Today, AstraZeneca and the Seroquel debacle are on the front page of the Washington Post. I’m posting some of my favorite snippets but I encourage you to read the entire article linked above.
A Silenced Drug Study Creates An Uproar
By Shankar Vedantam
Washington Post Staff Writer
Wednesday, March 18, 2009; Page A01
The study would come to be called “cursed,” but it started out just as Study 15.
It was a long-term trial of the antipsychotic drug Seroquel. The common wisdom in psychiatric circles was that newer drugs were far better than older drugs, but Study 15’s results suggested otherwise.
As a result, newly unearthed documents show, Study 15 suffered the same fate as many industry-sponsored trials that yield data drugmakers don’t like: It got buried. It took eight years before a taxpayer-funded study rediscovered what Study 15 had found — and raised serious concerns about an entire new class of expensive drugs.
Study 15 was silenced in 1997, the same year Seroquel was approved by the Food and Drug Administration to treat schizophrenia. The drug went on to be prescribed to hundreds of thousands of patients around the world and has earned billions for London-based AstraZeneca International — including nearly $12 billion in the past three years.
The results of Study 15 were never published or shared with doctors, even as less rigorous studies that came up with positive results for Seroquel were published and used in marketing campaigns aimed at physicians and in television ads aimed at consumers. The results of Study 15 were provided only to the Food and Drug Administration — and the agency has strenuously maintained that it does not have the authority to place such studies in the public domain.
The saga of Study 15 has become a case study in how drug companies can control the publicly available research about their products, along with other practices that recently have prompted hand-wringing at universities and scientific journals, remonstrations by medical groups about conflicts of interest, and threats of exposure by trial lawyers and congressional watchdogs.
Details of Study 15 have emerged through lawsuits now playing out in courtrooms nationwide alleging that Seroquel caused weight gain, hyperglycemia and diabetes in thousands of patients. The Houston-based law firm Blizzard, McCarthy & Nabers, one of several that have filed about 9,210 lawsuits over Seroquel, publicized the documents, which show that the patients taking Seroquel in Study 15 gained an average of 11 pounds in a year — alarming company scientists and marketing executives. A Washington Post analysis found that about four out of five patients quit taking the drug in less than a year, raising pointed doubts about its effectiveness.
The average of 11 pounds seems pretty low, I assumed it would be more around 20 pounds in a year, but maybe that’s because I gained 40 pounds in two months on low dose of Seroquel!
An FDA report in 1997, moreover, said Study 15 did offer useful safety data. Mentioning few details, the FDA said the study showed that patients taking higher doses of the drug gained more weight.
In approving Seroquel, the agency said 23 percent of patients taking the drug in all studies available up to that point experienced significant weight increases, compared with 6 percent of control-group patients taking sugar pills. In 2006, FDA warned AstraZeneca against minimizing metabolic problems in its sales pitches.
In the years since, taxpayer-funded research has found that newer antipsychotic drugs such as Seroquel, which are 10 times as expensive, offer little advantage over older ones. The older drugs cause involuntary muscle movements known as tardive dyskinesia, and the newer ones have been linked to metabolic problems.
Far from dismissing Study 15, internal documents show that company officials were worried because 45 percent of the Seroquel patients had experienced what AstraZeneca physician Lisa Arvanitis termed “clinically significant” weight gain.
In an e-mail dated Aug. 13, 1997, Arvanitis reported that across all patient groups and treatment regimens, regardless of how numbers were crunched, patients taking Seroquel gained weight: “I’m not sure there is yet any type of competitive opportunity no matter how weak.”
In a separate note, company strategist Richard Lawrence praised AstraZeneca’s efforts to put a “positive spin” on “this cursed study” and said of Arvanitis: “Lisa has done a great ‘smoke and mirrors’ job!”
Eight years after Study 15 was buried, an expensive taxpayer-funded study pitted Seroquel and other new drugs against another older antipsychotic drug. The study found that most patients getting the new and supposedly safer drugs stopped taking them because of intolerable side effects. The study also found that the new drugs had few advantages. As with older drugs, the new medications had very high discontinuation rates. The results caused consternation among doctors, who had been kept in the dark about trials such as Study 15.
The federal study also reported the number of Seroquel patients who discontinued the drug within 18 months: 82 percent.
Jeffrey Lieberman, a Columbia University psychiatrist who led the federal study, said doctors missed clues in evaluating antipsychotics such as Seroquel. If a doctor had known about Study 15, he added, “it would raise your eyebrows.”