University of Minnesota admits missteps in second schizophrenia drug study

In the second local case to raise questions about patient safeguards during research, the University of Minnesota has acknowledged missteps in the care of a Rosemount man who claimed he was coerced during inpatient hospital confinement into enrolling in a schizophrenia drug trial.

While a yearlong investigation concluded that a university psychiatrist did not coerce the man to enroll, or force him to remain in the study against his will, it found that caregivers prematurely prepped him for the study before he gave consent, and failed to pass along key safety information that could have influenced his decision to participate.

In a May 6 letter to the patient, Robert Huber, a U research official said the university was sorry that his "rights and welfare were compromised."

In an interview Friday, Huber said he appreciated the admissions, but said he remains upset that an agency hired by the university to conduct the investigation, FTI Consulting, never talked to him before concluding that he wasn't coerced.

Huber, 44, was taken to the University of Minnesota Medical Center in July 2007 with schizophrenia symptoms and confined for two weeks. During that time, he says, he received daily requests from Dr. Stephen Olson and others in the U's Psychiatry Department to volunteer for a drug trial involving an experimental medication called bifeprunox.

Huber said they repeatedly assured him the drug was safe — even though determining its safety was one of the very goals of the study — and showed him the cost of his hospital care if he didn't sign up and have the study pick up the tab.

Whether he was thinking clearly or not, Huber said he decided to enroll because he thought Olson would keep him in the hospital until he did.

"I was so afraid they were going to lock me up," he said.

The consultant report on the case disagreed, concluding that Huber had the wherewithal to consent to the study.

Huber's claims nonetheless echo those by the family of Dan Markingson, who died by suicide in May 2004 while enrolled in a U drug trial that was comparing the effectiveness of three approved antipsychotic drugs.

A review by Minnesota's Legislative Auditor in March cited concerns that Markingson was recruited by Olson, who also was his treating doctor and an adviser to the court on whether his patient should be committed. It also faulted the U for dismissing ethics questions raised by its critics.

Concerns over the recruiting of Markingson and Huber also helped trigger an overarching review, commissioned by the university's Senate Faculty, that found deficiencies in the ethical and safety oversight of psychiatric and other clinical research.

Following those reviews, the university's Psychiatry Department chairman stepped down and the U suspended recruiting into clinical psychiatric research. A committee of faculty and administration leaders is due by next week to propose changes to address the deficiencies.

Bifeprunox was being studied by Solvay Pharmaceuticals as the next advance in the treatment of schizophrenia. But a month after Huber enrolled in the drug trial, the U.S. Food and Drug Administration announced it would not be approving the medication. That action followed the death of a man in Europe who suffered severe liver complications while taking the drug.

The national trial was not halted, though, and Huber continued taking the medication through October 2007. In that three-month period, he experienced abdominal pains so severe that he required at least two visits to hospital emergency rooms — once by ambulance — and he said he contemplated suicide to make them stop.

Records indicate that Olson believed Huber's pains were "unlikely" to be related to the study medication, and might be psychosomatic.

Huber eventually disenrolled from the drug trial, though he said he received pressure to stay in. One caregiver warned him he would "get fat" if he switched to another antipsychotic that had weight gain as a known side effect.

The May 6 letter to Huber from Debra Dykhuis, executive director of the university's Human Research Protections Program, listed three problems with his care:

• Huber was asked not to eat or swallow anything one evening in preparation for a study-related blood test the next morning, even though he hadn't yet consented to the study in writing.

• Huber was not informed in August 2007 that the FDA had decided not to approve bifeprunox.

• Huber was not informed in his consent form of the risks of medication "washout,'' the process of taking him off all other medications before starting a new one.

The university has addressed all three problems, revising consent forms and asking all researchers to notify their Internal Review Boards when they receive letters from the FDA, said Brian Lucas, a spokesman for the university's Academic Health Center.

Months of medication adjustments following the study helped manage schizophrenia symptoms for Huber, who is unemployed due to his disability and living with relatives. The abdominal pains became less frequent and eventually disappeared.

On Friday, he said he hopes his complaint will lead to safer research and less aggressive recruiting of patients suffering their first episodes of psychotic illness.

"I would like for this to stop," he said, "for things to change."

Jeremy Olson • 612-673-7744