FDAers Query Chantix Study that Seeks Boxed Warning Removal

FDA reviewers say they identified concerns with the “ascertainment of the primary neuropsychiatric adverse event outcome that impacts interpretation” of an agency-required postmarketing trial which evaluated neuropsychiatric adverse effects in patients taking Pfizer’s Chantix (varenicline) and GlaxoSmithKline’s Zyban (bupropion). Pfizer has submitted a supplemental NDA that seeks removal of a Chantix boxed warning on serious neuropsychiatric adverse events NPS AEs, among other labeling changes. The agency’s concerns were outlined in a briefing document released in advance of a 9/14 advisory committee meeting being called to review the study results.

“In brief, the interview tools that were developed to optimally capture the neuropsychiatric adverse events of concern were not utilized to the extent intended to get a nuanced understanding of such adverse events,” the reviewers say. “In some cases, lack of information about the circumstances of events limited FDA’s ability to determine whether they were primary outcome events. Additionally, there was substantial variability among investigators in how the adverse event severity was coded and how the adverse event terms were applied, leading to variability in the number of neuropsychiatric adverse events included in the primary outcome. Finally, there was inconsistency in how suicidality cases were handled, with the Columbia Suicide Severity Rating Scale(C -SSRS) results not being reconciled with the adverse event reporting. All of these factors likely served to lower the overall number of primary outcome events, which may result in biasing towards a null finding.”