Author + information
- Received March 18, 2020
- Revision received April 30, 2020
- Accepted May 4, 2020
- Published online July 27, 2020.
- Alexander C. Fanaroff, MD, MHSa@ACFanaroff,
- Robert M. Califf, MDb,
- Robert A. Harrington, MDc,
- Christopher B. Granger, MDd,
- John J.V. McMurray, MDe,
- Manesh R. Patel, MDd,
- Deepak L. Bhatt, MD, MPHf,
- Stephan Windecker, MDg,
- Adrian F. Hernandez, MDd,
- C. Michael Gibson, MDh,
- John H. Alexander, MDd and
- Renato D. Lopes, MD, PhDd,∗ (, )@RenatoDLopes1
- aPenn Cardiovascular Outcomes, Quality and Evaluative Research Center, Leonard Davis Institute, and Cardiovascular Medicine Division, University of Pennsylvania, Philadelphia, Pennsylvania
- bVerily Life Sciences (Alphabet), South San Francisco, California
- cDepartment of Medicine, Stanford University, Stanford, California
- dDivision of Cardiology and Duke Clinical Research Institute, Duke University, Durham, North Carolina
- eBritish Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland
- fBrigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts
- gDepartment of Cardiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland
- hCardiovascular Division, Beth Israel Deaconess Medical, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Renato D. Lopes, Duke Clinical Research Institute, P.O. Box 17969, Durham, North Carolina 27715.
• Well-conducted RCTs have repeatedly contradicted practices supported by common sense and clinical observation.
• Common sense and clinical observation fail because of the inability to fully understand complex biopsychosocial systems.
• RCTs must be integrated into clinical practice to improve the evidence base in cardiology.
Concerns about the external validity of traditional randomized clinical trials (RCTs), together with the widespread availability of real-world data and advanced data analytic tools, have led to claims that common sense and clinical observation, rather than RCTs, should be the preferred method to generate evidence to support clinical decision-making. However, over the past 4 decades, results from well-done RCTs have repeatedly contradicted practices supported by common sense and clinical observation. Common sense and clinical observation fail for several reasons: incomplete understanding of pathophysiology, biases and unmeasured confounding in observational research, and failure to understand risks and benefits of treatments within complex systems. Concerns about traditional RCT models are legitimate, but randomization remains a critical tool to understand the causal relationship between treatments and outcomes. Instead, development and promulgation of tools to apply randomization to real-world data are needed to build the best evidence base in cardiovascular medicine.
Dr. Fanaroff has received a career development grant and honoraria from the American Heart Association; and has received grant funding from Boston Scientific. Dr. Califf was the Commissioner of Food and Drugs for the U.S. Food and Drug Administration from February 2016 to January 2017 and Deputy Commissioner for Medical Products and Tobacco for the U.S. Food and Drug Administration from February 2015 to January 2016; has served on the corporate board for Cytokinetics; has served as the board chair for the People-Centered Research Foundation; has received consulting fees from Merck, Biogen, Genentech, Eli Lilly, and Boehringer Ingelheim; and has served as a scientific advisor for Verily Life Sciences (Alphabet). Dr. Harrington has served as the Chairman of Medicine at Stanford University, President of the American Heart Association, and a member of the Board of Trustees at the College of the Holy Cross; and has received research grants from AstraZeneca and Bristol-Myers Squibb. Dr. Granger has received research grants from AKROS, Apple, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, the Duke Clinical Research Institute, the U.S. Food and Drug Administration, GlaxoSmithKline, Janssen Pharmaceuticals, Medtronic, Novartis, and Pfizer; and has received consulting fees/honoraria from Abbvie, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, CeleCor Therapeutics, Correvio, Espero BioPharma, Janssen Pharmaceuticals, Medscape, Medtronic, Merck, the National Institutes of Health, Novo Nordisk, Pfizer, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. McMurray has received fees (all fees listed paid to Glasgow University) for serving on a steering committee from AbbVie, Amgen, Bayer, Bristol-Myers Squibb, Cardiorentis, DalCor Pharmaceuticals, GlaxoSmithKline, Novartis, Oxford University–Bayer, and Vifor Pharma–Fresenius; has received fees for serving on an endpoint committee from Cardiorentis; has received fees for serving on an endpoint adjudication committee from Vifor Pharma–Fresenius; has received fees for serving as principal investigator of a trial from Theracos; has received fees for serving as co-principal investigator of a trial from GlaxoSmithKline and Novartis; has received fees for serving on a data and safety monitoring committee from Merck and Pfizer; has received fees for serving on an executive committee from Novartis; has received advisory board fees from Novartis; and has received fees for travel support from AbbVie, Amgen, Cardiorentis, GlaxoSmithKline, Novartis, Oxford University–Bayer, Theracos, and Vifor Pharma–Fresenius. Dr. Patel has received research grants to the institution from AstraZeneca, Bayer, Heartflow, Janssen, National Institutes of Health, Procyrion, and Medtronic; and has received consulting or advisory board fees from Bayer, Janssen, Medscape, and Amgen. Dr. Bhatt has received grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi, The Medicines Company, Roche, Pfizer, Forest Laboratories/AstraZeneca, Ischemix, Amgen, Lilly, Chiesi, Ironwood, Abbott, Regeneron, Idorsia, Synaptic, Fractyl, Afimmune, and Lexicon; has received other from FlowCo, Takeda, Medscape Cardiology, Regado Biosciences, Boston VA Research Institute, Clinical Cardiology, VA, St. Jude Medical (now Abbott), Biotronik, Boston Scientific, Merck, Svelte, Novo Nordisk, Cereno Scientific, and CSI; has received grants and other from PLx Pharma, Cardax, and PhaseBio; has received personal fees from Duke Clinical Research Institute, Mayo Clinic, Population Health Research Institute, Belvoir Publications, Slack Publications, WebMD, Elsevier, HMP Global, Harvard Clinical Research Institute (now Baim Institute for Clinical Research), Journal of the American College of Cardiology, Cleveland Clinic, Mount Sinai School of Medicine, TobeSoft, Bayer, Medtelligence/ReachMD, Ferring Pharmaceuticals, CSL Behring, and MJH Life Sciences; has received personal fees, nonfinancial support, and other from the American College of Cardiology; has received personal fees and nonfinancial support from the Society of Cardiovascular Patient Care; has received nonfinancial support from the American Heart Association; and has received personal fees and other from Boehringer Ingelheim. Dr. Windecker has received research and educational grants to the institution from Abbott, Amgen, BMS, Bayer, Boston Scientific, Biotronik, Cardinal Health, CardioValve, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Johnson & Johnson, Medtronic, Querbet, Polares, Sanofi, Terumo, and Sinomed; has served as an unpaid member of the steering/excecutive group of trials funded by Abbott, Abiomed, Amgen, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Polares, Sinomed, V-Wave, and Xeltis, but has not received personal payments by any pharmaceutical company or device manufacturer; and is a member of the steering/excecutive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr. Gibson has received grants and personal fees from Johnson & Johnson, Janssen Pharmaceuticals, Bayer Corp., Portola Pharmaceuticals, Angel Medical Corporation, and CSL Behring; has received grants from Bristol-Myers Squibb and SCAD Alliance; has received personal fees from The Medicines Company, Boston Clinical Research Institute, Cardiovascular Research Foundation, Eli Lilly and Company, Gilead Sciences, Inc., Novo Nordisk, Web MD, UpToDate in Cardiovascular Medicine, Amarin Pharma, Amgen, Boehringer Ingelheim, Chiesi, Merck & Co., Inc., PharmaMar, Sanofi, Somahlution, St. Francis Hospital, Verreseon Corporation, Boston Scientific, Duke Clinical Research Institute, Impact Bio, Ltd., MedImmune, Medtelligence, Microport, PERT Consortium, GE Healthcare, Caladrius Bioscience, CeleCor Therapeutics, and Thrombolytic Science; has equity in nference; and has received nonfinancial support from Baim Institute. Dr. Alexander has received research grants from Boehringer Ingelheim, Bristol-Myers Squibb, CryoLife, CSL Behring, GlaxoSmithKline, the U.S. Food and Drug Administration, and the National Institutes of Health; has received consulting/honoraria from AbbVie Pharmaceuticals, Bayer, Bristol-Myers Squibb, CryoLife, Inositec, Pfizer, Portola Pharmaceuticals, Quantum Genomics, the VA Cooperative Studies Program, XaTek, and the Duke Private Diagnostic Clinic; and has received reimbursement for personal expenses from Bristol-Myers Squibb, CryoLife, Inositec, Pfizer, the VA Cooperative Studies Program, and XaTek. Dr. Lopes has received research grants from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; and has received personal fees from Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received March 18, 2020.
- Revision received April 30, 2020.
- Accepted May 4, 2020.
- 2020 American College of Cardiology Foundation
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