By Nir Eyal and Tobias Gerhard

Perhaps the strongest argument against COVID challenge trials posits that they must choose between the Scylla of insufficient safety for volunteers and the Charybdis of insufficient social value. In particular, challenge trials that exclude old or unhealthy participants for their own safety may involve surprisingly low risk, but they cannot reveal vaccine impact in the most affected patient populations—old and unhealthy people. What is the point of developing, for example, a vaccine, if it is not tested in the populations most vulnerable to severe COVID outcomes? Or so the “generalizability” argument goes.

We provide a classification of different variants (no pun intended) of the “generalizability” argument against relying on COVID challenge trials. We then make several observations that, together, turn the generalizability argument on its head.

One observation is that every trial, including conventional phase III field trials, fails to generate enough information on some populations of interest. Another is that the currently-accepted way to address this is to generate that information through fast and benign immune-bridging studies like the ones that the US is currently conducting on children, who were excluded from field trials. A third observation is that immune-bridging studies rely on knowledge of the correlates of vaccine protection, which are discernable most easily and reliably through a challenge study. Therefore, the easiest way to establish this precondition for reliable immune-bridging studies and hence, for illuminating vaccine effects in diverse groups, goes through a challenge trial.

Our article makes additional observations and expounds a grain of truth in the generalizability concern about challenge trials.

Paper title: Do Coronavirus vaccine challenge trials have a distinctive generalizability problem?

Authors: Nir Eyal and Tobias Gerhard

Affiliations:

For NE – Center for Population-Level Bioethics and Departments of Philosophy (SAS) and HBSP (SPH), Rutgers University.

For TG – Center for Pharmacoepidemiology and Treatment Science and Ernest Mario School of Pharmacy, Rutgers University.

Competing interests: NE and TG declare having no financial conflicts of interests; NE serves on the Board of Advisors of 1Day Sooner, an unpaid position.