Will the Oct. 22 FDA COVID-19 vaccine EUA meeting discuss the statistical basis for requiring at least five severe cases in placebo group of Phase 3 vaccine studies? 

In reference to potential enhanced respiratory disease associated with COVID-19 vaccine candidates, the U.S. Food and Drug Administration briefing document for the Oct. 22 public advisory committee meeting on COVID-19 Vaccine Emergency Use Authorization states (on p. 11 of Appendix II):

“Sufficient cases of severe COVID-19 among study subjects to support low risk for vaccine-induced ERD (a total of 5 or more severe COVID-19 cases in the placebo group would generally be sufficient to assess whether the severe COVID-19 case split between vaccine vs. placebo groups supports a favorable benefit-risk profile or conversely raises a concern about ERD).”

What is the FDA’s statistical basis for this number of 5 or more? Will the FDA Vaccine and Related Biologic Products Advisory Committee (VRBPAC) that meets October 22 discuss the statistical basis for this number of 5 or more severe cases in the placebo group?

In addition, what is the definition of “a favorable benefit-risk profile”, or “a concern about enhanced respiratory disease (ERD)” based on statistical analyses using these required 5 or more severe cases in the placebo group?

Given that two companies (sponsors) have suggested they might submit requests next month to the FDA for EUA for their COVID-19 vaccine candidates, then soon they might reasonably be expected to perform (p. 14 of Appendix I). * “… interim analyses to assess risk of vaccine-associated ERD…”

Thus, discussion of the statistical basis for the FDA’s requirement of 5 or more severe cases in the placebo group of these Phase 3 studies and discussion at the Oct. 22 FDA VRBPAC would be helpful for public understanding of this FDA requirement.

*It is noted that Appendix I, from June 2020, focused mostly on licensure issues (one page only on EUA issues), whereas the more recent Appendix II focused on EUA issues (four pages).