The controversy over a recent neonatal clinical trial of oxygen therapy for premature babies offers two starkly different prescriptions for protecting babies from risky treatments in neonatal intensive care units.
One view, advocated by the federal Office for Human Research Protections and the advocacy group Public Citizen, is to warn their parents that participating in important, well-designed clinical trials is risky. Public Citizen even suggests prohibiting such studies altogether. The OHRP views the trial as one that involved “substantial risks,” because “the level of oxygen being provided to some infants, compared to the level they would have received had they not participated, could increase the risk of brain injury or death.” Public Citizen viewed the study as “highly unethical” because it “exposed 1,316 extremely premature infants to increased risks of either death or retinal damage.” The advocacy group called upon Health and Human Services to apologize to the parents of the babies who were enrolled in this study.
The researchers, the institutional review boards, and the Eunice Kennedy Shriver National Institute of Child Health and Development, which sponsored the study, apparently disagreed. In designing, reviewing, and conducting the study, they feared that the biggest risk to premature babies was to be treated with potentially toxic doses of oxygen while their doctors did not know which doses were safest. Instead of continuing these potentially risky practices, they decided to study the safety and effectiveness of different levels of oxygen. They didn’t think that the study added any risk to conventional therapy and so did not warn parents of potential risks.
At the outset of the study, reasonable people disagreed about the best dose of oxygen. Some thought that lower doses of oxygen were safer, others thought the higher doses were safer. Before the study was done, babies throughout the United States would get any and all doses within the range of acceptable doses, based upon the untested and therefore unscientific beliefs of their physicians. The study was designed to protect babies from the risks of these unscientific and necessarily idiosyncratic treatment choices.
So who is right? Was the study riskier than conventional treatment? If so, parents should clearly have been warned of these risks. If not, then no such warning was necessary.
Luckily, for this particular study, we know the answer. That is because the institutions involved collected and published data on all premature babies, not just those in the study. They can be found in two papers, one in The New England Journal of Medicine and one in Pediatrics. The first, published May 2010, reported survival rates and rates of severe eye disease for all outcomes for babies in the randomized trial. The other, published August 23, 2010, reported the same outcomes for all babies in the neonatal research network.
Here is what the data show. The babies in the “low oxygen” arm of the clinical trial had a mortality rate of 19.9 percent. The babies in the “high oxygen” arm of the study had a mortality rate of 16.2 percent. Babies in the network over all had a mortality rate of 24 percent. For severe retinopathy, the numbers are 8.6 percent (low oxygen group), 17.9 percent (high oxygen group) and 24.1 percent (overall group). These data have been available for three years. It is inexplicable that neither OHRP nor Public Citizen seem to be aware of these data or, if they are, that they can still claim that babies in the study were harmed by being denied conventional therapy.
When the study was designed, there was no reason to believe that being in the study and thus being randomized to higher or lower levels of oxygen was riskier than the standard treatment at the time. The data confirmed this prediction. Far from exposing babies to risk, the studies protected babies from the risks of conventional therapy. The study not only protected the babies in the study. It will protect hundreds of thousands of babies in the future from similar uncontrolled therapy.
It is shocking that OHRP and Public Citizen did not see fit to understand the study or to read the results before claiming that it was risky to babies. The study protected babies. Reckless and ill-informed opinion about highly ethical scientific studies is what truly puts babies at risk. It is OHRP and Public Citizen, not the investigators, who should apologize for irresponsible regulatory overreach and for egregious misinterpretations of the goals, conduct, risks, and results of an important study. Babies need to be protected from advocates like these.
John D. Lantos is professor of pediatrics and director of the Pediatric Bioethics Center at Children’s Mercy Hospital in Kansas City, Mo. He is the author (with William Meadow) of Neonatal Bioethics: The Moral Challenges of Medical Innovation (Johns Hopkins University Press, 2005). He was not involved in the oxygen-therapy trial in any way. Children’s Mercy Hospital is now a part of the NICHD Neonatal Research Network but was not at the time of the study in question.