In 2003, psychiatric researchers at the University of Minnesota recruited a mentally ill young man, Dan Markingson, into a study on an antipsychotic drug. Months later, the patient violently committed suicide; multiple allegations of unethical practices ensued. A March 2015 report from the state’s Legislative Auditor included evidence of coercion, conflicts of interest, and a deeply flawed research oversight system.1 University of Minnesota’s Human Research Protection Program has been placed under pending accreditation status.
“These are extraordinarily vulnerable patients,” says Carl Elliott, MD, PhD, a professor at the University’s Center for Bioethics. Many of the ethical issues in the Markingson case are likely occurring in many other academic health centers, he adds. These include financial conflicts of interest, poor institutional review board oversight, improper recruitment incentives, inadequate clinical care, and questionable study design.
“But the issue that really has not emerged at other institutions yet is the recruitment of subjects under an involuntary commitment order,” says Elliott. Markingson was under a “stay of commitment” that legally required him to abide by the treatment recommendations of his psychiatrist.
“How can consent under those circumstances be valid?” asks Elliott. “It is really difficult to see how anyone who has been involuntarily confined to a locked unit can give the kind of voluntary consent that one would like to see.”
The University of Minnesota announced late September that it would end recruiting of patients under 72-hour emergency holds into research studies. Spokesperson Dan Gilchrist says the University of Minnesota is committed to the highest ethical standards in its human research protection program, and is currently implementing more than 60 changes to its program.
“Regarding the specifics of the Markingson case, our president, Eric Kaler, has apologized to the family, and there are numerous public statements and appearances by him addressing this case and events of the past 11 years that have led us to where we are today,” says Gilchrist.
It’s unclear if other institutions are currently recruiting involuntarily committed patients for research studies. “No one is really monitoring recruitment, and the Common Rule [the Federal Policy for the Protection of Human Subjects] makes no mention of the issue,” says Elliott.
The appropriateness of enrollment in research in lieu of standard therapy is a central ethical concern for psychiatric patients enrolled in clinical trials, says Andrew Childress, PhD, assistant professor at Baylor College of Medicine’s Center for Medical Ethics and Health Policy in Houston.
“The Dan Markingson case is a good example of an ethically problematic decision to enroll an allegedly acutely psychotic patient into a study instead of providing him standard therapy for his first psychotic episode,” says Childress.
Researchers have an ethical obligation to ensure the safety of participants, adds Childress. Some patients with mental illness are at higher risk of self-harm or noncompliance with the protocol’s requirements.
“It would be problematic, from a safety standpoint, to include them without rigorous safeguards for monitoring them while they are in the study,” says Childress. A clearly unethical practice would be to enroll and retain a patient with mental illness in a study despite his or her objections, he adds.
“Since the aim of research is not to directly benefit the patient, but to produce generalizable knowledge, it would be unethical to override the objections of a patient whether they are decisionally capacitated or not,” Childress says.
Several reviews of the Markingson case have been completed. “Despite the many reports that now exist, none of them address what to me are some of the outstanding ethical issues related to psychiatric clinical research at the University of Minnesota,” says Leigh Turner, PhD, associate professor in the University’s Center for Bioethics.
It is unknown how many individuals were recruited while involuntarily confined to locked psychiatric units, or if others were recruited over the objections of family members who believed the individual lacked decision-making capacity, he says.
“Another key question is whether aggressive recruitment practices resulted in patients being enrolled in clinical trials when they should not have been approached, or when there were serious problems with how they were approached,” says Turner.
“The University’s psychiatric research scandal is on the course syllabi of numerous bioethics courses taught at other institutions,” notes Turner. “The Markingson case has been the subject of at least one ethics grand rounds.”
It is unclear, however, if other institutions are revising policies and practices in light of the issue. “I suspect senior officials at other universities have a habit of thinking that scandals which occurred elsewhere could not happen at their own institutions,” says Turner.
Researchers face “serious and challenging” ethical considerations when recruiting and enrolling psychiatric patients into clinical trials, says Turner. He says these reforms are needed to adequately protect patients with mental illness from research misconduct:
• Guarding against aggressive recruitment tactics.
While many individuals with mental illness have capacity to decide whether to participate in clinical research, mental illness can undermine decision-making capacity. “Patients need to be able to say no if they do not want to participate in clinical research,” says Turner. “They should not be badgered, they should not be pressured, and they should not be asked to participate again and again.”
• Assessing decision-making capacity carefully and thoroughly.
“The assessment needs to be done by individuals who have no stake in whether or not patients decide to participate in clinical studies,” adds Turner.
• Disclosing conflicts of interest to patients, research subjects, and other stakeholders.
“Furthermore, some conflicts of interest should not be allowed to exist,” says Turner. “Transparency, while important, does not solve all ethical issues.”
Conflicts of interest are “rampant” in academic psychiatry, adds Turner. “These can result in patients and research subjects being treated in an instrumental fashion rather than as living, suffering humans who deserve our care and respect,” he says.
• Listening and responding to the concerns voiced by family members.
This doesn’t mean that relatives’ concerns should trump choices of autonomous patients, or that family members’ concerns are always justified. “Still, these concerns should not be ignored or casually dismissed,” says Turner.
- Office of the State Legislative Auditor, State of Minnesota. A clinical drug study at the University of Minnesota Department of Psychiatry: The Dan Markingson case. Special Review, March 19, 2015.
- Andrew Childress, PhD, Assistant Professor, Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX. Phone: (713) 798-8164. Email: [email protected].
- Carl Elliott, MD, PhD, Professor, Center for Bioethics, University of Minnesota, Minneapolis. Phone: (612) 626-5347. Fax: (612) 624-9108. Email: [email protected].
- Leigh Turner, PhD, Associate Professor, Center for Bioethics, University of Minnesota, Minneapolis. Phone: (612) 626-4830. Fax: (612) 624-9108. Email: [email protected].
