Call for an accounting

I have my doubts about the efficacy of the growing welter of petitions for every possible cause, but at least we can express our concerns. There is now a petition to nvestigate psychiatric research misconduct at the University of Minnesota, my place of work, so I feel an obligation to bring it up.

Dan Markingson was mentally ill and committed suicide almost ten years ago. He was in bad shape and was committed for psychiatric care (he was suffering from violent delusions) when he was recruited into a study by AstraZeneca of anti-psychotic drugs. This was not a good idea; running an experimental clinical trial on patients at serious risk of doing physical harm to themselves and others is not recommended.

In fact, the CAFE study also contained a serious oversight that, if corrected, would have prevented patients like Dan from being enrolled. Like other patients with schizophrenia, patients experiencing their first psychotic episode are at higher risk of killing themselves or other people. For this reason, most studies of antipsychotic drugs specifically bar researchers from recruiting patients at risk of violence or suicide, for fear that they might kill themselves or someone else during the study. Conveniently, however, the CAFE study only prohibited patients at risk of suicide, not homicide. This meant that Dan—who had threatened to slit his mother’s throat, but had not threatened to harm himself—was a legitimate target for recruitment.

He was also signed on by his own consent: the consent of a committed mental patient with serious concerns about his competence, and against the wishes of his mother.

The petition does not assign blame, but only asks for an objective examination by external reviewers. You know there’s a problem when the university’s own bioethicists are supporting the call for investigation.

In 2009, the Minnesota state legislature passed “Dan’s Law,” which prohibits researchers from recruiting a patient under an involuntary commitment order into a psychiatric drug study. Media outlets such as Mother Jones, the St. Paul Pioneer Press, City Pages and Scientific American have published accounts of Dan’s story. His story was also featured in the documentary film, Off Label. In 2010, AstraZeneca, the sponsor of the study in which Dan died, settled federal fraud charges for $520 million, and a University of Minnesota psychiatrist was implicated. Last year, the Minnesota Board of Social Work found serious wrongdoing by the study coordinator for the research study in which Dan died.

More recently, evidence of fraud and serious privacy violations in psychiatric studies at the university have emerged. It is possible that other research subjects have died or suffered serious injuries, or that they have been mistreated in other ways. Bioethicists at the University of Minnesota itself have called for an external investigation, yet the university still refuses.

I signed it. I’d like to recommend that more people sign it.

Another scary aspect of this is the possible abuse of science. There’s some funny stuff going on in clinical trials…

A 2006 study in The American Journal of Psychiatry, which looked at 32 head-to-head trials of atypicals, found that 90 percent of them came out positively for whichever company had designed and financed the trial. This startling result was not a matter of selective publication. The companies had simply designed the studies in a way that virtually ensured their own drugs would come out ahead—for instance, by dosing the competing drugs too low to be effective, or so high that they would produce damaging side effects. Much of this manipulation came from biased statistical analyses and rigged trial designs of such complexity that outside reviewers were unable to spot them. As Dr. Richard Smith, the former editor of the British Medical Journal, has pointed out, “The companies seem to get the results they want not by fiddling the results, which would be far too crude and possibly detectable by peer review, but rather by asking the ‘right’ questions.

I’ve been reading Goldacre’s Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients. There really are grounds for more global concern.