Whether or not Chantix is actually related to any of these adverse events does not, in the end, matter all that much for the purposes of removing the label, just like it doesn’t matter if Tesla’s autopilot increases or decreases road fatalities. What matters is the FDA’s reputation. Someone somewhere in the future who happens to be on Chantix will commit suicide at some point. People unfortunately commit suicide sometimes. The phenomenon cannot be stopped entirely, and at least one of these people will be on Chantix. It will make headlines, and the FDA will have to defend itself without the use of complicated statistical graphs because nobody wants to see those.
It’s not like the FDA can point to a graph showing less people dying of smoking, attribute that to removing the boxed warning, and pat itself in the back in defense. The FDA will not be blamed for smoking deaths. It will be blamed for Chantix deaths if and when they happen, regardless of whether Chantix had anything to do with the death or not. That’s just how it is.
The Data Collection Problems
As for the actual problems with the data collection in this post-marketing trial, here are some excerpts from the FDA’s 500 plus page briefing document linked to above.
AN EXAMPLE OF ONE OF THE ORIGINAL NARRATIVES…DEMONSTRAT[ES] THE INADEQUACY OF THE ORIGINAL NARRATIVES IN PROVIDING INFORMATION NEEDED TO ASSESS EVENTS OF POTENTIAL INTEREST. IN THIS CASE, AN EVENT CODED TO THE TERM “SKULL FRACTURE” IS REPORTED IN THE NARRATIVE WITHOUT PROVIDING ANY CONTEXT FOR HOW THE PATIENT CAME TO SUSTAIN THE SKULL FRACTURE. (SUBSEQUENT INFORMATION REQUESTS REVEALED THE INJURY WAS INFLICTED BY HER BOYFRIEND, ALSO A TRIAL PARTICIPANT, A POTENTIALLY RELEVANT PIECE OF INFORMATION.)
Obviously, if the boyfriend hit the girlfriend while on Chantix, that could be termed a severe neuropsychiatric adverse event related to Chantix. It was characterized as unrelated, however. Maybe it was unrelated, but that’s beside the point.
Here’s more:
THE INSTRUCTIONS PROVIDED TO THE INVESTIGATORS FOR ASSESSMENT OF RELATEDNESS DO NOT APPEAR TO HAVE RESULTED IN A FULL CAPTURE OF POTENTIALLY RELATED EVENTS. EXAMPLES INCLUDE EMOTIONAL SYMPTOMS FREQUENTLY ATTRIBUTED TO “STRESS” OR TO SPECIFIC SOCIAL SITUATIONS, WORSENING SYMPTOMS OF A PREEXISTING PSYCHIATRIC ILLNESS ALMOST ALWAYS CODED AS “NOT RELATED TO STUDY DRUG,” AND ASSESSMENTS SUCH AS “THE INVESTIGATOR CONSIDERED THE SAE (SEVERE ADVERSE EVENT) OF FOOT FRACTURE TO BE NOT RELATED TO THE STUDY DRUG BUT DUE TO FRACTURED RIGHT HEEL” WERE PROVIDED. FOR THIS REASON, INVESTIGATOR ASSESSMENT OF RELATEDNESS HAS BEEN ALTOGETHER DISREGARDED IN THIS REVIEW.
One more:
THESE TYPES OF CASES FURTHER UNDERSCORED THE CONCERN THAT THE SEVERITY CRITERION FOR INCLUSION IN THE NPS ENDPOINT MAY HAVE BEEN INAPPROPRIATE TO CAPTURE EVENTS OF CONCERN. THERE MAY HAVE BEEN A DISCONNECT BETWEEN WHAT SUBJECTS WITH NO PREVIOUS PSYCHIATRIC ISSUES CONSIDER SEVERE (EVEN MISSING A DAY OF WORK) AND WHAT A HEALTH CARE PROVIDER ACCUSTOMED TO CARING FOR SERIOUSLY MENTALLY ILL PATIENTS WOULD REGARD AS “SEVERE” (POSSIBLY ONLY AN EVENT REQUIRING HOSPITALIZATION). HOWEVER, EVEN HOSPITALIZATION MAY NOT HAVE BEEN ASSESSED AS “SEVERE” BY SOME INVESTIGATORS; AN ADDITIONAL CASE WAS IDENTIFIED AMONG THE SAE NARRATIVES, WHERE A SUBJECT APPEARS TO HAVE BEEN HOSPITALIZED FOR DEPRESSION AFTER ABOUT 3 WEEKS OF TREATMENT WITH BUPROPION, BUT THE EVENT WAS ASSESSED AS “MILD” BY THE INVESTIGATOR. (“ON , THE SUBJECT EXPERIENCED DEPRESSION WHICH WAS CONSIDERED MILD IN INTENSITY AND SERIOUS DUE TO HOSPITALIZATION OR PROLONGED HOSPITALIZATION BY THE INVESTIGATOR.”
