By Lisa Seachrist
WASHINGTON — In a hearing Thursday that began with dramatic charges of unethical and racist behavior by biomedical researchers and ended with a discussion of informed consent, a House Government Reform and Oversight subcommittee reviewed the Inspector General's (IG) final report on Institutional Review Boards (IRBs).
The report, which saw only its name change in moving from draft to final form, details the stresses on the nation's system for protecting human participants from risks associated with biomedical research. The IG concluded the large-scale multisite clinical trials that have become commonplace have so stressed the voluntary institutional review system IRBs can no longer adequately ensure patient safety (see BioWorld Today, June 8, 1998, p. 1.)
"Institutional Review Boards are in jeopardy of being overwhelmed by the weight and complexity of their work," said Human Resources subcommittee chairman Christopher Shays (R-Conn.). "As a result, the 25-year-old system of review and oversight intended to insure ethical design and implementations of research protocols is in need of structural reforms."
In his opening remarks, Shays alluded to a New York Psychiatric Institute IRB that approved a study of childhood aggression as an example of his concerns.
The study appeared to enroll only Hispanic and African American children with siblings who had committed crimes, offered inadequate informed consent, and promised the children a gift in return for their cooperation. The study used a "Fenfluramine challenge" to get a measure of brain serotonin levels in the children.
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Ranking minority member Edolphus Towns (D-N.Y.) said the unanimous IRB approval of the project "raises serious issues concerning the review and approval of research.
"These children were chosen for the color of their skin and the actions of their sibling," Towns said. "Never, never, never should we have another Tuskeegee situation. Yet hear I sit with deja vu all over again."
Psychiatrists Timothy Walsh and John Oldham, of the New York Psychiatric Institute, which is associated with Columbia University, assured Towns that while the original protocol that the IRB examined did specifically exclude whites from the study, the investigators were told that was an unacceptable exclusion. The mix-up concerning the study arose when the researchers submitted an out of date protocol to the IRB two years later.
The National Institutes of Health's (NIH) Office for Protection from Research Risks (OPRR) currently has an active investigation into this particular study.
Towns also took issue with the study's payment of parents and children.
"Tell me any seven or eight year old getting a form saying they will get a gift who wouldn't sign it," Towns said. "In addition, the research provided payment to the parents for each test, providing an economic incentive."
Robert Levine, professor of medicine at Yale University, in New Haven, Conn., noted that patients are compensated for their time, not for the inherent risk of the research. He echoed concerns found in the IG's report that research participants were motivated by a perceived benefit for their participation whether it was monetary or simply hope.
"The difficulty is that it is necessary to do research that will have no direct benefit to the participants," Levine said. "And even when we explicitly point that out, people still enter studies hoping to get better. I can't remake human nature or human hopes."
The perception of benefit makes it difficult to ensure that patients are giving truly informed consent. However, Jonathan Moreno, a professor of biomedical ethics at the University of Virginia, in Charlottesville, noted that while many patients enter a study hoping for a cure for their disease, as they proceed in the study and realize they aren't going to get substantial benefit, they often continue because the research may help others.
"They don't start out with altruistic intent, but it kicks in later on," Moreno noted.
Shays focused on the oversight capabilities of the OPRR, which monitors the welfare of both animal and human participants in NIH-sponsored biomedical research.
Upon finding out OPRR initiates investigations of human studies only after complaints or catastrophic events, he said, "Incredibly, federal regulators know more about laboratory animals than they do about the human beings that subject themselves to research."
Greater oversight, however, will require much greater resources. When Shays asked OPRR Director Gary Ellis how large his staff was, Ellis responded that approximately 16 people were dedicated to overseeing human experimentation.
"Isn't that pathetic in your mind?" Shays asked.
"Those are your words," Ellis demurred. "They are rather meager resources though." *