Wisdom From Smoking Cessation Pioneers

 

A search of the medical literature on the topic “smoking cessation” finds 32,446 published articles, yet, surprisingly, there are no articles linked to this topic until the year 1980, and only 27 articles were published from 1981 to 1990.  Medical researchers primarily focused on smoking cessation in the last three decades -- 1991 to 2000 (4,481 articles), 2001 to 2010 (10,976 articles), and 2011 to the present (16,964 articles).  Despite this impressive volume of research, the U.S. still records 480,000 deaths annually due to smoking.

I was interested to learn more about the 1981-1990 period, as it preceded my entry into the field in 1994 (here, here and here).  I found that several prominent scientists and academicians, who are strong supporters of tobacco harm reduction, populated that period’s author list.  Here they are, followed by PubMed links: John Hughes (here and here), Jed Rose (here), Lynn Kozlowski (here), Ken Warner (here), Jack Henningfield (here), Ray Niaura (here), David Abrams (here) and Saul Shiffman (here).  Three of these articles, and their authors, deserve special mention.

Ken Warner’s 1989 article, “Implications of a Nicotine-Free Society,” clearly shows that this University of Michigan professor has been one of the most forward-thinking leaders in the tobacco research and policy field for many years.  He understood in 1989 that a “nicotine-free society” was not a panacea, and he boldly criticized both sides in the debate: “The tobacco industry implies that the demise of tobacco consumption would wreak havoc with the economy. By contrast, some antitobacco activists suggest that the end of tobacco use would yield a multibillion dollar fiscal dividend. Each argument is fundamentally flawed. The economic impacts of a nicotine-free society would be modest and of far less consequence than the principal implication: a significantly enriched quality and quantity of life.” 

I have some personal insight into Professor Warner’s commitment to tobacco harm reduction.  In 1999, US Tobacco made its first grant to the University of Alabama at Birmingham to support my work.  I contacted numerous well-known tobacco researchers, offering to fund my own travel in order to make presentations on an alternative approach to cessation for inveterate smokers.  The only person to respond was Ken Warner.  He hosted my speech and invited colleagues from across the Michigan medical center.  It was a rigorous event, at which my research and ideas were seriously challenged.  I was, and remain, profoundly grateful to Professor Warner for this amazing opportunity.

Jed Rose at Duke University is another prophet of tobacco harm reduction, and his work long pre-dated and anticipated the recent development of vapor products.  Consider his 1990 article,  “Low-nicotine Regenerated Smoke Aerosol Reduces Desire for Cigarettes.”  His group developed “an aerosol with many of the sensory qualities of cigarette smoke, but with only 3% of the tar and nicotine and none of the carbon monoxide of a typical commercial cigarette… Surprisingly, the smoke aerosol reduced self-reported desire for cigarettes as much as the commercial cigarette. This new method is a promising approach for evaluating the role of sensory cues in smoking, and it may also be useful as a clinical tool for smoking cessation.”          

Finally, there is legendary tobacco researcher Lynn Kozlowski (originally at Penn State, now at the University at Buffalo).  In 1989, he authored “Reduction of tobacco health hazards in continuing users: individual behavioral and public health approaches.”  The article was written for “those smokers who will not stop using tobacco,” for whom “methods are discussed for reducing the risks to health of continued tobacco use… For continuing smokers of cigarettes, fewer cigarettes per day and very-low-tar cigarettes are encouraged, provided filter-vents are not blocked by the smoker. Better yet would be a switch to smoking one or two non-inhaled pipes or cigars each day. Even better would be a switch to use of the minimum acceptable amount of smokeless tobacco or nicotine-containing gum.”  Professor Kozlowski even suggested that “public health measures (e.g., social restrictions, differential taxation, changes in package size) may be the most important means of bringing about less hazardous tobacco use among continuing users.”

In 1994 I started counselling inveterate smokers to switch to smokeless tobacco, and in 2017, my research group recommended “differential taxation” to Kentucky legislators to save smokers’ lives.  I am proud that our proposal was endorsed by Ken Warner and Ray Niaura.

 

 

Cigarette-Nicotine Fadeout Fails; NIH-Funded Researchers Back “Easy Alternative Sources of Nicotine”

Drs. Neal Benowitz and Jack Henningfield were respected tobacco researchers in 1994 when they introduced a flawed smoking cessation prescription: force smokers to quit by reducing the nicotine content of cigarettes (here).  I criticized the idea in my 1995 book, For Smokers Only (now available as an e-book with a bonus chapter on e-cigarettes).

In the 20 years since, the nicotine fadeout strategy has failed to gain traction, while the alternate concept of tobacco harm reduction has attracted substantial support.  When Drs. Benowitz, Henningfield and their anti-tobacco allies attempted five years ago to resurrect nicotine fadeout as an FDA regulatory strategy, I labeled it “the most idiotic idea ever proposed by tobacco control advocates” (here) and described “the disaster that would result from radical reduction (prohibition) of nicotine in cigarettes” (here).

Today we have a fresh clinical trial (abstract here) from Dr. Benowitz that may mark the last gasp for this scheme.

Dr. Benowitz and coworkers enrolled 135 smokers who were “interested in a reduced nicotine cigarette study, and not interested in quitting smoking in the next 6 months.”  Eighty participants “smoked five levels of progressively lower nicotine content cigarettes, the first four levels being smoked for 4 weeks each.  The lowest nicotine content cigarette was smoked for 7 months.  [I call this the fade-out group.]  The control group smoked their usual brand of cigarettes for 12 months.”  Everyone got a year’s worth of free cigarettes, and information was collected for one additional year.

The results were dismal, starting with completion rates.  Smokers were paid to participate, which may have prompted 87% of the control group to complete the first year and 69% to make it through the second; the rates in the fade-out group were 46% and 38%.

The authors reported that “Quit rates were low in both [fade-out] and control groups, and not significantly different between groups at any time.”  That is an understatement.  The quit rate, validated by lab studies, was 2% among controls at one year and at two years.  Among the fade-out group, the rates were 3.8% at one year and 7.5% at two years.

There’s more bad news.  At one year, 43% of fade-out smokers admitted they had violated the study protocol by smoking regular cigarettes.

Dr. Benowitz likely intended the study to provide cover for the FDA to gradually reduce cigarette nicotine levels to near zero.  Instead, as he acknowledged, the fadeout theory was disproven: “Simply reducing the nicotine content of cigarettes alone may be insufficient to extinguish smoking behavior.”

Importantly, Dr. Benowitz concedes that “…easy access to alternative sources of nicotine (such as nicotine medications or electronic cigarettes) may be needed to achieve cessation of

cigarette smoking.”

Dr. Benowitz, welcome to Tobacco Harm Reduction.

A final note: I recently discussed how the National Institutes of Health have influenced the debate about tobacco harm reduction by doling out massive grants to university researchers nationwide (here).  The Benowitz study was supported by four grants from the National Cancer Institute and the National Institute on Drug Abuse; the total taxpayer tab was $29.2 million.

Federal Judge to FDA: Tobacco Advisory Panel Tainted by Conflicts of Interest

“The presence of conflicted members on [FDA Tobacco Products Scientific Advisory Committee, TPSAC] irrevocably tainted its very composition and its work product” and “the Committee’s findings and recommendations…are, at a minimum, suspect, and, at worst, untrustworthy.”  So ruled federal judge Richard Leon this week (here).

A lawsuit by Lorillard et al. claimed that the FDA appointment of TPSAC members Neal Benowitz, Jack Henningfield and Jonathan Samet was “arbitrary, capricious, an abuse of discretion, and otherwise not in compliance with the law” because they had conflicts of interest.  The evidence was abundant and uncontested.  Here are excerpts from the judge’s opinion:

“Since the 1980s, Dr. Benowitz has consulted for numerous pharmaceutical companies about the design of the NRT and other smoking-cessation drugs.  He consulted for affiliates of Pfizer, Inc. and GlaxoSmithKline (GSK) as to such products, even while serving on the TPSAC…Dr. Benowitz has also served as a paid witness for lawyers suing tobacco-product manufacturers.  He testified as a paid expert witness while serving on the TPSAC, and…he was designated to testify in 585 pending tobacco cases.”

“Before and while serving on the TPSAC, Dr. Henningfield consulted for GSK and other drug companies as to NRT and other smoking-cessation drugs.  He also had ownership interest in a company that was developing a patented NRT drug.  Dr. Henningfield has testified as an expert for GSK and for lawyers suing tobacco-product manufacturers… he was designated to testify in 350 pending tobacco cases.”

“Dr. Samet received grant support from GSK at least six times, including in 2010.  He also led the Institute for Global Tobacco Control, funded by GSK and Pfizer.  Dr. Samet also testified for lawyers suing tobacco-product manufacturers…he was designated to testify in two pending tobacco cases.”

Judge Leon’s ruling notes that the composition of TPSAC is different from other FDA advisory committees, because the enabling legislation bans any expert “who received ‘any salary, grants, or other payment or support’ from any tobacco company in the 18-month period prior to serving on the TPSAC.”  

TPSAC was structured to exclude qualified authorities who have had industry support.  Experts with industry support are not precluded from serving on other FDA advisory committees, in which scientific issues are more important than industry demonization.   

Judge Leon noted that the provision should apply evenly to any conflict of interest: “If Congress deemed that past remuneration from tobacco companies constituted a conflict of interest, it stands to reason that past remuneration from direct competitors of those companies, such as manufacturers of smoking-cessation drugs, would also constitute a conflict of interest.”

Judge Leon’s ruling bars the FDA from using a 2011 TPSAC report on menthol, and it also “enjoins the FDA to reconstitute TPSAC’s membership so that it complies with the applicable ethics laws.”  Dr. Samet is the only conflicted member remaining on TPSAC, as chair (until 2016).  Another member, Claudia Barone, may have a conflict, because she received a Pfizer Educational Grant through 2013 and was appointed to the TPSAC on April 1, 2014 (here).

Although the ruling applies specifically to committee actions on menthol cigarettes and dissolvable products, it is relevant to all TPSAC activities until conflicted members are removed.

It is common for experts to be co-opted by financial support from organizations committed to a tobacco free society, a euphemism for the obliteration of the tobacco industry (an objective that is at odds with the principle of regulation).  Any individual who is funded by organizations such as the American Cancer Society, the American Heart Association, the American Lung Association, the National Cancer Institute, the Centers for Disease Control and Prevention, or the Robert Wood Johnson Foundation should be ineligible for membership on TPSAC.

(Updated July 23)

Imagining Tobacco Without Nicotine

In June, I called attention to the unscientific proposal by two FDA tobacco advisory committee members, Drs. Jack Henningfield and Neal Benowitz, to radically reduce nicotine in cigarettes in order to force smokers to quit and prevent children from starting to smoke (read my post here). They are now the co-authors of another thinly veiled call for reducing nicotine to “non-addictive levels” in cigarettes, just published in the journal Tobacco Control (abstract here).

Henningfield and Benowitz are joined by fellow committee member Dr. Dorothy Hatsukami, the National Cancer Institute’s Dr. Cathy Backinger (read about her previous pronouncements here), FDA staffer Dr. David Ashley, and Mitch Zeller, a lawyer. Zeller works for a consulting firm employed by GlaxoSmithKline, the pharmaceutical manufacturer that last week called on the FDA to ban dissolvable tobacco products (read about it here). According to Dr. Elizabeth Whelan of the American Council on Science and Health, “GSK is clearly trying to protect its own market…” by eliminating tobacco products that it perceives as competition with its medicinal nicotine products.” (For insights on medicinal nicotine’s dismal track record, see my previous blog post).

The Tobacco Control article is an urgent call for research that would inform policy decisions regarding reduced nicotine cigarettes. Here are the questions these “six leading tobacco research and policy experts” (as they describe themselves in their press release) want answered about reducing cigarette nicotine content:

"What is the nicotine threshold dose(s) for addiction…? What are the effects of reduced nicotine cigarettes on the brain in adult smokers and in adolescents…? What is the extent of compensatory smoking…and what interventions can be used to minimize compensatory smoking, such as making nicotine available through less hazardous delivery systems (e.g. nicotine replacement therapy)…? What are the effects of reduced nicotine cigarettes in subpopulations (consumers who smoke for self-medication purposes such as those with comorbidity or who are severely addicted)…and how can negative consequences be mitigated? What would be the public’s reaction…? How could we frame the message and educate the public…? What are the potential unintended consequences from reduced nicotine cigarettes, how can [the consequences] be determined and monitored, and what needs to be done to mitigate against negative consequences?"

In other words, these “experts” can’t even define a threshold dose for nicotine addiction, and they are clueless about the effects of radically reducing nicotine in cigarettes. Yet, their press release (here ) makes nicotine prohibition sound like the perfect solution. Dr. Hatsukami ignored all those important questions, proclaiming in the release that “Reducing the nicotine in cigarettes to a level that is non-addicting could have a profound impact on reducing death and disability related to cigarettes and improving overall public health.” It appears that she has already reached conclusions before the research is performed.

Lawyer Zeller was even more fanciful: “Imagine a world where the only cigarettes that kids could experiment with would neither create nor sustain addiction.”

Unfortunately, it doesn’t take an active imagination to appreciate the disaster that would result from radical reduction (prohibition) of nicotine in cigarettes. One need only look at the nation’s reaction to alcohol prohibition, as chronicled by Daniel Orient in his outstanding book, Last Call (description here).

In 1914, U.S. per capita beer consumption was 20 gallons. In anticipation of alcohol prohibition, launched in 1920 by the 18th Amendment to the Constitution, breweries produced an alcohol-free drink, informally called near beer. Six months into prohibition, sales of near beer plummeted, and brewers turned to a more attractive and profitable alternative: malt syrup, the key ingredient for making beer. It was sold in grocery stores across the nation, and it spawned a mini-industry offering filters, bottles, bottle stoppers, and most importantly, yeast. It is not a coincidence that California vineyards survived Prohibition in a similar manner. Millions of Americans legally consumed alcohol during Prohibition by making their own beer and wine.

The prohibitionists’ response to home brewing was to call for more prohibition. In 1925, Wayne B. Wheeler, a key prohibition architect (profiled here), asked one of his friends in Congress if “the time is ripe to prohibit the sale and distribution of these malt syrups and malt supplies.” Orient writes, “It wasn’t, nor would it ever be.”

Near beer, which tasted like real beer, didn’t sell precisely because it didn’t provide alcohol, an addictive drug with benefits. Today, neo-prohibitionists, with little research and a lot of imagination, are trying to sell Americans on near cigarettes that are devoid of addictive but rewarding nicotine.

Is the time ripe for such foolishness, especially when smokers have increasing access to vastly safer smokeless alternatives? It isn’t, nor will it ever be.

Does Dual Use Jeopardize Smokeless Tobacco’s Role in Harm Reduction? Absolutely Not

One year ago, I briefly discussed the “dual use” of cigarettes and smokeless tobacco by men in the U.S. (post here). Dual use is the object of persistent complaints by American tobacco control extremists. For example, in 2002, Dr. Jack Henningfield, currently a member of the FDA tobacco products scientific advisory committee, was first author of a commentary describing theoretical adverse consequences of dual use (citation here). Despite his concerns, Henningfield acknowledged that “There are virtually no data that currently exist on the safety of such use or the degree to which such use will foster the perpetuation of smoking or contribute to reduced overall smoking…The issue warrants further study.”

That study has now been done, and the results have been published online in Nicotine & Tobacco Research (abstract available here). In a review of 17 published research studies that had data on the health risks from dual use versus those from smoking, almost all of which have appeared since 2002, Kimberly Frost-Pineda and colleagues conclude that “…there are not any unique health risks associated with dual use of smokeless tobacco products and cigarettes, which are not anticipated or observed from cigarette smoking alone.” The authors further commented that “some data indicate that the risks of dual use are lower than those of exclusive smoking.”

Frost-Pineda and colleagues also found evidence from both American and Swedish longitudinal studies that dual users were more likely than exclusive smokers to quit smoking, but less likely to become completely tobacco-abstinent. For example, one American study (abstract here) found that 11% of dual users were tobacco-abstinent after 4 years of follow-up, compared with 16% of exclusive smokers. However, 80% of exclusive smokers were still smoking at the 4-year follow-up, while only 27% of dual users were smoking; 44% were still dual users and 17% were exclusive smokeless users. The differences between smokers and dual users in Swedish follow-up studies are even more impressive.

This excellent review will present major problems for Henningfield and other FDA panelists, including Greg Connolly, Dorothy Hatsukami, Jonathan Samet and Neal Benowitz, because they have established solid records opposing tobacco harm reduction. Samet, the panel’s chair, summed up this opposition in a 2009 article in the Journal of the American Medical Association (citation here ): “Snus, a moist snuff that is low in tobacco-specific nitrosamines, has received particular attention because it has been widely used in Sweden, apparently with little increase in risks for cancer and cardiovascular disease. However, there is concern that strategies to introduce lower-risk products will diminish efforts to promote prevention and cessation.”

For over 40 years, “prevention and cessation” efforts have largely failed. But tobacco prohibitionists continue to focus on those objectives, while raising a host of largely theoretical concerns about the substitution of smokeless tobacco for cigarettes. Now, scientific research shows that the “problem” of dual use is not a problem at all.

A final note: The authors of the dual use study are employees of Altria Client Services, which is owned by the parent company of Philip Morris and U.S. Smokeless Tobacco. They should be complimented for this contribution to the scientific literature on tobacco harm reduction. The editors of Nicotine and Tobacco Research deserve kudos for reviewing and publishing this manuscript.