Thoughts About the Decision to Participate as a Subject in Medical Research

I just saw a discussion on the ethics of medical research. A panel of experts from different backgrounds responded to questions from a strong moderator. Most of the questions were hypotheticals.

The emphasis was on case controlled studies of new drugs for very sick or terminally ill patients. It was pointed out that ethical review panels would review the protocol for any such study, and it there was reason to believe that it would be unethical to give some of the participants in a proposed study a placebo instead of the drug to be evaluated, a case control study would not be approved. A senior official from the U.S. Food and Drug Administration said that about one-third of case control study products are not approved because of the risks that are discovered of side effects, and about one-quarter of the products are eventually approved. Thus, experience has indicated that of those drugs that are approved for case control studies, about as many do harm to the subjects as help them, and about half are no better than the drugs given to the control group (placebos or drugs used in current practice).

I was surprised that there was little recognition that the ill patient should normally be the one making an informed decision as to whether or not to participate. It was pointed out that very ill patients often are not in the best conditions to make decisions, and that they should seek advice from family, religious counselors, or personal physicians.

It occurred to me that all the people involved in this situation have personal interests:

• The scientist who created the drug, who wants to believe that all his work has been worthwhile;
• The company that would manufacture the drug, which wants to make a profit, and its representatives;
• The scientists from an organization such as NIH who might be running the project if it is public rather than private, and whose professional reputations are more favored by a study with positive results done expeditiously and inexpensively;
• The personal physician, who is paid for the treatment that the patient receives outside the study;
• Family members, who are known often to make decisions for a patient that the patient him/herself would not make;
• The religious adviser who presumably is advising in terms of his personal religious beliefs and the welfare of the whole family.

I was also impressed by the limited view of the patient's interests. It seemed to be assumed that the patient would only be interested in saving his/her own life and minimizing the effects of the illness. There was little or no attention paid to the fact that people have altruistic beliefs, and some would find participating in medical research rewarding because of the benefit it could bring to others. Nor was there much recognition that people sometimes want to be left alone; those in the final stages of a terminal disease may simply want to go out as painlessly and in as much dignity as possible, or to have the time and ability to make final arrangements.

For medical research conducted by private companies, the patient/subject of the study may have to pay a significant cost, especially if his/her insurance will not cover the experimental procedure. While the professionals did not seem to think the cost was significant, I am reasonably sure that many people would chose not to burden their families with debt in order for a chance to prolong life. (Recent studies of new cancer treatments proved to prolong life for a matter of a few weeks, and the quality of that life could not have been that great.) Indeed, perhaps because of the format, there was little thought given to the degree of discomfort the patient might experience as a result of the experimental treatment.

All of this ignores the common, taken for granted things: Is there confidence in the doctors and their staff? Is the facility accessible to the patient and his/her family? Is the quality of care perceived as good? Does the caregiver deal with the patient and his/her situation holistically or just focus on the disease?

Fortunately, all the participants agreed that honesty was required by those enrolling subjects in such a study, as well as full disclosure. They agreed that an applicant for the study should not be enrolled without a full explanation of the risks and potential benefits involved (assuming the patient can be so informed), even if the person asks to sign up without the explanation. Indeed, there seemed to be a feeling that potential subjects should be encouraged to weigh the participation carefully, and discuss it with a range of people. So too, the subject must be allowed to depart from a study if he/she so chooses.

Of course, the entire discussion above assumes that the decision maker is acting more rationally than most of us act at any time, even or especially in a life a death decision. People often succumb to peer pressure, doing what their neighbors or support group does rather than what they think is the best option for themselves given their specific circumstances.

It is fortunate that we have institutionalized systems in which medical practitioners are well trained, and physicians are licensed. It is fortunate that we have institutionalized systems in which standards of care are defined and protected. It is fortunate that we have institutionalized systems to guard and assure the ethical conduct of research. Even if we choose poorly, the outcome is likely to be at least acceptable, if not optimal.