Kudos to the FDA: E-Cigarettes Are Tobacco Products

On April 25, the FDA abandoned its claim that e-cigarettes are drug delivery devices. In an open letter published on the agency’s website (here), Tobacco Center Director Lawrence Deyton and Drug Center Director Janet Woodcock acknowledged that e-cigarettes are tobacco products and would be subject to regulations under the 2009 Tobacco Act. This is consistent with the January 2010 decision by federal judge Richard Leon (discussed here).

This is a victory on several counts for smokers and for our nation’s public health. First, the FDA decision guarantees that e-cigarettes, which have helped many smokers quit, will remain on the market.

Second, as the Deyton-Woodcock letter indicates, FDA regulation of e-cigarettes will subject them “to general controls, such as registration, product listing, ingredient listing, good manufacturing practice requirements, user fees for certain products, and the adulteration and misbranding provisions, as well as to the premarket review requirements for ‘new tobacco products’ and ‘modified risk tobacco products.’” These requirements will promote the marketing of safe and quality-controlled products.

Finally, this decision could allow pharmaceutical companies to reposition nicotine medicines as recreational alternatives to cigarettes. Today, these products are sold with a therapeutic claim for smoking cessation, but they are expensive, unsatisfying and FDA-approved only for temporary use (10-12 weeks). That accounts for their dismal success rate of only seven percent among smokers (evidence here). I believe pharmaceutical companies should enter the recreational nicotine market with products that satisfy smokers indefinitely and are cheap enough to compete directly with cigarettes. Clearly, the tobacco industry is poised to compete in this new market -- Reynolds American owns Niconovum (here) and British American Tobacco recently formed Nicoventures (here).

In my 1995 book “For Smokers Only” (description here), I shared my perspective on recreational nicotine for smokers:

“Smokers derive a lot of pleasure from smoking tobacco. You may be reading this book because you or your loved one actually enjoys lighting up a cigarette and taking several deep puffs. A smoke may be especially welcome when you are in a stressful situation or when you need to relax. Or you may enjoy smoking when you need to concentrate on a difficult problem at work or at home. Cigarette smoking can activate that mental pressure-relief valve, which is followed by the feeling that the problem can be solved, the crisis will pass. These feelings are real, and not just a figment of your imagination.

“Many tobacco opponents claim that these sensations are not truly pleasurable, but are merely the satisfying of induced cravings and avoidance of withdrawal symptoms. One of the big advantages of the smokeless tobacco solution is that it addresses either view of smoking equally well. That is, it doesn't matter if you are a smoker who is unwilling to quit because you enjoy tobacco, or if you are unable to quit because of nicotine craving and withdrawal. Because in either case you recognize the potential life-shortening effects of this nicotine delivery system. In either case the smokeless tobacco solution can work for you.”

Smoking has been the problem; smoke-free tobacco and nicotine can be the solution. In making the right call on e-cigarettes, the FDA has facilitated that solution.

Nicotine Delivery and Satisfaction: Snus is Superior

In a small, but impressive, clinical study just published in Nicotine & Tobacco Research, Drs. Erik Lunell and Margareta Curvall demonstrate that snus is a superior substitute for delivering satisfying nicotine doses to smokers (abstract here). Dr. Curvall is a scientist employed by Swedish Match.

Lunell and Curvall recruited 15 smokers (9 men, 6 women) who had never used snus or nicotine gum to use two snus 1-gram snus products (in packets) and 4-milligram nicotine gum during three visits to a clinic in Helsingborg, Sweden. The subjects abstained from smoking for 12 hours the night before each visit.

The researchers measured the amount of nicotine in the used products and found that a higher proportion was extracted from the gum than from the snus products. This is understandable, because the gum was chewed, while the snus was simply placed under the upper lip. Nevertheless, blood nicotine levels from snus were higher after 30 minutes than those from the gum, and the increases were also faster for snus. The snus products took less time than the gum to deliver the maximum nicotine level (37 versus 46 minutes), but the differences were not statistically significant.

The most important finding was that the snus products had higher subjective scores than the gum for overall “product strength” (also referred to as “head rush”, “buzz” or “hit”). This means that the snus products were more enjoyable than the gum, even though all products reduced the craving or urge to smoke to about the same extent. Another interesting finding is that snus resulted in significantly less mouth and throat burn than the gum five minutes after use.

Lunell and Curvall concluded “that Swedish snus produces a higher maximum blood nicotine concentration, in shorter time and with a quicker onset of ‘head rush’ in smokers naïve to snus, compared with the 4 mg [nicotine] chewing gum in spite of a smaller ingested dose…The quicker onset of ‘head rush’ and supposedly higher satisfaction from snus may partly explain the widespread use of snus in Sweden in attempts to stop smoking.”

This study is additional proof that smokeless satisfies smokers.

Smoking Gun: Manipulating Definitions

A report just published in Nicotine & Tobacco Research (abstract here) draws an obvious conclusion: How surveys define cigarette smokers and smokeless tobacco users influences the prevalence rate of dual use (consumption of both products).

Robert Klesges and colleagues used information obtained from Air Force recruits to show that if dual users are defined as using both products daily (a narrow definition), prevalence of dual use will be low. However, if dual users are defined as using either product once in the past month (a broader definition), prevalence of dual use will be high.

It is not surprising that Dr. Klesges found that defining tobacco use influences survey results. In 2001, he co-authored a study (with first-author C. Keith Haddock, abstract here; hereafter called Haddock-2001) that perfectly demonstrates how definitions can be manipulated to produce desirable results. Haddock-2001 purported to show that smokeless tobacco use is a gateway to smoking among Air Force recruits; it has been widely cited in American prohibitionist attacks on smokeless tobacco. In fact, its results are based on manipulation of definitions.

Haddock-2001 studied 14,340 men (average age, about 20 years) who had never smoked when they reported to Air Force basic training in 1995 and 1996. After one year, Dr. Haddock followed up with 7,865 subjects, finding that 1,099 of them were smoking. That’s a 14% smoking initiation rate among 20-year old men after one year in the Air Force! At one year, Haddock-2001 also found that, compared with recruits who had never used tobacco before basic training, recruits who were current smokeless users were 2.33 (95% Confidence interval = 1.84 – 2.94) times more likely to be smoking.

First, how did 14% of first-year never-smoking Air Force recruits start smoking? It turns out that this number is grossly inflated. In 1999, Drs. Klesges and Haddock had published a study of these same recruits (abstract here; hereafter called Klesges-1999), in which they reported that only 8% of never smokers had started to smoke after one year in the Air Force.

The discrepancy between Haddock-2001 and Klesges-1999 is due to differences in the category definitions of smoking, summarized in this table.

Different Definitions of Smokers in Klesges-1999 and Haddock-2001
Category	Klesges-1999	Haddock-2001(%)
At Enrollment
Never Smoker	Never smoked a cigarette	Never Smoked regularly
Experimental Smoker	Smoked on one or two occasions, never regularly	Not mentioned
Ex-smoker	Smoked regularly, but quit	Smoked regularly, but quit
Current Smoker	Smoked regularly, at least one cigarette per day	Smoked regularly, at least one cigarette per day
At One Year
Current Smoker	Smoked even a puff in last 7 days	Smoked even a puff in last 7 days

At enrollment, Klesges-1999 identified a group of “experimental smokers,” 26% of whom became smokers at the one-year follow-up. But Haddock-2001 never mentioned experimental smokers, which means that they were in the “never-smoking” group at enrollment; that significantly accounts for the 14% initiation rate, instead of the 8% rate found in the Klesges-1999 report.

It is likely that many Haddock-2001 smokeless tobacco users were also experimental smokers. The only apparent reason to eliminate the experimental smoker category and effectively shift those subjects to the never-smoking category was to bolster the case for labeling smokeless tobacco use as a gateway to smoking.

Dr. Haddock also defined current smoking differently at enrollment than after one year of follow-up. Good practice in scientific investigation is to establish definitions and stick with them throughout a research project. As the table shows, Haddock-2001 defined a current smoker at enrollment as smoking at least one cigarette per day, but then defined a current smoker at one-year as someone who smoked even a puff in the last 7 days.

The manipulation of smoking definitions in Haddock-2001 casts considerable doubt on its claim that smokeless tobacco use is a gateway to smoking.

American Cancer Society Withholds Important Information About Tobacco Use and Risk

Last week, I discussed how the American Cancer Society (ACS) misinforms Americans about the risks of smokeless tobacco use (here). The ACS is also withholding important information that has profound implications for FDA regulation of smokeless tobacco.

I wrote to ACS president John Seffrin in September 2010, asking the organization “to fully and publicly disclose important information from its Cancer Prevention Study II (CPS-II) regarding the health risks associated with tobacco use. Notwithstanding the fact that this information has been in the possession of the ACS for years, it has not been made public. The tobacco regulatory and research community, as well as the American public, need access to this information in order to validate significant differences in the health risks associated with smokeless tobacco use compared with smoking in the U.S.”

I noted that the ACS has released highly selective bits of information about smoking and smokeless tobacco use:

“The ACS has provided the Centers for Disease Control and Prevention (CDC) with risk estimates for cigarette smokers, which are derived from a 6-year follow-up of CPS-II. For many years the CDC has used these risks to estimate that smoking kills 400,000 Americans every year. Although these estimates serve as the cornerstone for federal government actions regarding smoking, there is no way to validate them, because the ACS has never published the risks or released the CPS-II data on which they are based.

“In addition to smoker risk estimates, the ACS must release complete risk estimates for smokeless tobacco users and smokers who switched to smokeless tobacco. Previous ACS releases have been highly selective and incomplete, and none are directly comparable because the ACS used different follow-up intervals. As I noted, the ACS provided unpublished risk estimates derived from a 6-year follow-up of CPS-II for smokers. For smokeless tobacco users, ACS investigators have published risk estimates using an 18-year follow-up of CPS-II; for switchers, ACS and CDC investigators have together published risk estimates using a 20-year follow-up.”

I explained why this information was important for FDA regulation:

“There are compelling reasons why the ACS should release this information. Officials at the U.S. Food and Drug Administration (FDA), which now has regulatory authority over tobacco products, may not be aware that the health risks from smokeless tobacco use are vastly lower than those from smoking. Earlier this year, Lawrence Deyton, director of the FDA Center for Tobacco Products, Principal Deputy Commissioner Joshua Sharfstein and Commissioner Margaret Hamburg authored a commentary about tobacco regulation for the New England Journal of Medicine, in which smoking and tobacco use were used synonymously. These physicians wrote that ‘tobacco use causes more than 400,000 deaths in the United States annually…,’ and they described ‘tobacco products’ as ‘the leading cause of preventable death in the United States.’ If the ACS and the FDA are committed to reducing the morbidity and mortality from tobacco use, the first critical step must be to recognize that all forms of tobacco use are not equally risky. That critical issue was overlooked in the New England Journal of Medicine commentary.

“When FDA officials characterize all tobacco products as equally lethal, they are effectively denying smokers lifesaving information about safer cigarette substitutes. A 2004 study, in which ACS Vice President Emeritus Michael J. Thun participated, concluded that ‘…smokeless tobacco products pose a substantially lower risk to the user than do conventional cigarettes. This finding raises ethical questions concerning whether it is inappropriate and misleading for government officials or public health experts to characterize smokeless tobacco products as comparably dangerous with cigarette smoking.’ ”

I strongly urged the ACS to end its misinformation campaign by releasing ALL of its risk data:

“The public health is not well served when information that can save lives is buried and/or ignored. The selective and incomplete provision of risk information by the ACS is contrary to its public health mission and will only serve to hamper the FDA from undertaking an independent assessment of this issue in pursuit of its overarching mission: reducing the harm associated with tobacco use.

“I urge the ACS to release comparable risk estimates for male smokers, smokeless tobacco users and switchers in CPS-II for all three follow-up periods, 6-years, 18-years and 20-years. In addition, the ACS should release the CPS-II data, so that the risk estimates for all tobacco users can be validated by external scientists. I would be happy to meet with ACS officials to discuss this request.

“Dr. Deyton has confirmed that the FDA’s ‘objective is to use the best available science to develop and put into action effective public health strategies to reduce the enormous toll of illness and death caused by tobacco products.’ I strongly urge you to release these data and risk estimates, which constitute the best available science distinguishing the health risks related to smoking from those related to smokeless tobacco use. Because this matter has implications for future regulatory actions by the FDA, I have sent copies of this letter to relevant FDA officials.”

The ACS response was written by Chief Medical Officer Otis W. Brawley on December 1, 2010. He explained why the ACS would not share its data:

“[The ACS] have not found it productive to share the CPS-II data with researchers supported by the tobacco industry, because of their repeated misuse and misrepresentation of the data.”

I have conducted research on tobacco harm reduction for almost 20 years; published numerous studies in professional journals; written dozens of articles in the general media; and given hundreds of lectures. No one has ever accused me of misusing or misrepresenting any data.

The ACS continues to misinform Americans, and especially American smokers, about the vast difference in health risks related to smoking versus smokeless tobacco use. This is vitally important because the CPS-II survey is the only source for comparable information about the health risks from smoking and smokeless tobacco use.

FDA regulation of tobacco should not compromised by the withholding or selective release of critical data by the American Cancer Society.