Federal Appeals Court to FDA: E-Cigarettes Are Tobacco Products, Not Medicines

One month ago a federal appeals court affirmed Judge Richard Leon’s decision requiring the FDA to regulate e-cigarettes as tobacco products, rather than as drug-delivery devices, as the agency had attempted to do. This week the appellate court rejected the FDA’s request to review the decision, so the only remaining option for the agency is to appeal to the Supreme Court (here).

The FDA had decided that e-cigarettes were being sold without sufficient evidence of safety and efficacy – the expensive and time-consuming regulatory challenge that all drug manufacturers must address. The agency had begun seizing shipments, triggering the suit.

As I noted one year ago (here), Judge Leon found that the 2009 “Tobacco Act applies to ‘tobacco products,’ which Congress defined expansively as ‘any product made or derived from tobacco that is intended for human consumption’…Congress enacted the Tobacco Act to confer FDA jurisdiction over any tobacco product – whether traditional or not – that is sold for customary recreational use, as opposed to therapeutic use. As such, the Tobacco Act, in effect, serves as an implicit acknowledgment by Congress that FDA's jurisdiction over drugs and devices does not, and never did, extend to tobacco products, like electronic cigarettes, that are marketed in customary fashion for purely recreational purposes.”

The reaction from nicotine prohibitionists has been predictable. Matthew Myers, president of the Campaign for Tobacco-Free Kids, called the decision “wrong on the law, wrong on the facts…” and he urged “the government to appeal this ruling.”

Why is Mr. Myers so upset? According to the New York Times, he was a primary author of the Tobacco Act (link here). The legislation placed “any product made or derived from tobacco that is intended for human consumption” under FDA control.

It is wonderful irony that the courts have interpreted Myers’ legislation to free a potentially broad array of recreational nicotine products from drug regulation. It is also a dramatic, positive development for tobacco harm reduction, public health and millions of inveterate smokers, effectively accomplishing what I first advocated in 1995 – deregulation of nicotine. (link here)

This week I was interviewed about the e-cigarette issue by www.AllTreatment.com, which focuses on ways of making treatment and recovery more accessible to anyone struggling with addiction. That interview is available here.

New Study Documents the Health Effects from Snus Use: Almost Zero

A detailed review of epidemiologic studies regarding snus use has just been published online by Regulatory Toxicology and Pharmacology (abstract here). Author Peter Lee, a UK epidemiologist, concludes: “Using snus is clearly much safer than smoking. While smoking substantially increases the risk of cancer and cardiovascular diseases, any increase from snus use is undemonstrated, and if it exists is probably about 1% of that from smoking.”

Dr. Lee confirms what I have been asserting since 1994: Smokeless tobacco use is 99% less hazardous than smoking, and the magnitude of risk, if it exists, is difficult to measure using modern epidemiologic methods.

Lee reviewed the evidence from over 150 studies covering many diseases. Previously, he published separate meta analyses involving smokeless tobacco use and all cancers (abstract here), dental problems (abstract here), pancreas cancer (here), oral cancer (here), and circulatory diseases (here).

The hallmark of Lee’s analytic approach is to use all of the published evidence in a systematic and unbiased manner. This is in direct contrast to anti-tobacco advocates like Dr. Paolo Boffetta, who cherry pick the data and use only numbers that confirm their pre-existing belief that smokeless tobacco causes disease. Pancreas cancer is an excellent example.

In 2008, Boffetta published a meta analysis (abstract here) in which he claimed that snus use is a risk factor for pancreas cancer. He cited two studies, one from Norway (here) and another from Sweden (here). The Norway study reported a risk increase among all snus users (Relative Risk = 1.7, Confidence Interval = 1.1 – 2.5) but not for a subset of snus users who were never smokers (RR = 0.9, CI = 0.2 – 3.1). The Swedish study reported exactly the opposite: There was virtually no risk among all snus users (RR = 0.9, CI = 0.7 – 1.2), but the subset of snus users who never smoked had an increased risk (RR = 2.0, CI = 1.2 – 3.3).

Dr. Boffetta chose only to use the elevated risks, even though they were from different groups. As Lee points out, “For pancreatic cancer, Boffetta cited only the increases for never smokers from the [Swedish] study and for the whole population from the [Norwegian] study, not mentioning the lack of increase for the whole population for the construction workers and for never smokers for the Norway cohorts.”

It is important to note Dr. Boffetta was an author of both studies; that makes his selective use of data from them even more objectionable.

Another issue raised by Lee about another Boffetta meta analysis (here) claiming that snus use is a risk factor for fatal – as opposed to non-fatal – heart attack and stroke. In a 2009 blog post, I noted that Boffetta’s claim was questionable (here): “Boffetta found that smokeless users had no significant risk for all heart attacks and strokes but had elevated risks for fatal cases. It logically follows that smokeless users probably had LOWER risks for NON-FATAL heart attacks and strokes.” Lee echoes my concern: “Anyway, an association for fatal cases but not for all cases seems unlikely unless implausibly snus protects against non-fatal cases.”

Finally, Lee reviewed epidemiologic studies to answer this question: Does snus encourage initiation of smoking or discourage quitting? His conclusion: “There is no good evidence that introducing snus in a population would encourage smoking initiation or discourage cessation.”

This is an especially important point, because RJ Reynolds has just launched a campaign encouraging smokers to switch completely to Camel Snus (article here). While apparently in full compliance with FDA tobacco regulations, the ads have enraged prohibitionists like Matt Myers, who said that Reynolds should “stop its insidious marketing of tobacco products in ways that seek to discourage smokers from quitting and keep them hooked on nicotine...The ads are trying to take advantage of people trying to end all uses of tobacco.”

Myers is wrong about many things. Most smokers are not trying to achieve abstinence, but they are interested in enjoying tobacco in a safer manner. As Dr. Lee documents, snus is a vastly safer cigarette substitute.

Scientific Evidence Supporting FDA Regulatory Action of Menthol Cigarettes: Essentially Nil

In March, the FDA Tobacco Products Scientific Advisory Committee (TPSAC) is scheduled to release recommendations for agency regulation of menthol cigarettes. This is a highly charged issue, racially, politically and legally. Additionally, the TPSAC recommendations and any subsequent regulations will be harbingers of the FDA’s future handling of smokeless tobacco and tobacco harm reduction.

Dr. Lawrence Deyton, director of the FDA Center for Tobacco Products, has stated 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.” (here)

Last year, the “best available science” on menthol was reviewed by the American Council on Science and Health, a science-driven organization that has been anti-smoking for decades. I was an expert reviewer of that report (available here), which concluded that any differences in health effects from smoking menthol versus non-menthol cigarettes are inconsequential.

The ACSH report used the available scientific evidence to answer a series of questions:

1. Does cigarette mentholation affect initiation, dependency, and cessation?

ACSH: “Overall, the evidence summarized in this section does not suggest that mentholated cigarettes are associated with any independent reduction in age of starting to smoke (‘starter product for youth’), increase in cigarette consumption or dependency (‘greater addiction potential’)… Data from the Federal Trade Commission in 2006 indicate that the menthol percentage of the total cigarette market has been remarkably stable over the last 35 years. If menthol cigarettes were more addictive than non-menthol, or otherwise increased likelihood of usage, then menthol’s share of market would have steadily increased over the last 35 years.”

2. Does mentholation affect the metabolism and clearance of nicotine and other smoke constituents?

ACSH: “Although there are only a few studies, cigarette mentholation does not appear to have any major effects on either the absorption of nicotine and smoke, or the metabolism and elimination of tobacco smoke constituents.”

3. Does cigarette mentholation affect smoking behavior?

ACSH: “Taken as a whole, the data presented here are inconsistent with the idea that mentholation may affect how a cigarette is smoked so as to increase uptake of toxic smoke constituents through a ‘unique stimulatory sensation.’”

4. Could menthol cigarettes be claimed [by manufacturers] to be “healthier”

ACSH: “Any such health claims without rigorous substantiation would instantly attract the attention of numerous regulatory authorities, such as the Federal Trade Commission. Since these authorities have continued for decades to allow the sale of mentholated cigarettes, it is safe to assume that mentholated cigarettes do not differ in any substantial way from non-mentholated cigarettes in terms of generalized health claims.”

5. Does mentholation of cigarettes affect other smoke constituents, and is the subsequent toxicology any different?

ACSH: “The in vitro and in vivo toxicological properties of mentholated and non-mentholated cigarettes appear to be virtually identical.”

6. Does menthol affect airway patency?

ACSH: “…[M]enthol does not ‘help the poison go down,’ since if this were the case there would be substantial increases in the various biomarkers of smoke exposure, which is clearly not the case.”

7. Does mentholation increase the risk of lung cancer in smokers?

ACSH: “It appears to be very unlikely from the cumulative evidence that cigarette mentholation increases the risk of lung cancer, and may even protect from it.”

8. Does mentholation increase the risk of other diseases?

ACSH: “Overall, available epidemiological data on cancers other than lung cancer do not suggest any important pathogenic role of cigarette mentholation…Incidences of other diseases do not seem to differ between smokers of mentholated and non-mentholated cigarettes, and mortality rates are similar.”


The ACSH report also comments on the societal consequences of a menthol cigarette ban:

“An FDA ban of menthol in cigarettes would affect 25% of the near 50 million U.S. smokers. The affected smokers are largely minorities who have a strong preference for mentholation, and the arbitrary removal of this choice by the FDA would almost certainly result in the rapid establishment of a black market, possibly accompanied by ‘do-it-yourself’ attempts to modify non-menthol cigarettes through potentially more risky attempts at ‘home mentholation.’ Neither of these scenarios represents the actions of a society dedicated to the factual, unbiased, and scientific assessment of the biological effects of consumer products.”

The bottom line: There is essentially no published scientific evidence for any FDA regulatory action that restricts or removes menthol cigarettes from the American market.

Camel Dissolvables and Anti-Tobacco Dissembling

On December 20, R.J. Reynolds Tobacco Company announced that it was discontinuing Camel Dissolvable test marketing in Indianapolis, Columbus, Ohio and Portland, Oregon (here). The response from Matthew Myers (here), president of the Campaign for Tobacco-Free Kids, speaks volumes about the U.S. anti-tobacco crusade’s faulty logic.

According to Myers, “The Camel dissolvable products appeal to children in that they are easily concealed and colorfully packaged, shaped and flavored to resemble mints or gum.” He ignores the fact that dissolvables are tobacco products and are thus subject to a complete sales prohibition to anyone under 18 years in all 50 states.

Myers also blamed tobacco manufacturers for an increase in smokeless tobacco use by children: “Most troubling, the most recent data on youth tobacco use, included in the Monitoring the Future Survey released just last week, shows a significant increase in smokeless tobacco use among high school students. Among 12th graders, 8.5 percent used smokeless tobacco in 2010, a 39 percent increase since 2006…The increase in smokeless tobacco use also comes as some smokeless manufacturers have sought to portray their products as a less hazardous alternative to cigarettes.”

Myers’s use of the Monitoring the Future Survey was very creative. Why use 2006 as a comparison year? Because in 2006, smokeless tobacco prevalence was unusually low – in fact, the lowest in the 25-year history of the survey. This makes the 8.5 percent prevalence in 2010 seem like a substantial increase. Actually prevalence was 8.4% in 2009 and 1999, and even higher before that.

It is disingenuous for Myers to blame manufacturers for tobacco use by teenagers. While it’s true that 8.5% of 12th graders used smokeless tobacco and 19.2% smoked cigarettes in 2010, 21.4%, smoked marijuana. What industry does Myers hold responsible for marijuana use among children?

Teenage substance use fluctuates, which permits zealots to cherry-pick findings for dramatic, but highly misleading, story lines. If tobacco use is down, zealots take credit; if tobacco use rises, they blame industry.

Gandhi said an error does not become truth by reason of multiplied propagation, nor does truth become error because nobody sees it. Tobacco opponents continue to dissemble on harm reduction and the risks associated with smokeless tobacco. But the facts endure, and they will continue to sustain a transformation in nicotine and tobacco use.

Quit-Smoking Medicines and Episodes of Violence

A new study published in Public Library of Science One (available here) reports that two drugs widely prescribed to help smokers quit -- varenicline (brand name Chantix) and bupropion (brand names Wellbutrin and Zyban) - are associated with thoughts or acts of violence towards others.

The study was conducted by Thomas Moore at the Institute for Safe Medication Practices, and colleagues from Harvard and Wake Forest Universities. Moore et. al. analyzed data from the FDA Adverse Event Reporting System, extracting all serious adverse event reports for drugs with 200 or more cases received from 2004 through September 2009. The researchers focused on homicide, homicidal ideation, physical assault, physical abuse and violence related symptoms. They reported the number of events, as well as proportional reporting ratios (PRRs), which allows for comparison of the proportion of violence events for each medicine with the proportion from all other evaluable drugs (those in wide clinical use with adequate post-marketing surveillance).

Moore found that “among 484 evaluable drugs, 31 drugs met the study criteria for
a disproportionate association with violence, and accounted for 1527/1937 (79%) of the violence cases…Varenicline has the largest number of reported violence cases (n = 408), [and] the highest proportion of violence cases (PRR= 18.0).”

The PRR for varenicline was so high that it was in a class all by itself. As Moore and colleagues noted, “We have previously examined varenicline’s association with serious psychiatric symptoms including aggression/violence [references omitted]. The aggression/violence case series for varenicline was consistent with these data but revealed other features that may or may not occur in cases attributed to other drugs. These features include early onset of psychiatric symptoms (usually within a few days), a senseless act of aggression/violence directed at anyone who happened to be near by, and resolution of the symptoms upon discontinuation.”

Moore also found that bupropion, an antidepressant prescribed to aid smoking cessation, was also associated with violence, although at a much lower rate (35 episodes, PRR = 3.9). As he and his associates note, “bupropion is indicated for both depression and as an aid to smoking cessation, so those results are not limited to the smoking cessation population.”

Moore also studied pharmaceutical nicotine, which was associated much less frequently with violent episodes (11 cases, PRR = 1.9).

Tobacco prohibitionists like the American Cancer Society often claim that tobacco harm reduction is unnecessary, since medicines represent the gold standard for smoking cessation. This study demonstrates that the gold standard is substantially tarnished. At a minimum, the Cancer Society should update its website discussion of smoking cessation (here). The current version promotes varenicline and bupropion, but fails to mention the drugs’ possible side effect of violent behavior.

POTUS Puffing?

On December 10, White House press secretary Robert Gibbs was asked pointed questions about whether President Obama had quit smoking. Gibbs responded by saying, “I've not seen or witnessed evidence of any smoking in probably nine months,” which prompted an optimistic headline in the Washington Post: “Obama Kicks His Smoking Habit.” But after watching the video of Gibbs’ actual comments (available here), one is left with the impression that the press secretary was practicing plausible deniability; he never actually said President Obama had quit smoking.

Two and a half years ago, in June 2008, I wrote to then-Senator and presidential candidate Obama, encouraging him to consider practicing tobacco harm reduction. I also submitted my letter to the Chicago Tribune, which published it on June 22. The text of that letter (also available here) is as relevant to millions of Americans, and very likely the President, as we move into 2011 as it was two years ago:

An Open Letter To Barack Obama

Dear Senator Obama:

I viewed with great interest your recent comments about your struggle to quit smoking. As a professor of medicine at the University of Louisville with a long-term research program focused on tobacco use and its consequences, I strongly believe that your discomfort is entirely unnecessary; your dependency on cigarettes can readily be resolved.

First, understand that you are not alone. Some 25 million adult Americans are inveterate smokers – that’s about 50% of all who smoke. They are unable or unwilling to stop using tobacco and nicotine. For them, conventional quit-smoking tactics, which require abstinence, simply don’t work.

A growing number of public health experts – including Britain’s Royal College of Physicians, one of the world’s oldest and most prestigious medical societies – believe that inveterate smokers could benefit from alternative tobacco products that are effective quit-smoking aids and vastly safer substitutes for cigarettes.

The Royal College has observed that “smokers smoke predominantly for nicotine” and “nicotine itself is not especially hazardous.” You probably appreciate that nicotine is among the most powerful of addictive substances. But nicotine doesn’t cause any smoking-related disease. In fact, nicotine itself is about as safe as caffeine, another addictive drug consumed safely by millions of Americans.

Research and consumer experience show that smokers can obtain satisfying doses of nicotine from smoke-free (and spit-free) tobacco products. Available as small packets or pellets of tobacco that are placed inside the upper lip, modern smokeless tobacco products can be used invisibly in all social settings, including stressful press conferences.

Most importantly, smokeless tobacco products are 98% safer than smoking. While no tobacco product is completely safe, the majority of cigarette smokers are routinely misinformed – by government agencies and by anti-tobacco extremists – about the relative safety of smokeless products. Unlike cigarettes, smokeless does not cause lung cancer, heart disease or emphysema. Smokers rightfully worry about mouth cancer, but they should take comfort in the fact that the risk for mouth cancer with smokeless is far lower than it is with cigarettes. Statistically, smokeless users have about the same risk of dying from mouth cancer as automobile users have of dying in a car wreck.

In fact, switching from cigarettes to smokeless provides almost all of the health benefits of complete tobacco abstinence.

Substituting satisfying and vastly safer sources of nicotine for cigarettes is called “tobacco harm reduction”. Tobacco harm reduction has worked in Sweden, where men have smoked less and used more smokeless tobacco over the past century than in any other Western country. The result: Swedish men have the lowest rates of lung cancer – indeed, of all tobacco-related deaths – in the developed world.

A colleague and I recently published research, based on an analysis of the federal government’s National Health Interview Survey, documenting that tobacco harm reduction has also worked for American smokers.

The Royal College characterized harm reduction as “a fundamental component of many aspects of medicine and, indeed, everyday life, yet for some reason effective harm reduction principles have not been applied to tobacco smoking.” It concluded, “If nicotine could be provided in a form that is acceptable and effective as a cigarette substitute, millions of lives could be saved.”

Senator, your genuine desire to quit tobacco altogether is commendable. But if you find this goal unachievable, like millions of inveterate smokers, I urge you to switch to smokeless tobacco for your physical and emotional wellbeing. In doing so, you can provide inspiration for American smokers, and you can effect a profound positive change in the nation’s public health. Yes, you can.

Sincerely,

Brad Rodu
Professor of Medicine
Endowed Chair, Tobacco Harm Reduction Research
University of Louisville

Snus Not Linked to Colorectal Cancer

Researchers from the Swedish Karolinska Institute have published a study in the International Journal of Cancer showing that snus use is not a risk factor for cancers of the colon, rectum and anus among Swedish men (abstract here).

Caroline Nordenvall, from the Department of Medical Epidemiology and Biostatistics, and colleagues studied over 300,000 male Swedish construction workers who enrolled in a health program from 1971 to 1992. The workers were followed for up to 37 years, and Nordenvall calculated the relative risks (RRs) for cancer of the colon, rectum and anus among smokers and snus users.

Compared with non-users of tobacco, smokers had RRs of 1.08 (95% Confidence Interval = 0.99 – 1.19) for colon cancer and 1.16 (CI = 1.04 – 1.30) for rectal cancer. These are very small increases, and only the latter is statistically significant. The RR for anal cancer among smokers was 2.41 (CI = 1.06 – 5.48). Although smoking has been implicated for many years as a risk factor for anal cancer, the sexually transmitted human papillomaviruses are known causes of this malignancy. Information on sexual behavior or venereal infections, not found in this study, might affect Nordenvall’s risk estimate for smoking.

Snus users did not have significantly elevated risks for any of these cancers. The RRs were 1.08 (CI = 0.91 – 1.29) for colon cancer, 1.05 (CI = 0.85 – 1.31) for rectal cancer and 0.61 (CI = 0.07 – 5.07) for anal cancer.

Nordenvall concluded her study with the following: “Our results from a large and homogenous cohort of Swedish male construction workers with up to 37 years of
follow-up do not convincingly support an important role of tobacco use in the etiology of colorectal cancer. As expected, an increased risk of anal cancer was associated with smoking.”