria. Investigators of oral health systematic reviews should perform sensitivity analyses based on the adequacy of blinding in included trials.