Wednesday, July 31, 2013

Three Must-Read Articles Supporting Tobacco Harm Reduction

These outstanding recent publications belong in every tobacco harm reduction library. 

1.  Dr. Lynn Kozlowski on e-cigarettes

Kozlowski, dean of the School of Public Health at the University at Buffalo, has published an excellent article in the Huffington Post (here) encouraging smokers to switch to e-cigarettes and encouraging the FDA to use light-touch regulation to keep e-cigs on the market and competitive with deadly cigarettes. 

Kozlowski is a giant in the tobacco research field and a long-time advocate of harm reduction.  He noted in 1984 (abstract here) and 1989 (abstract here) that smokeless tobacco conferred fewer risks to users and therefore might serve as an effective substitute for cigarettes.  He argued in 2003 that there was little evidence that smokeless use was a gateway to smoking, because the majority of users never smoke or smoked cigarettes prior to using smokeless (abstract here), and he has argued persuasively that smokers have a fundamental human right to accurate information about safer forms of tobacco use (abstracts here and here).

2.  Christopher Snowdon on tobacco harm reduction

Snowdon, author of Velvet Glove, Iron Fist: A History of Anti-Smoking (2009, available here), has published a devastating critique of the resistance to tobacco harm reduction in Europe (read it here).  He writes that “The sale of the two least hazardous recreational nicotine products – e-cigarettes and Swedish snus – are banned in many countries despite growing evidence that they can play an important role in reducing the smoking rate…The prohibition of safer tobacco products has led to unnecessary deaths in the European Union and elsewhere.  It is highly likely
that the prohibition and excessive regulation of e-cigarettes will also lead to unnecessary premature deaths.”

Snowdon argues that “The neo-prohibitionist approach is unjustifiable from the perspective of both personal liberty and population health.”  Although he focuses on the European snus ban and the strangulation of e-cigarettes by the EU tobacco directive, Snowden excoriates the FDA for making the designation of smoke-free tobacco products as “reduced risk” dependent on impossible-to-obtain proof that they won’t adversely affect population health.

3.  Thomas Lesnak on the booming cigarette black market

Lesnak, recently retired from the U.S. Department of Justice, Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF), writes in the Daily Caller (here) that the cigarette black market is worth $10 billion.  “That is the widely accepted figure our government estimates is lost each year from tobacco trafficking schemes,” he notes.

I recently described New York City as a “prohibition prison” (here); Lesnak agrees.  He writes, “When politicians say that increasing taxes lowers smoking rates, what they aren’t saying is that higher costs have driven a large percentage of the market – disproportionately youth smokers – to illicit cigarettes.  Millions of New Yorkers now reside within a short walk or a cab-ride from smoke shops that sell 200 cigarettes in plain plastic bags for $10.  Referred to as ‘rollies’ or ‘baggies,’ they feature no health warnings, and produce no tax revenue…Today, it is estimated that 60 percent of the cigarettes sold in New York City are illicit.  Most of these cigarettes are smuggled in from low-tax states like Virginia, North Carolina and Maryland.”

Lesnak correctly diagnoses the problem: “we’re criminalizing tobacco smokers, small and family retailers, and our youth, who are now forced into buying illicit products.  If these sound reminiscent of the failures of Prohibition, it’s because these are the same problems we faced early in the last century as a result of those similarly veined, well-intended policies.  We know exactly how that experiment turned out.  And yet, politicians continue to ignore those lessons.”

Unfortunately, the former federal agent also ignores the lessons of Prohibition and recommends the wrong treatment: “…stiffer penalties, well-funded enforcement, and stronger cooperation among agencies, as well as state and local governments.”  Such measures make the black market more violent and destroy government credibility.  There is little enthusiasm in America for penalizing personal behaviors, especially those that are enjoyed by millions of people.  Instead, politicians should eliminate prohibitive tobacco taxes, legislation and regulation.

Friday, July 26, 2013

FDA Preliminary Scientific Evaluation of Menthol: Inadequate for Regulatory Action

The FDA Tobacco Products Scientific Advisory Committee in 2011 reported that menthol had a negative impact on public health.  This week, the FDA released a “Preliminary Scientific Evaluation of the Possible Public Health Effects of Menthol Versus Nonmenthol Cigarettes,” (available here) and announced a 60-day public comment period.  This is the opening salvo in FDA regulatory action that could eliminate or restrict around 30 percent of the American cigarette market (here). 

This post examines the evidence for regulating menthol provided in the preliminary scientific evaluation.

The FDA considered the effects of menthol on several smoking parameters, including smoke chemistry and toxicity, biomarkers, smoking patterns, marketing and consumer perception, smoking initiation and progression, nicotine dependence, and smoking cessation. 

Here are the report’s major findings (I have provided PubMed links to some of the important studies cited by the report):
Smoke Chemistry/Toxicity

There were no significant findings: “…menthol in cigarettes is not associated with increased or decreased smoke toxicity.”


There were no significant findings: “…menthol in cigarettes is likely not associated with increased or decreased levels of biomarkers of exposure.”

Smoking Patterns

The evaluation confirmed what is already widely acknowledged – that menthol cigarettes are more popular among certain groups, especially African Americans, women and, in some studies, younger smokers.

Marketing and Consumer Perception

There were no significant findings: “…a clear relationship cannot be drawn.”

Smoking Initiation and Progression

While the report concluded that “menthol in cigarettes is likely associated with increased initiation and progression to regular use of cigarette smoking,  this finding is based on remarkably mixed data, described in this passage:
“…There is no indication that menthol smokers first experience cigarette smoking any earlier or later than nonmenthol smokers (Pletcher et al., 2006; Okuyemi et al., 2004; Gandhi et al., 2009).  However, data regarding age of onset of regular smoking are mixed. Six studies found no difference (Hyland et al., 2002; Okuyemi et al., 2004; Okuyemi et al., 2007; Cubbin et al., 2010; Stahre et al., 2010; Lawrence et al., 2010 – males only), two found that menthol smokers began regular smoking at a later age (Fagan et al., 2010; Fernander et al., 2010), and two found that menthol smokers began regular smoking at an earlier age (Lawrence et al., 2010 – females only; Nonnemaker secondary data analysis).”
Nicotine Dependence

The report concluded that “…menthol in cigarettes is likely associated with increased dependence.”  This position defies some key research – “[Cigarettes per day] and [the Fagerström Test for Nicotine Dependence], two measures that have historically been used to assess nicotine dependence, find no consistent effect of menthol” – and appears to be largely “based on findings of TTFC [time to first cigarette]” and other scales of dependence.  Let’s look at the “findings of TTFC.”

One of the main sources for such data is a 2010 study by Fagan) which found that only moderate menthol smokers (6-10 cigarettes per day, or cpd) were 22 percent more likely than regular smokers to have a cigarette within 5 minutes of waking.  Strangely, menthol had no effect among light (< 5 cpd) and heavy (11+ cpd) smokers.  A study by Collins and Moolchan in 2006 reported a higher percentage of 5-minute TTFC among adolescent menthol smokers seeking cessation treatment, a highly selective population that is not representative of all menthol smokers.  The FDA dismisses the results from four other studies, some positive and some negative, because they didn’t analyze the first five minutes after waking, which the FDA apparently views as the standard.  The report also discusses several studies that are not peer-reviewed, even though “…more consideration was given to peer-reviewed studies.”

The FDA conclusion conflicts with a 2012 study that was not included in the report (available here). It found that “Smoking behaviors may vary by menthol, but menthol was unassociated with dependence.”

Smoking Cessation

The FDA report concluded that “…menthol in cigarettes is likely associated with reduced success in smoking cessation, especially among African American menthol smokers.”  Once again, the finding was based on decidedly mixed results.

The report discussed nine cohort studies that had a vast range of outcomes.  Three found no differences in cessation between menthol and nonmenthol smokers (Hyland et al., 2002; Cropsey et al. 2009; Murray et al., 2007), and the report criticized two of them.  “A fourth study (Blot et al., 2011) found no difference between African American smokers but that White menthol smokers were more likely to have quit.  Of the remaining five cohort studies, four found worse cessation outcomes for menthol smokers compared to their nonmenthol counterparts ([only three references were cited here] Pletcher et al.,2006; Okuyemi et al., 2003; Harris et al., 2004), and one had a trend towards menthol smokers having worse outcomes (Foulds et al., 2006).”

Six cross-sectional studies had varied results regarding menthol and cessation: “…two (Fu et al., 2008; Muscat et al., 2002) failed to find significant differences between menthol and non-menthol smokers [The report appears to cite the wrong study by Fu et al., this one by the same author is more relevant  ]…three [studies] found that menthol smokers had worse cessation outcomes as compared to their nonmenthol smoking counterparts [references were not provided], while one (Gundersen et al., 2009), found that African-American and Latino menthol smokers had worse cessation outcomes as compared to their nonmenthol smoking counterparts while the reverse was true for White smokers.” 

The above FDA description of the Gundersen study is a disturbing misappropriation of research results.  The agency implies that the cessation outcome was worse in both African-American AND Hispanic menthol smokers.  Hispanic menthol smokers had worse cessation outcomes (adjusted odds ratio, AOR= 0.61, 95% Confidence Interval, CI=0.39-0.97), but the cessation rate for African American menthol smokers was NOT significantly lower (AOR=0.78, CI=0.56-1.09).  Statistical significance was reached only when both groups were combined as “Non-White”.  In fact, Gundersen describes the overall result for all menthol smokers: “The odds of being a former smoker does not differ statistically or substantially relative to nonmenthol smokers.”

The bottom line: Numerous studies showed mixed results for menthol and cessation, with some suggesting that menthol might be associated with reduced cessation among African Americans and with increased cessation among whites. 

The FDA preliminary evaluation – reflecting data from numerous studies – does not provide evidence of any significant differences between menthol and regular cigarettes with respect to smoking initiation, addiction to nicotine or cessation.  There is no justification for an evidence-based decision by the FDA to ban or otherwise restrict the menthol content in cigarettes.  

Thursday, July 18, 2013

Clinical Trial Evidence: E-Cigarettes Aid Smoking Cessation/Reduction

A new clinical trial provides clear evidence that e-cigarettes are effective in helping smokers quit or reduce cigarette consumption.  The results were published in PLoS One by Pasquale Caponnetto and colleagues at the University of Catania (Italy) (available here). 

Dr. Caponnetto enrolled 300 smokers who were not interested in quitting, and split them into three groups. Each group received free e-cigarettes with a different fluid for 12 weeks: Group A received 7.2 mg. nicotine cartridges; Group B got 7.2 mg. cartridges for 6 weeks followed by 5.4 mg. cartridges for six weeks; Group C received flavored cartridges with no nicotine.  Participants returned every two weeks through week 12, when the intervention formally ended; follow-up occurred at weeks 24 and 52.  At each visit, investigators measured cartridge use, cigarette consumption and exhaled carbon monoxide levels; they also measured saliva levels of cotinine, a nicotine metabolite and marker, at weeks 6 and 12.

At week 12, 33% of participants reported that they had reduced cigarette consumption by half or more, or had quit smoking completely.  At one year, 10% reported smoking reduction and 8.7% reported complete cessation.  Two problems commonly associated with smoking cessation were gauged: withdrawal symptoms were seen only occasionally; weight gain was not observed at all.  Other than some throat irritation reported in the first two weeks in Groups A and B, no other complaints were voiced. 

Why wasn’t the success rate higher?  A significant factor was a low rate of satisfaction with the products used in the trial.  Caponnetto and colleagues comment that “Many respondents complained of the frequent failures, lack of durability, difficulty of use (it takes time to familiarize with the puffing technique), and poor taste of the product tested.”  Substantial improvements in e-cigarette design and function have been observed since the trial was initiated in 2010, suggesting that satisfaction rates, and therefore cessation/reduction rates, might be higher if the study were to be repeated today.

Only about 60% of smokers completed the study, which confirms the difficulty of using the clinical trial model for evaluating consumer behavior.  I am familiar with these challenges.  In 1995, at the University of Alabama at Birmingham, I directed the first-ever clinical trial employing tobacco harm reduction; our results were published in the American Journal of Medicine (abstract here).  We enrolled 63 smokers in a pilot study in which we recommended that they switch to Skoal Bandits, the only widely available pouched smokeless tobacco product at that time.  At one year, 31% of men and 19% of women had attained smoking cessation, for an overall success rate of 25%. An additional 7% of subjects had reduced their cigarette consumption by at least 50%.  Unlike the current study, nearly all of our smokers wanted to quit, but had failed repeatedly with nicotine replacement therapy, which was available only through prescription at that time.  

The current study is well designed and well executed.  These were hard-core smokers with no interest in quitting, yet one year later almost one in five smoked fewer cigarettes or none at all.  Caponnetta and colleagues provide solid evidence that e-cigarettes can accelerate the worldwide transformation in tobacco use (described here  ).