In 2003, Dan Markingson, 26, was enrolled in a clinical trial at the University of Minnesota aimed at comparing several drugs to treat schizophrenia. Despite the explicit demands of his mother, Mary Weiss, to pull him out of the trial, investigators demurred. Less than six months later, Markingson committed suicide in a gruesome manner — nearly decapitating himself with a boxcutter.
Weiss sued the university; Markingson's doctor, Stephen Olson; drug maker AstraZeneca, which designed and funded the trial; and Dr. Charles Schulz, chair of psychiatry at University of Minnesota and, with Olson, a co-investigator of the study. Weiss' suit never made it to trial; a district court judge dismissed parts of it in 2008. Weiss settled with Olson for $75,000, which didn't even cover her legal fees.
But investigations into whether lapses of judgment and ethics at the university led to Markingson's death are continuing, both internally and in the media. The design of the drug trial — known as the CAFE trial, which found that AstraZeneca's drug Seroquel was of "comparable effectiveness" to the other two atypical antipsychotics studied — has been widely called into question.
The doctors involved, Olson and Schulz, are also known to have collected hundreds of thousands of dollars from industry in speaking and and consulting fees, including from AstraZeneca. And the university, under its arrangement with AstraZeneca, made more than $15,000 for each patient it enrolled in the trial — by contrast, had the university treated Markingson, a patient on public assistance, outside of the trial it would have made little income.
In December, eight bioethicists from the university — including Carl Elliott, interviewed earlier by TIME here — called for the appointment of an independent board to investigate what went wrong. Meanwhile, ongoing media reports on the case reveal deep problems with the way clinical drug trials are designed, funded and carried out.
In 2008, the St. Paul Pioneer-Press published an investigation of the Markingson death, which was followed up by Elliott himself in a horrifying exposé for Mother Jones magazine in late 2010. On Wednesday, Minneapolis City Pages revisited the story, with yet more revelations about Schulz' connections with AstraZeneca.
Writes Andy Mannix:
The issue will soon come to a head. The U of M has been investigating a complaint about Schulz's connections to Big Pharma and is expected to issue the results in a matter of weeks.The City Pages story includes distressing allegations about Schulz' previous involvement in studies of Seroquel (quetiapine), funded by AstraZeneca. The article suggests that as far back as 2000, data were spun at a meeting of the American Psychiatric Association (APA) to make the drug seem better than existing medications on the market, including the older drug Haldol (haloperidol).
"If there's any question that the investigation was superficial, it ought to be by an independent group that can determine what the facts are," says Jerome P. Kassirer, former editor of the New England Journal of Medicine, who is familiar with the circumstances surrounding the Markingson case. "It looks worrisome to me."
"The data don't look good," AstraZeneca publications manager John Tumas wrote on March 23, 2000. "What seems to be the case is that we were highlighting the only good stuff, and that our own analysis supports the 'view out there' that we are less effective than Haloperidol and our competitors."The story also includes information on the payments received by the doctor: an estimated $150,000 to $180,000 between 1999 and 2004, which Schulz disclosed in depositions with Weiss' attorney. But for his part, Schulz denies any allegations of wrongdoing, and says that he began studying quetiapine for the treatment of schizophrenia even before it was branded as Seroquel by AstraZeneca and pushed as a money-maker. He told City Pages in an email, "I haven't been particularly focused on quetiapine, in my opinion, but on the best ways to help schizophrenic people."
Yet Schulz painted a much rosier picture at the APA conference just two months later. Despite AstraZeneca's findings that Seroquel did not perform as well as older antipsychotics, Schulz declared it "significantly superior" to haloperidol, a competing medication.
Sadly, this story is about more than just one young man's needless death or one psychiatrist's relationship with one drug company. All of these exposés reveal huge problems with the systems designed to protect the safety of patients in clinical drug trials, and even larger problems stemming from the close financial ties between pharmaceutical companies and the myriad researchers who are supposed to test their products independently.
If we want safe and effective medications, the system that tests them needs to be as transparent and influence-free as possible. Dan Markingson is far from the only victim here.