title: Event Rates in Randomized Clinical Trials Evaluating Cardiovascular Interventions and Devices.
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.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Karim D
authors.initials: KD
authors.lastname: Mahmoud
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Lennon
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. Electronic address: holmes.david@mayo.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Holmes
mesh_terms: D002318:Cardiovascular Diseases / Q000601:surgery*; D013504:Cardiovascular Surgical Procedures / Q000295:instrumentation* / Q000706:statistics & numerical data*; D004867:Equipment Design; D006801:Humans; D016032:Randomized Controlled Trials as Topic