Media Duped by Flawed Advocacy-Funded Study Championing Champix (aka Chantix in USA) from Pharmabuse's blog

Everyone can agree that smoking cessation is a good thing. But the admirable goal of getting more people to quit smoking does not justify biased research which potentially puts more lives in danger.

The media is asleep at the wheel again, running headlines about a recently published U.K. study, acquitting the smoking cessation drug varenicline -- marketed in the U.S. as Chantix and in the U.K. as Champix -- of earlier reports of the drug causing serious neuropsychiatric adverse events, such as changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. [The foregoing reported adverse events are verbatim from the drug's FDA-approved warning label.]

The FDA's concerns about Chantix were so serious that they prompted the agency to require the drug's manufacturer Pfizer to conduct and develop a Risk Evaluation and Mitigation Strategy (REMS), a rare step that has only been taken in a handful of cases.

Then, conveniently, along comes a study that absolves the drug once and for all of suspicion, clearing the way for millions more patients to be prescribed what cancer advocacy groups believe is a life-saving drug.  Whew, we can all breathe a collective sigh of relief, and wipe the worry from our brows, right?

Not so fast.

One of the more troubling aspects of the study is that it was funded in part by Cancer Research UK, an advocacy group that makes no bones about developing policy "to inform Government decisions related to cancer and research and communicates our views to key decision makers."  We should be wary of advocacy groups funding research that supports the biased points they're trying to make. Not to pick on any group in particular, but would anyone take seriously a study funded by Scientology that concluded psych drugs are bad?  Absolutely not.  Which is probably why the Church of Scientology, reported to have deep pockets, has not funded scientific research to that effect.  Yet there seems to be a double standard when it comes to advocacy groups that many deem to be worthy causes, whereby their sponsored research is taken at face value.       

Research shows that pharma-sponsored studies typically return results favorable to the sponsor.  Why would advocacy group-funded research be any different?

Then there is the thorny issue of trying to unravel the funding sources of Cancer Research UK, which does not acknowledge receiving corporate donations in its annual report.  The report acknowledges receiving £122 million in funding last year from direct giving, which the advocacy group says includes gifts from over a million people, further noting that "[m]ore than nine out of 10 of the donations we receive are less than £10."  It is understandable why the advocacy group would want to stress the quantity of donations rather than the identity of the larger donors, but doing so doesn't bring us any closer to understanding from whence they got their funding.  After all, if 900,000 [nine out of ten] people gave £9 [less than £10], then the group has only accounted for £8.1 million of the £122 million in direct giving it received last year.

The important issue of the group's funding sources and potential direct financial conflicts of interest with the pharmaceutical industry aside, there is no doubt that Pfizer's research objectives conveniently dovetail with Cancer Research UK's, as is evident by the drug makers web site proudly entitled "Working in Partnership with Cancer Research UK."  The term "evidence-based research" is as ubiquitous in the pharmaceutical world as "cloud services" is in the IT space.  But no amount of throwaway clichés can overcome the fact that sponsored so-called evidenced-based research is still biased.

Then there's the issue of where the study was published -- the Lancet, where two-thirds to three-quarters of the published trials are pharma-sponsored.  Reprints of pharma-sponsored and pharma-favorable trials are a vital funding source for medical journals in general. 

But wait, there's more.  Two of the study's authors, Daniel Kotz and Robert West, have received funding for a smoking cessation trial and other research directly from Pfizer, the manufacturer of the drug being studied, scratch that, being heralded as free of negative effects.  According to the study's credits, Daniel Kotz "
originally conceived the study and drafted its funding application, and drafted the report."
 
How do sponsored studies consistently achieve results favorable to their sponsors?  Through deliberately flawed (ie. rigged) study design.

Take for instance the laundry list of neuropsychiatric adverse events that the FDA requires Pfizer to include on the drug's label.  Cancer Research UK's hand-picked doctors (it should be noted that only one of the study's six listed co-authors is actually a medical doctor) cherry-picked depression and self-harm as the only two neuropsychiatric adverse events to study -- to the exclusion of mania,
psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide.

Incredibly, whereas completed suicide is a reported adverse event, the study's designers "
censored patients who were lost to follow-up because they left the practice or died."  For all we know, some of the patients who died during the study may have committed suicide.

Likewise, of the 51,450 patients taking varenicline the study's authors identified, 1,287 or 2.5% were excluded from the study.  For all we know, the excluded patients using varenicline may have experienced neuropsychiatric events (and cardivascular, which the study also examined).

The reason given for the exclusion?  No match with patients using Nictotine Replacement Therapy (NRT).  The study compared patients taking varenicline to NRT and bupropion (marketed as Zyban and Wellbutrin).  The study identified 106,759 patients using NRT.  Even though the NRT group's sample size was more than double the size of the varenicline group, the study's authors want us to believe that among patients using varenicline there was no match with patients using NRT 1,287 times.  Then, as if by some cosmic coincidence, the study's authors excluded exactly 2.5%, or 164 out of 6,557 patients using bupropion for the same reason.  Though the bupropion sample size is dramatically smaller than the NRT and varenicline groups, the amount of bupropion patients excluded for no match with NRT is the exact same percentage as varenicline.

The identical 2.5% exclusion rate for bupropion and varenicline patients is not a mathematical coincidence.  The 2.5% exclusion rate for bupropion patients was most likely done to match the percentage of varenicline patient exclusions, so the study's authors could say, "See, we excluded the same percentage of bupropion patients as varenicline," to distract your attention away from the fact that they just made 1,287 varenicline patients disappear.  Classic magic trick.

As if to confirm that the study is advocacy-sponsored research in support of advocacy policy, the study's authors conclude, "These findings suggest an opportunity for physicians to prescribe varenicline more broadly, even for patients with comorbidities, thereby helping more smokers to quit successfully than do at present."

The media is either woefully stupid (unlikely), or deliberately has its head in the sand.  One can only wonder to what extent pharma ads buy media looking the other way when such blatantly biased studies are paraded out.

Meanwhile, more credible research into reported varenicline adverse events concluded "that acts of violence towards others are a genuine and serious adverse drug event that is associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and serotonin reuptake inhibitors were the most strongly and consistently implicated drugs."



   
   

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