Determination of hospitalization type by investigator case report form or adjudication committee in a large heart failure clinical trial (β-Blocker Evaluation of Survival Trial [BEST])
Abstract
Background End point committees are routinely used to adjudicate efficacy and safety end points in clinical trials. The 2,708-patient β-Blocker Evaluation of Survival Trial (BEST) originally determined hospitalization type via investigator case report forms (CRFs), which captured whether a hospitalization was due to worsening heart failure (HF). Recently, the BEST End Points Committee (EPC) completed a blinded adjudication of all hospitalizations, allowing a comparison of the CRF method to the EPC method of determining hospitalization type. We sought to compare the investigator-determined mode of hospitalizations with the adjudicated events, to quantify the degree of agreement, and to compare the clinical trial results by method of event classification.Methods The BEST EPC reviewed all 5,086 hospitalizations that occurred in BEST. Events were identified using investigator-reported hospitalizations, as well as those documented by FDA Form 3500 (MedWatch) reports.Results The investigators identified more HF hospitalization events than adjudication (2,466 vs 1,729, P < .0001, paired analysis). Eight hundred thirty-four (34%) HF hospitalizations identified in CRFs were not confirmed by adjudication. Ninety-seven (6%) adjudicated events were not identified by the investigator reported method. One thousand six hundred thirty-two events were similarly identified by both methods.Conclusions The EPC adjudication identified fewer HF hospitalizations than did the investigator reported method with no change in the hazard ratio for this end point. Our findings suggest that independent end point committees may improve reliability through reduced variance, thus providing similar outcome results with fewer events and no increase in CIs.
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Efforts to standardize the identification of events by adjudication typically exclude many events that are regarded as clinically meaningful by the treating physician.
“efforts to standardize the identification of events by the process of adjudication typically exclude many events that are regarded as clinically meaningful by the treating physician.11–14”
From Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial (2021) · cites this paper as [13]
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- Authors
- Carson, P., Fiuzat, M., O'Connor, C., Anand, I., Plehn, J., Lindenfeld, J. A., Silver, M., White, M., Miller, A., Davis, G., Robertson, A. D., Bristow, M., & Gottlieb, S.
- Affiliations
- United States Department of Veterans Affairs (US)
- ARCA Biopharma (United States) (US)
- Minneapolis VA Health Care System (US)
- National Heart, Lung, and Blood Institute (US)
- Advocate Christ Medical Center (US)
- Montreal Heart Institute (CA)
- University of Florida Health Science Center (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Fiuzat, Mona
- ORCID
- Venue
- American Heart Journal
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 160
- Issue
- 4
- Pages
- 649-654
- ISSN
- 0002-8703 (ISSN-L)
- OpenAlex
- W2030555037
- Cited by
- 31
- References
- 17
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Food and Drug Administration
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Keywords
- heart failure hospitalization, adjudication committee, beta-blockers
- MeSH terms
- Adrenergic beta-Antagonists, Female, Heart Failure, Hospital Records, Hospitalization, Humans, Male, Middle Aged, Research Personnel, United States, Survival Rate, Treatment Outcome, Hospital Mortality, Clinical Trials Data Monitoring Committees
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