Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Nov 17;76(20):2368-2378.
doi: 10.1016/j.jacc.2020.09.544.

Conduct of Clinical Trials in the Era of COVID-19: JACC Scientific Expert Panel

Mitchell A Psotka  1 , William T Abraham  2 , Mona Fiuzat  3 , Gerasimos Filippatos  4 , JoAnn Lindenfeld  5 , Tariq Ahmad  6 , Ankeet S Bhatt  7 , Peter E Carson  8 , John G F Cleland  9 , G Michael Felker  10 , James L Januzzi Jr  11 , Dalane W Kitzman  12 , Eric S Leifer  13 , Eldrin F Lewis  14 , John J V McMurray  15 , Robert J Mentz  10 , Scott D Solomon  7 , Norman Stockbridge  16 , John R Teerlink  17 , Muthiah Vaduganathan  7 , Orly Vardeny  18 , David J Whellan  19 , Janet Wittes  20 , Stefan D Anker  21 , Christopher M O'Connor  22
Affiliations
Review

Conduct of Clinical Trials in the Era of COVID-19: JACC Scientific Expert Panel

Mitchell A Psotka et al. J Am Coll Cardiol. .

Abstract

The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S. Food and Drug Administration, the National Institutes of Health, and industry members. A series of meetings were convened to address the challenges caused by the COVID-19 pandemic, review options for maintaining or altering best practices, and establish key recommendations for the conduct and analysis of clinical trials for cardiovascular disease and heart failure. This paper summarizes the discussions and expert consensus recommendations.

Keywords: COVID-19; clinical trial; endpoint ascertainment; heart failure.

PubMed Disclaimer

Conflict of interest statement

Author Relationship With Industry Dr. Psotka has received consulting fees from Amgen, Cytokinetics, and Windtree; and has received grant support from the U.S. Food and Drug Administration. Dr. Abraham has received consulting fees from Abbott, Boehringer Ingelheim, CVRx, Edwards Lifesciences, and Respicardia; has received salary support from V-Wave; and has received research support from the U.S. National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Filippatos has received consulting income from Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor; and has received lecture fees from Merck. Dr. Lindenfeld has received consulting fees from Novartis, Abbott, ResMed, V-Wave, CVRx, and Cytokinetics. Dr. Ahmad has received consulting fees from Amgen, Cytokinetics, Relypsa, and Novartis. Dr. Bhatt has received consulting fees from Sanofi Pasteur; and participates in clinical endpoint committees for the U.S. National Institutes of Health. Dr. Cleland has received consulting fees from Abbott, Amgen, Bayer, Medtronic, Novartis, Pharmacosmos, Vifor, Bristol Myers Squibb, and Servier; and has received research grants from Amgen, Bayer, Novartis, Pharmacosmos, Vifor, Bristol Myers Squibb, and Servier. Dr. Felker has received research grants from the National Heart, Lung, and Blood Institute, American Heart Association, Amgen, Merck, Cytokinetics, and Roche Diagnostics; and has received consulting fees from Novartis, Amgen, Bristol Myers Squibb, Cytokinetics, Medtronic, Cardionomic, Relypsa, V-Wave, Myokardia, Innolife, EBR Systems, Arena, Abbott, Sphingotec, Roche Diagnostics, Alnylam, LivaNova, Windtree Therapeutics, Rocket Pharma, and scPharmaceuticals. Dr. Januzzi is a trustee of the American College of Cardiology; has received grant support from Applied Therapeutics, Novartis Pharmaceuticals, and Abbott Diagnostics; has received consulting income from Abbott, Janssen, Novartis, Pfizer, Merck, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Boehringer Ingelheim, Janssen, and Takeda. Dr. Kitzman has received consulting fees from AstraZeneca, Bayer, Novartis, Merck, Pfizer, Boehringer Ingelheim, AbbVie, DCRI, and Corvia; has received grant support from AstraZeneca, Bayer, and Novartis; and has stock in Gilead. Dr. Lewis has received consulting fees from Novartis; and has received institutional research grant support from Amgen, Novartis, and Sanofi. Dr. McMurray has received financial support from Bayer, Cardiorentis, Amgen, Oxford University, Theracos, Abbvie, DalCor, Pfizer, Merck, Novartis, GlaxoSmithKline, Bristol Myers Squibb, Vifor-Fresenius, Kidney Research UK, and AstraZeneca. Dr. Mentz has received consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Boston Scientific, Janssen, Luitpold, Medtronic, Merck, Novartis, and Sanofi; and has received research grants from Akros, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, GlaxoSmithKline, Gilead, InnoLife, Luitpold/American Reagent, Novartis, Otsuka, ResMed, and the U.S. National Institutes of Health grants U01HL125511-01A1 and R01AG045551-01A1. Dr. Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, U.S. National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and has received consulting fees from Akros, Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Corvia, Cytokinetics, Gilead, GlaxoSmithKline, Ironwood, Merck Sharp & Dohme, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, and Cardiac Dimensions. Dr. Teerlink has received consulting fees from Amgen, Bayer, Cytokinetics, Novartis, and Stealth Health; and has received research funding from Abbott, Amgen, Bayer, Bristol Myers Squibb, Novartis, and scPharmaceuticals. Dr. Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541); and has served on Advisory Boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Vardeny has received consulting fees from Novartis; and has received research grants from AstraZeneca and Sanofi Pasteur. Dr. Whellan has received grant support from the U.S. National Institutes of Health (R01AG045551). Dr. Wittes reports that the company for which she works, Statistics Collaborative, has contracts with many companies, some of which are developing treatments for heart failure. Dr. Anker has received clinical trial–related fees from Abbott Vascular, Servier, Vifor, Bayer, Boehringer Ingelheim, Thermo Fisher, Respicardia, and Novartis. Dr. O’Connor has received research support from Roche Diagnostics and Merck; has been a consultant for Bristol Myers Squibb, Merck, Windtree, and Neurotronik; and is a co-owner of Biscardia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Central Illustration
Central Illustration
Management of Coronavirus Disease-2019 Impact on Non–Coronavirus Disease-2019 Clinical Trials Coronavirus disease-2019 (COVID-19) has globally affected clinical trial performance, patient behavior, and clinical care. Most clinical trial sites ceased site-based enrollments and procedures; adverse event reporting declined for enrolled patients. Patient mobility declined in response to governmental orders and fear of infection, and patient-care changes include widespread reductions in cardiovascular hospitalizations and increased numbers of at-home cardiac arrests, which may be due to COVID-19 or cardiovascular conditions. We evaluate methods to promote valid remote endpoint ascertainment, adjudication of COVID-19 and non–COVID-19 events, and suggest considerations for careful statistical analysis plan and protocol alterations that may be made in consultation with regulators.
Figure 1
Figure 1
Trial Timeline Statistical Assessment The progression of a clinical trial from design to completion, color coded by proximity to database lock and analysis (dark green = ready for analysis; dark red = inappropriate for analysis). This concept can help assess initiation and stopping decisions. For instance, given difficulties with recruitment and enrollment, trials with fewer than approximately 20% of endpoints collected in the dark red period may consider pausing initiation or recruitment in consultation with regulators, until COVID-19 has waned. Alternatively, trials with >80% of endpoints collected in green, may recalculate their power and consider stopping the trial to avoid the consequences of COVID-19 on endpoint ascertainment, adjudication, and statistical analysis plan (SAP) adjustment; with at least 80% of events collected, there may be only a modest 10% decrement in statistical power. Trials with approximately 20% to 80% of endpoints collected need to consider how best to adapt to the issues covered in this paper, including remote endpoint collection, methods to minimize missing data, and SAP modifications.
See this image and copyright information in PMC

References

    1. WCG Resource Center: COVID-19 and Clinical Trial Operations. https://www.wcgclinical.com/covid-19/ Available at:
    1. Medidata . Release 4.0. 2020. COVID 19 and Clinical Trials: The Medidata Perspective.https://www.medidata.com/en/insight/covid-19-and-clinical-trials-the-med... Available at:
    1. U.S. Food and Drug Administration FDA Guidance on Conduct of Clinical Trials of Medical Products During COVID-19 Public Health Emergency. 2020. https://www.fda.gov/media/136238/download Available at:
    1. National Institutes of Health Guidance for NIH-funded Clinical Trials and Human Subjects Studies Affected by COVID-19. 2020. https://grants.nih.gov/grants/guide/notice-files/NOT-OD-20-087.html Available at:
    1. European Medicines Agency Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) Pandemic. 2020. https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/gui... Available at: