Thank you for the opportunity to speak today. I’m Dr. Diana Zuckerman, president of the National Center for Health Research. I’m trained in psychiatric epidemiology at Yale Medical School, I’m a former faculty member at Vassar and Yale and a researcher at Harvard , and I’ve taught Research Methods courses, and those are the perspectives I bring with me today. Our Center has no financial ties to Chantix or its competitors or to Chantix lawsuits.
We all know that smoking kills thousands of Americans and it is very difficult to quit. That’s why we believe that Chantix should be available as an option for those who can use it safely.
At the same time, patients and their physicians need a clear black box warning for Chantix so they know to stop taking it when necessary
The challenge today is: which data should the FDA believe? Mark Twain once said there are 3 kinds of lies: Lies, damn lies, and statistics. I am a scientist and I believe in statistics, but I also know they can be easily manipulated to support a particular point of view.
Your task today is to make sense of conflicting data and decide which to believe. They include:
- Observation Studies based on hospital records
- Adverse Reaction Reports from physicians
- Reports from Patients
Meta Analysis is a valuable tool but its accuracy depends on the quality of each study and whether they fit together. Meta analysis results can be useful or inaccurate depending on which studies you include and exclude. No justification was given of why most studies on Chantix were excluded and only 5 were included in the meta analysis, including one study of schizophrenics, one study of depressed patients, and 3 studies of mentally healthy patients. It is important to study schizophrenics and depressed patients, but those data should not be mixed together with 3 studies that exclude such patients. No justification was given for that decision, but you heard from the FDA that most psychiatric events were in those two groups of mentally ill patients, clearly biasing the results.
To consider the studies showing no association between Chantix and psychiatric side effects, it is important to understand what happens to people with acute psychiatric events related to medication. As the FDA speakers pointed out, most do not end up in hospitals or the ER. Many of these psychiatric side effects are not reported in medical records. Because psychiatric commitment laws depend on acts of violence, not threats of violence, many people with dramatic psychiatric symptoms end up in jail, not in hospitals. In fact, some studies show that there are more mentally ill individuals in the criminal justice system than in psychiatric facilities — certainly those who suddenly behave violently toward others are likely to be put in jail, not in a hospital or ER.
There’s another, more positive reason why these psychiatric side effects might not be measured in a large study. Fortunately, many stop quickly because patients or their doctors realize they should stop taking the drug, thanks to the black box.
For all these reasons, most of the studies that Pfizer is relying on are fatally flawed.
How can we make sense of the studies showing no impact in light of the thousands of reports of psychiatric side effects?
- The studies cited did not evaluate all psychiatric side effects, they focused on depression and suicidal thoughts and behaviors
- Those studies did not interview patients – a shortcoming of many large databases
- They relied on hospital records, which research shows missed 82% of adverse psychiatric events
- Some also relied on ER or medical records – which is better than hospital records, but will still miss a lot of data
What about studies showing a significant increase in psychiatric events? We all know that adverse reaction reports are the tip of the iceberg – it’s a voluntary system of reporting. Compared to medical records, they can have a richness of information. And while they are far from perfect, the sheer volume of thousands of reports – many more than for other drugs – is very compelling.
I’ve spoken with some patients who took Chantix, and their reactions are distinctly different from many other drug side effects, and don’t fit neatly into the categories that most of the Pfizer studies evaluated. For example, I spoke to a man who was so besieged with uncontrollable thoughts that he locked his door at work and wouldn’t let anyone in. His thoughts were so terrible that he just couldn’t deal with anyone. That psychiatric reaction would be unlikely to fit into any of the studies. Or a man who was so frightened that he hid in the corner of his bedroom under a blanket, trying to escape the uncontrollable thoughts by being as small as possible – trying to feel safe. What study would accurate evaluate that?
If this Advisory Committee ignores the compelling psychiatric adverse reactions that have been reported, it would discredit thousands of doctors who made thousands of reports. It would also discredit thousands of patients who reported them. And it would send the message to the FDA to stop their Adverse Event Reporting systems, because what is the point of having such systems in place if you ignore thousand of such reports?
We need better studies, and I hope the post-market study underway will be better. Based on previous research, we know that such studies must include very large numbers of patients, and must follow patients for a long enough time – not all reactions are within 30 days. And, the studies must include patients’ reports of their side effects
- The studies Pfizer is citing are fatally flawed because they omit most psychiatric adverse reactions
- Deleting the black box would send the message that thousands of doctors’ reports don’t count, including suicides and homicides
We strongly urge you to urge the FDA to keep the black box warning to protect patients and that you strengthen rather than weaken that boxed warning. And, since the meta analyses are fatally flawed, as I and others have pointed out, the FDA should delete the misleading meta-analyses info from the Chantix label.