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Missing data in randomized controlled trials testing palliative interventions pose a significant risk of bias and loss of power: a systematic review and meta-analyses

Hussain, Jamilla A.; White, Ian R.; Langan, Dean; Johnson, Miriam J.; Currow, David C.; Torgerson, David J.; Bland, Martin

Authors

Jamilla A. Hussain

Ian R. White

Dean Langan

David C. Currow

David J. Torgerson

Martin Bland

Abstract

Objectives To assess the risk posed by missing data (MD) to the power and validity of trials evaluating palliative interventions. Study Design and Setting A systematic review of MD in published randomized controlled trials (RCTs) of palliative interventions in participants with life-limiting illnesses was conducted, and random-effects meta-analyses and metaregression were performed. CENTRAL, MEDLINE, and EMBASE (2009-2014) were searched with no language restrictions. Results One hundred and eight RCTs representing 15,560 patients were included. The weighted estimate for MD at the primary endpoint was 23.1% (95% confidence interval [CI] 19.3, 27.4). Larger MD proportions were associated with increasing numbers of questions/tests requested (odds ratio [OR] , 1.19; 95% CI 1.05, 1.35) and with longer study duration (OR, 1.09; 95% CI 1.02, 1.17). Meta-analysis found evidence of differential rates of MD between trial arms, which varied in direction (OR, 1.04; 95% CI 0.90, 1.20; I 2 35.9, P = 0.001). Despite randomization, MD in the intervention arms (vs. control) were more likely to be attributed to disease progression unrelated to the intervention (OR, 1.31; 95% CI 1.02, 1.69). This was not the case for MD due to death (OR, 0.92; 95% CI 0.78, 1.08). Conclusion The overall proportion and differential rates and reasons for MD reduce the power and potentially introduce bias to palliative care trials.

Publication Date 2016-06
Journal Journal of clinical epidemiology
Print ISSN 0895-4356
Electronic ISSN 1878-5921
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 74
Pages 57-65
Institution Citation Hussain, J. A., White, I. R., Langan, D., Johnson, M. J., Currow, D. C., Torgerson, D. J., & Bland, M. (2016). Missing data in randomized controlled trials testing palliative interventions pose a significant risk of bias and loss of power: a systematic review and meta-analyses. Journal of clinical epidemiology, 74, 57-65. https://doi.org/10.1016/j.jclinepi.2015.12.003
DOI https://doi.org/10.1016/j.jclinepi.2015.12.003
Keywords Systematic review, Meta-analysis, Palliative care, Randomized controlled trials, Missing data, Differential mortality
Publisher URL http://www.sciencedirect.com/science/article/pii/S089543561500579X
Additional Information This article is maintained by: Elsevier; Article Title: Missing data in randomized controlled trials testing palliative interventions pose a significant risk of bias and loss of power: a systematic review and meta-analyses; Journal Title: Journal of Clinical Epidemiology; CrossRef DOI link to publisher maintained version: http://dx.doi.org/10.1016/j.jclinepi.2015.12.003; Content Type: article; Copyright: © 2016 The Authors. Published by Elsevier Inc.

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