The U.S. Food and Drug Administration (FDA) is questioning whether or not Pfizer’s study of neuropsychiatric effects of Chantix, the smoking cessation drug, accurately reflects the risks. Pfizer conducted the clinical trial upon request from the FDA, following a high rate of suicidal thoughts linked to Chantix. The study also included GlaxoSmithKline Plc’s Zyban, another smoking cessation drug.
The FDA is reviewing the findings to determine whether or not the “black box” warning for suicidal thoughts, changes in behavior and depressed mood can be removed. The agency released a report questioning the consistency of how neuropsychiatric side effects were recorded. “The trial was designed in a well-intentioned attempt to capture somewhat ill-defined and complex neuropsychiatric phenomena,” the FDA report states. “However, many problems in the implementation were apparent upon review of the collected data.”
According to Bloomberg, Chantix sales garnered $671 million last year.
Among patients who have been previously diagnosed with a psychiatric disorder, a neuropsychiatric side effect was reported in 6.5 percent of patients on Chantix and 6.7 percent of patients on Zyban, compared to 4.9 percent taking a placebo. Among patients who have not been diagnosed with a psychiatric disorder, a neuropsychiatric side effect was reported in 1.3 percent of patients taking Chantix compared to 2.2 percent on Zyban and 2.4 percent taking a placebo.
The FDA report said the neuropsychiatric side effects in the study were not recorded with enough detail to reflect how they affected patients. The severity of these side effects was assessed inconsistently, staff said. Additionally, the report said that in some cases researchers downgraded side effects such as coding reports of “anger” as “irritability”.
FDA staff also scrutinized whether researchers had a conflict of interest, noting that fewer side effects were reported among those who received fees in excess of $25,000 compared to those who received fewer or no payments. The report noted that the difference may be due to chance, considering the small sample size.
In response to this, chief development officer for Pfizer’s cardiovascular and metabolic unit James Rusnak said the study was blinded. In other words, researchers could not tell who was receiving a drug or a placebo. “The idea of blinded study is to remove bias,” he said to Bloomberg. “Even if you have payments and even if those payments bias the investigators in favor of your drug, the investigator has no idea which is your drug. They can only guess.”
Diana Zuckerman, president of the National Center for Health Research said the report indicates that the FDA doubts “integrity of the data.” She told Bloomberg, “FDA clearly seems to be saying we can’t trust the results of this study — the way it was coded, the way it was analyzed, and by the way there’s conflicts of interest,” The National Center for Health Research is part of a coalition of consumer groups who want the warning to stay.