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Still no solution in the struggle on safeguards

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The Boston Globe OnlineBoston.com Boston Globe Online / Nation | World
Still no solution in the struggle on safeguards

By Dolores Kong, Globe Staff, 11/18/98

George Annas & Leonard Glantz "THERE'S NO QUESTION that research is important, but not at the expense of patients," said George Annas, chairman of Boston University's health law department. At left, Leonard Glantz, BU professor of health law.
(Globe Staff Photo / Suzanne Kreiter)

Last of four parts

Shamed by revelations that for 40 years the US government allowed black ''volunteers'' to suffer and die from untreated syphilis, federal officials now attempt to limit medical experimentation on most of society's more vulnerable populations.

Prisoners, children, pregnant women, fetuses - all are covered by special regulations that restrict their involvement in medical research, allowing it only in certain circumstances and under tight supervision.

People with mental illness have no such protection, even though a federal panel in the wake of the Tuskegee, Ala., syphilis experiments that began in 1932 included the mentally ill in its call for special safeguards.

''It's a gaping hole,'' said Cliff Zucker, executive director of Disability Advocates Inc. in Albany, N.Y., a group that represents the mentally ill.

To this day, some psychiatric specialists are conducting medical experiments in which research subjects are allowed to grow sicker.

Over the years, the psychiatric research community has adamantly opposed any move to restrict its work, arguing that its approach is an important avenue for understanding the underlying biology of mental illness and developing new antipsychotic medicines. But none of the newly approved drugs to combat mental illness can be traced to these types of studies. And critics say psychiatric drugs should be developed the same as other drugs - first through animal testing, then with humans already sick with the disease, and never by provoking psychosis or by misleading subjects about the nature of the research.

For the past two years, a 17-member national commission has been studying the issue. Yesterday it called for tougher research standards to protect the mentally ill.

Opposition from psychiatric researchers has been heavy.

''Barriers to this sort of research could slow down dramatically the accelerating advances we have seen in recent years,'' Dr. Joseph T. Coyle, chairman of Harvard Medical School's department of psychiatry, told hundreds of participants at a National Alliance for the Mentally Ill meeting in Washington, D.C., in July.

Coyle later wrote to the National Bioethics Advisory Commission, which is drafting the new guidelines, arguing that to single out people with mental illness for special protections would be to stigmatize them.

Such a move, he added in an interview, ''represents a rather naive understanding of complex factors that can affect decision-making.''

Coyle's letter on behalf of the nearly 30,000-member Society for Neuroscience, a major research organization, joined more than 50 critical letters by research and pharmaceutical representatives to the commission. Some were little more than a form letter, with a few key paragraphs repeated verbatim on different stationery.

The presidentially-appointed bioethics panel is wrapping up a two-day meeting in Miami today and is expected to send its final recommendations to the White House within months. The commission yesterday recommended boosting representation of people with mental disorders on local review boards and requiring greater researcher accountability.

In the meantime, however, there is little to rein in zealous researchers.

The current supervisory structure, in the words of one medical ethicist, is ''wheezing'' and has been compromised by close relationships between researchers and reviewers.

''It's an overwhelmed system of review that is being asked to handle a pace of research, a level of research, that it just wasn't built to do,'' said Arthur Caplan, a University of Pennsylvania medical ethicist. ''It's very incestuous.''

Oversight bureaucracy overworked and understaffed

What little federal oversight exists is largely handled by a small bureaucracy within the National Institutes of Health, the government office that funds much of the research.

Fourteen federal officials in charge of protecting human research subjects are responsible for monitoring nearly 5,000 local review boards, which in turn examine hundreds, if not thousands, of psychiatric research projects a year.

In June, the inspector general's office of the US Department of Health and Human Services called for an overhaul of the review board framework. A congressional subcommittee, chaired by Representative Christopher Shays, a Connecticut Republican, plans to file legislation next year to create a national review committee to bolster protection for research subjects.

The local review boards are the cornerstone of the current system. Review-board members are supposed to abide by the ethical principles embodied in the Nuremberg Code of 1947 and the Helsinki Declaration of 1964.

In practice, however, the boards are usually overworked and poorly trained.

For example, Dr. Dorothy Rosenthal, a physician who headed a review board at the University of California, Los Angeles in the 1980s during a long-running schizophrenia study, acknowledged in a court deposition that she was not familiar with the Helsinki Declaration. She said she had a ''vague recollection of that as a title,'' but didn't ''have a clue as to what was contained in it.'' The deposition was taken as part of a lawsuit against UCLA filed by two families affected by the research.

Critics say these part-time boards often do not have the time or expertise to judge the scientific merit of a proposal and may end up approving the examination of research questions that have been answered by other studies.

A federal report issued in June found that the six boards it examined were swamped with cases, with an average increase of 42 percent in initial examinations of studies during the past five years. Some boards were vetting as many as 2,000 research protocols a year. One received an average of 200 reports a month of ''adverse events,'' or episodes of side effects and other bad outcomes.

With so much work and so little time, the report concluded, board members often can only flip through the pages of a report for studies they are charged with monitoring. One board member, for instance, said he will only raise questions about an ongoing study ''if a patient has died,'' according to the report.

In only the rarest of cases did review board members interview subjects to make sure they understood they were in a study, not in treatment.

Perhaps an even greater problem is conflict of interest. Board members often are the colleagues of the researchers they are reviewing. Sometimes they work at the same institutions; often they know each other professionally and socially. Many of these board members may themselves be facing peer approval in the future.

''It's hard to criticize colleagues' work. It's hard to prevent colleagues from doing the kinds of research they want to do,'' said Leonard Glantz, professor of health law at the Boston University School of Public Health. Glantz served as a consultant to the first US commission to call for special research protections for the mentally ill, in 1978.

With research institutions increasingly relying on pharmaceutical firms for support, review board members face yet another conflict. One of the academic medical centers visited by the federal inspectors derived nearly $200 million, or about 25 percent of its budget, from research. Much of this was commercially funded.

It is the old question, said Jay Katz, a Yale University professor emeritus of law, medicine, and psychiatry: ''Who should then guard over the guardians?''

That same question might be asked of the short-staffed federal agency charged with watching over thousands of local boards.

The Office for Protection from Research Risks is part of the National Institutes of Health, the federal agency that has both funded and conducted some of the psychiatric research that has prompted the renewed calls for special protections for the mentally ill.

''There's too much self-interest,'' said Katz, adding that he believes that the office, known as OPRR, should be independent of the agency financing most of the research. Katz served on the 1972 federal panel that examined the Tuskegee study.

OPRR has investigated only a handful of the more than two dozen federally funded institutions that have conducted psychiatric ''challenge'' or ''withdrawal'' studies over the last 25 years. These were studies in which mentally ill patients were either pushed towards psychosis with amphetamines or other powerful stimulants or deprived of their medication to examine the return of psychotic symptoms.

When the agency does find problems, it has no authority to fine or discipline, only to call for changes so that the institution complies with its main oversight tool - the ''assurance'' document, an upfront promise by the institution that it will abide by federal research regulations.

At a congressional hearing in June, Gary B. Ellis, director of OPRR, defended his agency and the local review boards.

''What is the possibility of a catastrophic failure in human judgment running through six or more layers? I would characterize that possibility as `slight,''' testified Ellis, who did not return several phone messages requesting an interview.

Stronger voice urged for the mentally ill

The most apparent conflicts, however, are those that exist among researchers and within the National Alliance for the Mentally Ill, an organization made up of mentally ill and their family members. NAMI has come under fire from other mental health groups for failing to speak out strongly enough for people with mental illness.

The Virginia-based nonprofit organization gets more than $3 million annually from pharmaceutical companies for various purposes, and its research arm has even been funding at least one ongoing schizophrenia challenge study.

Laurie Flynn, NAMI's executive director, said she did not know that the NAMI Research Institute was funding a challenge study until the Globe brought it to the attention of another NAMI official, Wesley Alcorn, national president of the organization's consumer council.

''We are troubled by these studies. We need to understand much more about the justification for them,'' Flynn said. ''It seems to us that they are high-risk studies and we do not want to expose people to this kind of challenge if there is another way to move science forward.''

She said that NAMI has set up different foundations to accept industry donations to avoid having the main organization be influenced by pharmaceutical companies.

For example, the main organization has a foundation to fight stigmatization of the mentally ill, which receives $3.2 million annually from nine pharmaceutical companies, Flynn said. But NAMI itself gets less than 10 percent of its annual $4.2 million budget from private industry.

Flynn is on the presidential bioethics commission as a representative of the mentally ill. Although Flynn said she supports research protections, last month she urged fellow commissioners not to proceed with a recommendation that, she believes, would categorize routine procedures as risky. Such restrictions would deter research.

Alcorn, who has been diagnosed with mental illness, expressed outrage that NAMI funded challenge studies and said the voice of mentally ill patients has been minimized within the organization.

Earlier this year, Dr. E. Fuller Torrey, a leading schizophrenia researcher and director of the NAMI Research Institute in Bethesda, Md., blasted Alcorn in a letter he sent to NAMI officials, calling him ''grandiose and clearly experiencing a recurrence of some symptoms of your illness,'' and accusing him of ''fear mongering.''

Alcorn had organized opposition to Torrey's Treatment Advocacy Center, an Arlington, Va., organization started with NAMI funding, which he said supported involuntary commitment of the mentally ill and forced medication. Torrey has long been seen as a friend and powerful advocate for the mentally ill, which made his letter to Alcorn all the more disheartening to Alcorn and his supporters.

For other people who have been diagnosed with mental illness, the attitude of such scientists is a major reason they want special research protections.

''Are people being subjected to research with the potential of being beneficial to them? Or are they being asked by researchers to participate as useful guinea pigs?'' asked Judi Chamberlin, an associate with the National Empowerment Center, a mental health advocacy group based in Massachusetts.

''Why should you participate in a study for the advancement of someone's career?'' Chamberlin said.

For some scientists, however, medical research is not a choice for the mentally ill, but an obligation, to advance medical knowledge.

''All persons living in society have a moral responsibility to participate in efforts to promote and contribute to the present and future welfare of that society. Research is one of those obligations,'' says a statement of principles by the American College of Neuropsychopharmacology, which consists of psychiatrists and scientists whose work focuses on the neurobiological bases of psychiatric illness.

The organization's 1998 statement on ethical conduct in research also says that ''in certain studies, it is possible to deceive the subject concerning the nature of the experimental interventions if such deception does not alter objective risk.''

Oakley Ray, the college's executive secretary and a Vanderbilt University professor of psychology, psychiatry, and pharmacology, acknowledged that some members have ''disagreed vehemently'' about deception in research and that the statement is currently up for revision.

''It's one of those situations that needs to be continually updated,'' said Ray, whose group has weighed in against restricting psychiatric research, saying it is ''likely to paralyze'' the quest for knowledge and treatment of mental illnesses.

But James Childress, a University of Virginia professor and member of the National Bioethics Advisory Commission, said that rather than paralyzing research or stigmatizing people with mental illness, special protections will help restore people's faith.

Research, he said, ''can't go forward unless there's confidence on the part of potential subjects and their families that important rules and guidelines are protecting subjects' rights and interests.''

Even though the commission has neither looked for nor found widespread abuse in psychiatric research, there are enough problems to demand change, Childress said.

For George Annas, chairman of Boston University's health law department and a consultant to the 1970s commission that first called for special protections for the mentally ill, the time for minimizing the possibility of doing harm to one more vulnerable class of people is long overdue.

''There's no question that research is important, but not at the expense of patients,'' Annas said. ''Some things you have to do to protect people.''

End of series

This story ran on page A01 of the Boston Globe on 11/18/98.
© Copyright 1998 Globe Newspaper Company.

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