I recently read an article about research misconduct at a prominent university that serves as a good case study of how stakeholders can help mitigate risk when they work collaboratively and what can happen when they don’t.
This story reminded me of an article I wrote several years ago, when I was the Chair of an Institutional Review Board, about a similar factual scenario at another major research university. Given how easy it is for relationships between stakeholders to become frayed, the idea of integrating basic ethical principles such as respect, beneficence and justice, with shared accountability, to mitigate risk, is one that can be adopted by any organization working in a regulated industry to counter the rise of stakeholder dysfunction.
My old article follows below:
A breakdown of the Belmont Circle: A case study.
Although still unfolding, an article that ran on October 7, 2009, in the Huffington Post entitled Government Orders Columbia To Tell Patients ‘True Nature’ of Drug Study presents a case study of what happens when the safety net that is supposed to exist to protect human research subjects fails. One way of understanding this safety net, which is created by the relationship between the stakeholders, is to view it in terms of a circle. This story also provides a good example of what can happen when the circle, the Belmont Circle, gets broken.
The Belmont Circle
Steve Peckman, writes in A Shared Responsibility for Protecting Human Subjects, Institutional Review Board, Management and Function, pp. 16-20 (2006), that the Belmont Circle is the idea of the integration of the three ethical principals of the Belmont Report (Respect, Beneficence, Justice) with the three levels of accountability (Institutional, Investigator and Institutional Review Board (IRB)) that should exist to ensure the protection of human research subjects.
The first part of the Belmont Circle requires that there be respectful interaction between the research institution, the IRB and the investigator to build understanding and trust between all stakeholders. It is only through this respectful relationship that a culture can be fostered that is free of hostility and in which the importance of IRB review and regulatory compliance is accepted as the way to ensure the ethical review and conduct of research to protect research subjects.
The second part of the Belmont Circle requires that the institution, the IRB and the investigator apply the concept of beneficence, i.e. doing good, with each other. This is accomplished by fostering a culture of shared accountability based on the understanding that no single entity, be it the institution, the IRB or the researcher, can act alone to ensure the protection of human research subjects.
The third part of the Belmont Circle requires that no single party bear an unfair burden in ensuring the safety of human research subject volunteers. This is accomplished through equal distribution of responsibility among all stakeholders. For instance, a revolving membership on the IRB could be instituted, to not only create an equitable distribution of burdens, but also serve as an educational tool to instruct all stakeholders about their responsibilities and obligations.
Between December 1999 and February 2001 a study was conducted at New York-Presbyterian Hospital/Columbia University Medical Center (“Columbia”). The study tested blood expanders commonly administered by anesthesiologists and combat medics when patients or soldiers have lost significant amounts of blood. Previous studies had shown that at high doses these substances would cause hemorrhaging. One purpose of the study was to test whether a new formulation of one of these expanders was less likely to trigger hemorrhaging at high doses. Ultimately, two subjects died shortly after receiving the blood expander at issue and more than two dozen other subjects required blood transfusions.
Although concerns were raised by two physicians with the IRB, in 2000, these concerns appear to have been cast aside on the basis that it was merely professional rivalry with the primary investigator. In 2002, five months after the study ended after repeated complaints from the same two physicians, Columbia finally took disciplinary action against the principal investigator on the basis that he did not properly disclose, to the IRB or the subjects, the nature of the risks of the study and had failed to promptly report adverse events.
The principal investigator subsequently filed a lawsuit that challenged Columbia’s claims and decision alleging that proper consent was obtained, that there were no misrepresentations of the study design or purpose, that hospital officials had been fully informed and that the hospital’s punitive actions against him were meant to hide weakness in its own hospital procedures. See, lawsuit documents here. A confidential settlement was reached in 2003 and the principal investigator left Columbia for another major research hospital.
What followed, over the course of the next six years, was a series of investigations that revealed a number of disconcerting facts and allegations. Foremost among these, was that the consent form approved by the IRB failed to advise potential subjects that they might be given high doses of fluids that might increase the risk of significant hemorrhaging, even though previous studies had shown that at high doses these substances would cause hemorrhaging. Additionally, allegations surfaced that some of the subjects, who were Spanish speaking patients of the hospital admitted through the emergency room, may have had limited fluency and may not have understood the informed consent form that they signed.
Also alarming in this case, was that there was no expert in blood expanders on the IRB and that no member of the IRB examined the published studies about the risks of bleeding caused by high levels of the blood expanders being tested. Further, the IRB was so pressed for time, that one member of the IRB, a surgeon, reportedly said, “When we do these reviews we are presented with the investigator’s stack of IRB stuff, . . . [m]ost of us barely get to read the birthday cards from our kids . . .”
Columbia ultimately found that the IRB was unaware of those risks in part because it “failed to adequately use data provided” by the hospital’s departments of surgery and anesthesia which also reviewed the study. Columbia also concluded that the consent form failed to inform subjects of the risk of hemorrhaging.
The Office of Human Research Protection (OHRP) concluded that the study was carried out with ethical and regulatory violations and may have caused harm to subject volunteers. As early as 2003 OHRP suggested that Columbia re-consent the patients (informing them that the study may have put them at greater risk than they had been told when they gave informed consent). Columbia however, decided that there was no need to tell the patients, even though it concluded that neither patients nor the IRB “were adequately informed of the risks posed by one of the treatments in the study” on the basis that the medical outcomes did not satisfy the definition of harm.
In June 2009, OHRP, once again, demanded that Columbia contact the subjects and advise them that they were not properly informed of the nature of the study, the risks involved and the consequences of their involvement. What Columbia will do in response, remains to be seen, but if history is any guide, nothing.
This case offers an important learning opportunity if one considers the events that transpired at Columbia through the prism of the Belmont Circle. Doing so, one must ask how might things gone differently if the three ethical principals of the Belmont Report (Respect, Beneficence, Justice) had been integrated with the three levels of accountability (Institutional, Investigator and IRB) at Columbia?
The inescapable conclusion is that, even though the regulations charge the IRB with the responsibility of ensuring the safety of human research subjects, an IRB cannot do it alone. To comply with the federal mandate of ensuring human research subject safety, all the stakeholders: the institution, the investigator and the IRB must work together. Through their work, the stakeholders must foster a culture in which mutual respect and cooperation are prized as the means through which regulatory compliance is achieved and human research subject safety is ensured.
Copyright © Roberto Veloso, Attorney at Law. All rights reserved.