The University of Minnesota has halted the recruiting of patients for all its psychiatric drug studies, including 14 underway and three in the pipeline, until problems with oversight and safety monitoring of psychiatric research on campus are addressed.
The decision comes in the wake of a critical external review and legislative audit that raised ethics concerns about the recruitment and treatment of a patient in a schizophrenia drug study who died by suicide a decade ago.
The length of the suspension and its impact on research is unclear.
Recruitment for studies examining drug therapies for autism, depression, substance abuse and schizophrenia has been suspended, regardless of whether researchers had any connection to the trial in which the patient died. Examples include Dr. Kathryn Cullen’s study of whether a dietary supplement reduces self-harm behaviors in teens, and the university’s arm of a national, industry-funded trial of an experimental drug for obsessive-compulsive disorder.
Cullen said a colleague was about to enroll four families into a study of therapy and medication approaches to adolescent depression, but now he’ll probably lose them: “It’s hard enough to get our projects done without hindrances like this. It’s difficult to recruit families.”
Still, she supports the suspension as a step to improving her department’s credibility.
Nothing will change for patients already enrolled in trials, but others will have to wait to participate until an independent review board examines oversight of the studies and determines that they minimize the risk of patient harm, said Dr. Brian Herman, the university’s vice president for research.
“We just need to make sure … that the danger to the patient has been minimized and the approach by which the patient consented and was asked to participate in a trial was correct,” he said.
Recruiting ethics were central to the concerns in the case of Dan Markingson, who died at age 27 in May 2004 while enrolled in a national study, called CAFE, that compared the effectiveness of three antipsychotic drugs on new cases of schizophrenia. The U’s leader of the study, Dr. Stephen Olson, was also treating Markingson and advising a judge whether Markingson should be committed to a locked psychiatric facility. Holding so many influential roles drew concerns from the Minnesota mental health ombudsman when she reviewed Markingson’s death in 2005. The practice was prohibited by state legislation in 2009.
On Thursday, legislative auditor James Nobles said Olson’s multiple roles — coupled with the fact that he was behind on enrollment for CAFE and at risk for getting dropped from the national study — raised “very serious concerns” that the psychiatrist could have used his influence to recruit Markingson.
“Dan Markingson … was highly vulnerable when he was enrolled in the drug study,” Nobles testified at a Senate Education Committee hearing.
Herman said he is starting the process of hiring a private institutional review board (IRB) to examine the recruiting and safety protocols of the U’s psychiatric drug research. He estimates it will take an independent IRB two to four weeks to determine whether there are safety concerns in any of the studies, and to tell Herman if the U can resume enrollment.
However, it is possible that approval from this board would only be a first step before researchers could resume recruiting.
State Sen. Terri Bonoff, DFL-Minnetonka, intends to file legislation in April that delays recruitment to psychiatric drug studies until the university complies with ethics standards and patient protections outlined in an external review that was submitted to its Faculty Senate last month.
U bioethicist Carl Elliott has been a leading critic of the university’s treatment of Markingson and his family since media reports first detailed the case in 2008. Suspending research recruiting was a necessary step given the problems raised in the psychiatric department, Elliott said, but he has concerns about leaving it to the administration to select a consultant.
“Clearly the university leadership can’t be trusted to police itself, when they are themselves deeply implicated in the scandal,” he said. “Any solution is going to have to come from the outside.”
The list of affected studies includes two by Olson, who remains in charge of the schizophrenia research program in the U’s psychiatry department.
Cullen’s study of a dietary supplement had almost reached its enrollment goal of 20 teens and will run out of grant funding in June, so the psychiatrist said she will probably wrap that one up. Another study is testing an anesthetic drug on adolescents whose depression symptoms aren’t improving.
Recruitment is only midway, and Cullen is nervous that a prolonged suspension could be damaging to that research. She understands the university’s action, though.
“We are in a position where we need to prove ourselves,” she said. “Whatever steps we can take to do that, we need to do those steps.”