Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study
1 Institut National de la Santé et de la Recherche Médicale, U1138, Equipe 22, Centre de Recherche des Cordeliers, Paris, France
2 Assistance Publique-Hôpitaux de Paris, Hôpital Bretonneau, Service d’Odontologie, Paris, France
3 Université Paris Descartes - Sorbonne Paris Cité, Faculté de Chirurgie Dentaire, Unité de Recherches Biomatériaux Innovants et Interface EA4462 Montrouge, France
4 Assistance Publique-Hôpitaux de Paris, Hôpital Charles Foix, Service d’Odontologie, Ivry- sur-Seine, France
5 Université Paris Descartes - Sorbonne Paris Cité, Faculté de Médecine, Paris, France
6 Département d’Informatique Hospitalière, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France
7 Unité de Recherches Biomatériaux Innovants et Interface EA4462, 1 rue Maurice Arnoux, Montrouge 92120, France
BMC Medical Research Methodology 2014, 14:64 doi:10.1186/1471-2288-14-64Published: 11 May 2014
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.
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.
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 (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).
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.