Making Statistical Sense of the Molnupiravir MOVe-OUT Clinical Trial
Thorlund et al.,
Making Statistical Sense of the Molnupiravir MOVe-OUT Clinical Trial,
The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.21-1339 (Review)
Discussion of concerns with the MOVe-OUT trial, including the reversal of the treatment effect post-interim analysis.
Thorlund et al., 11 Mar 2022, peer-reviewed, 5 authors.
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Am. J. Trop. Med. Hyg., 00(00), 2022, pp. 1–4
doi:10.4269/ajtmh.21-1339
Copyright © 2022 by The American Society of Tropical Medicine and Hygiene
Perspective Piece
Making Statistical Sense of the Molnupiravir MOVe-OUT Clinical Trial
Kristian Thorlund,1* Kyle Sheldrick,2 Gideon Meyerowitz-Katz,3 Sonal Singh,4 and Andrew Hill5
1
Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada; 2University of New South
Wales, Kensington, Australia; 3School of Health and Society, University of Wollongong, New South Wales, Australia; 4Department of Family
Medicine and Community Health, UMass Chan Medical School, Worcester, Massachusetts; 5Department of Pharmacology and Therapeutics,
University of Liverpool, Liverpool, United Kingdom
Abstract. Oral therapies for the early treatment of COVID-19 may prevent disease progression and health system
overcrowding. A new oral therapeutic named molnupiravir has been promoted as providing an approximately 50% reduction in death or the need for hospitalization. The clinical trial evaluating this drug was stopped early at the recommendation of the Data Safety and Monitoring Board after approximately 50% of the sample had been recruited. At the point of
discontinuing the trial, approximately 90% of the planned sample had been recruited and had available follow-up data
accessible. We discuss issues about the study conduct, analysis, and interpretation, including 1) the authors and sponsors presented the interim analysis as the primary analysis; 2) communication between sponsors and the Data Safety
and Monitoring Board was insufficient; 3) the treatment effects reverse when examining only the post-interim analysis
population, and are substantially attenuated when examining the full data; 4) the choice of primary analysis is incorrect; 5)
analysis of lost-to-follow-up patients favors the study drug; and 6) other known molnupiravir trials were not presented in
the primary study findings. As a result of methodological and statistical concerns, it seems that external trials, separate
from those supported by the sponsoring company, are required to determine the utility of this drug.
Since the COVID-19 pandemic began, there has been a
need for effective vaccines and treatments. The early vaccine trials allowed rapid development and deployment of
highly effective vaccines, but treatments for COVID-19 have
been slow to develop. The greatest successes among treatments have been those conducted in patients with advanced
disease in hospitals.1 Much more elusive have been interventions for early treatment of COVID-19, when patients are
not yet hospitalized.1 Clinical trials in this population are
challenging because most patients will never be hospitalized
regardless of interventions so..
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