Monday, August 06, 2012

Study Finds Only a 12% Three-Month Success Rate for NRT Among Smokers with HIV Infection; Could Electronic Cigarettes Do Better?

A new study published online ahead of print in the journal Nicotine & Tobacco Research reports that the combination of telephonic counseling and nicotine replacement therapy (NRT) resulted in just a 12% three-month cessation rate among HIV-infected smokers.

According to the study: "Participants completed 12 weeks of telephone counseling and either varenicline or NRT. Varenicline was encouraged as the preferred intervention; NRT was used for those unable/unwilling to take varenicline. Adverse events (AEs), related to pharmacotherapy, were monitored. Biochemically confirmed abstinence at 3 months was examined. ... Among participants on varenicline (n = 118), the most common AEs were nausea, sleep problems, and mood disturbances. One person reported suicidal ideation; there were no cardiovascular complications. ... The percentages of confirmed abstainers were 11.8% in the NRT group and 25.6% in the varenicline group."

The Rest of the Story

Since the one-year cessation rate would be expected to be no more than half to three-fourths of the three-month rate, we can infer from the study that the long-term success rate of NRT among these smokers is no better than about 6-9%. This is a dismal rate of long-term effectiveness.

Preliminary clinical trial evidence suggests that among unmotivated smokers, the six-month success rate of electronic cigarettes may be as high as 22.5%, with 54% of smokers either quitting completely or cutting down on their smoking amount by at least half.

Thus, there is at least preliminary evidence that electronic cigarettes show a lot more promise as an effective smoking cessation tool than NRT products. Despite this scientific evidence, numerous anti-smoking groups, researchers, and advocates, as well as public health agencies including the FDA itself are discouraging the use of electronic cigarettes because they have not been "proven" to be "safe and effective."

Meanwhile, mood disturbances were a common side effect of varenicline (Chantix) in this study and there was one case of suicidal ideation out of 118 patients. This is a rate of 0.85%, which, if truly attributable to Chantix, is completely unacceptable. If the observed case of suicidal ideation was indeed due to Chantix, then based on the number of Chantix users in the U.S. (approximately 1.8 million patients per year receive Chantix prescriptions.), one would expect about 15,000 cases of suicidal ideation due to Chantix. This is obviously unacceptable, and if known before drug approval, this risk would never have been tolerated by the FDA and the drug would not have received approval.

The most surprising aspect of the study is that despite the finding of a 0.85% rate of suicidal ideation among Chantix users, the study concludes that Chantix appears to be safe.

Even more surprising is the fact that the study authors are willing to even comment on the safety profile of Chantix given the sample size of 118 and the three-month follow-up. This sample size is not adequate to draw any meaningful conclusions about the safety profile of the drug, given the concerns about its effects on mood disturbances and suicidal ideation. Neither is the follow-up long enough to draw meaningful conclusions about the drug's safety profile.

I have no idea whether any of the study authors have a conflict of interest by virtue of having received money from Pfizer or other drug companies, but I am going to go out on a limb and bet my readers that there is a conflict of interest because of the huge apparent bias in the study. It's difficult for me to even imagine that researchers would publish a study on the safety of varenicline with only 118 subjects. Although the primary purpose of the study was to test the effectiveness of varenicline compared to NRT in smoking cessation, the title of the paper is: "Safety of Varenicline Among Smokers Enrolled in the Lung HIV Study."

Although I don't have access to the full study because the journal does not provide access and my institution does not subscribe to this journal, I am now going to investigate each of the co-authors for any financial links to Pfizer or other drug companies and report back to you in the next paragraph. ...


... Here are the results of my investigation:

It turns out that, indeed, one of the study authors has received research funding in the past from Pfizer, and has participated in research that was funded in part by GlaxoSmithKline and Bristol-Myers Squibb. She also participated in another study that was funded in part by Bristol-Myers Squibb. I recognize that the research funding from Pfizer was well in the past, but the financial relationship could well result in a subconscious bias that operates well into the future. I would certainly be grateful to any company that funded me early in my career and that gratitude would not end for many years.

It's getting to the point where I can read a study and have a pretty good idea whether there is a conflict of interest before I even get to the Acknowledgments section. This is because subconscious biases can often be readily apparent to objective readers, as is the case in this study, where the paper is presenting on the safety of Chantix even though the sample size is woefully inadequate to draw any meaningful conclusions. The finding of a suicidal ideation rate of 0.85% among varenicline users certainly does not provide any reassurance that the drug is "safe and effective."

The rest of the story is that evidence is accumulating that NRT is not particularly effective and that Chantix is not particularly safe. Nevertheless, entrenched biases in the anti-smoking movement are contributing to the continued promotion of these drugs to the public as being safe and effective, while at the same time, smokers are being discouraged from using electronic cigarettes, for which there is at least preliminary evidence that they may be much more effective than the "approved" products.

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