Under fire from researchers and ethicists, the U.S. government agency responsible for protecting patients involved in scientific studies is backing away from a decision to sanction the leaders of a clinical trial involving premature infants after finding that the researchers failed to disclose the trial's full risks. "We have put on hold all compliance actions," the U.S. Office for Human Research Protections (OHRP) announced in a 4 June letter to the University of Alabama, Birmingham (UAB), which led the trial. OHRP also says that it plans to hold a public meeting to discuss the controversy, with an eye toward clarifying the rules for providing informed consent.
OHRP's move came a day before The New England Journal of Medicine published two pieces urging OHRP to reconsider the sanctions and expressing support for the researchers who designed and carried out the trial. "[W]e respectfully disagree with the conclusions of the OHRP," wrote three senior officials from the National Institutes of Health (NIH), which funded the study, including NIH Director Francis Collins. "Allowing the decision to stand would be unfair to the investigators and institutions involved," wrote a group of several dozen prominent bioethicists and pediatric researchers.
The controversy came to public light in early April, after the nonprofit group Public Citizen alerted reporters to a 7 March letter from OHRP to UAB. It concluded that the 23 institutions involved in the trial, known as SUPPORT, had failed to fully disclose its risks. The letter also asked UAB to prepare a "corrective action plan." The trial, which ran from 2005 to 2009, provided 1316 extremely premature infants with different oxygen concentrations to better understand how to prevent the blindness that sometimes accompanies the treatment. The trial's results, published in 2010 in The New England Journal of Medicine, indicated that infants receiving lower oxygen levels were more likely to die, but less likely to become blind, than babies receiving higher levels. All of the babies received oxygen levels that were within then-accepted standards of medical care. OHRP concluded, however, that consent forms didn't adequately spell out the possible consequences, including death, of being at one end of the range or the other. And Public Citizen argued that parents would not have signed their children up for the trial if the risks had been fully explained.
The controversy sparked extensive discussion in biomedical research circles, and the trial got harsh ethical reviews in public forums such as websites. But OHRP's 4 June letter seeks to calm the waters. "OHRP has become aware of widespread misunderstanding about the risks that are required to be disclosed in obtaining informed consent for certain types of clinical trials," the letter states, adding that "we wish to emphasize that OHRP does not and has never questioned whether the design of the SUPPORT study was ethical."
But the issues involved are complex, the letter notes, and "[g]iven their importance, we recognize OHRP's obligation to provide clear guidance on what the rules are with regard to disclosure of risks in randomized studies whose treatments fall within the range of standard of care. We are committed to doing that, and doing it promptly." Not only will the agency "engage in the usual notice and comment process with regard to draft guidance," it says, "we will also conduct an open public meeting on this topic."