Wednesday, June 30, 2010

Down the Rabbit Hole: Tobacco Control Through Radical Nicotine Reduction

June 22 marked the one-year anniversary of the Tobacco Act, which gave the FDA regulatory authority over tobacco products. Anti-tobacco extremists like Matthew Myers were delighted: “It's remarkable what the FDA has been able to accomplish in this first year.”

But the occasion was notable for another reason, the re-emergence of the most idiotic idea ever proposed by tobacco control advocates: Force smokers to quit by reducing the nicotine content of tobacco products. The Tobacco Act permits the FDA to reduce nicotine to any level above zero, thus allowing de facto nicotine prohibition.

Nicotine prohibition has been championed in the Washington Post (read it here) and elsewhere by Dr. David Kessler, former FDA commissioner and former medical school dean at the University of California/San Francisco.

This strategy was introduced in a 1994 commentary in the New England Journal of Medicine by Dr. Neal Benowitz and Dr. Jack Henningfield, tobacco opponents who now sit on the FDA tobacco products advisory panel. An ethics watchdog group has challenged their appointments based on conflicting financial interests (read it here). Their nicotine prohibition scheme, based on several highly speculative assumptions, casts doubt on their ability to provide the FDA with sound counsel.

Benowitz and Henningfield adopted, without hard evidence, the position that smokers of five or fewer cigarettes per day, are not addicted to nicotine. They even acknowledged the weakness of their assumption, commenting: “Of course, there is no sharply demarcated threshold level, and there are some people who smoke fewer than five cigarettes per day and have great difficulty in quitting and others who can smoke more than five cigarettes per day and quit with ease.”

Building on this unscientific position, Benowitz and Henningfield opined that “an absolute limit of 0.4 to 0.5 mg of nicotine per cigarette should be adequate to prevent or limit the development of addiction in most young people.” They believed that “the level of nicotine in tobacco could be reduced gradually, with a goal of reaching a target nicotine level over perhaps 10 to 15 years.”

Benowitz and Henningfield acknowledged that reducing nicotine could harm the nation’s 45 million current smokers. “Switching from higher-yield to lower-yield cigarettes has been shown to result in smoking more cigarettes or smoking more intensively [overcompensation], both of which are associated with increased exposure to carbon monoxide and other toxins.” But they were willing to make an unacceptable compromise: “Even if there is some element of overcompensation and smokers are exposed to increased levels of toxins, their short-term (10-year) risk may be offset by the long-term benefit of a greater likelihood that they will stop smoking (as cigarettes become less satisfying) and by the enormous benefit of preventing nicotine addiction in future generations.”

This radical nicotine reduction scheme would put smokers’ lives at risk, even though Benowitz and Henningfield admitted that “a threshold level for nicotine addiction is a theoretical concept.” In their commentary, they conceded that the theory “that restricting levels of nicotine would prevent addiction needs to be verified empirically,” but they reversed course in a subsequent letter to the journal: “There is no way of empirically testing the proposition that nonsmokers would be less likely to become addicted to low-nicotine cigarettes as we define them.”

Simply put, the Benowitz-Henningfield nicotine prohibition plan is to expose current smokers to increased levels of toxins over a 10-year period, in the hope that they will stop smoking in the long term, and that children might never start. They recognize that their plan needs to be tested, yet they acknowledge that testing is impossible. It is reminiscent of an Alice in Wonderland musing, “Sometimes I believe in as many as six impossible things before breakfast.”

The FDA must not follow Benowitz and Henningfield down the rabbit hole of nicotine prohibition.

Wednesday, June 23, 2010

Canadians Who Care About Tobacco Harm Reduction

Toronto’s Non-Smokers’ Rights Association has just become the first Canadian organization to endorse tobacco harm reduction. Together with the Smoking and Health Action Foundation, the NSRA published “Harm Reduction in Tobacco Control: What is it? Why should you care?”

The report (available here) is an accurate and balanced discussion of the issue. It describes smokeless tobacco products (including Swedish snus) and e-cigarettes, and it makes the following recommendations:

1. “Establish a regulatory framework for nicotine products.”

In theory, this is a reasonable approach; a regulatory agency could evaluate all tobacco and nicotine products with consistent criteria. The report suggests that “…availability, price/taxation, and permitted forms of promotion should all be related to the level of risk inherent in their use.” It is unfortunate that American legislation giving the FDA authority over tobacco contained no provisions for regulating tobacco products according to risk.

2. “Shift current tobacco users to the least harmful nicotine product – [pharmaceutical] nicotine replacement therapy.”

The report recommends that smokers be given accurate information about nicotine, specifying that it “is not the harmful substance in cigarettes.” It also points out that pharmaceutical nicotine should be made more affordable and accessible.

3. “Shift smokers who are unable to quit or unwilling to make a quit attempt to a less harmful product – snus.”

The report strongly counsels against misinforming smokers: “The public has the right under Canadian tort law to accurate information about the relative risks of using tobacco products and to make choices based on the facts. The current warning on smokeless tobacco products, ‘This product is not a safe alternative to smoking,’ is woefully inadequate as it provides no information regarding relative risks.

“Governments and health organizations must improve messaging, both on the product and in other media, about the relative risks of cigarettes, smokeless tobacco products, and non-tobacco nicotine products to ensure that the public is better informed and does not rely on tobacco companies for risk information.”

Although NSRA doesn’t trust tobacco manufacturers, it’s ironic that governments and health organizations are now the dominant sources of inaccurate risk information.

4. “Monitor the impact of alternative nicotine products.”

The report calls on “Health Canada and or other government authorities” to “conduct post-market surveillance of the promotion…” and “health impact of alternative nicotine products” like e-cigarettes, as well as safer smokeless alternatives. That’s a reasonable requirement. In comparison, the U.S. FDA legislation requires manufacturers of safer tobacco products to prove that they will have no population effect BEFORE they are marketed (described here).

The NSRA joins three other respected professional organizations in endorsing tobacco harm reduction. In 2006, the strategy was endorsed by the American Council on Science and Health, whose mission is to promote sound science in regulation and in public policy and to assist consumers in distinguishing real health threats from purely hypothetical ones. Throughout its history, ACSH has published many articles about the health risks of smoking, and it has held the tobacco industry accountable for its role in the devastating toll from tobacco. In the late 1970s, ACSH founder Elizabeth Whelan published a landmark anti-smoking book, A Smoking Gun: How the Tobacco Industry Gets Away with Murder. More information is available here.

In 2007, Britain’s Royal College of Physicians, one of the oldest and most prestigious medical societies, strongly endorsed tobacco harm reduction. The Royal College concluded “…that smokers smoke predominantly for nicotine, that nicotine itself is not especially hazardous, and that if nicotine could be provided in a form that is acceptable and effective as a cigarette substitute, millions of lives could be saved… Harm reduction is 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.” The Royal College report is available here.

In 2008, the American Association of Public Health Physicians became the first U.S. medical organization to formally adopt a policy of “…encouraging and enabling smokers to reduce their risk of tobacco-related illness and death by switching to less hazardous smokeless tobacco products.” Their report is available here.

It is gratifying to see the sound medical principles of tobacco harm reduction being adopted by the broader public health community.

Wednesday, June 16, 2010

The Bermuda Triangle of Tobacco-Specific Nitrosamines

Let’s start this post with some indisputable facts about smokeless tobacco:

1. Despite decades of epidemiologic research, long-term use of Swedish or American smokeless tobacco products (other than dry powdered snuff) has not been associated in a significant way with ANY disease.

2. Just like the foods we consume, contemporary smokeless tobacco products contain trace amounts of contaminants.

3. Tobacco-specific nitrosamines (TSNAs) are contaminants found only in tobacco products. They are present in vanishingly small concentrations – mainly in the single-digit parts-per-million range.

4. Two TSNAs, labeled NNN and NNK, have been designated by advisory organizations as human carcinogens, based entirely on laboratory experiments; there is no supporting evidence from human studies.

5. A recent meta-analysis concluded that modern smokeless tobacco products have cancer risks that are so low that they are not measurable with any precision by modern epidemiologic methods.

Again: These facts are indisputable. This is important because the FDA tobacco product advisory committee has just launched an investigation into tobacco product constituents. As a consequence, there will be a lot of talk about levels of bad constituents. With respect to smokeless tobacco, most of this will be nonsense. Let’s look at TSNAs.

It’s a given that, regardless of current TSNA levels, anti-tobacco extremists will call for reductions. However, since there is virtually no evidence that current TSNA levels are associated with ANY measurable cancer risks, it is inconceivable that a reduction in levels will produce any measurable benefit.

Tobacco prohibition advocate Dr. Deborah Winn, in a congressional hearing exchange with Congressman Steve Buyer (transcribed in my recent post here), argued for reduced TSNAs, but with no epidemiologic evidence that they are related to cancer now, nor that reductions would have any health effect:

Buyer: Do you acknowledge that if I can reduce the [TSNAs] in a product, that I can reduce the risk?

Winn: There’s no epidemiologic evidence that shows that that is the case. It’s certainly important that [TSNA] levels be reduced.

Some tobacco manufacturers want the FDA to take action on TSNAs, primarily because they make lower TSNA products. For example, Star Tobacco president Paul Perito issued a press release after the FDA meeting on June 8 (here), stating: “It is our hope that the FDA will… publish a list of the toxicants and carcinogens that are well documented to be linked with tobacco harm…” It is fair to ask Mr. Perito, What specific carcinogen has been documented to be linked with what specific tobacco harm? No legitimate scientist has demonstrated such a connection.

It is reasonable to expect tobacco manufacturers to maintain TSNAs at their historically low levels. It is entirely unreasonable to require further reductions without a scientific rationale relating such change to risk reduction, unless the goal is to drive the industry out of existence. Smokers and smokeless tobacco users should not be sucked into this Bermuda triangle of extremism.

Wednesday, June 9, 2010

Dr. Winn’s Misinformation and Congressman Buyer’s Remorse

When the FDA eventually looks at low-risk alternatives to cigarettes, it will ask experts at the National Cancer Institute for advice on relative risks. Dr. Deborah Winn, a 30-year veteran provider of misinformation about smokeless tobacco (evidence here and here), will be the NCI’s lead authority. Regrettably, Dr. Winn has proven incapable or unwilling to distinguish the risks related to combustible and smoke-free tobacco.

I recently reviewed Dr. Winn’s testimony before the House Subcommittee on Health. All 3.5 hours of this tirade against smokeless tobacco is available (here). Her appalling disregard of facts was highlighted in the following exchange (occurring at about 1 hour 57 minutes) with Congressman Steve Buyer:

Buyer: I’m trying to reconcile a couple of acknowledge that there is a continuum of risk within tobacco products…smoking to smokeless, pharmaceutical to quitting…a continuum of risk, you acknowledge that, correct? From very high risk to very low risk, you acknowledge that?

Winn: Um, quantitating it at high or low, they all have risks.

Buyer: You acknowledge that there’s a continuum of risk, from very high risk to very minimal risk, you acknowledge that?

Winn: Very high risk to moderate risk.

Buyer: To moderate risk? So if I can with proven science say that there is a product on the market that would remove 99% of the nitrosamines, you would define the 1% as moderate?

Winn: Um…all smokeless tobaccos have some risk of health effects.

Buyer: That’s correct. I concur with that. Now let me go back and acknowledge this. Let’s not play games. Do you acknowledge that there is a continuum of risk, from very high risk to very low risk, to the health effects with the use of tobacco products?

Winn: Some tobacco, for example, chronic obstructive pulmonary disease...

Buyer: All right, all right, I’m not going to quibble with you...because it appears that if you will not even acknowledge that there’s a continuum of risk, then you’re placing yourself in the camp of complete abstinence. Now I will concur with you that tobacco products are not healthy. I concur with that. But to ignore that there is a continuum of risk from very high risk, cigars, to very low risk, which would be a product…Let me ask it this way…If you are able to put a product on the market that reduces the nitrosamines, does that eliminate, then, health risks?

Winn: What causes us concern under those circumstances is the population effect that might be influenced by people smoking and adopting a smokeless tobacco product.

Buyer: Do you acknowledge that if I can reduce the nitrosamines in a product, that I can reduce the risk?

Winn: There’s no epidemiologic evidence that shows that that is the case. It’s certainly important that nitrosamine levels be reduced.

Buyer: So, are you saying to me then, that an Orb or a Stick that has 99% reduced nitrosamines is just as harmful as smoking a cigar? That’s what your statement is saying.

Winn: Yes.

Buyer: And you concur with that?

Winn: Um, assessing nitrosamine levels or reduced nitrosamine products is under the purview of the FDA. So I would…

Buyer: Great. Your staff just gave you that so you could read it. But just answer the specific question.

Winn: We don’t know that there is any level of nitrosamines known to be safe.

Buyer: [Laughs] Wow. So you are unwilling to recognize the differentials of risk within tobacco products. That’s what I’m hearing from you. You do not acknowledge that there is differential risks among tobacco products?

Winn: There is a continuum of risk.

Buyer: Thank you, thank you. We got there, didn’t we? We got there. There is a continuum of risk. Now why is that important? It’s important because, as a country, those who are advocates of an abstinence approach are locking us in to a system of failure…

This is a harbinger of what will transpire as abstinence-only federal nannies slowly tighten the regulatory noose around snus and other smokeless alternatives to cigarettes. Even worse, Congress is losing the only member who understands tobacco harm reduction, and has the courage and integrity to challenge the misinformation spewing from prohibitionists. Steve Buyer will not stand for re-election in 2010, which is a terrible setback for American smokers.

Wednesday, June 2, 2010

Congressional Craziness: Requiring Population-Level Proof for Harm Reduction

In 2009, anti-tobacco extremists won adoption of the Tobacco Act, which is likely to effectively prohibit tobacco manufacturers from participating in tobacco harm reduction.

The Tobacco Act forbids manufacturers’ communication with consumers about the relative risks of different tobacco products. This prohibition is not limited to commercial speech (i.e., advertising); it could be applied to essentially any public statement by tobacco company scientists or executives. If a manufacturer wants to market a tobacco product as a lower-risk alternative to cigarettes, Section 911 of the law contains evidentiary requirements that are nearly impossible to fulfill, even though the product already has been proven to be safer than cigarettes.

Section 911 is aptly numbered; it will significantly extend a tragic health crisis for legions of inveterate cigarette smokers.

In order to market a smokeless product as a less harmful alternative to cigarettes, a manufacturer has to satisfy the FDA that (a) the product will “significantly reduce harm and the risk of tobacco-related disease to individual tobacco users; and (b) benefit the health of the population as a whole taking into account both users of tobacco products and persons who do not currently use tobacco products.”

Is it possible to implement a clinical trial that could evidence the population benefit of safer tobacco alternatives? A recent analysis, published in Regulatory Toxicology and Pharmacology, attempts to provide an answer. The first author of the study (abstract here) was Lenn Murrelle from Altria; collaborators included statisticians and epidemiologists from consulting firms. It does not provide much hope that a clinical trial will ever be conducted.

Murrelle and colleagues start with some reasonable assumptions. First, they propose to study a very low-risk cigarette alternative such as snus. They designed the clinical trial to include four groups: continuing smokers, smokers who quit altogether, smokers who switch to snus, and nonsmokers. The latter group is important because of the Tobacco Act’s mandate to monitor possible future snus use among those who never used tobacco.

Murrelle used lung cancer as the outcome measure, which was the only practical choice. Smoking is the dominant risk factor for lung cancer, and snus use plays no role in this disease, so this maximizes the differences between continuing smokers and those who quit or switch. In fact, Murrelle assumed that the lung cancer rate among smokers who switch to snus would be the same as that among quitters.

Murrelle et al. found that a clinical trial would need to enroll 8,000 subjects (2,000 in each of the four groups) and follow them for 5 years in order to see differences in lung cancer between smokers who quit or switched to snus, and those who continued to smoke. Most clinical trials enroll a few hundred subjects at most, so 8,000 is an enormous number.

Such a trial, including 5 years of follow-up, would cost tens of millions of dollars. But that’s not the only problem. First, an ethical review board would never permit an investigator to assign a smoker to keep puffing. Challenges with the switch-to-snus group include finding an acceptable product, monitoring compliance and consumption, and determining who pays for the products. The quit-altogether group would be almost impossible to maintain, because sustained quit rates among smokers are so miserable. Finally, it would be terribly awkward to enroll people who don’t currently use tobacco, because they would have to be truthfully informed about the entire study.

The “claim” that might result would be very narrow: “Switching to this (specific) snus product could reduce your risk of lung cancer to the level of quitting tobacco altogether.” Murrelle and colleagues point out that if manufacturers want data for claims involving other diseases and/or products having smaller risk differentials than snus and lung cancer, they might have to enroll up to 10 times the number of subjects. That’s as many as 80,000!

Congress invoked this virtually unattainable population standard under the influence of tobacco prohibitionists. It is important to point out that setting such an extraordinarily high evidentiary bar is unprecedented. For example, consider the lack of such an evidentiary requirement to support the federal requirement for automobile seatbelts, another type of harm reduction. First pioneered by Swedish carmakers Saab and Volvo, (history here), seat belts were mandated by the federal government for all new automobiles starting January 1, 1968 (regulation here). While there was adequate laboratory evidence that wearing seat belts provide protection (but in rare instances slightly increase risks, similar to smokeless), there was virtually no population-level proof until this decade that seat belts actually save lives (an example).

It would have been disastrous if Congress had passed a bill in 1968 requiring population-level evidence before seat belts could be marketed for harm reduction. The same applies to smokeless tobacco.