Parents weren’t fully aware of the risks associated with a medical research trial they allowed their babies to participate in.
MINNEAPOLIS, Minnesota — It is estimated that approximately 15 million babies are born prematurely every year, with over 1 million of these infants dying from preterm birth complications. Preterm birth is recognized as the leading killer of newborns throughout the world, and, according to the World Health Organization, the number of preterm births is on the rise.
With three-quarters of all preterm deaths thought to be preventable, there has been a push to ascertain flaws in the delivery of care to premature newborns and to develop strategies that will not only reduce the rate of near-birth deaths, but also minimize the rate of health complications for these infants later in life. If it is possible to determine the survivability of certain procedures, a set list of procedures can be published for use in communities where specialized care is unavailable, allowing for a faster response and a higher rate of preterm survival.
In 2005, the Eunice Kennedy Shriver National Institute of Child Health and Health Development Neonatal Research Network — a member organization of the National Institutes of Health, the nation’s premier funder of biomedical research — in collaboration with the National Heart, Lung and Blood Institute and the National Center for Research Resources, initiated a research trial involving extremely premature (24 to 27 weeks gestation), low-weight births.
However, questions on the ethics of this trial — the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) — have caused many to consider the value of such experimentation.
Experimenting on the vulnerable
In the case of premature infants, full organ development has not occurred, and typically, a preterm infant will need artificial respiration to supplement breathing. Within an hour of birth, these infants are intubated and provided a high oxygen air flow — the oxygen range of these air flows is above 85 percent, though atmospheric air only has an oxygen content of approximately 21 percent.
As oxygen is a highly volatile, highly reactive element, being in an environment with too high a concentration of oxygen can break down or severely interfere with bodily function. The practice of putting infants in a high-oxygen environment came under attack when many infants became blind from oxygen toxicity.
In an attempt to find strategies toward avoiding these complications, the National Institute of Child Health and Health Development instituted SUPPORT in 2005. At 22 research hospitals across the nation, 24- to 28-weeks gestation extremely premature births requiring external ventilation were split into two research groups. One group would receive an oxygen saturation between 85 to 89 percent oxygen, while the other group would get a saturation between 91 to 95 percent. The newborns’ parents would be advised of the testing and would be asked to give consent.
In copies of the trial’s parental consent forms, it is apparent that while the trial did warn parents about known dangers of oxygen toxicity, including blindness, it did not take extra steps to educate the parents on the risks involved with signing their infants up for the trial. For example, in a normal intubation procedure, the air flow pressure and oxygen concentration are adjusted according to the specific needs of the infant. However, as the trial required the infants to stay in rigid ranges of saturation, the infants’ healthcare team would be limited in the adjustments they could make, needlessly endangering them.
Additionally, the consent forms, drafted from a common template, typically included provisions that rendered participating hospitals not responsible for complications that occurred during the course of the trial. The trial offered no financial consideration to the participants and counted on the parents’ inclinations to support research to encourage their participation. If additional care would be needed due to involvement in the trial, the participating hospital would be obligated to address the issue, but only at the expense of the parents and the parents’ insurance policy.
In 2013, the Department of Health and Human Services’ Office of Human Research Protection found that the University of Alabama at Birmingham had inadequately warned parents of the risks associated with participation in the trial.
“It would have been appropriate for the consent form to explain (i) that the study involves substantial risks, and that there is significant evidence from past research indicating that the level of oxygen provided to an infant can have an important effect on many outcomes, including whether the infant becomes blind, develops serious brain injury, and even possibly whether the infant dies; (ii) that by participating in this study, the level of oxygen an infant receives would in many instances be changed from what they would have otherwise received, though it is not possible to predict what that change will be; (iii) that some infants would receive more oxygen than they otherwise would have, in which case, if the researchers are correct in how they suppose oxygen affects eye development, those infants have a greater risk of going blind; and (iv) that 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,” read the office’s determination letter.
However, the Office of Human Research Protection ruled that the university was not solely at fault, as there were widespread misunderstandings across the entire trial, and in general, concerning a certain classification of clinical trials. (According to a spokesperson for the Department of Health and Human Services, the Office of Human Research Protection is currently drafting guidelines for research conducted or sponsored by the department that would help clarify what constitutes foreseeable and disclosable risks.)
Despite this, many feel that the National Institutes of Health has acted in bad faith regarding this investigation. Public Citizen, a consumer advocacy group, obtained, via a Freedom of Information Act request, a draft of a letter in which the Office of the Secretary and the Office of the Assistant Secretary of Health knowingly permitted the director of the National Institutes of Health to interfere with the Office of Human Research Protection’s compliance oversight investigation of SUPPORT. Further, additional documents obtained by Public Citizen show that National Institutes of Health officials had undue access to the compliance investigation drafts and were allowed to both edit and delay the University of Alabama at Birmingham’s determination letter, including delaying any and all sanctions.
“This experiment has been characterized as a comparison of two parts of standard care. We reject that notion. The intervention that was delivered to these babies — the low and high oxygen targets — was anything but usual care and presented serious risk to the babies, including the risk of death and brain injury if they did not receive enough oxygen or eye disease if they got too much,” Dr. Michael Carome, director of Public Citizen’s Health Research Group, told MintPress News.
“Fundamentally, our initial concerns are related to the inadequacies of informed consent. The consent forms failed to disclose the true intent of the research, which was to find if babies are more likely to die or go blind depending on the oxygen target the baby was exposed to, and failed to disclose the dangers the trial may impose.”
He also noted that due to the lack of disclosure, parents believed they were enrolling their newborns in low-risk research. “And this is something we cannot condone.”
Asleep at the switch
Under normal circumstances, human experimentation is monitored by institutional review boards or independent ethics committees, which are charged under federal law and federal departmental regulations with approving, requesting modifications to, and disapproving research on the basis of the protection of human subjects from physical or psychological harm. Institutional review boards have drawn criticism in recent years for the lax or nearly non-existent oversight from the Office of Human Research Protection. Due to the fact that the office does not have the resources or manpower to actively investigate the review boards, the review boards operate — for the most part — on the “honor system,” entrusted to be impartial and faithful toward maintaining ethical standards. However, a 2006 study of 528 university medical centers’ institutional review board members found that over one-third had industrial financial ties and other conflicts of interest, and that over one-third rarely or never disclose these conflicts of interest to other board members.
As securing a federal research grant adds prestige to a university, there is pressure to not only win one, but also to do whatever is necessary to maintain good relations with the granting department. While there are no indications to suggest that the institutional review boards were encouraged by the National Institutes of Health to “look the other way,” it is clear that none of the SUPPORT research centers’ review boards made any public objections.
“I remember them telling me they were a support group who would pretty much hold my hand through the developmental process,” Sharrissa Cook, the mother of an extreme premature baby, told The Daily Signal.
“He was so tiny. I was a first-time mom. I didn’t have a clue. I didn’t know what to expect.”
Cook has indicated that if she knew the truth, she would have never signed her child, Dreshan, up for the trial in 2006.
“[Dreshan] was already at a slim chance of surviving; why would I make his chances of surviving more slim?”