Background

The events surrounding the suicide of Dan Markingson in a clinical trial at University of Minnesota’s Department of Psychiatry may be alarming, but they are not new.  Back in the 1990s, when the university was working its way towards a crippling probation by the National Institutes of Health for yet another episode of misconduct (this time in the Department of Surgery, by transplant surgeon John Najarian), the Department of Psychiatry hosted several spectacular cases of research wrongdoing, two of which resulted in faculty members being disqualified from conducting research by the FDA.

The first was the case of Dr. Barry Garfinkel, the head of Child and Adolescent Psychiatry. Garfinkel was the principal investigator for a $250,000 Ciba-Geigy study of Anafranil, an antidepressant, to determine if the drug was effective for obsessive-compulsive disorder in adolescents. Unfortunately, Garfinkel was not the most scrupulous researcher.  According to newspaper reports, Garfinkel falsified data, submitted forms for psychiatric evaluations that didn’t actually take place, and instructed his research assistant to give therapy to subjects even though she had no medical training.  For this Garfinkel wound up in federal court, where he was sentenced to six months in federal prison, six months of home detention, 400 hours of community service, and was fined $214,000.

Even more impressive than Garfinkel’s fraud were the actions taken by University of Minnesota administrators to protect him.  After the whistleblower that alerted the university was fired, the Dean of the Medical School, David Brown, made a secret agreement with Garfinkel to keep the university investigation hidden for nearly four years.  The university spent nearly $180,000 in legal fees to maintain that secrecy.  When the FDA got involved, the university refused to share its findings until the FDA had them subpoenaed. The university later claimed in a press release that it had cooperated with the FDA – a claim that an FDA official told the Star Tribune he found “offensive.”  He said, “This is not what I would characterize as cooperation.”

The University of Minnesota was still under fire for covering up the Garfinkel fraud in 1993 when yet another psychiatric scandal emerged.  Dr. James Halikas, a tenured professor in the Department of Psychiatry, had gotten permission from the FDA to test a drug called gamma hydroxybutyrate, or GHB, for opiate addiction.  He began by recruiting uneducated Hmong refugees who did not speak English.  The Hmong patients had become addicted to opium in Laos, where the drug is often used as a painkiller. Although they had come to the university to get methadone maintenance treatment, the patients had discovered that the methadone clinic was closed to them.  This was because Halikas had decided that Southeast Asians were taking up too many spots at the clinic.  He was only admitting non-Asians.

According to the FDA, Halikas enrolled ten of those Hmong patients in his GHB study.  Although they complained bitterly that GHB didn’t work and repeatedly asked for methadone, it was not until a formal complaint was lodged by another faculty member, Dr. Sheila Specker, that an investigation was triggered.  It soon became clear that Halikas had never actually obtained informed consent from his subjects.  In fact, it is not even clear that the subjects even knew they were in a research study.  (This was not because Halikas didn’t know better; he was a member of the university’s Institutional Review Board.)  According to a later investigation by the FDA,several of the subjects were severely depressed and at risk of suicide, and should have never been enrolled in the study, even if they had given their consent.  Although Halikas told the Star Tribune that GHB is “so mild that it has been used in Europe as a children’s sedative,” it is in fact a central nervous system depressant that is illegal in many countries and is sometimes used as a date rape drug.  At the time of the study it had been linked to seizures and coma.  The FDA found that Halikas had dispensed it in dangerously high doses.

According to the Star Tribune, although the university investigated the complaint about Halikas, it did not inform state licensing officials who have jurisdiction over the drug program.  Nor did it bar Halikas from conducting research.  That did not happen until 2000, when the FDA formally“disqualified” him as a clinical researcher.

Perhaps most alarming of all was the case of Dr. Faruk Abuzzahab, a clinical faculty member and former professor in the department who was investigated by the state medical board and found to be responsible for the deaths and injuries of 46 separate patients under his care. Many of these unfortunate people were psychotic, drug-dependent and suicidal.  According to the Minnesota Board of Medical Practice, Abuzzahab had “enrolled psychiatrically disturbed and vulnerable patients into investigational drug studies without ensuring that they met eligibility criteria to be in the study and then kept them in the study after their conditions deteriorated.” The board had judged Abuzzahab a danger to the public and suspended his license, citing “a reckless, if not willful, disregard of the patients’ welfare.”

According to the Boston Globe, one of Abuzzahab’s subjects was a forty-one-year-old woman named Susan Endersbe, who had struggled with suicidal thoughts and had a diagnosis of schizophrenia.  Endersbe had been doing well on her medication when Abuzzahab enrolled her in a trial of an investigational antipsychotic drug.  When she was taken off her regular medication, she became suicidal.  Abuzzahab gave her a day pass to leave the hospital without supervision; she threw herself into the Mississippi River and drowned.  (In 2007, according to the New York Times, Abuzzahab was still conducting clinical trials and still working for the pharmaceutical industry.)

By the early 2000s, the Seroquel scandals at Minnesota were getting started.  The new chair of the Department of Psychiatry, Charles Schulz, was working on the “smoke-and-mirrors”study of Seroquel that would get him into trouble later, when internal AstraZeneca documents were unsealed in litigation.  And a within another few years, his colleague, Stephen Olson, was recruiting subjects into the CAFÉ study of Seroquel, which resulted in a grisly death for at least one subject, Dan Markingson.

Despite its long history of problems with industry-sponsored research, the University of Minnesota has declined to take action to clean up conflicts of interest.  In 2009, the Senate Finance Committee investigated the chairman of spinal surgery, Dr. David Polly, for failing to disclose $1.2 million he had been paid to consult for the device manufacturer, Medtronic.  A series of investigative reports in the New York Times in 2007 targeted the industry ties of Minnesota psychiatrists, including some connected to the university. When the scandals began to escalate, Dr. Deborah Powell, then the dean of the university’s medical school, appointed a task force to devise a new conflict-of-interest policy. The policy was discarded after the Minneapolis Star Tribune revealed that the co-chair of the task force, Dr. Leo Furcht, had funneled $500,000 of university grant money into his own private company, which he later sold for $9.5 million.  According to the Star Tribune, Powell said “she did not inform the rest of the task force members about the sanctions against Furcht. ‘I did not think it was relevant, she said.”  Furcht remains chairman of the laboratory medicine and pathology department at the university.