U ethics profs seek inquiry into drug study, subject's death

Eight University of Minnesota bioethics professors are asking the Board of Regents to investigate a drug study that lost a participant to suicide six years ago.

In a letter to the board Monday, the professors questioned whether U psychiatrists lacked ethical judgment in enrolling the victim, Dan Markingson, a schizophrenic who may have lacked the wherewithal to consent to research. They also questioned whether financial incentives from AstraZeneca, the drugmaker funding the study, presented conflicts for the researchers, Dr. Stephen Olson and Dr. S. Charles Schulz.

The criticisms aren't new: The May 2004 death drew reviews by the U.S. Food and Drug Administration and the state mental health ombudsman, a lawsuit by Markingson's mother, and media investigations. The FDA found no fault by the university. A judge excused the U of M and Schulz, chairman of the U's psychiatry department, from the mother's lawsuit. Olson then settled the case.

But now the criticism is coming from leading ethicists within the institution.

"While it is understandable that some of our colleagues will have little interest in revisiting this case and the ethical issues it raises, we are persuaded that there is a disturbing and unjustifiable gap between how the University has responded to this death and the careful, critical investigation it warrants," the professors wrote.

U leaders will take the letter seriously and take the protection of human research subjects seriously, said the U's general counsel, Mark Rotenberg. He stressed that other government entities have found no causal link between the study and the death.

"The fact that this is tragic doesn't mean the treating physicians did anything wrong," he said.

Protecting subjects

Among the new critics is Mary Faith Marshall, a bioethics professor who served on federal panels regarding the protection of human research subjects. She also served on an advisory panel that investigated conflicts of interest after the 1999 death of Jesse Geslinger, a participant in a gene transfer study at the University of Pennsylvania.

Whether or not the U was at fault, Marshall said the institution owes Markingson's mother, Mary Weiss of Cottage Grove, an apology and an investigation. She called Markingson's death "an example of a failure" to protect research subjects.

Markingson's delusions resulted in his confinement to a unit designed at the University of Minnesota Medical Center, Fairview, to screen patients for clinical studies.

A judge later stayed Markingon's commitment to a state hospital if he agreed to follow the outpatient treatment plan offered by Olson, his psychiatrist. Olson then enrolled Markingson in the study, which was funded by AstraZeneca to test whether its antipsychotic, Seroquel, was as safe and effective as competing drugs.

The lead author of the letter is Carl Elliott, a U of M bioethicist who wrote an article in Mother Jones magazine recently about Markingson's death and researchers' financial ties to the drug industry. Elliott also testified with Weiss for the passage of "Dan's law," which prohibits mentally ill patients under civil commitments in Minnesota from consenting to research.

Other bioethicists who signed the letter: Dianne Bartels, Joan Liaschenko, Dr. John Song, Leigh Turner, Susan Craddock and Joan Tronto.