In a clinical trial the therapy is decided by a pseudo random number generator. How can this be ethical ? People are treated differently for no reason related to different interests different values and priorities or even different merit (assuming merit can differ).There is a utilitarian rational for clinical trials. Through such trials doctors learn, and that knowledge is useful to future patients. But this rationale is utterly rejected as ethically unacceptable, because it was used to justify depraved experiments.

I think the current discussion of the ethics of clinical trials is based on a mixture which is partly consequentialist and partly deontological, and that it is incoherent, because people feel the need to claim it is totally both, while the two are inevitably in conflict.

So it is asserted that physicians must act in the interest of the patient – each and every patient. It is also argued that clinical trials are morally acceptable. This does not make sense.

It is only possible if the expected welfare of the patients is identical under the two treatments over which one randomizes. Any difference, no matter how tiny, in expected welfare would compel the use of only the current standard therapy, or of only the new experimental therapy.

I think the failed effort to avoid this is to reject the concept of expected welfare. It is argued that it is OK to do one or the other because one does not know which is better for the patient.

It would be OK if one were to say all probabilities must be rounded to 0, 1 or 0.5 so we don’t know means each is exactly equally likely. However, this approach would make life strange and brief. In particular it would rule out general anesthesia for any procedure not necessary to save a life. The chance of death is very low but demonstrably not zero. Don’t operate unless you would operate with a 50% chance of killing the patient would rule out almost all surgery. We must make choices under uncertainty and can’t pretend that all uncertainty is the same and survive for long.

Consider 2 examples.

Another is that there are 2 treatments, and, with best estimates, with treatment A the probability that the patient lives is 50% and with treatment B the probability is 30%.

Another is that there are 2 treatments, and, with best estimates, with treatment C the probability that the patient lives is 50% and with treatment D the probability is 30%.

According to current medical ethics, one must provide treatment A not treatment B but one may chose treatment D or treatment C. This always is based on the assertion that the interests of the patient is all that matters. Yet I have assumed that, for the patient, the two pairs of choices are identical. This can’t make sense.

In the first case there is an unobservable difference between patients of type 1 or type 2 where if they are type 2, then treatment A kills them on the spot. 10% of people are of type 2 (as learned from decades of painful experience). If someone is of type 1, their chance of surviving with treatment A is 5/9. In contrast with treatment B all have a 30% chance of living. With decades of painful experience it is known with essentially complete certainty that the probabilities are 50% and 30%.

In the second case, there aren’t two types, but the evidence on treatment C is preliminary based on a small (phase II) trial. The fraction who survived in the trial was 50% but the 95% confidence interval is 20% to 80%. The null that the true chance is 30% is not rejected at standard confidence intervals. By standard reasoning it is time for a phase III trial with randomization.

In each case, we know that giving A not B might cause a patient to die who would otherwise live and our best estimate of the probabilities of survival are higher with A than with B and higher with C than with D. I think the difference is that one learns something by randomizing and giving half of the patients D and that this outweighs the expected deaths due to the randomization.

I think it is possible to believe people have a right to care, and also conduct randomized trials, if one says there must be a standard of care, and all people have right to that. That one may deviate if the weight of evidence suggests that an experimental therapy is better, but that such deviation is a matter of utilitarian total expected welfare maximization not individual rights which trump average interests.

But it is not easy or comfortable to believe this, so I think that doctors have decided to rely on statistics but reject the very concept of probability. The logical inconsistency might cause some discomfort. It would cause more if the concept of probability weren’t so utterly alien to normal human thought. But in any case the tension between believing in rights and believing those rights don’t always trump utilitarian calculations clearly causes more discomfort.

“with treatment A the probability that the patient lives is 50% and with treatment B the probability is 30%.”

If we already knew these numbers, then we wouldn’t be doing the study. We are doing them because we dont actually know which is better. In general we are comparing a new therapy with the tried and true therapy. Also, a number of RTCs are stopped midway when it is discovered that one treatment is clearly superior than the other.

In the specific case of your small study with a success rate of 50% we all know that study is underpowered and we cant really draw meaningful conclusions from it.

Steve

steve:

Just curious, Do you believe in the change in doing fewer randomized clinical trials resulting from the 21st Century Cures Act as opposed to its pushing real world testing is more effective?

As Steve said, you don’t know ahead of time how effective the various treatments are, that is why you are doing the trials. Additionally, when the differences are as extreme as indicated in the example, sometimes they will halt the trial early and put all the participants on the better (whether it is the new or old) treatment. For potential life and death new treatments, they will sometimes begin trials on those with little chance to survive with current treatments. That way they minimize the downside risk in case the new treatment is significantly less effective than the established one. Only when a few of of THOSE patients show improvement and/or few negative consequences do they broaden the trials to those that have much chance of survival.

The initial example where you know beforehand what the odds are remind me of those “is it justified to torture one person to find out where the bomb that will kill many is located,” hypotheticals. Which is then used to justify torturing MANY people because they MIGHT know something useful. Like many things, the ethics of human trials are never perfect and we should always be striving for improvement. But it is NOT a new question, and we have come a LONG way since the Tuskegee experiment.