The article, "Making a Killing," focuses on the deeply troubling case of Dan Markingson, a 26-year-old Minnesotan who took his own life after he was prevented from leaving a University of Minnesota clinical trial comparing Seroquel to Zyprexa and Risperdal. AstraZeneca, which manufactures Seroquel, not only sponsored that trial but also gave $782,000 to the two U of M psychiatrists who oversaw Dan Markingson's participation in a clinical drug trial." As this blog noted last June, in an earlier post on the Markingson case ("When Drug Trials Go Terribly Wrong"), state payment records indicate that drug companies as a whole had given "$88 million in gifts, grants and fees to Minnesota doctors and caregivers since 2002."

The Mother Jones article includes even-more unsettling evidence of malpractice. Not only were sales reps at AstraZeneca "instructed to tell doctors that Seroquel doesn't cause diabetes, even though the company knew about the link to diabetes as early as 1997. Internal correspondence also reveals company officials discussing how to hide or spin potentially damaging studies" other than the one involving Mr. Markingson. "'Thus far, we have buried trials 15, 31, 56,' wrote a publications manager in 1999. ‘The larger issue is how do we face the outside world when they begin to criticize us for suppressing data.'"

How indeed? One answer lies in the fact that AstraZeneca now faces more than 25,000 civil suits. In April 2010, the drug maker also "agreed to pay $520 million to settle two federal investigations and two whistleblower lawsuits alleging that it had marketed Seroquel illegally and concealed its health risks."

Notes Elliott, "internal correspondence" at AstraZeneca "repeatedly refers to Study 15 as a ‘failed study,' and company officials discuss possible ways to spin or bury it. ‘I am not 100% comfortable with this data being made publicly available at the present time,' wrote Richard Lawrence, a senior AstraZeneca official, in 1997. ‘However I understand that we have little choice. . . Lisa [Arvanitis, a company physician] has done a great "smoke-and-mirrors" job.' Lawrence referred approvingly to a strategy that he said would "put a positive spin (in terms of safety) on this cursed study.'"

Beyond the most troubling aspects of the Markingson case is what Elliott brings to light about drug trials across the board, including the systemic failure of large numbers of institutional review boards (IRBs) to address them.

"The largest of the new private industries are contract research organizations (CROs)," he notes, "which range from small niche agencies to multinational corporations that manage all aspects of clinical trials, from ethics approval and subject recruitment to the submission of clinical data to the FDA."

"CROs," he continues, "have been involved in some notable clinical trial scandals. In the 1990s, Pharmaceutical Product Development, or PPD, one of the largest, was implicated in a notorious fraud scheme carried out by Dr. Robert Fiddes, who used his Southern California Research Institute to falsify records and invent patients while conducting trials for nearly every major pharmaceutical company."

"In 2006, at a trial site at a hospital near London, six healthy subjects nearly died after the CRO Parexel paid them 2,000 pounds each to become the first humans to test an experimental compound. In 2005, Bloomberg News reporters discovered that SFBC International Inc. was paying undocumented immigrants to serve as drug guinea pigs in a converted Holiday Inn. The Miami motel was subsequently demolished for fire and safety violations, and the company changed its name to PharmaNet. In 2009, PharmaNet was acquired by JLL Partners, a New York hedge fund."

"There are about 40 for-profit IRBs operating in the US," Elliott concludes in a final sidebar, "generating more than $100 million in annual revenue. Some for-profit IRBs are professional and serious-minded, while others present a more entrepreneurial face. Take Liberty IRB, a for-profit IRB in Florida that boasts on its website that it is the winner of the 2008 ‘Make Mine a Million $ Business' competition, a contest described as ‘a cross between The Apprentice and American Idol.'"

Is this how we want powerful, sometimes life-threatening pharmaceuticals tested and approved?

At such moments, it's worth reminding ourselves that Americans account for two-thirds of the global market for antidepressants and antipsychotics. The consequences of having such meds reviewed by for-profit companies under the auspices of the drug companies runs far-deeper than one seriously faulty trial in Minnesota. Let's not overlook that the University of Minnesota recently concluded a trial to determine whether Seroquel, the above antipsychotic, with all its myriad problems and side effects, might be beneficial to people with public-speaking anxiety.

You might think that the known risk of diabetes, hypoglycemia, and rapid weight gain, among many others, would finally dissuade drug companies and researchers from conducting such trials. You'd be wrong.

You can download Elliott's article here (Mother Jones requires your email first).

www.christopherlane.org