Law Professors Seek to End Common Conflict of Interest in Clinical Research

In a new article, two University of Virginia law professors offer a solution to the conflicts of interest that can arise when physicians who are participating in medical studies also advise patients in the study.

Professors Lois Shepherd and Margaret Foster Riley, who are both experts in health law and bioethics, recently discussed their article, "In Plain Sight: A Solution to a Fundamental Challenge in Human Research," which will be published by the Journal of Law, Medicine, and Ethics.

The article notes that there is an inherent conflict of interest when physician-researchers combine their medical research with treatment of their patients. Can you elaborate on the nature of this conflict? Why does it need to prevented?

The conflict is fairly straightforward — the aim of clinical research is to produce knowledge for the benefit of future patients, while the aim of clinical practice is for physicians to help the patients in front of them. This conflict means that physician-researchers are not able to provide patients in a research study the independent, individualized judgment and advice usually expected of a physician; instead, they must follow a research protocol. Some people think that the conflict can be eliminated by disclosing the conflict to the patient. But recent psychological data shows that doesn't work and may even make the situation worse. While the conflict can't be entirely prevented — because clinical researchers are going to be providing clinical treatments — we offer a way of minimizing it.

What are some notable examples that illustrate the problems you're describing?

In practical terms, the conflicting aims of research and clinical care can mean that a patient enrolled in research can receive a placebo rather than the drug being studied. Sometimes we may not know which is likely to be better, but other times a physician may have a pretty good idea of which may be better for an individual patient.

Similarly, the patient might receive medications at dosages or intervals that the researchers want to test rather than dosages or intervals that are individually suited to the patient. Patients may also have to discontinue some of their other medications during a research study, or be subjected to other differences in the management of their condition.

And, then, of course, we can't forget that research subjects may be subjected to treatment — such as surgical procedures or drugs — whose safety and efficacy are unproven. For example, in one important study in the mid-1990s, patient-subjects were asked to undergo an experimental small-incision surgery for the removal of colon cancer tumors rather than the standard large-incision surgery. It was unknown whether the small-incision surgery might actually carry a greater risk of reoccurrence of cancer, and the only potential benefits were a shorter hospital stay or recovery period. This does not mean the study was unethical (and in fact, it was very successful), but we have to remember that patient-subjects are generally enrolling in studies for the benefit of others rather than themselves. But how are they to judge whether that's a good idea, if no one with medical expertise is looking out for their best interests?

You suggest that existing safeguards — such as institutional review boards and data safety monitoring boards — are insufficient in preventing these conflicts of interest. Why is that?

IRBs are charged with considering whether a particular research study is ethical as a whole, not whether it is a good choice for a specific individual subject.They also tend to focus on safety rather than other, additional interests a patient may have — in comfort and general well-being, for example. Data safety monitoring boards also focus on safety and generally have no direct contact with subjects in the study.

You propose that the best solution would be to require each research subject in a clinical study to have a physician who is not involved with the study. How do you envision this being implemented?

We propose that IRBs determine which studies require an independent physician to provide advice and monitoring for patient-subjects. The types of studies we are most concerned about are those that pose material risks to patient-subjects, involve potentially vulnerable populations, or deviate substantially from the medical standard of care. In some instances the patient-subject's primary care physician or regular specialist could serve as her or her independent physician-adviser.

An independent physician-adviser would do what physicians do generally in terms of advising patients: after reaching an understanding of the patient's medical condition, physicians engage patients in conversation about the alternatives for treatment, about the patient's understanding of those alternatives, about the patient's goals and values, and, when certain treatment options are superior for promoting the patient's health, the physician will recommend those treatments. The physician-adviser would also want to make certain that the patient appreciates the essential differences between receiving personalized medical care and participating in the proposed research and also that he or she understands that a research subject has a right to withdraw from a study at any time.

Do you anticipate any resistance to your proposal? What objections do you foresee?

Anytime you propose a major shift in the way things are done, you're bound to get resistance. Some people may object that participation in research will go down if patient-subjects receive independent expert advice about participating. We think this is not necessarily true, as physician-advisers might encourage participation in appropriate research studies. To the extent some participants decide not to participate in some studies after better understanding the risks and alternatives, we do not see this as a bad outcome, as it assures that those who do participate are doing so knowledgeably and for good reasons.

We also imagine objections based on cost, although we do not think the independent physician-adviser would add much expense to the research enterprise as a whole. In addition, the benefitsof research are generally shared by everyone, but as things stand now, the burden of foregoing individualized medical care is being borne by the patient-subject. We believe patient-subjects deserve medical attention that is on par with that received by people who are not research subjects. Certainly, they should not receive less. Research subjects are already voluntarily undertaking the risks of research, and we should not ask them to go it alone — to undergo medical "treatment" without medical "care."

How did you become interested in this topic?

The two of us co-teach a class on Human Subjects Research Regulation and Ethics and regularly engage in conversations about what's wrong (or what's right) with the way things are currently done in clinical research. We also both serve on the [University of Virginia's] IRB and are therefore familiar with the research environment. When we started talking about this particular subject, we realized our views were similar — not just with respect to the problem — but also with respect to the solution. It seemed time to write an article.

How does this article fit in with the rest of your scholarship?

Both of us write in the area of health law, policy, and ethics, although our emphasis is somewhat different. Lois Shepherd writes mainly in bioethics, often on end-of-life issues. Mimi Riley writes about biomedical research and regulation. With this article, our interests dovetailed nicely. Because our interests are different but overlap, we've found that we make a good team.

What will you be working on next?

We wrote this article as a law review article. To expand its influence in the medical community we will likely need to "translate" it in some shorter articles aimed at a physician audience. We are also about to embark on a project analyzing the ethics of medical malpractice and the "reform" efforts associated with it. A lot of work has been done from a policy or economic perspective, but less from an ethics perspective. We think that without that perspective, any effort to "reform" malpractice law will be incomplete.