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

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.

Clinical Trial Registration in Oral Health Journals

“…In a previous meta-epidemiological study, we found that split-mouth trials contributed half of the evidence in metaanalyses of oral health research (Smaïl-Faugeron et al 2014). These results support the use of all available evidence in systematic reviews, including that from split-mouth and parallel-arm RCTs.…”

Desenhos de estudos epidemiológicos boca-dividida e paralelo: uma revisão da literatura

“…Em relação ao efeito "carry-across", SMAÏL-FAUGE-RON et al (13) relatam que não existe um método que consiga testar ou avaliar a sua extensão durante a intervenção. Por essa razão, a possibilidade da interferência de um tratamento no outro deve ser considerado antes de decidir qual o desenho de estudo será utilizado e, na evidência de sua presença, o estudo boca-dividida deve ser descartado.…”

“…Esse tipo de delineamento é bastante observado na Odontologia, pois é desenvolvido na cavidade bucal (11). Aqui são feitos tratamentos diferentes no mesmo indivíduo, dividindo-se a boca em partes: hemiarcadas, quadrantes ou sextantes (12,13).…”

Evaluation of intraosseous computerized injection system (QuickSleeper™) vs conventional infiltration anaesthesia in paediatric oral health care: A multicentre, single‐blind, combined split‐mouth and parallel‐arm randomized controlled trial

“…We also compared intervention effect estimates between the split‐mouth and parallel‐arm RCTs by z ratio tests (the difference in effect estimates between the two RCTs divided by its standard error). Because the effect estimates from the two RCTs were consistent, we combined them by using an inverse‐variance weighting meta‐analysis approach: the combined effect estimate is a weighted average of the two effect estimates, each effect estimate being weighted by the inverse of its variance . We also performed a subgroup analysis by arch (the same statistical methods were applied).…”