Welcome to Ethics Consult -- an opportunity to discuss, debate (respectfully), and learn together. We select an ethical dilemma from a true, but anonymized, patient care case, and then we provide an expert's commentary.
Last week, you voted on if it was ethical to skirt U.S. rules and conduct research in Africa?
Yes: 42%
No: 58%
And now, bioethicist Jacob M. Appel, MD, JD, weighs in.
Medical research in the U.S. has a checkered record of experimenting on vulnerable populations. Much of the lay public now knows of the Tuskegee syphilis experiment (1932-1972), during which government researchers observed the natural course of syphilis in a cohort of impoverished African American men while denying treatment to them.
Other well-known troubling studies have also been conducted in the U.S. -- on developmentally impaired children at the Willowbrook State School in New York, to investigate hepatitis; and on prisoners at Stateville Penitentiary in Illinois, to learn more about malaria. Historian Harriet Washington reviews much of the chilling history of research on African Americans in her book (2007).
Such experiments led to a public outcry and eventually to passage of the National Research Act (1974) and the creation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report of 1979 and the U.S. Department of Health and Human Services' Common Rule of 1981 resulted in the establishment of institutional review boards (IRBs) designed to prevent such abuses in the future.
During the HIV/AIDS epidemic of the 1980s and 1990s, researchers found that their sincere efforts to create cheaper and more effective drugs were hampered by IRB rules. Some turned abroad, to nations like Uganda and Thailand, to conduct studies that could not have been conducted in the United States.
Many of these protocols were designed to expand knowledge of existing interventions and lacked what is known as "clinical equipoise," a genuine uncertainty as to whether one treatment is better than another. Others tested a novel treatment while withholding an existing treatment known to be effective.
The proposed osteomyelitis study, for instance, does the latter. Advocates for this kind of research argue that the subjects, while not receiving treatment that meets the standard of care in developed nations, nonetheless end up no worse off -- and usually better off -- than they would be without participating. Some subjects do receive a treatment that may work. All receive general medical care. Without the experiment, none of the subjects would likely receive either of these benefits. Of course, one might logically conduct the experiments in impoverished or isolated communities within the United States on the same grounds -- except that no IRB would ever approve such an arrangement.
Health ministers in several nations have welcomed Western scientists to set up such studies, hoping the results would improve healthcare access. In contrast, Marcia Angell, a former editor of the New England Journal of Medicine (NEJM), has been one of the fiercest critics of such a two-tiered system of research norms. To Angell, Western doctors are ethically obligated to uphold the same standards elsewhere in the world as they do in the U.S.
A closely related challenge is what is to be done with data that science later concludes were obtained through unethical experimentation. At the extreme are the results of medical experiments conducted at Nazi concentration camps. Harvard surgeon Robert Berger (1930-2016) identified 30 such projects, the best known of which were the immersion-hypothermia experiments conducted under Nazi doctor Sigmund Rascher at Dachau. An increasing consensus exists that the data from these experiments is not of scientific value, a position advanced by Berger and Arnold Relman, another former NEJM editor, but the studies have nonetheless been cited in several dozen journal articles.
As late as the 1980s, hypothermia expert Robert Pozos offered a spirited defense of the potential value of these experiments. Whatever the particular worth of Nazi data, one might ask who "owns" the legacy of this research: Should the few individual survivors of these ghastly experiments or those groups who speak for victims of the Holocaust more generally have any say in determining the use of the data?
In a NEJM commentary in 1990, Angell staked out an absolutist position against using data from experiments in the developing world that could not be conducted ethically in the United States. She observed that opponents of the "use of such data believe that it would tend to blunt the horror of what happened and thus in a sense dishonor those who died and offend the sensibilities of those who survived."
Yet her primary objections were more forward-looking: namely, that publishing unethical data of any sort would encourage other scientists to continue to act unethically. Since publication is the currency of academic science, the hope was that removing the principal incentive for misconduct might reduce such malfeasance.
Angell's opinion proved highly influential; many other editors have followed her lead. Whether ethical or not, the researchers in the osteomyelitis scenario might have trouble finding a major journal willing to accept their resulting article for publication.
Jacob M. Appel, MD, JD, is director of ethics education in psychiatry and a member of the institutional review board at the Icahn School of Medicine at Mount Sinai in New York City. He holds an MD from Columbia University, a JD from Harvard Law School, and a bioethics MA from Albany Medical College.
And check out some of our past Ethics Consult cases:
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