Monday, June 11, 2012

Simpson's Paradox and Seroquel

The paradox

Say a company tests two treatments for an illness. In trial No. 1, treatment A cures 20% of its cases (40 out of 200) and treatment B cures 15% of its cases (30 out of 200). In trial No. 2, treatment A cures 85% of its cases (85 out of 100) and treatment B cures 75% of its cases (300 out of 400)....

So, in two trials, treatment A scored 20% and 85%. Also in two trials, treatment B scored only 15% and 75%. No matter how many people were in those trials, treatment A (at 20% and 85%) is surely better than treatment B (at 15% and 75%), right?

Wrong! Treatment B performed better. It cured 330 (300+30) out of the 600 cases.

(200+400) in which it was tried--a success rate of 55%...By contrast, treatment A cured 125 (40+85) out of the 300 cases (200+100) in which it was tried, a success rate of only about 42%.

The Seroquel Connection

Are Veterans Being Given Deadly Cocktails to Treat PTSD? Part 4

Seroquel’s ability to cause cardiac arrest and sudden death is well-known. A search of the U.S. National Library of Medicine database yields 20 articles linking “Seroquel” and “sudden death,” 24 linking “Seroquel” and “QT prolongation” (a heart disturbance that can lead to death), 55 linking “Seroquel” and “toxicity,” and others linking Seroquel with the terms “cardiac arrest” and “death.”

A 2005 article in the Journal of Forensic Sciences says Seroquel was detected in 13 postmortem cases and the cause of death in three and states, “little information exists regarding therapeutic, toxic, and lethal concentrations.”

A 2003 article in CNS Drugs reports: “Some patients have died while taking therapeutic doses” of atypical antipsychotics like Seroquel and that “toxicity may be increased by coingestion of other agents.”

“The second-generation antipsychotics were termed ‘atypical’ based on misconceptions of enhanced safety and efficacy,” Dr. Grace Jackson, a former Navy and Veterans Administration psychiatrist and author of “Drug-Induced Dementia and Rethinking Psychiatric Drugs,” said in an interview.

“In 2002 and 2003, according to a VA study published in 2007, 20 to 30 percent of demented veterans died within the first 12 months of beginning treatment with an antipsychotic,” says Jackson.

“When you combine antipsychotics with antidepressants, benzodiazepines, and anti-epileptics—especially in Iraq/Afghanistan veterans who have likely sustained traumatic brain injuries—you have potential lethality from sleep apnea, endocrine anomalies, and opioid intoxication.”

Seroquel’s record of causing sudden cardiac death was even on the docket at last year’s FDA hearings, which Stan and Shirley White and Janette Layne attended.

According to Dr. Wayne Ray, who testified before the FDA’s Psychopharmacologic Drugs Advisory Committee, one study involving 93,300 users of antipsychotic drugs, half of whom were on atypical antipsychotics, showed that such users were at double the risk of a “sudden, fatal, pulseless condition, or collapse … consistent with a ventricular tachyarrhythmia occurring in the absence of a known, non-cardiac cause.”

Dr. Ray, professor of preventive medicine at Vanderbilt University School of Medicine, published the findings in an article titled “Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death,” in the New England Journal of Medicine last year.

When committee members asked Dr. Ray how AstraZeneca’s own studies, presented earlier at the hearings, could show no risk—like the White-Layne VA Inspector General report—he said the drug company data was skewed by “Simpson’s paradox,” the same statistical manipulations that made Vioxx look safe.

No comments: