In the Winter 2020 edition of Update Magazine I discussed remdesivir (Veklury), Gilead’s FDA-approved therapy for patients with serious manifestations of COVID-19. Specifically, I took issue with the WHO’s Solidarity study showing that nearly 3,000 people receiving remdesivir were not more likely to survive infection with SARS-CoV-2 than those receiving only standard of care. The WHO preliminary findings seem to be in direct contrast to the findings of the Adaptive COVID-19 Treatment Trial 1 (ACTT-1). Who should we believe? What do the conflicting results mean?
On January 5th, there was a roundtable held at the French National Assembly where they discussed final Solidarity results (even though the WHO hasn’t released the full study yet). As you can see and hear for yourself, remdesivir does have a statistically significant mortality benefit for oxygenated patients. Confirmation can be found at the 1:52 mark.
As I mentioned in my Update Magazine article, if you dig into WHO’s data on mortality, you find an interesting and important outcome. WHO’s preprint manuscript contained a meta-analysis of existing studies of remdesivir. The preprint reported a 99% confidence interval, rather than a 95% confidence interval, in the subtotal of the largest population: non-ventilated patients. This is unusual, given that a similar meta-analysis on steroids for COVID-19 used a 95% confidence interval across all studies and for subtotals. That meta-analysis was authored by the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group.
If we apply the same meta-analytic approach for remdesivir that WHO used for steroids, an important finding becomes immediately clear. Across all studies, among COVID-19 patients not on ventilators, there is a statistically significant 20% (RR=0.80, 95% CI: 0.67, 0.95) reduction in mortality with remdesivir treatment compared to control. Note that the vast majority of patients (3,309 of 3,818, or 87%) receiving remdesivir (Table 1) were not ventilated. Keeping a fifth of those people alive (despite the limitations of the study) seems like a pretty big deal. One would think that WHO would want to shout this from the medieval Geneva rooftops.
For now, we’ll have to settle for confirmation at the 1:52 mark.
On January 5th, there was a roundtable held at the French National Assembly where they discussed final Solidarity results (even though the WHO hasn’t released the full study yet). As you can see and hear for yourself, remdesivir does have a statistically significant mortality benefit for oxygenated patients. Confirmation can be found at the 1:52 mark.
As I mentioned in my Update Magazine article, if you dig into WHO’s data on mortality, you find an interesting and important outcome. WHO’s preprint manuscript contained a meta-analysis of existing studies of remdesivir. The preprint reported a 99% confidence interval, rather than a 95% confidence interval, in the subtotal of the largest population: non-ventilated patients. This is unusual, given that a similar meta-analysis on steroids for COVID-19 used a 95% confidence interval across all studies and for subtotals. That meta-analysis was authored by the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group.
If we apply the same meta-analytic approach for remdesivir that WHO used for steroids, an important finding becomes immediately clear. Across all studies, among COVID-19 patients not on ventilators, there is a statistically significant 20% (RR=0.80, 95% CI: 0.67, 0.95) reduction in mortality with remdesivir treatment compared to control. Note that the vast majority of patients (3,309 of 3,818, or 87%) receiving remdesivir (Table 1) were not ventilated. Keeping a fifth of those people alive (despite the limitations of the study) seems like a pretty big deal. One would think that WHO would want to shout this from the medieval Geneva rooftops.
For now, we’ll have to settle for confirmation at the 1:52 mark.
