Site selection in global clinical trials in patients hospitalized for heart failure: perceived problems and potential solutions

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• 作者：Mihai Gheorghiade (1)
  Muthiah Vaduganathan (2)
  Stephen J. Greene (1)
  Robert J. Mentz (3)
  Kirkwood F. Adams Jr. (4)
  Stefan D. Anker (5)
  Malcolm Arnold (6)
  Fabio Baschiera (7)
  John G. F. Cleland (8)
  Gadi Cotter (9)
  Gregg C. Fonarow (10)
  Christopher Giordano (11)
  Marco Metra (12)
  Frank Misselwitz (13)
  Eva Mühlhofer (14)
  Savina Nodari (12)
  W. Frank Peacock (15)
  Burkert M. Pieske (16)
  Hani N. Sabbah (17)
  Naoki Sato (18)
  Monica R. Shah (19)
  Norman L. Stockbridge (20)
  John R. Teerlink (21)
  Dirk J. van Veldhuisen (22)
  Andrew Zalewski (23)
  Faiez Zannad (24)
  Javed Butler (25)
  
• 关键词：Heart failure ; Site selection ; Clinical trials ; FDA
• 刊名：Heart Failure Reviews
• 出版年：2014
• 出版时间：March 2014
• 年：2014
• 卷：19
• 期：2
• 页码：135-152
• 全文大小：505 KB
• 作者单位：Mihai Gheorghiade (1)
  Muthiah Vaduganathan (2)
  Stephen J. Greene (1)
  Robert J. Mentz (3)
  Kirkwood F. Adams Jr. (4)
  Stefan D. Anker (5)
  Malcolm Arnold (6)
  Fabio Baschiera (7)
  John G. F. Cleland (8)
  Gadi Cotter (9)
  Gregg C. Fonarow (10)
  Christopher Giordano (11)
  Marco Metra (12)
  Frank Misselwitz (13)
  Eva Mühlhofer (14)
  Savina Nodari (12)
  W. Frank Peacock (15)
  Burkert M. Pieske (16)
  Hani N. Sabbah (17)
  Naoki Sato (18)
  Monica R. Shah (19)
  Norman L. Stockbridge (20)
  John R. Teerlink (21)
  Dirk J. van Veldhuisen (22)
  Andrew Zalewski (23)
  Faiez Zannad (24)
  Javed Butler (25)
  
  1. Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, 645?N. Michigan Avenue, Suite 1006, Chicago, 60611, IL, USA
  2. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  3. Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, USA
  4. University of North Carolina School of Medicine, Chapel Hill, NC, USA
  5. Centre for Clinical and Basic Research, IRCCS San Raffaele, Rome, Italy
  6. Division of Cardiology, University of Western Ontario, London, ON, Canada
  7. Novartis Pharma AG, Basel, Switzerland
  8. Castle Hill Hospital, Hull York Medical School, Kingston-Upon-Hull, UK
  9. Momentum-Research, Inc., Durham, NC, USA
  10. Division of Cardiology, University of California, Los Angeles, CA, USA
  11. Quintiles, Cardiovascular and Metabolic Therapeutic Delivery Unit, Durham, NC, USA
  12. Division of Cardiology, University of Brescia, Brescia, Italy
  13. Bayer Healthcare Pharmaceuticals, Berlin, Germany
  14. Bayer Vital GmbH, Leverkusen, Germany
  15. Department of Emergency Medicine, Baylor College of Medicine, Houston, TX, USA
  16. Division of Cardiology, Medical University of Graz, Graz, Austria
  17. Department of Medicine, Henry Ford Hospital, Detroit, MI, USA
  18. Department of Internal Medicine and Cardiology, Nippon Medical School Musashi-Kosugi Hospital, Kanagawa, Japan
  19. National Heart Lung and Blood Institute, Bethesda, MD, USA
  20. Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
  21. Section of Cardiology, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, CA, USA
  22. Department of Cardiology, University of Groningen, Groningen, The Netherlands
  23. Novartis Pharmaceutical Corporation, East Hanover, NJ, USA
  24. Inserm CIC 9501 and U961, Université de Lorraine, CHU Cardiology, Nancy, France
  25. Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
  
• ISSN：1573-7322

文摘

There are over 1 million hospitalizations for heart failure (HF) annually in the United States alone, and a similar number has been reported in Europe. Recent clinical trials investigating novel therapies in patients with hospitalized HF (HHF) have been negative, and the post-discharge event rate remains unacceptably high. The lack of success with HHF trials stem from problems with understanding the study drug, matching the drug to the appropriate HF subgroup, and study execution. Related to the concept of study execution is the importance of including appropriate study sites in HHF trials. Often overlooked issues include consideration of the geographic region and the number of patients enrolled at each study center. Marked differences in baseline patient co-morbidities, serum biomarkers, treatment utilization and outcomes have been demonstrated across geographic regions. Furthermore, patients from sites with low recruitment may have worse outcomes compared to sites with higher enrollment patterns. Consequently, sites with poor trial enrollment may influence key patient end points and likely do not justify the costs of site training and maintenance. Accordingly, there is an unmet need to develop strategies to identify the right study sites that have acceptable patient quantity and quality. Potential approaches include, but are not limited to, establishing a pre-trial registry, developing site performance metrics, identifying a local regionally involved leader and bolstering recruitment incentives. This manuscript summarizes the roundtable discussion hosted by the Food and Drug Administration between members of academia, the National Institutes of Health, industry partners, contract research organizations and academic research organizations on the importance of selecting optimal sites for successful trials in HHF.