Health Letter, May 2016
By Michael Carome, M.D.
If you’re not outraged,
you’re not paying attention!
Read what Public Citizen has to say about the biggest blunders and outrageous offenses in the world of public health, published monthly in Health Letter.
On June 16, 1966, Dr. Henry Beecher, then a professor of anesthesiology at Harvard Medical School, published his seminal paper, titled “Ethics and Clinical Research,” in The New England Journal of Medicine (NEJM). Without naming names, Beecher described 22 unethical human experiments conducted by leading medical schools, hospitals, government agencies and industry. One common theme for many of these studies was the apparent failure of researchers to obtain the voluntary informed consent of the subjects.
Disclosures of unethical research such as those made by Beecher prompted the federal government four decades ago to issue regulations intended to protect human subjects involved in research and prevent unethical studies. These regulations, which were last updated in 1991, are based on three fundamental ethical principles: respect for persons, beneficence and justice.
The regulations require that most federally funded human research be reviewed and approved by a committee called an institutional review board (IRB) before the research begins. In its review, IRBs must ensure that research is ethical and meets criteria specified in the regulations. The regulations also mandate that researchers obtain and document the voluntary informed consent of all subjects, except in limited circumstances involving low-risk research.
Despite these regulations, researchers at leading medical schools and hospitals across the U.S. continue to conduct unethical human experiments with alarming frequency, with the results of many of these studies appearing in prestigious medical journals such as the NEJM.
Recent examples that garnered widespread media attention include the SUPPORT study — an oxygen experiment involving premature babies at approximately two dozen neonatal intensive care units — and the FIRST and iCOMPARE trials — experiments testing the effects of longer resident work shifts on patient mortality. For each of these trials, lack of adequate informed consent was among the serious ethical lapses.
On April 20, Public Citizen called public attention to another unethical human experiment that was published in the NEJM in July 2015. The purpose of the study was to test whether cooling kidneys before a transplant would result in fewer post-transplant complications in the recipient patients. In the study, 572 patients received kidneys from deceased donors whose bodies either were kept near normal body temperature or were slightly cooled following declaration of brain death. Prior to the study, the researchers acknowledged that both the benefits and, importantly, the risks of such cooling for transplant recipients were unknown.
The IRB at the University of California, San Francisco (UCSF) — the lead institution for the study — incorrectly determined that this research constituted “nonhuman subjects research under U.S. federal law, since the patients were deceased.” The IRB concluded that this study solely involved deceased kidney donors, failing to recognize that the living kidney recipients were human subjects.
As a result of this clear blunder, UCSF’s IRB failed to adequately review and approve the experiment in accordance with human subjects protection regulations and failed to ensure that the researchers obtained voluntary informed consent from participating patients. The complete lack of informed consent represented a serious violation of the rights of the patients who were the unwitting guinea pigs in this experiment.
The study was funded by the Department of Health and Human Services through a grant from the Health Resources and Services Administration and was conducted, in part, by the Department of Veterans Affairs. Public Citizen has asked HHS’ Office for Human Research Protections (OHRP) and the VA’s Office of Research Oversight (ORO) to launch an investigation and to appropriately sanction all institutions engaged in the study for failing to protect the human subjects of this research.
The patients enrolled in the research also deserve the truth about their involvement in the experiment as well as a clear explanation of how and why the authorities responsible for protecting them got it so wrong.
The steady stream of unethical human experiments shows no signs of ebbing, now 50 years after Beecher highlighted the troubling frequency of unethical research and 40 years after federal regulations were issued to protect the subjects of human experiments. Five decades ago, Beecher concluded that one of the most important components of a system for ensuring ethical human experimentation is the presence of “an intelligent, informed, conscientious, compassionate, responsible” researcher.” Ultimately, we are going to need to find more researchers that possess these attributes.