Event Rates in Randomized Clinical Trials Evaluating Cardiovascular Interventions and Devices

Karim D. Mahmoud, Ryan J. Lennon, David R. Holmes*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    2 Citations (Scopus)

    Abstract

    Randomized clinical trials (RCTs) are considered the gold standard for evidence-based medicine. However, an accurate estimation of the event rate is crucial for their ability to test clinical hypotheses. Overestimation of event rates reduces the required sample size but can compromise the statistical power of the RCT. Little is known about the prevalence, extent, and impact of overestimation of event rates. The latest RCTs on 10 preselected topics in the field of cardiovascular interventions and devices were selected, and actual primary event rates in the control group were compared with their respective event rate estimations. We also assessed what proportion of the nonsignificant RCTs was truly able to exclude a relevant treatment effect. A total of 27 RCTs randomizing 19,436 patients were included. The primary event rate in the control group was overestimated in 20 of the 27 RCTs (74.1%) resulting in a substantial relative difference between observed and estimated event rates (mean -22.9%, 95% confidence interval -33.5% to 12.2%; median -16.3%, 95% confidence interval -30.3% to -6.5%). Event rates were particularly overestimated in RCTs on biodegradable polymer drug-eluting coronary stents and renal artery stenting. Of the 14 single end point superiority trials with nonsignificant results, only 3 (21.4%) actually resulted in truly negative conclusions. In conclusion, event rates in RCTs evaluating cardiovascular interventions and devices are frequently overestimated. This under-reported phenomenon has fundamental impact on the design of RCTs and can have an adverse impact on the statistical power of these trials to answer important questions about therapeutic strategies. (C) 2015 Elsevier Inc. All rights reserved.

    Original languageEnglish
    Pages (from-to)355-363
    Number of pages9
    JournalAmerican Journal of Cardiology
    Volume116
    Issue number3
    DOIs
    Publication statusPublished - 1-Aug-2015

    Keywords

    • RENAL-ARTERY STENOSIS
    • SAMPLE-SIZE CALCULATIONS
    • LEFT ATRIAL APPENDAGE
    • NON-INFERIORITY TRIAL
    • PATENT FORAMEN OVALE
    • MEDICAL THERAPY
    • RESISTANT HYPERTENSION
    • MYOCARDIAL-INFARCTION
    • PERCUTANEOUS CLOSURE
    • WARFARIN THERAPY

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