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The news that researchers involved with a study of premature infants allegedly did not properly inform parents about the risks oxygen treatment posed to their vulnerable babies has some wondering how the protection system broke down.
Recently, a government agency said that the study, which took place between 2004 and 2009, should have been more explicit in its consent forms the risks associated with the treatment.
"I'm surprised that this could even happen," said Arthur Caplan, a bioethicist at New York University School of Medicine's Division of Medical Ethics, who was not involved with the study. "[There's] no real excuse for not being clear about risk," Caplan said.
The study, which involved about 1,300 babies born between 24 and 27 weeks of pregnancy, examined the use of oxygen to help premature infants breathe. Specifically, the researchers wanted to know what oxygen levels would provide the greatest benefit to the babies while minimizing the risks associated with the treatment. Studies done in the 1950s and '60s found that high oxygen levels increased the risk of blindness, but later, there was concern from doctors that levels that were too low would increase their likelihood of death.
The standard treatment for preemies is to provide them with oxygen levels between 85 and 95 percent, based on the judgment of a given doctor and the wishes of the parents. Attempting to find the best level, the study randomly assigned preemies to one of two groups: a low oxygen group (in which oxygen levels were kept between 85 and 89 percent) and a high oxygen group (in which oxygen levels were kept between 91 and 95 percent).
Because the study did not employ a new treatment — rather, it studied the standard treatment in hopes of improving it — those tasked with reviewing the study's ethics may have been less aggressive about what needed to be included on the consent form, Caplan said.
To participate in the study, parents signed a consent form, which stated that "because all of the treatments proposed in this study are standard of care, there is no predictable increase in risk for your baby." (In medical research, "the standard of care" means the treatment that is currently considered the best for a certain condition)
The study's protocol was reviewed and approved by the institutional review boards at 23 prestigious institutions, including the University of Alabama at Birmingham, which lead the study. Institutional review boards generally review studies to determine if they are well-designed, and carried out properly and ethically.
But after an investigation, the U.S. Office for Human Research Protections (OHRP), said in a letter that the study should have informed parents more explicitly of the risks of blindness and death known to be associated with the treatment.
Ultimately, the rates of blindness and death in the study were the same in both the low- and high-oxygen groups. But the risk of death before leaving the hospital was increased in the low-oxygen group, while survivors of this group had a reduced risk of blindness. The results were published in 2010 in the New England Journal of Medicine.
While the OHRP said that the researchers had reason to believe the results would show differences between the two groups, that doesn't mean that the aim of the study was bad, Caplan said.
"Just because it's standard of care, doesn’t mean that we understand the best thing to do," Caplan said. "Standard of care may have emerged by custom, habit, luck — and never really been put to careful scrutiny," Caplan said.
A study like this can improve standard of care, but it's important to be clear about risk — not just on consent forms, but in all communication with parents, Caplan said.
George Annas, chair of the Department of Health Law, Bioethics & Human Rights at Boston University School of Public Health, said he agreed. "Informed consent is a process, not a form," Annas said. "You can't just give them a form — you have to really explain what's going on."
The study concluded that there was one additional death for every two cases of blindness prevented by using lower oxygen levels. It emphasized the need to be cautious when using low oxygen levels because of this increased risk of death. The American Academy of Pediatrics may consider recommending a tighter range of oxygen levels for use in preemies in part because of results of this study.
In a statement, Richard B. Marchase, vice president for research at the University of Alabama at Birmingham, said: "OHRP guidance is invaluable to any research institution committed, as we are, to constantly improving patient outcomes through research and patient care. Per OHRP feedback, we will ensure that any future consent form clearly delineates risks to all arms of a study as completely as possible."
Pass it on: The news that a study involving premature infants allegedly did not properly inform parents about the risks of treatment is surprising and inexcusable, bioethicists say.