title: Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  We 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 (45 split-mouth and 48 parallel-arm RCTs). [corrected]. 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).
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1138, Equipe 22, Centre de Recherche des Cordeliers, Paris, France. violaine.smail-faugeron@parisdescartes.fr.
authors.forename: Violaine
authors.initials: V
authors.lastname: Smaïl-Faugeron
authors.forename: Hélène
authors.initials: H
authors.lastname: Fron-Chabouis
authors.forename: Frédéric
authors.initials: F
authors.lastname: Courson
authors.forename: Pierre
authors.initials: P
authors.lastname: Durieux
mesh_terms: D018865:Dental Research / Q000379:methods*; D006801:Humans; D016017:Odds Ratio; D009909:Oral Health; D016032:Randomized Controlled Trials as Topic