- Pfizer seeks to cut black box warning on side effects
- Report says researchers inadequately captured adverse events
Pfizer Inc.’s study of neuropsychiatric effects of its smoking cessation drug Chantix may not have adequately captured the number of adverse events, potentially biasing the research in favor of the drug, U.S. regulators said.
The clinical trial, which the U.S. Food and Drug Administration requested after a high rate of suicidal thoughts and suicides were linked to Chantix, also included GlaxoSmithKline Plc’s Zyban, another drug used to help smokers quit. The FDA is weighing whether Pfizer can cut the boxed warning on Chantix regarding potential changes in behavior, depressed mood and suicidal thoughts.
In a report released Monday, the FDA staff raised questions about a lack of consistency in how the company study recorded neuropsychiatric events. The agency posted the report ahead of a meeting of outside experts scheduled for Wednesday in Silver Spring, Maryland to advise the FDA on possible changes to the boxed warnings on Chantix and Zyban. Chantix brought in $671 million in sales for New York-based Pfizer last year, according to data compiled by Bloomberg.
“The trial was designed in a well-intentioned attempt to capture somewhat ill-defined and complex neuropsychiatric phenomena,” FDA staff said in the report. “However, many problems in the implementation were apparent upon review of the collected data.”
The study was difficult to design, partly because it was trying to capture 16 different categories of neuropsychiatric side effects, which could be further broken down into 261 separate preferred medical terms, said Larry Samuels, Pfizer’s global medical development lead for Chantix. For example, “agitation” was one of the 16 side effects that could be defined as “restlessness,” “disturbance in attention,” or a condition called hyperkinesia that can manifest as muscle spasms, Samuels said.
The study that the FDA staff examined found that among patients who had already been diagnosed with a psychiatric disorder, 6.5 percent of patients on Chantix and 6.7 percent of those on Zyban experienced a neuropsychiatric side effect, compared to 4.9 percent taking a placebo. Of patients who had not been diagnosed with a psychiatric disorder, 1.3 percent taking Chantix experienced a neuropsychiatric side effect compared to 2.2 percent on Zyban and 2.4 percent taking a placebo.
FDA staff said the researchers conducting the trial didn’t record side effects with enough description to provide insight into the impact on patients and inconsistently assessed the severity of the side effects on patients’ lives. Researchers also downgraded the harshness of some side effects, for example coding patient-reported “anger” as “irritability,” the report said.
The report also raised the question of whether researchers who had received fees in excess of $25,000 for speaking on behalf of Chantix may have underreported side effects in the trial. Overall, 32 trial sites where researchers received $25,000 or more observed a lower percentage of neuropsychiatric events than researchers who received less than that sum, the report said. The difference could be attributable to chance due to the small sample size, according to the report.
James Rusnak, chief development officer for Pfizer’s cardiovascular metabolic unit, said that the study was blinded, meaning that doctors who helped conduct it didn’t know whether patients were getting a drug or a placebo. Any doctors who might have downplayed side effects would have done so across the board and thus wouldn’t affect the final outcome, he said.