Federal Medical Research Regulations Must Accommodate Modern Medicine

In the 1960s and '70s Americans were shocked by press accounts of unethical medical experiments involving prisoners, institutionalized children, elderly nursing home residents and the now infamous Tuskegee Syphilis Study on African American men. In response, the federal government issued regulations that have governed research with human subjects ever since. These regulations require that research receive prior ethical review and that, for most types of research, people who participate as study subjects provide their express informed consent.

The research landscape has changed considerably over those forty years, however, as has our health care system. For the first time since they were passed in the 1970s, the federal government is considering making significant modifications to the regulations. One big question is: Should these revisions include ways for research to be better integrated into regular medical care? That is, how can we make it easier to learn from everyday medical practice?

Enormous investment in biomedical science over the last 40 years has produced many important advances in areas like cancer care and medical imaging. And yet, we still know remarkably little about which common treatments work best for which patients. When you go to the doctor with back pain, for example, there is limited science and almost no evidence to guide your doctor in determining whether you are likely to be helped by physical therapy or you should go right to surgery. When you need to start blood pressure medicine for the first time, there are dozens to choose from: wouldn't it be nice to know if one was better, or better for someone with your medical history?

Clinical comparative effectiveness research (CCER) is a type of medical research that is intended to fill this critical gap in medical knowledge. CCER studies compare the safety and effectiveness of different, widely used treatments for the same medical problem. For example, they will often compare drugs that have already been approved by the U.S. Food and Drug Administration (FDA) and that large numbers of patients are regularly prescribed. Therefore, these CCER medical studies will generally pose no additional medical risks beyond what those patients would experience in their routine medical care. A study might assign different approved, widely used blood pressure drugs to different patients and compare who did better or what their side effects were through aggregated data outcomes from patients' electronic health records. Alternatively, different clinics or offices could be randomly assigned to use one or another of these approved drugs, while allowing either physicians or patients to opt out and choose a different treatment.

Many health policy experts and institutions are arguing that our doctors' offices, clinics and hospitals increasingly must be transformed into "learning health care systems" in which CCER, as well as research to improve patient safety, becomes routine. In a learning health care system, each medical appointment would be an opportunity to systematically study, in real time, the health effects of how a patient was treated compared to the health outcomes of other patients with the same problem, some of whom received a different treatment. Right now, most of those learning opportunities are lost because there is no systematic commitment to generating new knowledge from everyday medical practice.

From an ethics perspective, making this commitment is important. Systematic learning from everyday practice should lead to higher quality medical care, identifying what is essential to deliver and what is wasteful or even potentially harmful. At the same time, ethics requires that we figure out what types of protections should be in place for patients when this kind of learning occurs. Should prior review and express informed consent still be required if the medical care that is being evaluated is not in any sense experimental, and the physician and patient remain in control of the patient's treatment? Or is it acceptable for this kind of activity to be integrated in clinical practice, with limited or no prior review and only a general consent by patients to certain types of learning activities?

Unfortunately, the proposed changes to federal research regulations do not address these important questions about CCER studies. The good news is that the changes suggest reducing the oversight requirements for studies that pose no or minimal risk, in order to allow ethics review committees to concentrate their efforts on high risk research that deserves careful attention. However, the proposed changes focus on streamlining review for behavioral and social science research only, and do not include the sorts of CCER studies we have just described among the kinds of minimal risk research that would be eligible for less regulatory oversight.

This is a mistake.

We are as concerned as anyone that there be no return to the days when violations of human rights in medical research were all too common. It is critical that the highest standards of oversight and ethics be maintained for research involving human subjects. At the same time, it is equally critical that we avoid over-protecting patients from research that poses no risks and has the potential to serve everyone's common interest in improving the quality and safety of medical care. Learning health care systems will only work if all of us -- health professionals, patients and federal regulators -- work together to get this balance right.