Exploring the gray area in the bioethics of clinical trials


People are more comfortable with black and white, and less so with gray. This isn’t a reference to artwork, but rather the way that things work in the world. There is right and wrong, left and right, and one side of the fence, or the other.

“Gray” happens in medicine and quite frequently in the realm of bioethics, the study of ethical and moral implications of new biomedical discoveries, advances and new and not-so-new procedures. When clinicians grapple with whether an organ transplant should be performed over a family’s objections, for example, that is bioethics.

Alabama-led study under scrutiny

In March, a federal agency known as the Office for Human Research Protections notified the University of Alabama that it was not compliant with U.S. Department of Health and Human Services regulations for the protection of human research subjects. UAB was the lead investigator in this study, which included 23 institutions, among them Stanford, Duke, Emory and Yale.

HHS said the risks of the study, which compared the effect of two different oxygen levels in babies’ blood, were not properly communicated to the parents of some 1,300 infants in the permissions forms and that the risks included blindness, neurological damage and death. The study was conducted between 2004 and 2009, and results were published in 2010.

I don’t agree with this response, and I’m not alone. Along with 45 bioethics and pediatrics experts from across the country—many of whom often disagree with each other on most any topic—I’ve authored a letter in the New England Journal of Medicine today that says this conclusion was an error and that it will have adverse implications for future research. The ruling has shifted questions of ethical uncertainty and complexity into ethical black and white.

A twist, and slight reversal from the federal government

Late last night, I learned that the Office for Human Research Protections sent a letter dated June 4 to the University of Alabama. In this letter, the Office acknowledged the controversy created as a result of the scrutiny, and said that the study design was complex. Officials said that they will conduct an open public meeting on the topic.

I welcome this late-breaking information, and hope that the behind-the-scenes work that took place, including our letter in NEJM, helped spur this change in response from the Office for Human Research Protections.

I generally agree that permission forms for the study probably could have been better. The researchers at these 23 academic institutions worked with their respective Institutional Review Boards, committees empowered by the federal government to review, approve and monitor research. It is not so clear that the boards’ decisions crossed the threshold to be unethical, which is essentially what the Office for Human Research Protections had said initially.

Doing our best as researchers to talk with parents involved in studies

We all need to do our best in talking with parents about research, so that they can make a decision that is right for them and their family. The permission forms are only one of the approaches in communicating with families. In fact, the permission forms often become dense with information and lengthy because we, as researchers, worry that we have missed information and that more is always better.

This makes the permission forms not only difficult for Institutional Review Boards to analyze, but also for parents to understand. How can we better respect parents, in this research relationship? We can have detailed conversations with them and make sure the study their child is taking part in is explained. Allow time for them to ask questions, too. And what is most challenging is that after some time passes, many people will not recall much of the discussion, based on what we know.

Were the extremely premature infants in intensive care units enrolled in the study harmed as a result of the research? It is not easy to answer that question. To speak frankly, babies unfortunately die in neonatal intensive care units because of the inherent risk – these children are extremely fragile, with a host of medical issues, including problems related to the treatments we provide.

It is difficult to distinguish the risks the study imposed versus the risks of being in intensive care. Yet it is important that we are continually trying to improve the care we provide so that babies will do better in these settings. In this particular study, researchers were trying to improve upon the standard for oxygen supplementation in premature babies. Creating standards, best practices and using what’s known as comparative effectiveness research leads to better and, hopefully, more cost-effective care for everyone.

I hope that the scrutiny given to this study leads to more dialogue and I stand ready with my colleagues to participate in any such discussions with federal agencies. The best way to move forward when controversy rears its head is by engaging scientists, clinicians, bioethicists, families and the general public. We are all aiming for the highest standards of ethics in research, after all.