I'll touch on 2 versions of flooding today, first with regard to the perhaps outdated FDA rules for acting on data in the midst of a pandemic and secondly with respect to the flood of calls and visits we all might experience if a COVID-19 vaccine is authorized for children later this month.
Has the FDA Become Antediluvian?
The term, said to have been used first in the 17th century, literally means "before the flood" (as in Noah, not Curt). I wasn't able to watch the FDA VRBPAC proceedings regarding Moderna boosters on October 14 but did catch almost all of the live presentations for the Janssen (J&J) boosters on October 15. I've perused all the meeting materials for both days. Suffice to say that this included a virtual "flood" of new data, but we should have formal ACIP/CDC recommendations for both sometime this week. Let me mention just 1 key study that leads to my charge of antediluvianism and is already misrepresented in the lay press.
The so-called "Mix and Match" study is an unpublished NIH-funded trial designed to determine whether it is safe to boost with a COVID-19 vaccine product different from that used in the primary series and to characterize the resulting immune response. Note that it was not designed to determine what is the best product to boost a particular primary series, but some pundits have attempted to skew the data to that purpose in spite of comments to the contrary by Dr. Kirsten Lyke who presented the data. While it is true that participants who originally received a dose of J&J vaccine had higher antibody levels when boosted with Moderna or Pfizer vaccines compared to a J&J boost, the study simply wasn't designed to know how that translates clinically. Limitations include the very small numbers of participants (50 in each of the 3 booster groups, or 150 total participants) as well as the short follow up period to date, only 29 days after the boosters. This is particularly important because it is already suspected that an adenoviral-vector vaccine similar to the J&J vaccine has very different antibody kinetics compared to the mRNA products leading to a much slower decline in antibody. With this difference, it could be that levels following a booster dose could continue to rise after 29 days and thus not yet detected in the NIH study. The NIH study is planned to measure these kinetics in the coming months. Also know that the trial enrolled down to age 18 years of age only.
I thought the FDA could have been a bit more flexible in allowing some conclusions regarding mix and match options starting even now, ergo my antediluvian reference. The study's safety data did not reveal any real concerns, and given those results I think it is biologically implausible that serious adverse events such as myocarditis are likely. Allowing mixing would make booster dosing much easier from a public health implementation standpoint. We'll see if some official FDA statement or ACIP recommendation permits mixing. Most importantly, in terms of public health no matter what we do with boosters the emphasis should be on vaccinating the unvaccinated.
Future Flood of Frantic Fonecalls
October 26 is circled and blocked off on my calendar. That's the day FDA/VRBPAC meets to discuss the Pfizer vaccine data for 5-11 year-old children. None of the meeting materials are posted yet, but it is likely that the antibody data in this immunobridging study look good if we believe Pfizer's press releases. What I'm not sure about is how much safety data FDA will require before authorizing use. This was a relatively small study, less than 10 thousand subjects even with an expanded safety cohort enrolled a few months after the start of the original study and thus shorter follow up period. If the vaccine is authorized for this age group, note that you can't use any old Pfizer vaccine stock you might have in your office. The doses are different and will be all new vials; it will take a bit of time to distribute.