controversial trial to test oxygen levels delivered to premature infants is facing fresh scrutiny following the disclosure of documents showing that researchers continued the experiment despite learning their oxygen monitors were malfunctioning.
On Wednesday, a watchdog group released a letter calling for a deeper investigation of the federally funded SUPPORT trial, which began in 2005 at two dozen hospitals across the U.S. and involved more than 1,300 infants.
The trial was intended to determine whether premature babies fare better with lower or higher levels of oxygen. It resulted in a clear conclusion: Lower oxygen levels were associated with higher rates of death among babies enrolled in the trial.
But the watchdog group Public Citizen said newly obtained public records show that investigators were notified in 2008 that oxygen monitors used in the trial were not working properly and might be delivering lower-than-expected oxygen levels to trial participants. The group, which sued the Department of Health and Human Services to obtain the documents, alleged that institutional review boards with oversight of the trial were not properly notified of the issue and that, despite potential safety risks, the researchers proceeded with the study and enrolled another 200 trial participants.
A spokeswoman for HHS said the agency was reviewing the new information.
A researcher involved in the trial defended the researchers’ handling of the issue. Dr. Rosemary Higgins, a National Institutes of Health neonatologist who helped supervise the trial, said in a statement that investigators, once made aware of the problems with the oxygen monitors, notified a committee that disseminated information to institutional review boards at participating hospitals. Those reports, she said, were shared with institutional review boards during the study.
Higgins also wrote that further investigation determined that the problem resulted in the delivery of higher — not lower — oxygen saturation levels to babies, and that all infants in the study received oxygen levels within the normal practice range at the time.
“Although the low oxygen group received more oxygen than intended, they received less oxygen than the high oxygen group, and so the decision was made to continue the trial,” Higgins said.
The study ultimately concluded that the premature infants in the low oxygen group had a higher death rate (20 percent) than babies in the high oxygen group (16 percent). A high level of oxygen also increased the risk of blindness.
Published results from the trial concluded that a calibration problem with the oxygen monitors resulted in the infants in the lower-oxygen group getting 1 percent to 2 percent more oxygen than was intended in the original protocol.
The study was led by the University of Alabama at Birmingham; another of its top investigators worked at the University of California, San Diego.
The controversy over the monitors is the latest of many questions to arise about the design and disclosures surrounding the SUPPORT trial. The Office of Human Research Protections — an agency within HHS — previously determined that risks of participating in the trials were not adequately explained to parents of the infants.
The office later issued a second determination letter that upheld the original finding, but suspended any sanctions against the University of Alabama at Birmingham. “In further recognition of the concerns noted above, we have put on hold all compliance actions against UAB relating to the SUPPORT case, and plan to take no further action in studies involving similar designs until the process of producing appropriate guidance is completed,” the letter said.
The agency has completed a draft of its guidance, but has not issued a final version. A spokeswoman for the agency said Wednesday there is no time frame for the completion of the final document.