Human Challenge Trials

In order to assess vaccines one must go through different phases of testing, phase 2 being test on humans via randomized control trials (RCTs). The standard RCT involves vaccinating thousands of people, half with a placebo (control group) and the other half with the test vaccine (treatment group). Scientists then track these people in their every day life and if the treatment group sees less infection or less severe symptoms to a statistically significant amount, then the vaccine works.

A challenge trial is a way to speed up the RCT process. It can show effective results with a sample size of only 100 people. Once again you vaccinate only half with the covid vaccine the others with a placebo. Only this time you purposefully give the 100 people Corona and see whether the different groups react differently.

You can imagine this brings about some ethical, and utilitarian problems. To better understand this lets think about when challenger trials would make sense. I will differentiate scenarios with two indicators:

1) Infectious rate (IR): The % of people who will get it worldwide (in a year) 2) Case Fatality Rate (CFR): number of deaths from case / cases

High IR, Low CFR

This is the Corona Case. Here I think it makes a lot of sense to expose 100 people to Rona. You can compensate these people with something like 500.000 euro and a lot of non-monetary prestige. This is fairly cheap for the scientists. On the other hand it can be very lucrative for the participants if we expect 1 person to die from this. You are going in with a value of statistical life of 50 millions (500.000/0.01). This can save millions of lives with very little cost.

Low IR, High CFR

This could be something like Ebola, where one has a low chance of IR but if you have it, it can be very deadly. Here I think challenger trials make little sense. If we say that IR is 0.5% and CFR is 90% then you are sending most of the participants to an early death while finding a cure to something that is extremely costly to roll out for such a low IR.

High IR, High CFR

This is the classic dystopian movie scenario. Here I would argue it would make sense for people to volunteer to save mankind. Here something like 30% of population could be saved by sending the sample size to their certain death.

Low IR, Low CFR

This is really a numbers game, thus a marginal call. If we are not doing it for covid, then we might also not do it here.

The ethics of challenger trials

Challenger trials and vaccines have a complicated interwoven history. Edward Jenner is known as the inventor of the vaccine in 1796. He tested his vaccine against smallpox by scraping “pus from cowpox blisters on the hands of Sarah Nelmes, a milkmaid who had caught cowpox from a cow called Blossom” and giving it to James Phillipps, the eight year old son of his gardener. Thereafter less gruesome challenger trials did lead to successful outcomes for Influenza, Cholera, Malaria, Typhoid Fever, Dengue Fever, and Zika. Nazis used previous challenger trials to justify their experimentation on human beings. All in all there are ups and downs in past challenge trials. I believe that the assessment of future challenger trials should stay untainted. The WHO has advised against challenger trials for Covid cause there is no simple cure when someone falls deadly sick (I would recommend reading their publication). “SARS-CoV-2 challenge studies may (at present) be thought to involve higher levels of risk and uncertainty than other commonly accepted human challenge studies because the pathogenesis of COVID-19 is currently poorly understood, there is no specific treatment available, and severe disease or death can occur in young adults” In my opinion that is a weak argument.

Experimental design differences

For those of us who like thinking about experiments, data, and sample biases, challenger trials pose interesting questions. An argument against challenger trials is that, by purposefully exposing someone to Covid, you aren’t exposing him to Covid the way it naturally occurs. This might skew data. In Malaria Challenger trials you actually put your hand in a glass cage and get to watch how malaria infested mosquitos bite you. This is not so simple with Covid. Are you letting someone who has covid cough on you? Should you spend an hour, a day, a week with someone who has covid? There are many different ways to get covid and some represent natural occurrences better than others. One could get the challenge trials awfully wrong when misconstruction the experimental design. These drawbacks need to be weighted against the drawbacks of classic RCTs: Do people behave differently when they get the jab? How easy and effective is it to track 100.000 people (about the number of people who took part in normal RCTs)?

Getting Real

With Covid vaccines being currently rolled out it might not make sense to do a challenger trial for this one. Still I think challenge trials would have made sense and might make sense in the future. To get real I have signed up to potentially partake in a challenger trial at https://www.1daysooner.org/ where at the moment 38.000 people volunteered.