U of M critics: Drug research reform needs work

Updated at 3:10 p.m. | Posted at 5 a.m.

University of Minnesota regents have approved initial steps they say will improve oversight of how the university treats its research patients.

Two recent reports have blamed the university for inadequately protecting vulnerable human test subjects. The reports were prompted by the 2004 suicide of a mentally ill man during a U of M clinical drug trial.

The university has stopped enrolling test subjects in 17 drug studies until the studies pass an external review.

Vice President of Research Brian Herman told regents Friday that a panel of faculty and outside experts will roll out a plan for further recommendations in May.

"Unfortunately, none of us can change what happened, but we can always dedicate ourselves to working tirelessly to ensure that our research is conducted in the safest and most ethical way possible," Herman said.

The university also will hold two forums on the subject in coming weeks.

Before the regents met, two of the university's biggest critics said the suggested reforms may not get to the heart of the problem.

U of M bioethicists Leigh Turner and Carl Elliott say last month's external review of university practices contains some solid recommendations — including tougher oversight of research and changes to prevent coercion of vulnerable patients into potentially risky drug trials.

But Turner said the review is quiet on the financial conflicts of interest that often push researchers to cut ethical corners. He and Elliott say it doesn't push the U of M enough to clean house of unethical personnel. They expressed concern that the university's initial attempt to strengthen oversight may suffer from its own conflict of interest.

Those problems must be solved, Turner said, if the university wants to prevent deaths and significant injuries in its research.

The recommendations suggested so far "are a good step," Turner said. But he called them "limited."

The university has suffered harsh criticism over the past month over the way it handles human subjects in its clinical drug trials — primarily in the Department of Psychiatry.

The criticism stems from the case of Dan Markingson, a mentally ill man who killed himself while participating in a commercially funded drug trial. Critics fear researchers coerced Markingson into taking part over the repeated objections of his mother, who repeatedly warned them that he was not mentally capable of giving proper consent and might kill himself.

A state legislative audit released last week said that it's not possible to say Markingson killed himself because of the study — but it did say the university failed to adequately protect him.

Among its nine findings, the report said Markingson "faced commitment to a state psychiatric hospital" if he refused to participate in the trial — a situation the audit said could be interpreted as coercive. It also stated that the university's research oversight board did not adequately look into Markingson's case. Another of its findings was that the leader of Markingson's drug trial suffered from conflicts of interest that clouded his judgment as to whether Markingson should participate in the study.

The audit's findings echoed many of the concerns voiced last month in an external review of the U's current research practices. To beef up protections, the review suggested several dozen reforms.

University President Eric Kaler said that in May he'll lay out a plan of reforms based on the external review. In the meantime, the U of M has suspended enrollment in 17 active and pending drug trials until they are reviewed by an independent oversight board.

Many focus on drugs designed to treat disorders such as depression, autism and schizophrenia, and half a dozen of the study titles mention a focus on adolescent cases.

Two of the academics at the center of the Markingson case — researcher Dr. Stephen Olson and Department of Psychiatry head Charles Schulz — each have two cases among those suspended.

The suspension already is causing some concern among some researchers.

Faculty and school officials say the delay could cause some expensive test drugs to expire before they're used, for example, leaving researchers unable to buy a new round when the suspension lifts. Hard-to-recruit test subjects who are turned away may not return, and unmet research deadlines may require some studies to shut down and researchers to return unused grant money. One faculty member also expressed concern that an aborted drug study could harm a researcher's ability to obtain funding for other studies.

Dr. Kathryn Cullen, an assistant professor, said she's not sure how long the suspension will last, but fears it could be weeks or months.

"Every moment counts," she said. "This research needs to move forward."

U of M has put out bids for an independent Institutional Review Board to check the suspended studies for red flags and recommend whether they get the green light, university spokeswoman Julie Christensen said.

Elliott, the bioethicist, is concerned that if the university uses a commercial review board to review current or future studies, it might suffer from a financial conflict of interest. If a board receives money from the institution it's paid to monitor, he said, it has an incentive not to be as critical as it should, lest it lose a university's future business.

"It's as if you were paying the body that is supposed to be regulating you," Elliott said.

Elliott said he's also concerned that such review boards often review cases from far away by reviewing their documentation.

"They have no sense at all of what's going on — on the ground — at the site they're supposed to be overseeing," he said.

What's needed, Elliott said, is for a state-sponsored entity to review the studies.

Christensen, the university spokeswoman, said in an emailed response that "all [oversight] boards, whether they are academic or independent ... are bound by the same sets of regulations. And all are subject to inspection by regulatory agencies."

Turner, Elliott's colleague, welcomed some of the administration's initial list of changes. They include beefing up the staffing of a key research oversight panel, better documenting its findings and preventing personnel from reviewing the work of their superiors.

Others proposals — such as the appointment of a community oversight board and visits to other universities to learn from them — Turner called "apple pie" ideas that couldn't hurt but don't get to the root of the problem.

Most of the meaningful reforms appear to be contained in the external review, which the legislative auditor concurred with, and that U of M officials say they will prioritize and carry out.

Turner said the most important of the recommendations focus on two areas:

Strengthening the oversight board. The board overseeing research has been seen as weak, understaffed and often devoid of the expertise necessary to properly review drug studies. Turner welcomed the additional personnel, and agreed with reviewers that the board should be made more responsive to complaints that something is going wrong in a study.

"You don't want [an oversight] board that's rubberstamping studies," he said.

Protecting patients against coercion. The external review calls on the U of M to ensure that patients have free choice in whether to participate, and that they truly understand the implications of undergoing a drug trial. That would involve checks to make sure patients have not changed their minds about participating and properly use surrogate decision-makers — such as family members — when necessary. Turner called the proposals perhaps the most important group set of reforms mentioned.

"You don't want anyone going into a study feeling forced or harassed," he said.

But Turner said the external review doesn't adequately address two areas he said are at the heart of meaningful reform: financial conflicts of interest within the research community and the ethical culture within the Department of Psychiatry.

Many physicians across the country receive payment from drug companies through consulting fees, junkets and honoraria for speeches. Such payments, Turner and Elliott say, can cloud their judgment.

"If you have a financial interest in pleasing a company that is giving you speaking and consulting fees," Elliott said, "it might lead you to make decisions about your research subjects that are not in their interests."

A lot of universities, Elliott said, prohibit researchers from receiving such fees from companies that sponsor their research.