Improving the regulation of human-subject research

President Shapiro is heading an effort to rethink the way human-subject experiments are regulated. As chair of the National Bioethics Advisory Committee — commissioned by President Clinton in 1995 — he directs efforts to improve human-subject research regulation.

The advisory committee operates on the resolution that every human-subject should retain the twin protections of informed consent and independent review of the risks and benefits associated with the research. It seeks to expand federal protection to all Americans, reduce confusion and unnecessary burdens created by myriad regulations and increase enforcement to ensure compliance.

Last December, NBAC released a draft report proposing changes to federal regulations to address what it perceives to be serious weaknesses in existing rules involving human subjects. But because the advisory panel made these recommendations during Clinton's term, it is uncertain whether President Bush will act on these recommendations.

According to Shapiro, however, there is bipartisan support for patient rights in human-subject experiments.

"We think we have some interesting things to say," he said. "The idea is that if you put together good reports they will eventually have an impact."

The Department of Health and Human Services had already acted on some of the recommendations before the draft was made public, indicating general agreement about needed regulatory reforms.

The current NBAC board's three-year term ends Oct. 1, however, and it is up to Bush to renew the current committee or appoint a new one.

The federal government has been regulating human-subject research since the early 1970s, when news broke of the infamous government-sponsored Tuskegee experiments.

For about 40 years, the United States Public Health Service had been conducting an experiment at Tuskegee to study the course of untreated syphilis. The agency, however, neglected to tell participants they were participating in the experiment.

Four hundred black men with syphilis and 200 uninfected men were recruited for the experiment. The men participated without informed consent and were routinely misled about the nature of some of the experimental procedures. For example, spinal taps were called "special free treatment."

By 1936, experimental results showed clearly that men infected with syphilis were far more likely to develop complications and had a death rate about twice as high as that of the control group. But even after penicillin was found to treat syphilis effectively in the 1940s, the infected men were not treated accordingly nor told about their options.

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In response to media coverage, in 1972, the Department of Health, Education and Welfare formed an ad hoc committee that proposed establishment of regulations involving human subjects. Following this recommendation, Congress passed the 1974 National Research Act, establishing institutional review boards to oversee all biomedical research involving human subjects funded by the Department of Health and Human Services. IRBs are committees established by institutions to oversee human-subject research and ensure that patients have the right to informed consent.

Though they are not necessarily uniform across institutions, IRB committees act according to principles known as the Common Rule. The Common Rule requires IRBs to weigh the benefits of the research to society against the experimental risks to individual research participants.

Shapiro's advisory committee recommended in the draft report — which was available for public comment through Feb. 17 — establishing a federal office to oversee all human-subject research, streamlining the regulatory process to reduce redundancy that does not improve the welfare of patients.

The recommendations also include extending regulations, which currently apply only to government-funded institutions, to include privately funded institutions. It also proposes that at least 50 percent of board members not be affiliated with the institution to reduce conflicts of interest. Federal regulations currently require at minimum one member of IRB boards to be unaffiliated.

Shapiro said that the comments on the report, which is being revised accordingly, were very favorable. Pharmaceutical companies, government agencies, IRB board members, and patient advocacy groups responded to the panel.

Among the comments were suggestions to reduce the 50 percent requirement because it might be "very difficult to find enough people," Shapiro said. Princeton's IRB equivalent — the Institutional Review Panel for Human Subjects — has just two members unaffiliated with the University. One is a local doctor and the other a member of the local community.

The other members include the associate director of the Office of Research and Project Administration, Registrar Joseph Greenberg, the director of student health, a University lawyer, the psychology departmental manager, several psychologists and a demographer.

There are also concerns about the competence and lack of expertise of outsiders, noted physics professor William Happer, chair of the University Research Board, which oversees Princeton's IRP. He said it would be difficult to find qualified people from the local community willing to volunteer their time to serve on the committee.

Psychology professor Philip Johnson-Laird, chair of IRP, agreed. "From my limited experience, it would be possible for Princeton to find more members from the local community and more non-scientists, but it might not be easy to find them," he said. "It requires a fair bit of work to be on the IRP, especially the reading of proposals, and is solely pro bono."

He said he does not believe the draft proposals will have much impact at Princeton because the University does not have a medical hospital.

Explaining the IRP's take on the NBAC proposals, Johnson-Laird said, "We thought that such requirements would be more useful for bio-medical research. Panels wholly from within institutions and made up wholly of biomedical scientists might be prepared to take bigger risks with research. This tendency could be checked by a panel containing non-scientists from outside the institution.

"Most of the research that comes to Princeton's panel is not biomedical, and it ends not to create either severe risks or major ethical issues," he noted.

At Princeton, faculty and students conduct research with human participants mostly in the social sciences, particularly in psychology.

Johnson-Laird noted that the IRP rarely rejects a proposal outright, though it often requires researchers to modify their plans. "The most frequent problems are such matters as protecting the confidentiality of individuals' responses in studies, ensuring that the participants receive a proper debriefing that explains the scientific purpose of studies, and trying to ensure that people don't leave an investigation feeling in any way belittled or upset."

"Instead, they should feel that they have made a useful contribution to advancing knowledge," he concluded.