Emergency Use Authorization for Vaccines to Prevent COVID-19 – Guidance for Industry

Another FDA guideline on COVID-19 has just been released and, given the pressing nature of the current pandemic, comes into immediate effect.

I’ve picked out a couple of sections from the guidance, along with my thoughts on each…

“...issuance of an EUA would require a determination by FDA that the vaccine’s benefits outweigh its risks based on data from at least one well-designed Phase 3 clinical trial that demonstrates the vaccine’s safety and efficacy in a clear and compelling manner.”

Would the FDA approve a vaccine based on a single phase 3 RCT that showed a statistically significant but borderline result on the primary endpoint? They would certainly be under intense political and public pressure to do so. No doubt they would mandate a second trial to confirm the results of the first, but would they be willing to risk that an untold number of people be given the vaccine before the results of the second trial were available? Safety comes into play of course, and a benign safety profile might lead a “what have we got to lose?” standpoint.

“….issuance of an EUA would include not only meeting the prespecified success criteria for the study’s primary efficacy endpoint as described in the guidance for industry entitled “Development and Licensure of Vaccines to Prevent COVID-19” (i.e. a point estimate for a placebo controlled efficacy trial of at least 50%, with a lower bound of the appropriately alpha-adjusted confidence interval around the primary efficacy endpoint point estimate of >30%) but also additional safety and effectiveness data….”.

The 50% point estimate and the lower 30% bound are interesting (and more clearly stated in https://www.fda.gov/media/139638/download ). An approved vaccine might not necessarily be the ‘cure’ that the generally population are probably hoping for and expecting. Interestingly, flu vaccines appear to offer around these levels of protection, as summarised very nicely by Shelly McNeil (Canadian Center for Vaccinology): https://www.who.int/influenza_vaccines_plan/resources/Session4_VEfficacy_VEffectiveness.PDF

Whether a COVID-19 risk reduction of this magnitude is sufficient to allow us to return to a normal life remains unclear to me. But I certainly hope so.