Please don’t operate a missile battery while reading this article
DRUG BUST by Alan Cassels
• The people’s briefing note on prescription drugs
In mid October, the US Food and Drug Administration convened a special meeting to look at whether or not varenicline, the controversial drug to stop smoking – called Champix in Canada and Chantix in the US – needed to continue to carry a black box warning indicating the drug could cause psychiatric side effects such as suicidal behaviour and aggression/violence.
Just to remind you, a “black box” warning on a drug is the equivalent of a cruise missile shot across the bow. It is the most serious warning found on a drug’s label, placed there because a grave safety issue has been identified. Almost every drug removed from the market has been preceded by a black box. In the case of Chantix – I’ll use the US name in this article – both the US FDA and Health Canada issued warnings in 2008 after it had been on the market about a year; the black box was applied in July 2009.
Both agencies had warned they had received adverse event reports linked to neuropsychiatric symptoms including depression, agitation, aggression, hostility and suicidal thoughts. There have also been reports related to insomnia, dizziness, loss of consciousness and seizures.
Officially, the FDA panel meeting in October was held at the request of Pfizer, who wanted the committee of drug safety and pharmacology experts to consider its request to remove Chantix’s black box warning.
In the hearing, many paid experts took Pfizer’s side, extolling the results of a large body of clinical trials and observational studies which couldn’t find these alleged adverse effects. On the other side was a consortium of five groups who presented a petition asking that the warning not only be kept, but strengthened. See www.ismp.org (Institute for Safe Medication Practices) for the Citizen Petition to Strengthen Chantix Warnings. The remarkable public service performed by these consumer advocates, in this case led by Thomas Moore of ISMP, is Nobel Prize-worthy. Based on the best and most objective reading of the accumulated adverse events reports, they asserted the drug needed a stronger black box, one which included other known effects such as the “risk of blackouts, convulsions and impaired vision.” They added that anyone working as a pilot, air traffic controller, policeman, fireman or as crew on a missile battery should avoid the drug. That makes sense to me, given that with aggressive impulses linked to the drug, mixing it with military hardware could be a deadly combination.
What makes this hearing so interesting are the voices of people who weren’t able to speak. I’m thinking of the 2,500 or so victims of Chantix who, according to Kim Witczak, were “silenced in their settlement agreements with Pfizer.” Kim knows what she is talking about. She is one of the most outspoken advocates for drug safety in the US, a role which she was thrust into after the death of her husband Woody, who committed suicide while taking the antidepressant Zoloft.
Kim has testified at a number of hearings concerning the safety of antidepressants, including hearings which led to an FDA-mandated black box warning which said SSRI antidepressants could cause children and youth to become suicidal. She was present at the hearings on Chantix, telling me in an email that she was “proud to represent the voices of families who live every day with the consequences of a failed drug safety system.”
The major difference between the hearings on SSRI antidepressants and the one on Chantix was that the SSRI hearings heard testimony from ‘real’ people affected by the drugs. At the Chantix meeting, no lawyers were present to testify against Chantix because Pfizer settled $300 million in lawsuits with 2,500 or so Chantix victims. We all know what happens when lawsuits settle: the documents, expert depositions and testimony are all sealed. Which is to say, a huge amount of information from real people potentially hurt by these drugs stays buried.
For me, the real question is how harmful is this drug? That’s a difficult question to answer because both the observational studies and the randomized trials might be unreliable. It’s quite possible that clever and selective data mining in observational trials and the biases inherent in randomized trials with limited numbers of patients and short follow-up could gloss over Chantix’s potential adverse effects. But what we do have are reports. Real world reports made by patients who were exposed to the drug and the doctors and pharmacists who saw the effects of the drug.
Prior to the FDA hearing, ISMP’s safety publication QuarterWatch reported Chantix accounted for more consumer and health professional reports of suicidal and homicidal thoughts in the US than any other prescription drug over nearly six years.
To bring this close to home, the province of BC started paying for Chantix in September 2011 as part of a province-wide smoking-cessation program. This might be a sound policy if the drugs we covered actually helped people quit and didn’t make them depressed or psychotic or cause them to have suicidal thoughts. But we know practically nothing about the effect of the policy. Thanks to a spate of Ministry of Health firings in September 2012, the evaluation of our Chantix policy was guillotined and never restarted. It is both cruel and ironic that Rod MacIsaac, the UVic student who was working on that research project, committed suicide after he was inexplicably canned.
With numbers supplied by the BC Ministry of Health, between September 2011 and July 2014, BC Pharmacare paid for 230,400 scripts for Chantix. It’s impossible to precisely determine exactly how many different people took the drug – because the length of scripts varies – but we can calculate conservatively that about 92,000 patients would have been prescribed a Ministry funded Chantix script. It’s important to add that, in May 2013, Health Canada took the step of making Chantix a second line drug. That is, it is not recommended as the first thing to be prescribed. Visit healthycanadians.gc.ca and search Champix and Zyban revision.
What I conclude from this is that, at the very least, hundreds of people in BC were probably made depressed by ingesting this drug while costing the taxpayer about $6.4 million – about $187,000 per month. How many BC smokers start to think about suicide (or complete it), become aggressive or violent, develop psychosis or have wildly troubling nightmares can only be a guess.
Buttressing the company’s arguments at the FDA hearings were truckloads of data, including four observational studies and 18 Pfizer-sponsored randomized trials all produced to demonstrate that the rates of neuropsychiatric events related to Chantix were no greater than placebo or a comparator drug. What I read into this is that if you want more drug industry-funded research – read my October column on data fracking to understand what I’m talking about – this is what we should expect: marketing not science.
Thomas Moore, who attended the hearing, showed me the “Alice in Wonderland” graphic he used as part of his presentation. He wrote that this helped “illustrate the odd spectacle of Pfizer paying $300 million to 2,500 Chantix victims and then trying to convince a panel of experts that these same potentially catastrophic adverse effects don’t exist.” At the end of the day, of the 18 experts deciding the outcome, 11 voted to retain the black box as is; six voted to strengthen it and only one delegate voted to remove the warning. The black box stays.
There are three lessons we need to remember:
1. Black box warnings are strong indicators that drugs designed to help people can often hurt them in unexpected ways.
2. Evaluating the effects of drugs in the real world is a public enterprise that should answer vital safety and effectiveness questions of interest to the public, not questions that support a company’s marketing plan.
3. The dead can’t speak and neither can those who have been stifled by lawsuits so we can only wonder what secrets they hold. The firings at the Ministry and the settled US Chantix lawsuits produced the same outcome: people who can’t share their stories.
Taking a drug you’re worried about? Just like Chantix/Champix, your drug could also have much bigger problems than those selling the drugs want you to believe.
Alan Cassels is a drug policy researcher in Victoria. You can follow him on twitter @AKECassels or at www.alancassels.com