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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

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.

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