ETHICS IN THE NATIONAL SPOTLIGHT

Several high-profile incidents have piqued interest in research ethics. Michelle Mello, assistant professor of health policy and law in the Department of Health Policy and Management, described some of them. Mello helped organize the symposium with the Dean’s Office, Richard Cash and Sofia Gruskin of the Department of Population and International Health, and Eric Rimm of the Department of Epidemiology.

Last year, the University of Pennsylvania settled a lawsuit brought by the family of Jesse Gelsinger, an 18-year-old man who died in a gene therapy trial. At Johns Hopkins Medical School, all research involving people as subjects was temporarily suspended after a healthy 24-year-old woman died in an asthma study. Incidents at other medical research centers also occurred.

"What we see in many of these cases are institutions and researchers being told after the fact that they have gotten it wrong," said Mello. "This is particularly upsetting to those of us who are involved in health research because we see ourselves as out there doing good in the world."

The big question, said Mello, is "How do researchers do right while doing good?"

THE NEED TO DEFINE STANDARDS OF CARE

David Hunter, professor of epidemiology in the Departments of Epidemiology and Nutrition, discussed the standard of care owed to participants in the control arm of a clinical trial. Hunter joined the panel in place of Daniel Wikler of the University of Wisconsin-Madison Medical School, who could not attend.

In 2000, the World Medical Association amended the "Declaration of Helsinki," a statement of ethical principles to guide medical research involving humans. One important amendment concerned the proper use of placebo as a study control, stating that in most cases, new interventions should be tested against the best current prophylactic, diagnostic and therapeutic methods rather than against placebo.

The use of placebo drew significant attention after the National Institutes of Health and the Centers for Disease Control and Prevention conducted studies of short-course regimens of AZT in Africa and Asia, offering placebo instead of the long-course regimens of AZT available in the US, explained Hunter.

The amendment to the "Declaration of Helsinki" provokes questions of its own. What is meant by "best current methods" is up for interpretation. Do the methods represent the best in the world, or those where the study is being conducted, or those in the sponsoring nation, which may be much wealthier and technologically more advanced than the study country, asked Hunter.

He said that research can be thought of as having slopes that illustrate the tensions between protecting human subjects and making trials affordable and scientifically sound. On the downhill slope, not using the highest standard of care can ill-serve the study participants. On the uphill slope, insisting on the highest standard of care may make studies unfeasible.

WHAT DO RESEARCHERS OWE TO STUDY PARTICIPANTS?

In the early 1970s, the US National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research issued the "Belmont Report," describing the basic ethical principles that should underlie biomedical and behavioral research involving human subjects.

The report delineated several principles, including one of justice, which subsequently received less attention than the others, said Ruth Macklin of the Albert Einstein College of Medicine. But the lack of attention does not diminish the importance of the idea because justice helps avoid exploitation.

Although researchers agree that exploitation should be avoided, not everyone adheres to the same definition. Macklin defined exploitation as occurring when wealthy or powerful individuals or groups take advantage of the poverty, powerlessness or dependency of others for their own ends without offering compensating benefits to the less advantaged.

What is owed to participants after a study’s completion is murky. Some scientists argue that nothing is owed after a study. Others see the need to continue providing services or medications, a situation that becomes more complicated when, for example, dealing with drugs taken for a lifetime.

The "Declaration of Helsinki" says that participants should be assured access to the best proven methods identified by the study, but both Macklin and Hunter pointed out that access is not always guaranteed. Years after short-course AZT treatments were shown to be effective in preventing perinatal transmission of HIV, the drugs are still not available to women in countries where the studies were conducted. The situation reflects a disconnect between researchers and policymakers, who can provide access to the fruits of research, said Hunter. Who should decide how those fruits are identified and distributed is debatable. Study sponsors, community members where the study takes place, and international organizations are all stakeholders. All of them should be involved in the decision, said Macklin.

THE ROLE OF RULES

Institutional Review Board (IRB) members may be the arbiters of rulemaking most familiar to scientists, but, ironically, sometimes their rules may add to the burden of conducting good research, argued Leslie London of the University of Cape Town. For example, while recognizing the importance of informed consent, London said the accompanying papers are sometimes so exacting and culturally insensitive, they can make study participants think the papers exist more to protect researchers than themselves.

Informed consent does not guarantee protection against potential abuse of participants’ rights. London described studies in South Africa in which HIV-positive pregnant women accepted the risk that they might receive placebo in AIDS research without knowing they could have possibly be enrolled in another type of study that would have provided some medication.

London said that ethics cannot be separated from scientific value. Sometimes, ethical challenges can become human rights opportunities, in which interventions and capacity-building can flourish, he said. The costs of these endeavors should not implicitly frame public health ethics, he concluded.

WHO BENEFITS?

The "Belmont Report" stipulates that the sum of research benefits to individuals and society must outweigh the risks of research. However, how one defines and distributes "benefits" is debatable.

Macklin, stepping in for K. Srinath Reddy of the All India Institute of Medical Sciences, who could not attend the panel, described the statements of several groups concerning the dispersal of research benefits to the communities studied.

The "Declaration of Helsinki" says that there should be a likelihood that research will benefit the population being studied. The statement is too vague, said Macklin.

The Council for International Organizations of Medical Sciences is revising a guideline that says research should be responsive to the health needs of the community being studied and that interventions should be made reasonably available. The guideline offers a strong presumption to offer products that result from a study to the people who participated, said Macklin.

The National Bioethics Advisory Commission agrees that research benefits should be made available to a community after a study, but allows researchers to explain why this may not occur—a large loophole, said Macklin.

UNAIDS offers guidance specific to AIDS vaccines, saying that if such vaccines were developed, they should be made available to all trial participants and others as soon as possible. This is the strongest statement of the bunch, said Macklin.

The Robert Wood Johnson Foundation funded the symposium, available to watch online at www.hsph.harvard.edu/foph/ethics.html.

The next Future of Public Health Symposium will be "The Future of Schools of Public Health" on Monday, April 1 from 1:30 p.m. to 3:30 p.m. in Kresge G-2. Open to the public.