Absolute Risk Reductions in COVID-19 Antiviral Medication Clinical Trials

Abstract

COVID-19 antiviral medications approved or authorized for emergency use by the U.S. Food and Drug Administration are reported to have high efficacy in preventing severe illness, hospitalizations, and deaths. However, reports for some of these antivirals use relative risk reductions from clinical trials without absolute risk reductions. The present paper reappraises recently published clinical trial data for the COVID-19 antivirals paxlovid, remdesivir, and molnupiravir, and reports absolute risk reductions, relative risk reductions, as well as number needed to treat to reduce severe illness, hospitalizations, and deaths. Relative risk reductions are 88.88% for paxlovid (95% CI: 72.13–95.56%), 86.48% for remdesivir (95% CI: 41.41–96.88%), and 30.41% for molnupiravir (95% CI: 0.81–51.18%), while absolute risk reductions are much lower at 5.73% for paxlovid (95% CI: 3.79–7.68%), 4.58% for remdesivir (95% CI: 1.79–7.38%), and 2.96% for molnupiravir (95% CI: 0.09–5.83%). Low absolute risk reductions and the high number of patients needed to treat to reduce severe COVID-19 infections, hospitalizations, and deaths challenge the clinical efficacy of antivirals approved or authorized by the U.S Food and Drug Administration. These findings apply to other populations with similar control event rates. Accurate information should be disseminated to the public when selecting treatments for COVID-19.

Polypharmacy and Medication Outcome Reporting Bias in Older Patients with COVID-19

“…Medication outcome reporting bias can occur when the treatment efficacy of an RCT is reported solely as relative risk reductions (RRRs), which overestimate medication benefits and exaggerate disease/illness risk reductions compared to unreported absolute risk reductions (ARRs). For example, a recent study of COVID-19 antiviral medications to reduce the risks of COVID-19 severity, hospitalizations, and deaths noted that the RRRs for paxlovid, remdesivir, and molnupiravir are 88.88%, 86.48%, and 30.41% respectively, but the corresponding ARRs are much lower at 5.73%, 4.58%, and 2.96% [9]. "Publication of complete trial results is important to allow clinicians, consumers, and policy makers to make better informed decisions about healthcare" [10].…”