Clinical trial for infants did not disclose study risks

Criticisms from a federal agency about the informed consent provisions of a study of oxygenation levels for low-birth-weight infants has stirred one of the most prominent medical ethics discussions in recent years. The conversation has gone beyond informed consent in research to look at knowledge and consent in medical practice itself.

In March of this year, the Office of Human Research Protections (OHRP) within the Department of Health and Human Services determined that “The Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT),” which was done on about 1,300 infants at 22 sites from 2004 to 2009, “was in violation of the regulatory requirements for informed consent, stemming from the failure to describe the reasonably foreseeable risks of blindness, neurological damage, and death.”

One of the study’s goals was to “learn the appropriate levels of oxygen saturation in extremely low-birth-weight infants by comparing a lower versus a higher range of levels of oxygen saturation.”

The OHRP said, among other things, that the template for the study’s consent form section on risks versus benefits did not mention any risks relating to randomizing the babies to higher and lower levels of oxygen, but the form suggested that it was a low-risk study.

Although it would have been unwarranted to predict which babies would have which outcomes, the OHRP said, there was sufficient information to know “that participation might lead to differences in whether an infant survived or developed blindness” compared with what might have happened if the child were not in the study.

The OHRP statement stirred significant argument, including a letter in the New England Journal of Medicine in which almost 4 dozen experts in ethics and regulatory issues said they disagreed that random assignment of infants carried additional undisclosed risks as compared with standard of care.

The arguments continued in an August meeting called by OHRP in Washington,

Nancy Kass, ScD, of the Johns Hopkins Bloomberg School of Public Health, told the meeting that there is a premise in clinical care that because professionals apply the “best knowledge to individual patients’ medical problems,” whatever risks are involved are reasonable trade-offs for the clinical benefits.

“Ethically, it cannot be defended that we have such different standards for when patients deserve to be given information by trusted health care providers about whether their recommended treatments are risky,” she said.

Jeffrey Drazen, MD, editor-in-chief of the New England Journal of Medicine, said that recently when he was working in an intensive care unit, he counted over 50 questions a day that could have been decided with a flip of a coin. “We need to do better than that if we are going to improve our health care system,” he said.

Jon Tyson, MD, MPH, of the University of Texas Medical School at Houston, noted the Institutional Review Board (IRB) Guidebook calls experimentation “the use of unproven therapies whether or not research is being performed.”

“So, babies, whether they were in this trial or not, whichever oxygen saturation goal their physician selected, were experimental subjects whether or not they were research subjects,” he said.

J. Michael McGinnis, MD, MA, MPP, senior scholar at the Institute of Medicine (IOM), who stressed his statement was not an IOM position, said that research and practice should now be viewed as part of a “continuous cycle of knowledge generation,” and the IOM has called for attention to any regulatory impediments.

The OHRP referred questions on the issue to a public affairs office that said there would be updated guidance, but is no timetable for its release.

MS FOXHALL is a freelance health writer in the Washington, DC, area. She has nothing to disclose in regard to affiliations with or financial interests in any organization that may have an interest in any part of this article.