We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.
Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04).
This is good evidence that remdesivir is useful as a therapeutic. The study is a gold standard randomized clinical trial without the typical confounding seen in observational studies. It does not have selection effects and the statistics indicate a high confidence in at least recovery effects. Median recovery time is 26% (4/15) faster for people administered the drug than people who received placebo and regular care. Remdesivir does not have proven mortality effects at this time.
So what is its value?
I think remdesivir has two value propositions in the United States. In the current environment where hospitals are currently not overrun, it has real value in reducing hospital stays by 26% and reducing PPE, supportive medication and staff time demands to treat any one patient. This is valuable.
In an environment where a region’s hospitals are being overwhelmed, surging remdesiver into a region has both the baseline value and then an add-on value. A region with an overwhelmed hospital system will have a case fatality rate several times higher than the same region with hospital capacity to spare. The faster recovery time means beds clear faster and the staff that would be committed to helping two patients recover per month would be available to care for almost three patients per month. This would be a fast way to surge effective care capacity into a region that is the equivalent of deploying a hospital ship or an army field hospital with the attached train staff.
In that scenario, remdesivir will likely have indirect mortality effects. Shorter lengths of stay means the effective hospital throughput is higher which means the length of time that a region is in an overload scenario is shorter. Some individuals who would have been admitted to the hospital during a slam period without remdisivir will be admitted to the hospital during normal(ish) operations with far lower mortality risk due to the increased throughput.
Using this logic, remdesivir has both immediate resource replacement value and mortality prevention value in some scenarios. These two value streams can be modeled to be a fairly large number under some modeling assumptions. The value of the mortality prevention by minimizing periods of slam will be a function of modeling both COVID-19’s inherent response to seasonality, our social responses, our public health responses and the length of time to widespread, effective vaccine deployment. The less optimistic an analysis is about any of these parameters, holding all else equal, the more valuable remdesivir will be. But a fairly large number could be justified under standard cost effectiveness models depending on the underlying assumptions about disease spread and regional overload scenarios.