A study in 1,316 premature infants has drawn a reprimand from U.S. officials who say parents of the babies weren’t adequately advised of “reasonably foreseeable risks,” including blindness and death.
The U.S. Department of Health and Human Services, in a letter dated March 7, said a research team led by Richard Marchase at the University of Alabama at Birmingham “failed to adequately inform parents of the reasonably foreseeable risks and discomforts of research participation.”
In the study, infants were given different amounts of oxygen, a critical component of their care. The parents weren’t told previous research suggested more oxygen may be tied to blindness and lower levels might boost the risk of death. The department’s letter was made public yesterday by Public Citizen, a watchdog group that criticized the HHS response as insufficient and urged U.S. officials to apologize to the families of the infants.
“The word ‘unethical’ doesn’t even begin to describe the egregious and shocking deficiencies in the informed-consent process for this study,” Michael Carome, deputy director of Public Citizen’s Health Research Group, said in a statement.
The Public Citizen communication, sent to Health and Human Services Secretary Kathleen Sebelius, urged the agency to review other studies on premature babies for similar breaches and investigate how its oversight of clinical trials failed in this case in order to prevent future mistakes.
The research sought to determine the ideal balance between the survival benefit for premature babies who received high levels of oxygen and their risk of a form of blindness linked to premature birth. The infants in the study were born from 24 weeks to 28 weeks of gestation. Newborns are considered to be full term after 40 weeks.
The study funded by the National Institutes of Health was carried out from 2005 to 2009 at 23 hospitals and medical centers. The amount of oxygen given was within the range commonly used to treat premature infants at the time. Doctors until then guessed the best level for each baby based on their understanding of earlier research and personal experience.
The infants who participated in the study were less likely to die than babies at the same institutions who weren’t in the trial, regardless of how much oxygen they received, Marchase said yesterday in a statement. The mortality rates were also lower than expected based on historical levels, he said.
The HHS criticism centered on the consent forms and the way they outlined the possible risks to infants, he said. There were no complaints about the medical approach, Marchase said. Physicians involved in the research at the 23 medical centers worked together to craft the consent form, which was approved by all their institutional review boards, he said.
Carome, Public Citizen’s deputy director, served on the HHS Office of Human Research Protections staff for 10 years before joining the government watchdog group. If the parents had known of the risks, it is likely “many, if not most, parents would not have allowed their babies to be in this study,” Public Citizen said in its statement.
The review of the issue is continuing, said Jerry Menikoff, director of HHS’s Office for Human Research Protections. The medical center will propose steps needed to correct the process and ensure parents and patients are properly informed in the future, then the agency will determine if those measures are appropriate, he said yesterday in a telephone interview.
There wasn’t a problem with the design of the study itself, which was examining an unresolved issue that is critical to the care of premature newborns, Menikoff said.
More education is needed to ensure that researchers and those who oversee them know what information should be provided, he said. The agency has an initiative under way to improve the process, he said.
“This is certainly the start of a longer process to make sure people know what occurred, why it was wrong and make sure that it doesn’t occur again,” Menikoff said.
The department’s letter last month was directed to the University of Alabama at Birmingham, which served as the lead medical center for a portion of the clinical trial. Most of the other 22 hospitals and medical centers that helped conduct the research were copied on the HHS letter, including Yale University in New Haven, Connecticut, and Duke University in Durham, North Carolina.
While premature babies are routinely given oxygen as part of their treatment, there have been calls for more study into the appropriate levels, HHS wrote in its letter to Marchase. Higher levels have been associated both with greater survival rates and higher rates of a retinal condition that can lead to blindness.
In the study, called Support, babies were split into groups receiving higher and lower oxygen levels, both within the range considered the general standard of care, the department wrote.
A higher percentage of babies given the lower oxygen levels died during the trial, while half as many cases of retinal damage were seen in the surviving infants, according to the results published in 2010 in the New England Journal of Medicine, the department said in its letter.
Researchers conducting the study in U.K. and Australian infants ended their work early as a result, the department said.
HHS requires researchers to disclose any “reasonably foreseeable risks and discomforts.” Researchers failed to inform parents of the risks and include an explanation of how the infants would be treated if they weren’t in the study, the department wrote.
The department asked the University of Alabama at Birmingham to provide a plan by March 22 to make sure future information given to parents and patients fully explains the risks and address all the necessary issues that should be covered when they give consent to participate in research.
The government’s “guidance is invaluable to any research institution committed, as we are, to constantly improving patient outcomes through research and patient care,” Marchase said in the statement. “We will ensure that any future consent form clearly delineates risks to all arms of a study as completely as possible, including studies in which all arms are operating within the accepted standard of clinical care.”
Public Citizen argued that the U.S. hadn’t gone far enough. The group said in its letter to Sebelius that each medical center should be required to show how it would avoid future deficiencies in consent as well as investigate its own oversight of the trial. The department also should identify and suspend any unethical similar research involving premature infants funded by HHS, the group said.