Ethics of clinical trials. Do they help the patient?

Ethical justification of a randomized clinical trial requires at the onset that the investigators be able to state an honest null hypothesis regarding the therapies to be compared. For example, in a randomized clinical trial with only two arms (A and B), it is necessary to state that there is no scientifically validated reason to predict that therapy A will prove to be either superior or inferior to therapy B. Moreover, there must be no therapy C known to be superior to A and B unless there is a cogent reason to reject therapy C; the population of research subjects will consist either of those in whom therapy C has been tried without success or individuals who are aware of therapy C and have rejected it for various reasons. Thus, theoretically, the patients enrolled in a randomized clinical trial are assured that they will receive one of the two best known therapies for their condition. At first glance, one might conclude that randomized clinical trials do, in general, help the patient. There are some features of at least some clinical trials, however, that may be detrimental to the interests of some patients. It commonly is said, for example, that patients in randomized clinical trials are deprived of the "good of personal care." The physician-investigator may be constrained by rigid protocol requirements from being responsive to the particular needs and desires of the patient. Additionally, the process of obtaining informed consent to randomized clinical trials may be preemptive: patients who might have chosen palliative care rather than chemotherapy may not be afforded adequate opportunity to make such a choice. Any randomized clinical trial should maximize the likelihood of helping the patient.