Cluster-randomized controlled trials evaluating complex interventions in general practices are mostly ineffective: a systematic review

J Clin Epidemiol. 2018 Feb:94:85-96. doi: 10.1016/j.jclinepi.2017.10.010. Epub 2017 Oct 31.

Abstract

Objectives: The aim of this study was to evaluate how frequently complex interventions are shown to be superior to routine care in general practice-based cluster-randomized controlled studies (c-RCTs) and to explore whether potential differences explain results that come out in favor of a complex intervention.

Study design and setting: We performed an unrestricted search in the Central Register of Controlled Trials, MEDLINE, and EMBASE. Included were all c-RCTs that included a patient-relevant primary outcome in a general practice setting with at least 1-year follow-up. We extracted effect sizes, P-values, intracluster correlation coefficients (ICCs), and 22 quality aspects.

Results: We identified 29 trials with 99 patient-relevant primary outcomes. After adjustment for multiple testing on a trial level, four outcomes (4%) in four studies (14%) remained statistically significant. Of the 11 studies that reported ICCs, in 8, the ICC was equal to or smaller than the assumed ICC. In 16 of the 17 studies with available sample size calculation, effect sizes were smaller than anticipated.

Conclusion: More than 85% of the c-RCTs failed to demonstrate a beneficial effect on a predefined primary endpoint. All but one study were overly optimistic with regard to the expected treatment effect. This highlights the importance of weighing up the potential merit of new treatments and planning prospectively, when designing clinical studies in a general practice setting.

Keywords: Cluster-randomized controlled trial; Complex intervention; Effectiveness; General practice; Shortcomings; Systematic review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • General Practice / methods*
  • Humans
  • Randomized Controlled Trials as Topic / standards*
  • Sample Size
  • Treatment Outcome