On August 28, 2013, the US Department of Health and Human Services held public hearings regarding appropriate informed consent procedures during clinical trials. Ethical issues with clinical trials have been raised for decades in the United States; the impetus for this particular hearing was the revelation that a clinical trial involving extremely premature babies did not use proper informed consent procedures. The SUPPORT clinical trial, whose results were published in the May 27, 2010, issue of the New England Journal of Medicine, was a randomized trial comparing prematurely born infants receiving oxygen saturation treatment. One group received treatment aiming to provide 85% to 89% oxygenation, and the other group received treatment aiming to provide 91% to 95% oxygenation. The aim of the trial was to determine whether a lower target oxygen saturation reduced the incidence of an eye disorder known as retinopathy among prematurely born infants.
The results of the trial demonstrated no reduction in the risk of retinopathy among infants in the lower target oxygen saturation group, but did show an increased risk of mortality in this group. The study’s authors noted that this finding was significant, because many clinicians had been recommending lower target oxygen saturation in order to reduce the risk of retinopathy. However, the researchers conducting the study made a crucial error: according to a letter sent by the Office of Human Research Protections (and additional, earlier correspondence), “the conduct of this study was in violation of the regulatory requirements for informed consent, stemming from the failure to describe the reasonably foreseeable risks of blindness, neurological damage, and death.” This lack of appropriate consent procedure is perhaps more disturbing because the SUPPORT study was conducted with taxpayer-funded federal grants.
In addition to the initial critique by the OHRP, the SUPPORT study was criticized by advocacy group Public Citizen. The advocacy group stated, “Because this study was funded by the NIH, the Department of Health and Human Services now has a moral obligation to formally apologize to the parents of all subjects enrolled in the study.” Additionally, Public Citizen called on HHS to hold hearings into the informed consent process in federally-funded trials — the hearings which were held on August 28.
Unsurprisingly, the individuals involved in funding the study wrote in support of the researchers’ behavior, as did a group of medical researchers unaffiliated with the study. The essence of these individuals’ defense of SUPPORT is that the results of the trial yield a benefit for future generations of prematurely born infants, because the trial indicated that the benefit of lower target oxygen saturation does not outweight the risk. Francis Collins, Alan Guttmacher, and Kathy Hudson, writing on behalf of the NIH, stated, “We are strongly committed to supporting critical research studies like SUPPORT, which inform clinical care by providing rigorous evidence for use in daily practice.”
Because the results of the trial yielded data useful for future clinical action, the NIH and the other supporters of SUPPORT seem to believe that the methodology used to gain consent from parents of extremely fragile children is irrelevant. One is put in mind of the many clinical trials using mentally ill children in institutions as research material, many of which are detailed in the book Against Their Will: The Secret History of Medical Experimentation on Children in Cold War America, by Allen Hornblum, Judith Newman, and Gregory Dober. The authors of this book painstakingly catalog dozens of clinical trials in which researchers used mentally ill children, orphans, children in institutions, and other vulnerable populations without informed consent in order to answer a difficult research question. Many of these trials yielded useful therapies or fine-tuned scientific knowledge about potential therapies, such as the meningitis vaccine trials conducted on mentally handicapped children in Pennsylvania in the early 1970s. However, the current standard for human research participants is not exclusively the merit of the scientific knowledge to be gained by the study; rather, HHS regulations at 45 CFR 46.116(a) clearly require “a description of any reasonably foreseeable risks and discomforts.”
It will be interesting to watch future developments in US government oversight of clinical trials. Of particular interest — and likely the subject of a future ventwing.com article — is the concept of “deferred consent,” in which research institutions opt incapacitated individuals into clinical trials with the intent of obtaining consent if the individual survives the treatment.