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

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.

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

• Acceptance Date: Dec 16, 2015
• Publication Date: 2016-06
• Deposit Date: Jan 22, 2016
• Publicly Available Date: Nov 23, 2017
• Journal: Journal of clinical epidemiology
• Print ISSN: 0895-4356
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 74
• Pages: 57-65
• 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
• Public URL: https://hull-repository.worktribe.com/output/384355
• 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.
• Contract Date: Nov 23, 2017