The Problem With Challenge Trials

Marcia Angell writes: There are two specific problems with even the most carefully done challenge studies of a Covid-19 vaccine. First, we still know very little about this novel virus, including what hidden or longterm effects it might have on even young, healthy volunteers. And second, will a vaccine be equally effective in the elderly and chronically ill, those who are most vulnerable to Covid-19? Elliott acknowledges this problem, but I think it may be more serious than he implies.

But more generally, I worry about the erosion of our hard-won ethical consensus (starting with the Nuremberg Code) that people should not be used as means to an end if they might be harmed. There is also a risk of bribery or coercion in enrolling volunteers, even if they are officially unpaid. I believe this erosion of our ethical standards, even for a good cause, would be a very unfortunate precedent. We would then be on the proverbial slippery slope downhill.

Carl Elliott replies: First, if research subjects in the United States are sickened or injured in a trial, they may well face financial ruin on top of their illness. Most sponsors require subjects to pay for their own medical care, and virtually none guarantees compensation for pain, suffering, or the inability to work. Second, many of the current industry sponsors of vaccine trials have a record of burying, spinning, and rigging their research. (The list of such sponsors includes Merck, for which Lipsitch consults.) Third, even if a trial leads to a vaccine, we have been given no guarantees that it will be made available to those who can’t afford it, raising the possibility that the sacrifices made in vaccine trials will yield benefits primarily to the rich and well insured.

None of these problems is unique to challenge studies. What is unique about those studies is the extraordinary number of people willing to volunteer without being told about the fine print. This is a recipe for exploitation. Eyal and Lipsitch claim their priority in their article was “to explain how to select participants with minimal likelihood of dying,” yet in the study design they proposed, some subjects up to the age of forty-five would be exposed to the coronavirus after getting only a placebo vaccine.

Like Marcia Angell, I’m disturbed by the use of subjects as a means to an end, especially when the risks are unknown. If I left the door to Covid-19 vaccine challenge studies ajar, I can think of no one better than Angell to close it. In fact, we may need to close a lot more doors. In Phase I trials, researchers routinely use subjects as a means to an end, even when the risks are significant and the subjects are vulnerable. That slope was slippery and we have reached the bottom. We need to find a way back up.

About Luke Ford

I've written five books (see My work has been covered in the New York Times, the Los Angeles Times, and on 60 Minutes. I teach Alexander Technique in Beverly Hills (
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