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Coronavirus (COVID-19)

Weighing the Benefits and Risks of Proliferating Observational Treatment AssessmentsObservational Cacophony, Randomized Harmony

Educational Objective
To understand the benefits and risks of proliferating observational treatment assessments

1 Credit CME

JAMA

Published Online: July 31, 2020

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Article Information and Disclosures

Robert M. Califf, MD¹;

Adrian F. Hernandez, MD, MHS^2,3;

Martin Landray, MBChB⁴

Author Affiliations

¹Verily Life Sciences (Alphabet), South San Francisco, California
²Duke Clinical Research Institute, Durham, North Carolina
³Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina
⁴Nuffield Department of Population Health, University of Oxford, Headington, Oxford, United Kingdom

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Amid the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, substantial effort is being directed toward mining databases and publishing case series and reports that may provide insights into the epidemiology and clinical management of coronavirus disease 2019 (COVID-19). However, there is growing concern about whether attempts to infer causation about the benefits and risks of potential therapeutics from nonrandomized studies are providing insights that improve clinical knowledge and accelerate the search for needed answers, or whether these reports just add noise, confusion, and false confidence. Most of these studies include a caveat indicating that “randomized clinical trials are needed.” But disclaimers aside, does this approach help make the case for well-designed randomized clinical trials (RCTs) and accelerate their delivery?¹ Or do observational studies reduce the likelihood of a properly designed trial being performed, thereby delaying the discovery of reliable truth?

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Article Information

Corresponding Author: Robert M. Califf, MD, Verily Life Sciences, 269 E Grand Ave, South San Francisco, CA 94080 (robertcaliff@verily.com).

Published Online: July 31, 2020. doi:10.1001/jama.2020.13319

Conflict of Interest Disclosures: Dr Califf reported being head of clinical policy and strategy at Verily Life Sciences and Google Health, an adjunct professor of medicine at Duke University and Stanford University, a board member for Cytokinetics, and former commissioner for the FDA. Dr Hernandez reported receipt of grants and personal fees from AstraZeneca, Amgen, Boehringer Ingelheim, Novartis, and Merck, personal fees from Bayer, and grants from Janssen and Verily, as well as being the principal investigator for the Healthcare Worker Exposure & Outcomes Research (HEROES) Program funded by the Patient-Centered Outcomes Research Institute. Dr Landray reported receipt of grants from Boehringer Ingelheim, Novartis, The Medicines Company, Merck, Sharp & Dohme, and UK Biobank and being co–chief investigator for the RECOVERY trial of potential treatments for hospitalized patients with COVID-19, funded by UK Research & Innovation and the National Institute for Health Research (NIHR).

Funding/Support: Dr Landray is supported by Health Data Research UK, the NIHR Oxford Biomedical Research Centre, and the Medical Research Council Population Health Research Unit.

Role of the Funder/Sponsor: Supporters had no role in the preparation, review, or approval of the manuscript or decision to submit the manuscript for publication.

Additional Contributions: We thank Jonathan McCall, MS (Duke Forge, Duke University), for editorial assistance. No compensation other than usual salary was received.

References

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.