Published: April 21, 2013
By Renee Elder — firstname.lastname@example.org
A Duke University researcher involved in a national clinical trial facing criticism for its handling of informed consent says his team made every effort to alert parents to the potential risks of oxygen therapy for premature infants.
If some parents failed to understand that giving higher or lower levels of oxygen to their children could result in serious health problems as well as benefits, Duke doctors stand ready to apologize, said Michael Cotton, a neonatology and pediatric physician at Duke University Medical Center.
“We want to maintain good communication with families, and I would say if a family didn’t understand what happened or what was going on, we would apologize for them not understanding,” Cotton said.
Duke is one of 23 hospitals that participated in a five-year clinical trial of oxygen treatments for newborns. The trial has been criticized by the Office of Human Research Protections, sparking a national debate over informed-consent practices in medical research. Informed consent in medical research refers to the process of making sure a patient or representative agrees to and understands the potential risks and benefits of a trial.
The oxygen trial was funded by the National Institutes for Health and ran from 2004 to 2009. It involved about 1,300 infants who were born an average of three months premature. About 50 of the babies were treated at Duke.
“Our goal was to help them understand what the study was about and what benefits came to the kids,” Cotton said. “I think we did a good job with that.”
However, last month, an oversight coordinator for the Office of Human Research Protections wrote a letter to study leaders at the University of Alabama at Birmingham that criticized the researchers for not providing detailed information about the known consequences of giving higher or lower levels of oxygen to premature infants.
Studies done over the past 50 years have clearly shown that higher oxygen levels are linked to development of an eye disease known as retinopathy of prematurity that can cause blindness, the letter states.
“The protocol included the usual section entitled ‘Risks and Benefits.’ That section did not identify any risks related to randomizing subjects to the low or high range of oxygen,” the letter said.
Thus, the letter noted, the “reasonably foreseeable risks of blindness, neurological damage and death” may not have been clear to the babies’ parents.
All the hospitals participating in the study used the same consent form, some with minor variations.
Supplemental oxygen has been given to premature babies since the 1940s, when it was found to improve function of immature lungs, increase life expectancy and reduce the risk of brain damage. In the 1950s, scientists discovered that too much oxygen can cause blindness, known as retinopathy of prematurity, which is caused by excess blood-vessel growth in the back of the eye.
The Academy of Pediatrics now recommends an oxygen saturation level of between 85 and 95 percent, and all babies in the study were given oxygen within that range.
“What the neonatology community was wondering about, and what we were wondering about, is whether there is an advantage of going higher or lower within that range,” Cotton said. “Studies were starting to suggest that the lower range might have some advantages, as far as lowering the risk of retinopathy of prematurity without raising the risk of death.”
To explore the question, the researchers gave half of the babies oxygen at the higher end of the recommended range and half at the lower end. The two groups were chosen by random assignment.
The overall study results showed that eye disease was twice as high for the infants given higher oxygen levels – 18 percent compared to 9 percent.
However, death rates were slightly higher in the lower oxygen-saturation group. Overall, the infants in the study fared as well or better than premature infants in a control group.
The Office of Human Research Protections has asked study administrators to review the consent form and the explanations of benefits and risks.
Cotton said Duke researchers did address the potential for retinopathy, but he couldn’t rule out the possibility that some parents did not fully understand the risk.
“This is a very challenging area – giving good understandable information about risks and benefits of choice ‘A’ and ‘B’ when both are within the range of clinical practice,” Cotton said. “We are all struggling with it.”
He said the concerns raised by the federal agency will spur Duke researchers to gather more feedback from patients who participate in clinical trials, refine the wording of documents and identify conversations that may be needed in the processes of obtaining informed consent for clinical trials.
“This deserves continuing attention; it deserves ongoing discussion and input,” Cotton said.
“It’s like most things, a work in progress. We can always do better.”
The trial was part of an ongoing effort by the national Neonatal Research Network to establish treatment guidelines for babies born prematurely, Cotton said.
He said the results will help improve care for pre-term babies who need oxygen to survive. For doctors at Duke, it will likely reverse a trend toward using a lower oxygen level.
“It would be hard to overestimate the importance of that trial,” the researcher said. “We’ve been given a better idea of a finer-tuned optimum point.”