Sunday, August 22, 2010

Slightly O/T: Seroquel® Exposé In Forthcoming Mother Jones

First, a sincere hat tip to Dr. Adriane Fugh-Berman at, and to The Insider at PharmaGossip, for reminding me about this.

This Mother Jones article should be read -- cover to cover -- by anyone familiar with the sordid history of the "atypical" antipsychotics (paging Salmon!) -- as much of the narrative likely applies to the studies legacy Schering-Plough used to clear New Merck's Saphris® (asenapine). In my estimation, Carl Elliott has a Pulitzer-worthy Seroquel® piece, here -- do go read it all:

. . . .On the surface, the study appeared benign. Its purpose was to compare the effectiveness of three “atypical” antipsychotic drugs, each of which had already been approved by the fda: Seroquel (quetiapine), Zyprexa (olanzapine), and Risperdal (risperidone). The study was designed and funded by AstraZeneca, the manufacturer of Seroquel, and it called for 400 subjects experiencing their first psychotic episode to take one of the three drugs for a year. AstraZeneca called it the “CAFE” study, which stood for “Comparison of Atypicals in First Episode.” The management of the CAFE study had been outsourced to Quintiles, a contract research organization, which was conducting it at 26 different sites. . . .

Yet the cafe study was not without risks. It barred subjects from being taken off their assigned drug; it didn’t allow them to be switched to another drug if their assigned drug was not working; and it restricted the number of additional drugs subjects could be given to manage side effects and symptoms such as depression, anxiety, or agitation. Like many clinical trials, the study was also randomized and double-blinded: Subjects were assigned a drug randomly by a computer, and neither the subjects nor the researchers knew which drug it was. These restrictions meant that subjects in the CAFE study had fewer therapeutic options than they would have had outside the study.

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. . . .

You. Must. Read. It. All.

It is this sort of study-design -- coupled with the schemes in a few states (like New Jersey, and Minnesota, apparently), in which no actual court or judge is involved, before an otherwise presumptively-competent adult is forcibly-held in a psychiatric ward, and then effectively forced onto very powerful medications -- that leads to these more-than-occasionally atrocious outcomes. Outcomes that defy Hippocrates' oath -- outcomes for which (in a reformed system) the treating health care professional must ultimately held responsible, if we are see meaningful changes.

[UPDATED: Apparently, Natasha Singer of The New York Times had written to recommend the above article -- on Friday night, as well. I missed hers -- but it is also a worthy read.]


Anonymous said...

would be nice if they emphasized the IRB/EC involvement in this as they are there to be the safety net, patient advocacy.

Condor said...

Interesting; I agree. The article features a full-page side-bar on the CRO role -- but only a few paragraphs on the IRB's intended, and actual, role(s) -- and the gap between the two, in this case.

Thanks -- do stop back!