Pandemic vaccine testing: Combining conventional and challenge studies

Abstract

Early into COVID, human challenge trials were considered, but usually as alternatives to conventional randomized controlled trials. Instead, assessment of authorized COVID vaccines, of further COVID vaccines, and of vaccines against future pandemics should combine both designs, in five different ways, including a wholly novel one that we elaborate, Viz., combining data from both designs to answer a single question.

Keywords: adaptive clinical trials as topic; coronavirus; ethics; randomized controlled trials as topic; vaccines.

FIGURE 1

The only three possible scenarios on how conclusive the RCT is as a standalone in (upper dark box) a conventional RCT of 30 000 volunteers (randomized 1:1 between a SARS‐CoV‐2 vaccine and control), compared to [lower dark box] a CCC approach that combines such an RCT with a challenge trial (the latter also randomized 1:1 between the same vaccine and control). This perspective argues that under all three possible scenarios, the latter outcome is preferable, as indicated by the “check” sign, and explained in the following three notes. Notes: * Here, the challenge trial provides additional efficacy and safety data that increase confidence and potentially enable vaccine comparison, as well as other valuable information on, for example, correlates of protection. ** Here, the challenge trial “tops up” proof of efficacy on infection and shedding and provides additional valuable information, for example, on correlates of protection. The conventional trial provides safety data on 15 000 vaccinated volunteers. *** Here, the challenge trial provides proof of efficacy on infection and shedding., Because data are insufficient to rule out widespread severity enhancement (there are too few subjects with exposure to vaccine+virus), additional safety data are required. If found safe, the vaccine can be authorized