Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study.

Violaine Smaïl-Faugeron,Hélène Fron-Chabouis,Frédéric Courson,Pierre Durieux

doi:10.1186/1471-2288-14-64

Abstract

BackgroundSplit-mouth randomized controlled trials (RCTs) are popular in oral health research. Meta-analyses frequently include trials of both split-mouth and parallel-arm designs to derive combined intervention effects. However, carry-over effects may induce bias in split- mouth RCTs. We aimed to assess whether intervention effect estimates differ between split- mouth and parallel-arm RCTs investigating the same questions.MethodsWe performed a meta-epidemiological study. We systematically reviewed meta- analyses including both split-mouth and parallel-arm RCTs with binary or continuous outcomes published up to February 2013. Two independent authors selected studies and extracted data. We used a two-step approach to quantify the differences between split-mouth and parallel-arm RCTs: for each meta-analysis. First, we derived ratios of odds ratios (ROR) for dichotomous data and differences in standardized mean differences (∆SMD) for continuous data; second, we pooled RORs or ∆SMDs across meta-analyses by random-effects meta-analysis models.ResultsWe selected 18 systematic reviews, for 15 meta-analyses with binary outcomes (28 split-mouth and 28 parallel-arm RCTs) and 19 meta-analyses with continuous outcomes (28 split-mouth and 28 parallel-arm RCTs). Effect estimates did not differ between split-mouth and parallel-arm RCTs (mean ROR, 0.96, 95% confidence interval 0.52–1.80; mean ∆SMD, 0.08, -0.14–0.30).ConclusionsOur study did not provide sufficient evidence for a difference in intervention effect estimates derived from split-mouth and parallel-arm RCTs. Authors should consider including split-mouth RCTs in their meta-analyses with suitable and appropriate analysis.

Highlights

Split-mouth randomized controlled trials (RCTs) are popular in oral health research
Lesaffre et al suggested that intervention effect estimates from split-mouth and parallel-arm RCTs may not be the same and recommended separate subgroup meta-analyses of split-mouth and parallel-arm RCTs to investigate systematic differences [9]. In this meta-epidemiological study, we aimed to assess if data from split-mouth RCTs were incorporated appropriately in meta-analyses and whether intervention effect estimates differ between split-mouth and parallel-arm RCTs in meta-analyses
We identified meta-analyses that included at least one split-mouth RCT and at least one parallel-arm RCT assessing a variety of conditions and interventions on binary or continuous outcomes

Summary

Introduction

Split-mouth randomized controlled trials (RCTs) are popular in oral health research. Meta-analyses frequently include trials of both split-mouth and parallel-arm designs to derive combined intervention effects. As compared with parallel-arm RCTs, split-mouth RCTs have the advantage that most of the variability of outcome among patients is removed from the intervention effect estimate for a potential increase in statistical power, each subject being its own control [4,5]. Systematic review authors frequently include trials of both split-mouth and parallelgroup designs to derive combined intervention effects. Carry-over effects (ie, contamination or “spilling” of the effects of one intervention from one site to another site) may induce bias in split-mouth RCTs [4]. The statistical analysis of split-mouth differs from that of parallel-arm

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