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 Hussain, Ian White, Dean Langan, Miriam Johnson, David Currow, David Torgerson, J Bland

    Research output: Contribution to journalReview articlepeer-review

    21 Citations (Scopus)

    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; I2 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
    Volume74
    DOIs
    Publication statusPublished - 1 Jun 2016

    Keywords

    • Differential mortality
    • Meta-analysis
    • Missing data
    • Palliative care
    • Randomized controlled trials
    • Systematic review

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