STATE-OF-THE-ART PAPER
End Points for Clinical Trials in Acute Heart Failure Syndromes
Larry A. Allen, MD, MHS*,*,
Adrian F. Hernandez, MD, MHS ,
Christopher M. O'Connor, MD and
G. Michael Felker, MD, MHS
* Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, Colorado
Duke Clinical Research Institute and the Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina
Manuscript received November 7, 2008;
revised manuscript received December 19, 2008,
accepted December 23, 2008.
* Reprint requests and correspondence: Dr. Larry A. Allen, Academic Office 1, 12631 East 17th Avenue, Mailstop B130, P.O. Box 6511, Aurora, Colorado 80045 (Email: larry.allen{at}ucdenver.edu).
Acute heart failure syndromes (AHFS) remain a major cause of morbidity and mortality, in part because the development of new therapies for these disorders has been marked by frequent failure and little success. The heterogeneity of current approaches to AHFS drug development, particularly with regard to end points, remains a major potential barrier to progress in the field. End points involving hemodynamic status, biomarkers, symptoms, hospital stay, end organ function, and mortality have all been employed either alone or in combination in recent randomized clinical trials in AHFS. In this review, we will discuss the various end point domains from both a clinical and a statistical perspective, summarize the wide variety of end points used in completed and ongoing AHFS studies, and suggest steps for greater standardization of end points across AHFS trials.
Key Words: acute heart failure syndromes/acute decompensated heart failure • end points • randomized controlled trial design
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Abbreviations and Acronyms
| | AHFS = acute heart failure syndrome(s) | | FDA = Food and Drug Administration | | LOS = length of stay |
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