Comments to FDA against removal of the black box warning for Chantix

Thank you for the opportunity to speak today. My name is Dr. Stephanie Fox-Rawlings and I am speaking on behalf of many members of the Patient, Consumer, and Public Health Coalition. The Coalition includes nonprofit organizations representing millions of patients, consumers, researchers, and doctors united to ensure that medical treatments are safe and effective.  The coalition does not have paid staff and does not accept funding from any outside sources, so I have no conflicts of interest.

Pfizer is once again asking the FDA to remove the black box warning that Chantix is associated with serious adverse events such as depression, hostility, agitation, suicidal thoughts, attempts, and completions. They want to replace it with the statement that these are associated with quitting smoking. They also want to remove the warning that there may be an increased risk for patients with a psychiatric illness. GlaxoSmithKline wants to remove REMs requirements for Zyban. They based these changes on one large, poorly executed clinical study.

It is important to point out that these black box warnings were initiated because of the enormous number of extremely serious psychiatric adverse events, including suicide and aggressive behaviors, associated with these smoking cessation products.  Research has also confirmed that some patients have extreme psychiatric responses that can be deadly to themselves and to others.  The purpose of these warnings is to let patients know that if they seem to be having uncontrollable feelings when on these drugs, that there is a good chance that getting off the drugs will solve the problem almost immediately.

Pfizer’s study concludes that Chantix does not have these risks but the FDA reviewers have clearly shown that there are extensive problems with how the data were collected and analyzed:

#1: The study measured psychiatric problems with something called the Neuropsychiatric Adverse Event Inventory (NAEI).  This is not a validated test so it was only supposed to be used to start the conversation about psychiatric symptoms.  Instead, it was used as a unvalidated checklist, which contributed to inaccurate data.  For example, it did not identify cases of suicidal behaviors that were identified by validated scales.

#2.  When patients reported psychiatric problems, those problems were not coded consistently.  The FDA pointed out that the staff doing interviews and coding were not always trained mental health professionals and didn’t seem to understand some of the categories they were coding.  Even worse, their very subjective measures of severity were sometimes completely incorrect: such as a patient who became severely depressed being coded as having a mild problem from taking Chantix.

#3: Since 70% had tried to quit smoking previously using one of these drugs, the study was biased toward people that had previously tolerated the drug.  This would drastically underestimate the percentage having serious adverse reactions.   In addition, anyone with suicidal thoughts or behaviors in the past year or anyone with self-injuring behaviors were excluded. While these patients should not be treated with a drug that could make these worse, this could again bias the results to make the drugs seem safer than they really were.

In summary, patients deserve access to smoking cessation treatments, but they also deserve warnings about the risks.  There remains considerable credible evidence that some patients are severely harmed by Chantix and Zyban, and those patients’ lives depend on warnings about the risks, so they will recognize that sudden suicidal, paranoid, or violent thoughts are side effects of the drugs.

Thank you for your time and consideration of our views.