Professors SHOCKED-SHOCKED by Clinical Trial Corruption

December 27, 2010

27 Dec | AHRP – The disturbing circumstances surrounding the enrollment and subsequent suicide of Dan Markingson (2004) after he was given an experimental antipsychotic drug, Seroquel, as a test subject in AstraZeneca’s CAFE trial – having been enrolled while he was hospitalized under an involuntary commitment order–are continuing to generate outrage and dismay.

The case against  AstraZeneca’s corrupt practices is well documented in courts of law and in civil and criminal settlements with the Department of Justice:  Kickbacks to physicians, rigged clinical trials in which company officials “cherry picked” the data to be disclosed while “burying” unfavorable study findings, the company’s use of “smoke and mirrors” to obscure Seroquel’s failed efficacy, AstraZeneca’s failure to warn that Seroquel can cause diabetes and other health problems, and its illegal off-label marketing of Seroquel.  On April 27, 2010, AstraZeneca and the U.S. Dept. of Justice reached a $520 million settlement.

But what of the case against the University of Minnesota and the psychiatrists who conducted the trial?  Their actions and the significant financial stake they had in the trial, have never undergone independent scrutiny.

Those familiar with the documented facts in the case, are convinced that the University of Minnesota and the psychiatrists who enrolled Markingson when he was mentally unstable–and who then refused to withdraw him despite his mother’s frantic pleas–are culpable for the tragic results.

This case encapsulates the corrupt practices that ensue when academia and the pharmaceutical industry become partners in joint financial ventures.

Adding insult to fatal injury, the University of Minnesota treated Dan Markingson’s mother, Mary Weiss, with callous disregard – an attitude comparable to that displayed by the Catholic Church toward victims of sexually abusive priests.

Over the past several years, articles in the St. Paul Pioneer Press, Minneapolis Post, City Pages, and Mother Jones magazine have suggested an alarming string of ethical violations – including gross conflicts of interest by the psychiatrists and the University;  recruitment of mentally incompetent subjects;  and the integrity of the study itself – which, if true, suggest serious problems in the way that clinical research is conducted and overseen at the university.

Dr. Charles Schulz, chief of psychiatry, and Stephen Olson, personally earned a combined $811,045 between 2002 and 2008 from pharmaceutical companies, including $261,364 from AstraZeneca, the sponsor of the CAFE Seroquel trial in which Dan Markingson was enrolled.

The Minneapolis Post reported: “The University of Minnesota benefited financially from the study: More than $300,000 went to the Department of Psychiatry.”

In a searing article in Mother Jones, Dr. Carl Elliott reported that the U of Minnesota Department of Psychiatry had earned $15,648 for each person it enrolled in the AstraZeneca Seroquel study.  And at the time that Markingson was enrolled in the study, Dr. Elliott wrote, the University was having a serious problem recruiting subjects – it risked being dropped by AstraZeneca as one of the study’s trial sites.

In 2000, Charles Schulz, chief of psychiatry at the University of Minnesota, gave a presentation at the American Psychiatric Association meeting in which he made misleading claims about the safety and efficacy of AstraZeneca’s antipsychotic, Seroquel, calling the drug “significantly superior” to Haldol. In an AstraZeneca press release, he stated: ” I hope that our findings help physicians better understand the dramatic benefits of newer medications…”

Dr. Schulz’ optimistic, but unsupportable statements belied the manufacturers’ own assessment of the data:

“The data don’t look good,” an AstraZeneca official, John Tumas, warned in an e-mail on March 23, 2000. That month, an internal company analysis of the raw data concluded: “It is clear that a claim of superiority for Seroquel over Haloperidol (Haldol) could not be generated using these data.”

In a 2009 interview with Pioneer Press , Schulz admitted that his prior statements were “exaggerated” and he acknowledged that his own study did not really show that Seroquel was more effective than the older drug.

“That’s a bit of a misunderstanding.”

But that message, by the chief of psychiatry at the University of Minnesota, carried weight with psychiatrists who were persuaded to prescribe Seroquel. AstraZeneca got the service they had paid him for. His (admitedly false claim about the drug’s efficacy) served as a useful marketing pitch to boost the drug’s  sales, which reached $4.5 billion annually.

Dr. Jerome Kassirer, the former editor of the New England Journal of Medicine, was prompted to express his disgust (September 15, 2010):

The conflict of interest is disgusting, and it seems quite likely that the boy’s death was an indirect consequence of the financial inducements of the study. At the very least, the university should have appointed an independent review board, dismissed all the hospital charges, and paid the boy’s mother damages.

In November, 2010, eight University of Minnesota faculty members of the Department of Bioethics, sent a letter to the university’s Board of Regents requesting the appointment of an outside panel of experts to investigate gross ethical issues raised by the 2004 suicide of Dan Markingson. (below)

Those ethical violations include:

…recruiting a mentally ill, possibly incompetent subject into a research study while he was under an involuntary commitment order; large financial conflicts of interest on the part of the university researchers conducting the study; a payment structure for the study which included financial incentives to recruit and retain subjects rather than provide them with standard therapy; an allegedly biased study design aimed at generating positive results for AstraZeneca rather than investigating a genuine scientific question; the failure of university researchers to address the legitimate concerns of Mr. Markingson’s mother, Mary Weiss, who warned that her son was suicidal and who attempted for months to have him removed from the study as his mental condition deteriorated; the apparent development of a specialized unit in Fairview Hospital designed to identify severely mentally ill subjects for recruitment into research studies; and finally, a failure of the institutional oversight system for protecting human subjects of research.

This case sheds light on how the commercialization of medicine devalues both the integrity of medical research and patients’ rights reducing both to a means in the service of a financial end.

But this isn’t the first case at the University of Minnesota.

In 1994 – ten years before the death of Dan Markingson – Dr. Bary Garfunkel, the Director of the University of Minnesota, Department of Child and Adolescent Psychiatry, was sentenced to prison for falsifying documents related to clinical trials of Anafranil.

In 1995, Dr. John Najarian was indicted by a federal grand jury for theft and tax evasion related to the illegal sale of ALG, an experimental drug whose sales amounted to $80 million most of which went to the University of Minnesota. This resulted in NIH placing severe restrictions on the University’s freedom to use research funds.

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