US. senators last week called for changes in the federal oversight of research involving human subjects after hearing hospital and university officials tell of confusion, financial conflicts of interest and lax monitoring in the current system.
Sen. William Frist (R-Tenn.), the Senate's only physician, said he is drafting legislation with bipartisan support and expects it to be passed in the Senate this year. Frist's comments followed a Senate Health, Education, Labor and Pensions Committee hearing on the subject.
Pressure on Congress to enact better federal guidelines for biomedical research involving human subjects has increased after the highly publicized deaths of two volunteer research subjects at prestigious universities. Jesse Gelsinger died while enrolled in a gene therapy trial at the University of Pennsylvania in 1999 and Ellen Roche died in connection with an asthma drug study at Johns Hopkins University, Baltimore, last year.
Biomedical research has grown dramatically in the past two decades. The budget of the National Institutes of Health, the principal agency that funds biomedical research, has increased to more than $20 billion in 2001 from $3 billion in 1980. Research by drug companies grew to $22.4 billion in 2000 from $1.5 billion in 1980.
Federal agencies and national hospital associations don't have statistics on how many hospitals operate clinical research programs.
The patchwork of federal regulations for biomedical research and the protection of human subjects has not undergone a "major revision" since the 1970s, said Marjorie Speers, the former acting director of the National Bioethics Advisory Commission, which last year recommended broad changes on human research oversight to President Bush.
But hospital officials said the need for better regulations and guidance is pressing.
"I face conflicts of interest every day," said Cherlynn Mathias, manager of the clinical trials department at 508-bed Harris Methodist Fort Worth (Texas). She told senators during the hearing that her job performance is based on how many people she enrolls in clinical trials.
Mathias said people with a life-threatening disease often are "desperate" to participate in clinical trials because that is the only way to get experimental medication. Sen. Edward Kennedy (D-Mass.), chairman of the Senate Health, Education, Labor and Pensions Committee, said he was concerned that potential subjects should be able to weigh the risks of participating in a trial without inappropriate influence from investigators conducting the trials.
Mathias, who alerted federal authorities to abuses of human subject protections at the University of Oklahoma, where she worked until 2000, said she struggles with meeting monthly quotas for enrolling subjects in research in her current job. "Sometimes that puts you into a situation where you are trying to talk people into going on clinical trials," Mathias said.
P. David Charles, M.D., assistant professor of neurology at Vanderbilt University School of Medicine, Nashville, and chairman of the National Alliance of Medical Researchers & Teaching Physicians, said federal regulations for informed consent of research subjects "can certainly be confusing."
Federal law doesn't require researchers to disclose their financial interests in a clinical trial to institutional review boards, which oversee research at individual facilities.
HHS' Office for Human Research Protections is developing financial conflict-of-interest guidelines but has not indicated when they will be published, spokesman William Hall said. Last year, the Association of American Medical Colleges issued a policy document on financial conflicts of interest for researchers that it "strongly urged" its members to adopt, said David Korn, M.D., the AAMC's senior vice president of biomedical and health sciences research.
"We have lots of regulations, but not necessarily the right regulations," Kennedy said of the current federal laws, which are administered by 17 agencies.
Mathias also said NIH studies are not receiving adequate oversight. "They seldom, if ever, send around a monitor," she said.
The National Bioethics Advisory Commission, which completed its work and disbanded last year, recommended to President Bush that a comprehensive set of regulations be created that would apply to all types of research involving human participants. The commission also recommended that an independent federal office be established to oversee research.
Frist said the legislation being developed in the Senate would provide a new set of regulations for human research oversight and set protocols for interaction among government agencies. He also said the bill would address how subjects consent to participate in clinical trials.
"Informed consent is one of the major issues that the commission addressed and struggled with," Speers said.
Speers, executive director of the Association for the Accreditation of Human Research Protection Programs, said all institutions with research programs, including teaching hospitals and community hospitals, should seek special voluntary accreditation.
The National Committee on Quality Assurance, which has a contract with the Veterans Administration to accredit its biomedical research programs that involve human subjects, will compete with the AAHRPP by offering voluntary accreditation for nonmilitary research programs next year, spokesman Brian Schilling said.