Challenge Trials for COVID-19 Trials Beginning

[swamidass (S. Joshua Swamidass)]

@sfmatheson

@T_aquaticus

t’s a really tough balancing act between the quality of data we get and the risk involved in the study.

I agree but I’m afraid I don’t see how the challenge trial is different. The standard trial lets people catch the virus somehow in the world. The challenge trial takes control of that. That’s the difference. That’s the only difference.

A standard trial would also include older patients, and those patients specifically excluded in the challenge trials discussed here. This means a challenge trial would not tell us directly how well the vaccine worked in the populations most at risk for serious complications. This is a significant disadvantage, especially because the populations most at risk are also those who will be first to receive the vaccine.

@sfmatheson

Almost none of the comments in this thread so far are relevant to the question of whether to introduce challenge trials in place of standard trials.

No one is suggesting we replace standard trials with challenge trials. Rather, standard trials and challenge trials would proceed alongside one another. Right?

@sfmatheson

I will expect that the conversation acknowledge the already-existing medical situations represented by living kidney donors, and that those who comment on SARS-CoV-2 challenge trials be willing to explain how living kidney donation is different.

There are many differences, and I’ve noted a few here.

1. In clinical studies, the population used has a dramatic effect on results. Challenge trials have a different population than standard trials, which makes them less translatable to practice. In contrast, the kidney donation studies would be using the exact same population of donors in the intended practice.

2. It isn’t possible to imagine a kidney donation trial without kidney donors. It is, in contrast, easy to envision standard trials that would produce the same (perhaps better) information, but just at a slower rate (maybe).

3. Kidney trials match very closely the intended treatment the intend test. Exposure in challenge trials is controlled (which increases statistical power) but we can’t expect them to mimic exposure the virus “in the wild,” which again reduces their translatability.

These are substantial differences from a kidney donor trial. Challenge trials vs. standard trials there is a trade off between the hope of increasing speed and the certainty of reduced translatability. This tradeoff is not part of the kidney donor example, and it may be importnat.