How to quit smoking cigarettes

Those who don’t know cessation study history are destined to repeat it

Chantix entered the quitting product market as a prescription aid at a time when nicotine replacement therapy or NRT was the clear front-runner. Nicotine gum was first approved by the FDA for prescription use in 1984 and was followed by the nicotine patch in 1991. Both the gum and patch were approved for over-the-counter (OTC) sales in 1996, the same year prescription nicotine nasal spray was approved. The nicotine inhaler and bupropion (Zyban) joined as prescription products in 1997. In 2002 the lozenge become the first nicotine delivery device to enter the market directly as an OTC product.

There was a feast to starvation difference between the intensity of support in randomized clinical trials and the OTC NRT studies. The OTC studies were needed to validate the FDA allowing the nicotine gum and patch to go from prescription to OTC in ‘96. OTC study participants sometimes received little more than the instructions that came inside the box.

A 2002 study by pharmaceutical industry consultants combined and averaged the seven over-the-counter nicotine patch and gum studies found that just 7% were still not smoking at six-months - a 93% relapse rate. Although another well-kept industry secret, the one-year OTC NRT rate is likely a bit less than 5%. Yes, a 95% failure rate and near 100% failure for second time users.

But NRT’s extremely dismal quitting rate did not become visible until forced to stand on its own and be evaluated for OTC use. Until then, NRT was allowed to hide behind an intensity-rich clinic experience which nourished quitting motivations far longer than normal. Let’s look back to a few of the more heralded early nicotine gum studies which often had heavy education, counseling and/or support elements too. How did their results compare to Chantix’s initial 22% one-year rate?

Is Chantix/Champix a step forward or back?

A 1976 nicotine gum study headed by Russell found that 23% of nicotine gum users were still not smoking at 1 year. The 1980 nicotine gum study by Raw produced a whopping 38% rate, in 1982 Jarvis found a 31% rate, in 1983 Schneider 30%, in 1984 Hialmarson 29%, in 1986 Daughton 31%, in 1987 Kornitzer 32%, and in 1989 Tonnesen boasted a 44% one year quit smoking rate.

The history of nicotine gum studies provided Pfizer confidence that intensively supportive Chantix (varenicline) studies should generate rather hefty and newsworthy one-year quitting rates. But it also knew that naked and alone, outside clinic doors, that nicotine gum proved at least three times less effective (using the low of 23% above to OTC NRT’s 7% six-month rate).

Clearly, taking a Chantix pill twice daily is vastly easier than chewing piece after piece of nicotine gum, often after the onset of a crave episode. True, but aside from the discouraging cost of a 12-week supply ranging from $321 to $516 (U.S.), Chantix users face the possibility of a long list of discouraging side effects that, without counseling, explanation or ongoing support may cause users to abandon its use. More about side-effects in a moment.

When used as a stand alone product, will Chantix’s OTC quitting rate compare to NRT’s OTC rate and be at least three times lower than the 22% average generated in Pfizer’s three comparable studies? We don’t yet know. Let’s hope that the above nicotine gum rates are not comparable as it could mean that Chantix’s real-world rate might actually be worse than nicotine gum’s.

When OTC NRT’s dismal six-month 7% quitting rate is contrasted to the boasts within pharmaceutical industry NRT marketing commercials, clearly both smokers contemplating quitting and children contemplating smoking are being seriously deceived about the ease of quitting with replacement nicotine.

Pfizer could have turned a new page in placing honesty and openness above corporate profits. But instead it has rewritten Aesop’s tortoise and hare fable to suggest that a “hare” who wanted varenicline too but whose expectations were shattered by assignment to the placebo group, can be fairly compared to a cold turkey who expected to endure and successfully navigate full-blown withdrawal. Pfizer knows that it cannot fairly pit its tortoise against real turkeys — who want to quit cold turkey — in open label/open method clinical trials without losing race after race, being exposed and forfeiting billions in profits.

So what’s the bottom line? What are your chances with Chantix or Champix? Clearly we do not yet know varenicline’s odds when used as a stand-alone aid. If gum’s performance is any indication we should not be surprised to see one year rates in the neighborhood of 1 in 20. But if a quitter is able to fully duplicate the richness and intensity of support offered in Pfizer’s formal clinical trials shouldn’t they expect to experience 1 in 5 odds of success or 22% at one year? Although we wish it were true, maybe not.

Newer Studies - New varenicline efficacy studies, comparing it to controls or other quitting methods have become available since this article was originally written in August, 2006. Studies providing insight into varenicline’s true value as a real-world stand alone quitting aid (its effectiveness), without intensely artificial and highly unrealistic levels of provider contact and interaction, will be shared under this subsection.

February 13, 2008 Aubin Varenicline/Nicotine Patch Study (link to free full text PDF copy) - This 52 week Pfizer funded study compared 12 weeks of varenicline (1mg twice daily) by 376 users to 10 weeks of stepped-down nicotine patch use (21mg to 7mg patches) by 370 patch users.

The 2008 Aubin study excluded 21% of applicants including but not limited to all with any “serious or unstable disease,” depression or other psychological disorder, or drug or alcohol dependence, abnormal lab tests or using any medication that might interfere with the study.

As with Pfizer’s five initial studies, the 2008 Aubin study did not seek to demonstrate how varenicline would compare to nicotine patch use under real-world battlefield conditions, but instead was designed to generate the most highest one-year rates possible. Like the initial studies it created intensely artificial study conditions that few if any real-world users will ever experience.

According to the study, “Counselling also occurred during every subsequent telephone and clinic visit.” The study identified 1 baseline visit, 12 treatment phase visits for varenicline users (10 for patch users), with clinic visits on weeks 13, 16, 24, 32, 40, 48 and 52, interspersed with telephone counseling on day 3, and weeks 14, 20, 28, 36 and 44. That’s at least 25 provider counseling sessions, each up to 10 minutes in length.

This intense counseling and support format resulted in proof that, at one year, 20.3% of nicotine patch users and 26.1% of varenicline users had most probably not smoked a cigarette within 4-5 hours of blowing into a carbon monoxide detector (carbon monoxide’s chemical half-life).

As with all varenicline studies to date, this study provides zero evidence that any participant actually arrested their chemical dependency upon nicotine - none. Instead, it focuses exclusively upon a single form of nicotine delivery, the most destructive, smoking, as evidenced by two factors: (1) “use of NRT during the 9 months of follow-up did not disqualify a subject,” and (2) self-reported abstinence was checked by sampling exhaled carbon monoxide levels that were permitted to be twice as high as recommended by some studies, 10ppm versus 5 ppm (parts per million).

More telling were actual participant answers when asked whether or not they had smoked a cigarette within the prior 7 days, what researchers term “7-day point prevalence of abstinence.” Amazingly, the study’s authors conclude that there …

“were no significant differences” between Chantix and nicotine patch users at either 6 months (varenicline 38.6% vs. patch 34.1%) or one year (varenicline 34.8% vs. patch 31.4%).

If Chantix performance without 25 counseling sessions declines proportionally to accepted nicotine patch rates generated under real-world conditions, just 7% at six months (see Hughes’ 2003), the 2008 Aubin study will someday be looked back upon as having foretold Chantix and Champix’s true worth as a stand-alone quit smoking pill, when used without counseling or support.

But which 2008 Aubin figures should we believe, the one-year expired carbon monoxide readings which would proportionally put Chantix’s six-month stand-alone rate at 9% (7/20=9/26), or one-year participant answers when asked whether or not they had smoked within the past 7 days, which produces a slightly lower six-month rate of 8% (7/31.4%=8/38.6%)?

Both 8% and 9% are lower than controls in U.S. Guideline evidence tables suggesting a natural six-month “on-your-own” quitting rate of 10-11%. If true the question becomes, in conducting varenicline risk-benefit analysis, after factoring in escalating concerns over loss of life, should the FDA immediately order Chantix to be pulled from the market (see “FDA Chantix Handling Betrayed Public Health” for additional insights).

28% applying for initial studies were denied participation

A second factor that could significantly diminish Chantix’s real-world performance rate is associated with a substantial percentage of smokers who applied to participate in each study but were denied.

In Gonzales 1,843 smokers were screened and 458 were excluded (25%), in Oncken 980 were screened and 333 excluded (34%), and in Jorenby 1,413 were screened and 386 excluded (27%). But why?

A partial list of those excluded includes those suffering from cardiovascular disease, alcohol abuse, major depression, panic disorder, systolic blood pressure greater than 150 or diastolic pressure greater than 95, a history of cancer, a body mass index (calculated as weight in kilograms divided by height in meters squared) of less than 15 or higher than 38; weight less than 45kg, those with a “clinically significant medical disease,” those over age 75 or younger than age 18, those smoking fewer than 10 cigarettes per day, and those known to have recently relapsed during NRT or Zyban quitting attempts. But why?

Most within these groups reflect populations that have historically been the most challenging to assist in quitting, including youth who often smoke fewer than ten per day. You would think that prior to any government approving any new medication, it would demand that early studies include all known human conditions, or that smokers reflected by any groups intentionally excluded be warned in all product marketing that it has not yet been tested for safety or efficacy in regard to them.

Clearly, Pfizer knew in advance that including difficult to treat populations, such as alcohol abusers, would have resulted in greater relapse rates, making final cessation figures less impressive. Looking at the seriousness, types and quantity of adverse events now being reported (see safety discussion below), one has to wonder if some of the excluded groups, if included, would have revealed serious safety concerns sooner. If so, prior to excluding them, was Pfizer aware that excluding them would, to some degree, hide safety concerns? In other words, did Pfizer believe in advance that excluding the above groups would both elevate quitting rates and diminish safety concerns?

Pfizer’s Chantix marketing has aggressively assaulted all smokers, including most that it intentionally excluded from its studies. A visit to Chantix.com on December 3, 2007, at first glance, appears inviting to nearly all smokers. The page asks “if Chantix is right for me” but provides few answers. Instead, Pfizer is crafty in shifting the information burden to U.S. physicians, by telling smokers to ask their doctor if Chantix is right for them.

But if you are within any of the excluded groups, your group probably has yet to be the focus of any serious study, and thus, at best, your doctor can only guess as to how Chantix or Champix will interact with your condition or medication. Most excluded groups will find that, as of today, we have little or no idea of your odds of success with Chantix or Champix, or your potential to experience adverse events, some of which may not yet appear on Pfizer’s “Full Prescribing Information” sheet.

Go to PubMed and search “varenicline” + key words associated with your condition or concern, to find out if it has yet been the focus of any study. Escalating concerns regarding varenicline side-effects are just now beginning to generate risk assessment papers for some excluded groups. But the number of quitters being evaluated and/or the haste with which these studies are being thrown together provides little confidence in relying upon their implications or conclusions.

For example, Pfizer’s studies excluded those with mental health issues. We now have an August 2007 case study of one smoker diagnosed with bipolar disorder, whose condition was stable for five years while taking valproic acid. This man started experiencing manic symptoms within a week of taking 1mg of varenicline twice daily, and had to be admitted to an inpatient psychiatric unit. Although noteworthy, bipolar patient mixing valproic acid and varenicline does not a “study” make.

But now it’s as if Pfizer is scrambling to plug leaks in a damn. Imagine trying to pass off old NRT and varenicline use data - data that included a brief medical history, with at least one question about mental health conditions - as a November 2007 safety study of varenicline use in patients with mental illness. Imagine declaring varenicline use safe in patients with mental illness when: (1) only 53 patients asserting mental illness thereafter used varenicline; (2) none of the 53 underwent any objective mental health evaluation (see DSM-IV and ICD-10 standards) at any time during the study (nor did the control group); and (3) the study makes no reference whatsoever to any mental health medication taken by any of the 53 patients. What this junk “mental illness” study did find was greater depression in varenicline users. Also one user experienced a “severe psychological reaction likened to a bad LSD trip, including anxiety, paranoia, confusion and impaired motor control.”

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