I’ve never been comfortable with the ethics of randomized controlled trials.
Sometimes, whether the new therapy is better than the standard therapy is just a coin-flip. But sometimes, it’s not: the odds are strongly in favor of the “experimental” arm over the “control” arm. Then it’s very hard to see how withholding the experimental treatment is in the interest of the patient; “consent” to a 50% chance of drawing the short straw is obtained only by refusing any chance of access to the new treatment to anyone who doesn’t consent.
The bioethics community, whose collective conscience is so tender it can find ethical objections to things that mere mortals regard as harmless or beneficial, seems to have no problem with this particular form of coercion. The justification is that, until the results are in, we don’t really know that you’re worse off in the control group. The Rev. Mr. Bayes would not agree.
The NYT reports on a trial of a new melanoma drug where the problem is especially acute. Some of the patients in the control arm are clearly dying, and the question is whether to allow them to “cross over” and get the experimental drug. But doing so would compromise the purity of the RCT, and so far the manufacturer and the physicians running the trial are standing pat.
One physician who sees the problem the same way I do expressed it better than I could:
We can’t let patients on the control arm cross over because we need them to die earlier to prove this point.
Another states what seems to me like a straightforward principle for deciding whether having a control group is ethical. Referring to the standard, grossly ineffective treatment, he said to the Principal Investigator for the trial:
If it was your life on the line, Doctor, would you take dacarbazine?
Clearly, the answer in this case is “no.” One clinician refers to dacarbazine, the current treatment, as “a drug we all hate and would rather never give a dose of again in our lives.”
The alternative to an RCT is to test the new treatment against the historical record. Predict the distribution of life expectancies – the endpoint in this case – for the people you’re treating, assuming you gave them the existing treatment. Then compare the actual distribution with the new treatment to that prediction. Yes, the placebo effect is an issue – though in this case it’s an open trial, not a blind trial, so it would be an issue anyway.
Yes, it’s second-best. But at some point, we need to stop sacrificing patients to that Idol of the Laboratory, the Randomized Controlled Trial.