Wednesday, August 25, 2010

More on Dan Markingson Case

at the University of Minnesota

from Hooked: Ethics, Medicine & Pharma

Dr. Howard Brody writes:

Back in April I blogged about the tragic case of Dan Markingson and the so-far-futile efforts of his mother, Mary Weiss, to get justice from the University of Minnesota:

Carl Elliott's book (mentioned in the last post) contains a brief synopsis of this case; but he goes into more detail in an article in the current Mother Jones, "Making a Killing." (To access, go to the Mother Jones current issue website,, and look for the title "Making a Killing." Click on that and you'll get a screen that will allow you to register for free access.)

In "Making a Killing," Carl not only describes the sad case but also puts it in the context of the pressure placed on universities today to compete for grant dollars with commercial research entities, all funded by a drug industry that is looking for marketing, not science. As Carl summarizes:

"If these experts [who have reviewed the study in which Dan Markingson was enrolled, and have declared it to be scientifically next to worthless] are right, then then the study in which Dan Markingson committed suicide was not simply a matter of inadequate informed consent, or financial conflicts of interest, or even failure to monitor a subject's care. The ethical breach was built into the study from the start. It is one thing to ask people to take risks for science, or the common good, or to help other people. It is another thing entirely to ask them to risk their lives for the marketing goal of [the sponsoring drug copmpany] AstraZeneca."

Carl throws a couple of other scary passages at us. When Ms. Weiss attempted to sue the University and its psychiatrists (a suit that was dismissed based more or less on a variant of sovereign immunity), her attorneys deposed the director of the U's Institutional Review Board (IRB) or research subjects ethical review committee, Moira Keane. The attorney asked what she thought was a routine question--didn't the IRB have the responsibility to protect human research subjects?--before proceeding to the issues under dispute. But Ms. Keane refused to admit that the IRB had any such responsibility. The attorney thought she had misunderstood (after all, the U-MN website says the purpose of the IRB is to "protect the rights and welfare of human research subjects") but Ms. Keane stood firm. In the end, all she would admit was that it was the role of the IRB to make sure that research investigators at the U had a plan to protect human research subjects. As Dr. Elliott then notes, this is as good as saying that the IRB at U-MN doesn't do a thing--since it was precisely to protect human subjects from the dangers of an overzealous investigator that IRBs were first created.

The next scary quote relates to how you can end up with a study like CAFE (the study in which Markingson was enrolled), which is basically jiggered from the start not to answer any legitimate scientific question, but to provide the drug company with marketing spin to sell their drug, and which can more or less be guaranteed to produce the answers that the company wants. In HOOKED and previously on this blog, I have described in detail some of the tricks used by study designers to rig outcomes. But the march of progress continues, and as journal editors, however belatedly, start to catch on to these little games, the goal posts move. Summarizing a 2006 study of research on atypical antipsychotics, Carl notes, "Much of this manipulation came from biased statistical analyses and rigged trial designs of such complexity that outside reviewers were unable to spot them."

The CAFE study, for those interested, appeared as: McEvoy JP, Lieberman JA, Perkins DO, et al. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. American Journal of Psychiatry 164:1050-60, 2007.
Some comments on this article:

Bernard Carroll: Past chairman FDA Psychopharmacologic Drugs Advisory Committee. Past chairman, department of psychiatry Duke University Medical Center.

This so called CAFE study in which the young man died seems to fit the description of what I have labeled experimercials - pretend clinical trials designed by marketers rather than by clinical research professionals.

And why, pray, are the CATIE investigators lending their names to this undistinguished and indefensible study? CATIE broke new ground by calling into question the efficacy/safety claims for second generation antipsychotic drugs pushed by the corporations.

The lead CATIE investigator, Jeffrey Lieberman, chair of psychiatry at Columbia University has some explaining to do. But then, this is the same Jeffrey Lieberman who wrote to the Wall Street Journal back in 2006 defending the indefensible Charles Nemeroff.

It looks to me like the operative principle here is just money - and that it matters not to a Jeffrey Lieberman whether the money is from NIMH for CATIE or from AstraZeneca for CAFE.

John Nardo:

This is truly an absurd story: made surreal by the design of the study in the first place; with criminal negligence in the responses to Ms. Weiss; but approaches the macabre when it gets to the deposition of Moira Keane. It's a little hard to follow why this suit was dismissed ["a suit that was dismissed based more or less on a variant of sovereign immunity"]. How does being in a "study" immunize people from malpractice or wrongful death?

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