February 7, 2003 -- New surgical options such as the artificial heart and deep-brain stimulation can extend life and quality of life, but often with risk, especially during early stages of their development. As is the case with new drugs, surgeons using new medical devices have to follow strict guidelines set by the U.S. Food and Drug Administration (FDA) and also get "informed consent" from patients after they are told about all aspects and risks of the procedure.

New surgical procedures that do not involve devices, however, are not regulated by the FDA or any other entities. When does innovation in surgical technique (not drugs or devices) cross the line and become a research experiment? In the June 2001 issue of the Journal of the American College of Surgeons, researchers at the University of Virginia Health System reported results from a survey of surgeons that addresses this unregulated area of medicine. The researchers also received a $180,000 grant from the Greenwall Foundation in New York to start a research group that will help determine new guidelines for conduct of trials and design an educational program to improve adherence to these policies.

How do surgeons determine the effectiveness of surgical techniques without testing them on human subjects? For example, liver transplantation involving grafts from living donors - originally designed to be a procedure in children - is a surgical innovation now used for adults with growing frequency without having been formally researched using adult subjects, according to the study’s co-authors, Jonathan Moreno, Ph.D., director of the U.Va. Center for Biomedical Ethics, and Angelique Reitsma, M.D., research associate at the center.

Innovations in surgery that begin in the operating room can turn into an experimental procedure. "Distinguishing between gradual implementation of minor surgical modifications and more permanent or extensive alterations of a technique is a challenge," the authors wrote. "This is especially true when modifications are made on an as-needed basis, for the benefit of the individual patient. However, a surgeon may begin to change his or her standard OR technique more permanently based upon experiences."

Angelique Reitsma, M.D., and Jonathan Moreno, Ph.D., of U.Va.’s Center for Biomedical Ethics discuss their ongoing project that examines the ethical aspects of regulation of research in new surgical techniques. The center recently received a $180,000 grant from the Greenwall Foundation in New York to start a research group that will help determine guidelines and an education program.

Experimental trials of surgical techniques present special problems in setting up double-blind experiments to compare effects of treatment vs. nontreatment. "The problem in doing a controlled experiment is that we’re talking actions and procedures, not drugs and devices, and that makes it harder to quantify and duplicate from case to case," says Moreno. "We think there’s an answer, but that’s part of the project."

The researchers sent a survey to 59 surgeons who had authored articles about new surgical procedures that appeared in medical journals between 1992 and 2000. The surgeons were asked if they considered their new procedures to have been researched in terms of federal definitions based on information supplied with the questionnaires.

All medical research institutions that receive federal funding are required by the National Research Act of 1974 to have institutional review boards (IRBs). These boards ensure that the institution's medical research studies with human subjects comply with federal standards for such experiments. The regulations, enforced by the Office for Human Research Protections of the Department of Health and Human Services, include the requirement that clinical study participants be informed of any safety issues before they consent to become enrolled in the trial. IRBs also are responsible for monitoring trials at their institutions. Private research studies conducted without federal funds do not always have IRB review. And, the authors note in their journal article, "there are no clear federal regulations pertaining to innovative surgical procedures." Self-imposed guidelines from the American College of Surgeons, they note, "remain open to individual interpretation and are not restrictive in character."

"It is presumably wrong to put somebody into an experiment without receiving their consent," Moreno says. "Our concern is whether research in surgery has been out of this loop of IRB review and how to make the rules suitable for the setting of surgery."

Reitsma said that some survey respondents expressed annoyance at the prospect of increased regulation, as well as doubt that federal regulators would know enough to make decisions affecting innovative surgery. But others thought guidelines, especially if partly developed by a peer-review process led by a professional society would actually help protect surgeons and patients.

"Innovative surgery is done especially with desperate patients, who surgeons want to help," Reitsma says. "They might say, we've never done this before, we think this might help, let's go ahead and do it. But if you subject ten patients to that new procedure specifically to determine its yet unknown efficacy, it becomes a research experiment, especially if you write about it and send it to a journal. Surgical innovation starts with a desire to help patients, but somewhere along the line it may become research when it didn't start out that way." Such research would then justify IRB review and sometimes informed consent of patients, who have now become research subjects.

The U.Va. bioethicists are working with the Ethics Committee of the American College of Surgeons as well as the Center for Survey Research at U.Va.’s Curry School of Education. They also have organized a research group that includes surgeons, other health care experts, lawyers, ethicists and others. "The first study was just a pilot," says Moreno. "Now we’re going to reach out to thousands of surgeons." The research group holds its first meeting in February 2003.

For more information:

Jonathan Moreno, Ph.D.
Director, Center for Biomedical Ethics
434-924-8274
E-mail: jdm8n@virginia.edu

Angelique Reitsma, M.D.
Center for Biomedical Ethics
434-243-9338
E-mail: ar6j@virginia.edu