VA Not Alone in Ethical Shortcomings
The federal orders last week to suspend research at the West Los Angeles Veterans Affairs Medical Center were unprecedented, but they trace back to an ethics problem that appears to be surprisingly common in U.S. clinical studies: failure to provide research subjects with adequate informed consent.
Too often, scholars and regulators suggest, informed-consent documents overstate the potential benefits of studies--and understate the potential risks. And hospital ethics committees are so overburdened that they frequently have only minutes to review complex research proposals.
Among the studies revealing rather extensive informed-consent problems was a 1997 Food and Drug Administration analysis of 194 hospital ethics review committees. It found that 74, or 38%, had “deficiencies” in informed-consent procedures.
Between 1980 and 1995, the FDA issued 84 enforcement letters to drug researchers. Analyzing 69 of those notices, the General Accounting Office identified “serious misconduct,” including “failure to obtain informed consent, forgery of subjects’ signatures on informed-consent forms, failure to inform patients that a drug was experimental and fabrication of data to make subjects eligible for study.”
In the light of such findings, the consent problems at the veterans hospital in West Los Angeles were not entirely out of the ordinary. “It’s only too familiar to people working in this area,” said USC law professor Alexander Capron, a member of the National Advisory Commission on Bioethics.
The trouble at the West Los Angeles facility, recently grouped into the VA Greater Los Angeles Healthcare System, began in 1993. That year, the U.S. Office for Protection From Research Risks notified medical center officials of problems with informed-consent procedures in research involving mentally ill people, according to documents obtained by The Times.
For instance, some consent documents failed to tell patients of all the foreseeable risks of participating in studies of antipsychotic medications.
Informed-consent violations were also at the core of cardiology research abuses reported last week by The Times.
The sweeping directives last week to stop clinical and animal research at the West Los Angeles hospital, the nation’s largest VA health care facility, came in related actions by the risk office and the U.S. Department of Veterans Affairs in Washington.
Both authorities were responding to violations of federal research regulations and widespread shortcomings in procedures for ensuring subject protections. No one was physically harmed by the oversight deficiencies, the VA undersecretary for health, Dr. Kenneth W. Kizer, said in a letter ordering the shutdown.
Hospital officials on Friday named an interim director for research to oversee the reorganization, which includes the creation of four review boards for evaluating research proposals, among them a special committee for overseeing research involving mentally ill people.
Known as the cornerstone of clinical research, informed consent is legally required to protect vulnerable people from exploitation and avoidable harm. The doctrine, codified after World War II in response to atrocities by Nazi physicians and scientists, has been part of U.S. law since the 1970s.
As mandated, informed consent must be written, voluntary and based on a clear, dispassionate account of the proposed research’s benefits and risks. Also, people must be told about alternative medical procedures that may be equal to or better than the experimental one.
The presidential Advisory Committee on the Human Radiation Experiments analyzed 125 recent clinical studies and found that one-third posed ethical problems--most often with informed-consent documents, the group reported in 1996.
“Some institutions and investigators know very well how to conduct an ethical clinical investigation, and that’s heartening,” said Ruth Faden, director of the bioethics institute at Johns Hopkins University School of Medicine. “At the other extreme, there are people who don’t conduct such investigations in an ethically acceptable manner, and that is very troubling.”
A 1998 report by the inspector general of the Department of Health and Human Services reached the “troubling central conclusion” that the hospital review board system was in jeopardy. It noted, among many things, that some boards spent only a minute or two to evaluate each complex clinical study.
Patient advocates Sidney Wolfe and Peter Lurie of Public Citizen’s Health Research Group said of the report, “The health and safety of thousands of human experimental subjects are also in jeopardy since the protection of people in these experiments is the most important function of the [review] system.”
However, a professional group of review board members criticized the government report as alarmist. “Most institutions are committed to protecting human research subjects, as are the [review board] members and staff,” said the Applied Research Ethics National Assn.
The National Institutes of Health last year commissioned a survey of 394 chairpersons of hospital ethics boards. The No. 1 problem they cited was that consent document “language [is] too technical or otherwise unclear” for lay people to understand. Significantly, about 9% of the chairmen said their board had suspended a research project because of “failure of [the] investigator to obtain informed consent.”
An NIH-sponsored survey of 632 clinical scientists showed that they spent an average of just 30 minutes explaining a research program to each prospective subject, and a third of them spent 10 minutes or less.
Another obstacle to clear understanding is the low literacy rate of many clinical study participants, frequently recruited from among society’s poorest and least-educated people. In a recent study of 1,760 patients attending public hospitals in Atlanta and Los Angeles, roughly half did not adequately comprehend a standard informed-consent document for invasive medical procedures such as surgery.
Despite extensive federal consent regulations, there are troubling gaps, scholars and officials say.
Numerous ethics groups are calling for reforms.
The National Bioethics Advisory Commission is advocating new regulations covering people with mental disorders that may affect decision-making capacity. Perhaps their most controversial proposal--countered by some mental health experts--is that people with mental impairments should not even be approached to take part in research that has no potential to benefit them if other people are available.
The Human Research Ethics Group, a coalition of about two dozen academics, recently called for new policies and laws, including laws covering consent in research that is not federally sponsored or overseen by the FDA.
Public Citizen’s Health Research Group has called for closer adherence to regulations requiring local review boards to include outside scientists, tighter regulation of advertisements that recruit patients for clinical studies, and a centralized national registry of clinical studies to facilitate monitoring of practices and results.
VA medical centers that conduct clinical research have a special responsibility to ensure that proper consent is obtained from patients, said George Annas, a Boston University law professor and ethics scholar. “You’ve got to be extra careful to do risky research at the VA,” he said. A lot of those patients “have got nowhere else to go for their care.”
