By Daniel R. Lucey M.D., MPH, FIDSA
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).
Daniel Lucey, M.D. MPH, FIDSA, FACP, is an infectious diseases physician and adjunct professor of infectious diseases at Georgetown University Medical Center, a senior scholar at the Georgetown University O’Neil Institute, Anthropology Research Associate, Smithsonian Museum of Natural History and a member of the Infectious Diseases Society of America Global Health Committee.He has served as a volunteer medical responder to outbreaks that included the West Africa Ebola crisis. He has collected information on outbreaks starting in 2001 with cases of anthrax in 2001, and including smallpox vaccination 2002, SARS 2003, H5N1 Flu 2004, MERS in 2013, and Ebola in April, 2014. He has gathered, and updated information on the spread of the coronavirus here since Jan. 6.