Are Phase I clinical trials ethical?

All clinical trials in the US and most other countries are approved by an Institutional Review Board, which must find the trial to be ethical. The basis for determining the ethical nature of a trial is the Nuremberg Code, adopted after the horrors of Nazi experimentation on humans were revealed.

The principal tenets of the Code are that that trial participants must freely consent to participate, must be fully informed of the potential risks, and must have some reasonable expectation of benefit.

It is the last point that is troublesome in the context of P1 trials.

Phase 1 trials are intended to determine the safety of a new drug, and (usually) to determine a maximally tolerated dose. They are often conducted on healthy volunteers. If these subjects are healthy, then how can they have a reasonable expectation of benefit in taking a drug to treat a disease that they do not have? Answer: they are paid, and/or receive free medical care.

You pay someone to get them to do something they otherwise would not. There is an inescapable element of coercion here. Libertarians will argue that so long as one is free to decline the offer of pay, there is no coercion. That is probably true for most Libertarians, who in my experience are an affluent bunch – they are well-represented among angel investors and venture capitalists. But for someone who is perhaps facing eviction for non-payment of rent, the freedom to decline pay may also be the freedom to go hungry or to live out on the street.

Paying a healthy person to participate in a P1 trial is not as dodgy as paying a healthy person for a kidney. But it is definitely on the same moral spectrum.

I’m not quite ready to say that P1 participation should be limited only to patients whom the new therapy is intended to treat. But this should be the baseline expectation, and the participation of healthy subjects should be reserved for exceptional circumstances. Or perhaps be limited to wealthy Libertarians.

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