Wednesday, September 24, 2008

Chantix Lawsuits Piling Up; Dangers from Severe Financial Conflicts of Interests of Tobacco Control Researchers and Institutions Revealed

According to an article in Lawyers USA, there are now at least 200 lawsuits that have been filed by the families of plaintiffs who allege that their loved ones committed suicide as a result of taking the smoking cessation drug Chantix (varenicline) or by plaintiffs who attempted suicide after starting Chantix. These cases were filed by a single law firm, which is investigating another 1,200 cases. Another firm is investigating 175 similar cases.

The plaintiff's attorney was quoted in the article as describing the cases as follows: ""Tragically, almost without explanation, these people commit suicide, often without any prior diagnosis of family or individual history of depression, psychosis or any other type of psychological conditions."

According to the article: "On Feb. 1, 2008, the Food and Drug Administration issued an alert that 'serious neuropsychiatric symptoms have occurred in patients taking Chantix.' The symptoms include 'changes in behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicides.' 'It appears increasingly likely that there is an association between Chantix and serious neuropsychiatric symptoms,' the FDA stated. ..."

"A study in May 2008 by the Institute for Safe Medication Practices, a prescription drug watchdog group based near Philadelphia, reported that in the fourth quarter of 2007, varenicline accounted for 988 serious injuries reported to the FDA, more than any other single drug. ... The Federal Aviation Administration has banned pilots and air traffic controllers from using Chantix; the drug has also been banned for use by commercial drivers." ...

"On Feb. 1, 2008, Pfizer strengthened its Chantix labeling to include stronger warnings about neuropsychiatric symptoms. In May 2008, it revised the warning again, advising physicians to discontinue Chantix immediately if patients become agitated, depressed or suicidal."

Conflicts of Interest Among Tobacco Control Researchers and Institutions

As I have reported here, the national recommendation that Chantix and other smoking cessation drugs be used to treat nicotine dependence in every smoking patient, including the conclusion that Chantix is a superior treatment to the nicotine patch alone and the decision to recommend Chantix despite its reported potential adverse effects, was made by a national expert panel that had severe financial conflicts of interests.

The panel's chair - Dr. Michael C. Fiore - "reported that he served as an investigator on research studies at the University of Wisconsin (UW) that were supported wholly or in part by four pharmaceutical companies, and in 2005 received compensation from one pharmaceutical company. In addition, he reported that, in 1998, the UW appointed him to a named Chair, which was made possible by an unrestricted gift to the UW from GlaxoWellcome."

Importantly, Dr. Fiore has reported "that he has lectured and consulted for Pfizer and has served as an investigator on research studies at the University of Wisconsin (UW) that were supported by GlaxoSmithKline, Nabi, Pfizer, and sanofi-aventis." Pfizer is the company that markets Chantix.

In addition, eight of the panel members, including its senior scientist, reported financial conflicts of interest with Big Pharma. They have received, or are currently receiving, funding from pharmaceutical companies. Most of the involved companies stand to gain from the clinical practice guideline's recommendations, because these companies manufacture drugs recommended by the panel.

On top of all of this, an article in the American Journal of Preventive Medicine (2008; 35:158–176) reported that funding for the Clinical Practice Guideline project was provided by the Robert Wood Johnson Foundation - which is heavily underwritten by the pharmaceutical company Johnson & Johnson - and by the University of Wisconsin Center for Tobacco Research and Intervention, which has received massive funding from pharmaceutical companies.

While these conflicts of interest were disclosed in the report itself, the Center for Tobacco Research and Intervention appears to present the recommendations of the guideline without disclosing the conflicts of interest. The CTRI website lists the panel members, but fails to reveal their conflicts of interest with Big Pharma. Web pages that provide further detail about some of the panel members, including its chair, also fail to disclose these severe conflicts of interest. The CTRI summary of Chantix fails to disclose the Center's history of research funding from Pfizer and also fails to cite the FDA's statement that "It appears increasingly likely that there is an association between Chantix and serious neuropsychiatric symptoms."

Not only is the CTRI website failing to readily disclose these financial conflicts of interest, but it appears to me that the expert panel's chair failed to disclose his recent financial conflicts of interest on the primary disclosure form. Since that form asks for disclosure of "all ... affiliations with or financial involvement ... with any organization or entity with a financial interest in or financial conflict with guideline matter or materials" and it specifically refers to "the past 5 years," it seems that the panel chair's admitted "outside consulting work on an annual basis [that] has ranged between about $10,000 and $30,000 or $40,000 per year" should have been disclosed. Instead, the panel chair stated that he does not currently accept honoraria or consulting fees from pharmaceutical companies, which misleads the public by implying that he has not accepted honoraria or consulting fees for the past 5 years.

Since his testimony acknowledging annual consulting fees from pharmaceutical companies was in 2005, it appears, at very least, that the panel chair had a conflict of interest to disclose for the years 2001-2005. Since the primary disclosure form was signed in 2006, it should have reported any consulting fees received from 2002-2006.

The conflicts of interest in tobacco control go beyond individual researchers. The institution itself has been conflicted by virtue of its sponsorship by Big Pharma. For example, the 2009 World Conference on Tobacco or Health is being sponsored by GlaxoSmithKline and Pfizer. The 2007 National Tobacco Control Conference was sponsored by Pfizer.

The Rest of the Story

One of the most basic ethical principles in terms of conflicts of interest in medicine is that individuals with financial conflicts of interest should not participate in supposedly independent scientific reviews that are intended to produce national recommendations for clinical practice.

This basic ethical principle was violated by those who participated on the expert panel and took part in producing national recommendations for the use or non-use of smoking cessation drugs despite their financial conflicts of interest with pharmaceutical companies that manufacture or market those very products.

Not only was the participation of these individuals on the expert panel inappropriate and unethical, but a major component of the institution of tobacco control - namely, its national and international conferences - have prostituted themselves by accepting sponsorship from pharmaceutical companies which have a direct interest in the scientific and policy research and issues being discussed at these conferences.

While I hate to admit it, I believe that these extensive conflicts of interest may have contributed to the magnitude of the Chantix problem because in the absence of such conflicts, I do not believe that these panels and conferences would likely have produced a recommendation that all physicians use pharmaceuticals to treat nicotine dependence and that Chantix is to be recommended despite its reported side effects.

The Chantix experience serves as a poignant (and tragic) reminder of exactly why it is that financial conflicts of interest are not to be tolerated in the formation of national clinical treatment policy. The presence of financial conflicts of interest produces a bias (even if subconscious) that is unacceptable when recommendations are being made that affect people's lives (i.e., clinical practice).

The bias in the Clinical Practice Guideline panel's analysis is apparent when one considers the research documenting that the overwhelming majority of successful quit attempts are unplanned. The planning of quit attempts by patients with medication provided by their physicians is, on a population basis, one of the least effective methods of smoking cessation.
Planned quit attempts are actually less successful than attempts that are unplanned. National smoking cessation policy and treatment of patients should therefore be based on efforts to motivate patients sufficiently to quit cold turkey, rather than to plan quit attempts for them.

The bias created by financial conflicts of interest with Big Pharma in tobacco control continues and can be seen in numerous research articles. For example, in response to the article documenting that unplanned quit attempts are the most successful, a researcher from the University of Vermont challenges the conclusions of that study. What is not disclosed is the fact that in 2006, the same researcher "accepted honoraria, fees or travel expenses from Academy for Educational Development, Atrium Healthcare, Cambridge Hospital, Celtic Pharmaceuticals/Xenova, Concepts in Medicine, Cowen and Companies, Cygnus, Edelman Bioscience, Exchange Supplies Ltd., Fagerstrom Consulting, Free and Clear, Health Learning Systems, Healthwise, JSR, Insyght, LEK Consulting, Maine Medical Center, Nabi Pharmaceuticals, New York Association of Substance Abuse Providers, Nabi Biopharmaceuticals, National Institutes on Health; Pfizer/U.S., Pfizer Canada, Pinney Associates, Sanofi-Aventis, Shire Health London, Temple University of Health Sciences, University of Wisconsin and ZS Associates."

What at first glance might appear to be an unbiased assessment of the state of the research turns out instead to be written by someone who has received money from a large number of pharmaceutical companies, including several that have a direct financial stake in consumers making planned rather than unplanned quit attempts.

The scientific integrity of the tobacco control movement has been tarnished by its lucrative financial relationship with Big Pharma. But what's worse, people's lives may actually be at stake in this game.

There is now strong evidence that the link between Chantix and suicidal behavior is real. When the FDA itself concludes that "It appears increasingly likely that there is an association between Chantix and serious neuropsychiatric symptoms" and forces Pfizer to put a warning on the drug label cautioning about these effects and when the organizations regulating pilots and commercial drivers have banned this medication, you know that you have a potentially serious problem at hand.

That tobacco control practitioners, organizations, and panels continue to recommend the use of this medication despite the apparent problem is questionable. That their decision to continue to recommend the use of this medication is biased on the basis of severe financial conflicts of interest with pharmaceutical companies in general and Pfizer in particular is inexcusable.

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