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

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

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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.

Original languageEnglish
Pages (from-to)57-65
Number of pages9
JournalJournal of Clinical Epidemiology
Early online date21 Dec 2015
Publication statusPublished - Jun 2016

Bibliographical note

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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