Read on Twitter
Finally had a chance to review FDA& #39;s COVID vaccine development guidance: https://www.fda.gov/media/139638/download.">https://www.fda.gov/media/139... Hard to improve on @AlecGaffney& #39;s excellent thread, but here are a few more thoughts. https://twitter.com/HollyLynchez/status/1277996024984895489">https://twitter.com/HollyLync...
First, @AlecGaffney covered this, but I was relieved after reading full guidance that FDA& #39;s going to demand protection from infection/disease and not just immune response. (Maybe immune response later, when it& #39;s better understood whether/what response could predict protection.)
Second, I was a bit surprised to see this: "If possible, early clinical studies should also exclude participants at high risk of SARS-CoV-2 exposure (e.g., healthcare workers)."
Those who are more expert can tell me more, but I was thinking even in early studies, vaccinating those at high risk of exposure could be helpful to move things along by giving some efficacy signals.
Third, some work for us ethicists...
"If the availability of a COVID-19 vaccine proven to be safe and effective precludes ethical inclusion of a placebo control group, that vaccine could serve as the control treatment in a study designed to evaluate efficacy with noninferiority hypothesis testing."
I think it& #39;s a bit different - and ethically easier - to withhold a safe/effective vaccine from consenting, healthy adults in a research study than to withhold safe/effective treatment from those already suffering from serious or life-threatening disease.
Why would you do this in either case? Maybe the safe/effective intervention is super expensive or otherwise problematic to distribute or administer. Maybe we could answer an important research question faster and more clearly in a placebo-controlled trial.
Gets at important questions about research standards of prevention/care and whether we really need equipoise or just consenting adults and an important research question (plus risk minimization).
Fourth, the challenge trial issue. FDA did not say "go ahead." What it said was *IF* it is "no longer possible to demonstrate vaccine effectiveness by way of conducting clinical disease endpoint efficacy studies," then CHIMs "may be considered."
Note that this is different from the widely discussed rationale for pushing challenge trials: that it would speed things up. Instead, what I read this to mean is that if the pandemic wanes and there wouldn& #39;t be enough natural exposure "in the field," challenge can be considered.
Tagging those interested in challenge trials here: @SeemaKShah @mlipsitch @ArthurCaplan @anetrid @1daysooner
FDA goes on to say that "logistical, human subject protection, ethical, and scientific issues, would need to be satisfactorily addressed." Since field exposure may wane while vaccine studies remain critical (b4 we have a strong/accessible vaccine), good to prep these issues now.
Fifth, and last, when discussing the possibility of emergency use authorization for a COVID vaccine, FDA acknowledges that using that pathway could make it difficult to complete important large efficacy RCTs.
FDA doesn& #39;t come right out and say it, but the reason why EUA would make these trials difficult is this: why would people enroll when they could get the vaccine outside the trial?
This is an issue not only for EUAs/COVID, but for FDA& #39;s accelerated approval pathway + similar proposals for marketing authorization prior to confirmation of safety/effectiveness. When you put access before data, you sacrifice critical data - and that& #39;s bad for patients.
