Remdesivir, developed by Gilead, has been in short supply, so the issue of which patients benefit most could be very important for deciding who receives the drug. The authors of the study argue that the difference in mortality rates resulted from the fact that there were fewer patients whose symptoms were more severe at the beginning of the study, resulting in less statistical power. But the benefit appeared much bigger among those who were less sick.
The severity of patients’ illness was rated on a scale of 1 (not hospitalized) to 8 (dead). The lowest score in the study was a 4, denoting hospitalization, but no need for extra oxygen. The largest group of patients scored a 5, meaning they did need oxygen.
Among patients who scored a 4, there was a 38% benefit in the speed of recovery. Among those who scored 5, there was a 47% benefit. But that benefit fell to 20% among those who scored a 6, meaning they were receiving high-flow ventilation, and a decrease of 0.05% among those who scored a 7, meaning they were intubated or on extracorporeal membrane oxygenation. Until more data are available, doctors and researchers are likely to debate whether to use remdesivir in sicker patients.
There have been concerns that the study’s main goal, originally based on changes in the 8-point score at day 15, was changed before the result was analyzed. Changing goalposts can be a sign that researchers are skewing the results. In the paper, the researchers explain that the concern was that Covid-19 illness was persisting much longer than had been expected. But that original goal, the odds of improvement in the 8-point scale on day 15, was 50% higher in the remdesivir group, a highly statistically significant result.
Some critics saw flaws in the study that could affect how its results are interpreted. The study was stopped after a data safety and monitoring board, a panel of outside experts charged with safeguarding patients in the trial, notified the National Institute of Allergy and Infectious Diseases, which was running the study, that there had been a statistically significant benefit of remdesivir.