This post is a part of our Bioethics in the News series. For more information, click here.
By James L Nelson, PhD
Quite some time ago as breaking news is measured—back on April 10th—the New York Times printed a story(1) on the Office of Human Research Protection’s (OHRP) official response to a five year, multi-center study: the Surfactant, Positive Pressure, and Oxygenation Randomized Trial, aka SUPPORT. In an effort to refine guidelines for the use of oxygen for premature infants, SUPPORT enrolled 1316 infants born at between 24 and 27 weeks of gestational age and randomized them to one of two treatment protocols. Contemporary practice was only weakly guided by data, but had generally settled on maintaining blood oxygen levels at levels ranging from 85-95%; just where in that range had been determined as much by clinical intuition as anything else. The children in the study were to be maintained within either an 85-89% blood oxygen range, or within a 91-95% level; the hope was to determine whether practice might become more precise.
The results, as reported in The New England Journal of Medicine(2) were somewhat surprising to clinicians. More of the children randomized to the lower level died—19.9%, contrasted with 16.2% in the higher group. On the other hand, the group maintained at 91-95% experienced a higher incidence of severe retinopathy—17.9, contrasted with 8.6. Perhaps an even bigger surprise was the letter OHRP wrote to the study organizers. OHRP found that the informed consent documents used in the study were deficient. Parents were not properly informed that that their children’s risk of death or damage could be affected by their participation in the study.
The Editorial Board of the Times called the informed consent lapse “startling and deplorable”(3), and in an entry on the Albert Einstein College of Medicine blog dated April 18, Ruth Macklin claimed “there is no doubt that the consent forms in this study of premature newborns failed to disclose what these parents should have been told before enrolling their infants in the research”(4). But at least some of the researchers involved in the study have made it clear that they’re doubtful about that, to say no more. In a reply to the Times editorial, three SUPPORT investigators claimed that there was no reason to list an increased risk of death as a risk of participation in the study, as “the best evidence showed that lower oxygen targets…resulted in less eye disease without a higher death rate.”(5)
Nor is it just among the researchers involved in the study that one finds OHPR skeptics. Several bioethicists, including David Magnus and Art Caplan in NEJM(6), and Ruth Faden and Renee Boss in a blog post from the Berman Institute of Bioethics at Johns Hopkins(7), have written to praise SUPPORT and bury OHRP—or at least its letter to the study leaders.
In what is to my mind the most authoritative of these critiques, John Lantos posts in The Hastings Center blog that criticisms of the study by OHRP and the advocacy group Public Citizen were not merely “off-target” but “dangerous” as well(8). “Off-target,” because SUPPORT’s critics tacitly assume what was only known after the study’s completion—that lower levels of blood oxygen were a greater threat to children’s lives than higher levels. “Dangerous,” because the OHRP’s careless response will discourage research, in part by making parents reluctant to participate in research. Indeed, as Lantos sees it, OHRP’s position rests on discounting completed research—which, at the time of the study, provided no basis for thinking that any position within the 85-95% band was more risky than any other.
The article’s text does indicate that a possible correlation between higher death rates and lower oxygen levels seem to have been on the researcher’s minds in designing the study. The authors note that SUPPORT results “add to the concern” that “oxygen restriction may increase the rate of death among preterm infants”(9). It’s natural to read this as suggesting that the SUPPORT study was in part motivated by pre-existing worries about greater risks of mortality at lower levels of oxygen support. Lantos’s post makes a distinction that might explain this apparent discrepancy. Determining whether a lower range was or was not safer in terms of mortality and morbidity was among the goals of the research; Lantos allows that the consent document for SUPPORT did not mention the study’s goals, and that they ought to have done so. But goals are different from risks—which were not, as he sees it, misreported. That would have been grounds for serious complain; the failure to state the goals he sees as a comparative peccadillo. For Lantos, it is OHRP whose behavior has been shocking, elevating the ongoing risk to babies inherent in neonatal practice by reducing the chances that further prospective randomized trials will help clinicians get a better grasp on what risks and benefits such children actually face.
Lantos, along with other OHRP critics, make such an effective case that one might wonder whether there was any moral (as opposed to legal or regulatory) reason for requiring consent at all. All babies enrolled in the study were treated according to the contemporary standard of care: no one had any reason to believe that any child’s assignment to either arm of the trial would have any impact on any outcome. No child therefore, was at added risk of harm. Nor was any child used as a “means to an end solely” since they were getting precisely the kind of treatment that, on the basis of medical knowledge, was most likely to help them. Further, apart perhaps from a decision that any treatment would not be in their child’s interest, it’s at least questionable whether parents have authority to prevent their children from getting oxygen support considered simply as a therapy: parents’ discretion with their children is wide ranging, but it doesn’t extend to exposing them gratuitously to grave risks. If therapy in such cases is close to mandatory anyway, and the research introduces no extra risks and is consistent with the respect due the children, why make any fuss about consent at all?
I’ll introduce another distinction by way of hazarding a reply. A parent’s decision to allow their child to be randomized to a position within the standard range doesn’t heighten their risks relative to what we know. Yet what a parent decides may well change what actually happens to her child. A given child could die if randomized to the lower range of support who might have lived if her physician had decided, based on clinical judgment or intuition or coin-flipping, to treat her at the higher range.
As it happened, this wasn’t likely—among the many useful things to be learned from Lantos is that study participants had better overall outcomes than children eligible for the study but not enrolled. Yet if my child had been one of those who were randomized to the low oxygen group and had died, I would have to live with the fact that my decision might have been one of the causal factors in my child’s death. I don’t think there’s anything idiosyncratic about such a reaction, and what it suggests is that arguably, moral responsibility, and certainly grief and guiltiness, track what we actually bring about, not only how rational we are in our choices. From that perspective, I should have wanted to know that the study was designed to answer an open question—were different positions within the customary range more or less dangerous for these tiny infants—and that my decision about participation was not routine, but could be of the highest consequence for my child.
The OHRP critics are very concerned not to discourage parents from participating in high quality research that targets pressing problem—that is, research like SUPPORT. They are right to be so. But to achieve that goal responsibly, we need to be alert to what matters to actual people, and not just to idealistic epistemic agents.
- Tavernise S. Study of Babies Did Not Disclose Risks, U.S. Finds. New York Times website. http://www.nytimes.com/2013/04/11/health/parents-of-preemies-werent-told-of-risks-in-study.html?pagewanted=all&_r=0. April 10, 2013. Accessed May 3, 2013.
- SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Early CPAP versus Surfactant in Extremely Preterm Infants. NEJM. 2010; 362(21): 1970-1979.
- NYT Editorial Board. An Ethical Breakdown. New York Times website. http://www.nytimes.com/2013/04/16/opinion/an-ethical-breakdown-in-medical-research.html. April 15, 2013. Accessed May 3, 2013.
- Macklin R. Informed Consent in Infant Research: Ethical Problems Remain. Albert Einstein College of Medicine Blog. http://blogs.einstein.yu.edu/?p=4403. April 18, 2013. Accessed May 3, 2013.
- Carlo WA, Bell EF, Walsh MC, for the SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Oxygen Saturation Targets in Extremely Preterm Infants. NEJM. April 17, 2013; DOI: 10.1056/NEJMc1304827.
- Magnus D, Caplan AL. Risk, Consent, and SUPPORT. NEJM. April 18, 2013; DOI: 10.1056/NEJMp1305086.
- Boss R, Faden R. Sensationalizing SUPPORT Harms Us All. Johns Hopkins Berman Institute of Bioethics Blog. http://bioethicsbulletin.org/archive/sensationalizing-support-harms-us-all/. April 25, 2013. Accessed May 3, 2013.
- Lantos JD. OHRP and Public Citizen Are Wrong about Neonatal Research on Oxygen Therapy. Bioethics Forum, a blog of the Hastings Center. http://www.thehastingscenter.org/Bioethicsforum/Post.aspx?id=6306&blogid=140. April 18, 2013. Accessed May 3, 2013.
- SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Target Ranges of Oxygen Saturation in Extremely Preterm Infants. NEJM. 2010; 362(21): 1959-1969.
James L Nelson, PhD, is a Professor of Philosophy and the Associate Dean for Graduate Studies in the College of Arts and Letters at Michigan State University.
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