Functional and Symptomatic Clinical Trial Endpoints: The HFC-ARC Scientific Expert Panel

Mitchell A Psotka; William T Abraham; Mona Fiuzat; Gerasimos Filippatos; JoAnn Lindenfeld; Tariq Ahmad; G Michael Felker; Richard Jacob; Dalane W Kitzman; Eric S Leifer; Eldrin F Lewis; Robert J Mentz; Richard Nkulikiyinka; Wei Ni; Daniel E Schaber; Abhinav Sharma; Scott D Solomon; Norman Stockbridge; John R Teerlink; Ellis F Unger; David J Whellan; Janet Wittes; Stefan D Anker; Christopher M O'Connor

doi:10.1016/j.jchf.2022.09.012

Functional and Symptomatic Clinical Trial Endpoints: The HFC-ARC Scientific Expert Panel

JACC Heart Fail. 2022 Dec;10(12):889-901. doi: 10.1016/j.jchf.2022.09.012. Epub 2022 Nov 9.

Authors

Mitchell A Psotka¹, William T Abraham², Mona Fiuzat³, Gerasimos Filippatos⁴, JoAnn Lindenfeld⁵, Tariq Ahmad⁶, G Michael Felker³, Richard Jacob⁷, Dalane W Kitzman⁸, Eric S Leifer⁹, Eldrin F Lewis¹⁰, Robert J Mentz³, Richard Nkulikiyinka¹¹, Wei Ni¹², Daniel E Schaber¹³, Abhinav Sharma¹⁴, Scott D Solomon¹⁵, Norman Stockbridge¹⁶, John R Teerlink¹⁷, Ellis F Unger¹⁶, David J Whellan¹⁸, Janet Wittes¹⁹, Stefan D Anker²⁰, Christopher M O'Connor²¹

Affiliations

¹ Inova Heart and Vascular Institute, Falls Church, Virginia, USA; U.S. Food and Drug Administration, Silver Spring, Maryland, USA. Electronic address: mitchell.psotka@inova.org.
² Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA.
³ Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA.
⁴ University of Cyprus Medical School, Shakolas Educational Center for Clinical Medicine, Nicosia, Cyprus.
⁵ Heart Failure and Transplantation Section, Vanderbilt Heart and Vascular Institute, Nashville, Tennessee, USA.
⁶ Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
⁷ Dublin, Ohio, USA.
⁸ Sections on Cardiovascular Medicine and Geriatrics, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
⁹ Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
¹⁰ Division of Cardiovascular Medicine, Stanford University, Palo Alto, California, USA.
¹¹ Research and Development, Pharmaceuticals, Bayer, Wuppertal, Germany.
¹² Eli Lilly & Company, Indianapolis, Indiana, USA.
¹³ Medtronic, Minneapolis, Minnesota, USA.
¹⁴ Division of Cardiology, McGill University Health Centre, McGill University, Montreal, Quebec, Canada; DREAM-CV Lab, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
¹⁵ Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹⁶ U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
¹⁷ Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California-San Francisco, San Francisco, California, USA.
¹⁸ Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
¹⁹ Wittes LLC, Washington, DC, USA.
²⁰ Department of Cardiology and Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research partner site Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany.
²¹ Inova Heart and Vascular Institute, Falls Church, Virginia, USA; Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA.

PMID: 36456063
DOI: 10.1016/j.jchf.2022.09.012

Abstract

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and the Academic Research Consortium (ARC) composed of patients, academic investigators from the United States and Europe, the U.S. Food and Drug Administration, the National Institutes of Health, payers, and industry. Members discussed the measure, remote capture, and clinical utility of functional and quality-of-life endpoints for use in clinical trials of heart failure and cardiovascular therapeutics, with the goal of improving the efficiency of heart failure and cardiovascular clinical research, evidence generation, and thereby patient quality of life, functional status, and survival. Assessments of patient-reported outcomes and maximal and submaximal exercise tolerance are standardized and validated, but actigraphy remains inconsistent as a potential endpoint. This paper details those discussions and consensus recommendations.

Keywords: clinical trial; functional endpoint; heart failure; intermediate endpoint; surrogate endpoint.

Publication types

Review

MeSH terms

Exercise Tolerance
Heart Failure* / therapy
Humans
National Institutes of Health (U.S.)
Quality of Life
Research Personnel
United States

Grants and funding

R18 FD006920/FD/FDA HHS/United States