On August 23, India’s award-winning online magazine The Wire took a look at how, “New Remdesivir Study Shows the Trouble With Bad Science.” On August 22, JAMA published an RCT of remdesivir for moderate COVID-19. The drug inhibits RNA enzymes needed for viruses to replicate, and is approved around the world for severe cases. The current study aims to expand this treatment to moderate cases of COVID-19. 584 patients from the US, Europe, and Asia with moderate disease were split into three treatment arms. Arm one got a ten-day course of remdesivir, arm two got a five-day course, and arm three got the “standard care” of antibiotics and steroids. Severity of COVID-19 was rated on a seven-point scale ranging from death (1) to “not hospitalized” (7). Participant’s clinical severity and also any side effects were rated at day 11.
Five-Day Group Shows Benefit, Ten-Day Group Does Not
On day 11, the five-day remdesivir arm patients, “were 65% more likely to achieve better clinical scores than the standard care arm.” Under the same “yardstick,” the ten-day remdesivir arm showed “no benefit.” The researchers concluded that the five-day group must have had a, “significantly different clinical status than those receiving standard therapy, with uncertain clinical importance.” Several “red flags” appeared: first, the sponsor is remdesivir manufacturer Gilead Sciences Inc. Next, the endpoint is “unimpressive” in that odds of better clinical status, “is quite vague” relative to other, more clinically meaningful measurements like mortality, hospital stay, need for oxygen, etc. Exploratory endpoints of time to recovery or “time to improvement in clinical status” were not helped by remdesivir.
Positive Results “Highly Suspect”
Of the 584 subjects, 80-85% had a score of 5 (hospitalized but not on oxygen). It is not clear how previous trial end-points for testing with severe cases, “can be applied to patients with moderate disease.” Also, the trial’s premises are “questionable”: given that remdesivir is very expensive, and given that folks with moderate COVID-19 have a 1% mortality rate, “it is impossible to justify remdesivir’s use without evidence of concrete clinical benefit.” That this trial was allowed to report its results as positive, and in favor of remdesivir, is “highly suspect.” This trial captures what is wrong with, “trials funded by the pharmaceutical industry in the context of the COVID-19 pandemic.” Using an ambiguous endpoint and a patient group that might not need treatment means, “this trial bears all the hallmarks of bad science.” The lack of response in the ten-day group is hard to make sense of. Since the three arms had “comparable characteristics” and the trial was randomized, “the benefit of remdesivir should have been apparent in both arms, not just one.”
The lead authors of the JAMA study are Christoph D. Spinner, MD, Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Munich, Germany; Robert L. Gottlieb, MD, PhD, Baylor University Medical Center, Dallas, Texas; and Gerard J. Criner, MD, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.