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Psychiatric research on humans must put the interests of research subjects first, Paul Appelbaum, M.D., told a Congressional panel in Washington, D.C., in June.
"We reject the claim that knowledge must be advanced at any price," said Appelbaum, APA secretary and chair of APA's Ethics Appeals Board. "If research cannot be performed without violating the rights of participants, it should not take place. Coercive techniques to obtain consent are unacceptable, as are inadequate or deceptive disclosures of information to potential subjects." But Appelbaum also noted that the participation of people with mental disorders is critical to psychiatric research.
Appelbaum, representing APA, spoke to the larger issues of psychiatric research but did not address any of the specific controversies that prompted the hearing.
Appelbaum was one of several psychiatrists who testified before the House Subcommittee on Human Resources of the Government Reform and Oversight Committee. The hearing focused on the role of institutional review boards (IRBs), which authorize and review research involving human subjects. There are an estimated 3,000 to 5,000 IRBs nationwide, most associated with academic settings, hospitals, and government agencies, according to information from the Department of Health and Human Services' Office of the Inspector General (OIG). The consensus from both panelists and witnesses was that the IRB system must be reformed.
The brunt of the subcommittee's wrath focused on a study conducted by John Oldham, M.D., and B. Timothy Walsh, M.D., at the New York State Psychiatric Institute (NYSPI) in Manhattan. Oldham is NYSPI's director, and Walsh is an NYSPI staff psychiatrist and cochair of NYSPI's IRB. Both testified to the subcommittee.
The NYSPI IRB signed off on a protocol in which research subjects were drawn from inner-city boys with an older brother who had been adjudicated a juvenile delinquent. The protocol involved giving the boys a single, oral dose of fenfluramine as an indirect measure of brain serotonin function, according to the statement submitted by Oldham and Walsh. The drug, which had been on the market for 20 years, was pulled off the market two years after the study was completed when a popular combination of fenfluramine and phentermine known as "phen-fen" was found to cause serious heart-valve damage with extended use. The NYSPI study is under investigation by the National Institutes of Health's Office of Protection From Research Risks.
The study has drawn harsh criticism from members of the African-American community. During the hearing, New York Representative Edolphus Towns (D) grilled Oldham and Walsh about the study's exclusion of Caucasian youngsters, about the use of fenfluramine, and about whether presenting the children with modest toys for agreeing to participate in the study constituted subtle coercion.
Oldham and Walsh were visibly tense during their testimony, but appeared to successfully defuse the controversy surrounding the study. In a statement submitted to the subcommittee, and summarized by Oldham and Walsh during the hearing, the two researchers testified that "the overwhelming majority of individuals" in the Manhattan and Bronx court system from which the participants were drawn were from minority ethnic groups. It was for that reason, they said, that all the subjects ended up being Hispanic or African American. The study, which involved 126 boys, was but the first phase of a larger plan that would have included a more ethnically diverse sample, they said. Fenfluramine was used to ascertain serotonin levels because researchers wished to see whether there was a link between serotonin and aggression, as suggested by earlier research. Ultimately 36 youngsters received a single dose of fenfluramine, and none suffered any damage. The research provided useful information on the relationship between rearing environment and serotonin levels, they testified.
Also touched upon in passing at the hearing were studies in which patients were taken off medications to test the effects of other medications, sometimes with disastrous results, and studies in which psychotic patients were administered hallucinogenic drugs such as ketamine and PCP to provoke psychotic relapses. None of the witnesses was involved in these studies, and none addressed or defended these studies during the hearing. One of the witnesses who testified on other matters spoke with Psychiatric News on condition of anonymity about the content and focus of the hearing. He expressed surprise that the subcommittee focused almost exclusively on the NYPSI study and hardly mentioned other, far more questionable studies.
The New York Times reported on some of those other studies in a story by Philip Hilts on May 19. According to Hilts, many of the controversial studies were brought to light by a New York-based advocacy group, Citizens for Responsible Care in Psychiatry, which takes the position that psychiatric research abuses are widespread.
The tone of the hearing was set by Subcommittee Chair Christopher Shays (R-Conn.). Twenty-five years ago, the IRB system was adequate for the quantity and complexity of human research, said Shays. But although "today's research environment has changed dramatically," IRBs have not. Federal regulators "know more about lab animals than they do about the human beings who subject themselves to medical research," he asserted. He called for central registration of IRBs, a reform supported by the Office of the Inspector General (OIG), whose deputy inspector general, George Grob, testified at the hearing.
Grob identified some of the problems facing IRBs. IRBs nationwide are "inundated with protocols," he said, and for that reason "review too much, too quickly, and with too little expertise." Many IRBs no longer make continuing review a high priority.
There is little attention devoted to evaluating the effectiveness of IRBs, either by the Department of Health and Human Services or IRBs themselves. And in many cases, IRBs face conflicts of interest where those on the review board have a relationship with the institution conducting the research.
Grob recommended giving IRBs more flexibility while holding them to a high standard of accountability. He also recommended redesigning the federal oversight process, requiring stronger continuing protection for human research subjects, and enhancing education of both researchers and IRB members regarding the ethics of human research.
Although there is no evidence that "widespread harm is being done to human subjects" under the current system, that system needs reform, said Grob. Given the growth in federal research funding, IRBs face even greater burdens in the immediate future, he noted. "We cannot afford to wait any longer to act."
Written testimony submitted to the subcommittee is posted at www.house.gov/reform/hr/index.htm. Other relevant Web sites include the National Bioethics Advisory Commission, www.bioethics.gov; the Office of the Inspector General at www.hhs.gov/progorg/oig; and the New York Times at www.nytimes.com.