Aims: To investigate the use of an enriched study design on the estimates of treatment effect in analgesic trials for chronic musculoskeletal pain.
Methods: Database searches were conducted from 2004 to 2014. We included randomized placebo-controlled trials evaluating pain medications for chronic musculoskeletal pain. Methodological quality was assessed using the PEDro scale. The estimates of treatment effect on pain and adverse events were compared between enriched and nonenriched designs. Metaregression was used to assess the association between the effect size estimate and the study design controlling for analgesic dose and methodological quality.
Results: We included 108 trials, of which 99 were included in the meta-analysis (n = 44 171). There were no overall differences in effect sizes between enriched and nonenriched designs for pain intensity. There was a significant difference for a reduction in any adverse events favouring enriched designs for opioids, but not for other analgesics or the outcome serious adverse events. There was an association between effect size and methodological quality, with failure to blind the outcome assessor and failure to use intention-to-treat analysis being associated with larger effect sizes.
Conclusions: There is no evidence that the use of an enriched study design changes the treatment effect size estimate for pain. There is some evidence that clinical trials that employ enriched designs report a reduced risk of adverse events in trials for chronic musculoskeletal pain, but it is unclear whether enriched designs influence estimates of serious adverse events. Features of trial design and study quality were associated with treatment effect estimates.

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British Journal of Clinical Pharmacology
Department of General Practice

Yamato, T.P. (Tie P.), Maher, C., Saragiotto, B., Shaheed, C.A. (Christina Abdel), Moseley, A.M. (Anne M.), Lin, C.-W.C. (Chung-Wei Christine), … McLachlan, A. J. (2017). Comparison of effect sizes between enriched and nonenriched trials of analgesics for chronic musculoskeletal pain. British Journal of Clinical Pharmacology (Vol. 83, pp. 2347–2355). doi:10.1111/bcp.13350