Thursday, May 31, 2012

Published Review of Individual Smoking Cessation Treatments Fails to Mention Electronic Cigarettes; Another Example of the Results of Financial Conflict of Interest?

A review article which provides a comprehensive review of individual smoking cessation treatments appears in the March issue of Tobacco Control. The article reviews many forms of individual therapy for smoking cessation, including nicotine replacement therapy, varenicline (Chantix), buproprion, nicotine agonists and other drugs, behavioral support, telephonic counseling, brief intervention by doctors, and a nicotine vaccine. The article is entitled: "Improving smoking cessation approaches at the individual level." The article appears in a special 20th anniversary edition of the journal Tobacco Control, whose articles look back at the progress over the past 20 years.

See: Aveyard P, Raw M. Improving smoking cessation approaches at the individual level. Tobacco Control 2012; 21:252-257. doi:10.1136/tobaccocontrol-2011-050348.

The Rest of the Story

The remarkable thing about this article is that it does not so much as mention electronic cigarettes as a potential smoking cessation strategy, despite the fact that this approach is being used by more than 2.5 million smokers in the U.S. I wouldn't expect the article to sing the praises of electronic cigarettes, but the fact that it doesn't even mention these novel and promising devices I find quite telling. The article is biased towards pharmaceutical smoking cessation aids.

But all becomes clear when one finally gets to the end of the article and sees the financial disclosures. Both authors have or have had financial conflicts of interest with pharmaceutical companies that manufacture smoking cessation drugs: "PA has undertaken consultancy and/or research for McNeil, Pfizer and Xenova (now Celtic) Biotechnology. MR has in the last 5 years had conference expenses reimbursed, been paid an honorarium for a talk and received freelance fees from Pfizer, but has not accepted support from the manufacturers of stop smoking medications in the last 4 years."

More specifically, it turns out that: "the UK Centre for Tobacco Control Studies (UKCTCS) [the home institution of one of the study authors] has received payment from Pfizer for PA's role on the advisory board for varenicline, and a grant from McNeil for PA's work on trials of a new product, and that both PA and the UKCTCS received payment from Pfizer, McNeil and Xenova (now Celtic) for consultancy, and that PA received payment from Pfizer for talks and educational presentations." So at least part of the funding received was related to consultation on the drug varenicline. Electronic cigarettes are a direct competitor of varenicline, nicotine replacement therapy, and other smoking cessation strategies, even quitlines, behavioral support, and telephonic counseling.

Moreover, while MR states he has not accepted support from drug manufacturers of stop smoking medications for the last 4 years, he is the author of a paper published in 2009 that acknowledges funding from Pfizer: "We gratefully acknowledge ... Doreen McIntyre and the Global Treatment Partnership for financial support of the survey... The Global Treatment Partnership is a project funded by Pfizer and other organisations hosted by the International Non-Governmental Coalition Against Tobacco (INGCAT), whose director is Doreen McIntyre."

It is becoming clear to me, and should be to my readers, that these financial conflicts of interest with Big Pharma are associated with profound bias in the reporting of research and analysis of policy in the literature. Here is a great example. A 20-year review article on individual smoking cessation treatment and advances in the field and it doesn't even mention electronic cigarettes.

Wednesday, May 30, 2012

Controversy Over Financially-Conflicted Chantix Safety Conclusions Gains Attention

The controversy over the conclusions of a Pfizer-funded researcher who believes that the existing research is enough to state that Chantix poses no cardiovascular risks gained prominent attention recently, as it was highlighted by Ed Silverman over at

In an article titled "Researchers Duel Over Chantix and Heart Risks," Silverman writes: "A spat has broken out among researchers over the extent to which the controversial Chantix quit-smoking pill is linked to cardiovascular risks. A meta-analysis that was published last week in BMJ found the drug, which is sold by Pfizer, does not increase the risk of heart attacks and strokes. The results contrast with a meta-analysis published last year that maintained Chantix does increase heart risks, a conclusion the authors of the latest study labeled “misleading.” ... “There is a simple explanation why this study could not detect a difference in cardiovascular risk. Because of a weak design it was unable to detect any effect on anything,” Thomas Moore, a senior scientist with the Institute for Safe Medication Practices and who serves as a consulting expert in the civil litigation regarding Chantix, writes us in an e-mail. “It would be a serious scientific error to make a safety claim based on a study that did not disprove the null hypothesis.”

The Rest of the Story

Thomas Moore points out the most critical point: that the existing research base consists of studies that were not powered to detect a small adverse cardiovascular effect of Chantix use. They were powered to determine whether Chantix is effective in smoking cessation. Because of the low power of these studies, even the meta-analysis - which combines the results of all of them - has wide confidence intervals around the estimate of risk and leaves open the possibility of a small, but clinically quite significant adverse cardiovascular effect of Chantix.

However, the conflicted researcher, who is funded by Pfizer - the manufacturer of Chantix - was willing to draw a definitive safety conclusion based on the inadequate existing data. The FDA recognizes the problem of the low sample sizes in these studies, and it is for this reason that the agency is requiring a study of 8000 patients (the individual studies generally have just a few hundred patients) to assess the cardiovascular risks of Chantix.

Another major issue with the conflicted researcher's work is that she excluded adverse events occurring more than 30 days after discontinuation of the drug. However, as pointed out by Dr. Sonal Singh from the Johns Hopkins Bloomberg School of Public Health in the Pharmalot article, the cardiovascular risk is not simply due to the presence of the drug in the bloodstream and researchers must look beyond simply 30 days after drug discontinuation: "Singh noted that his meta-analysis examined patients through the duration of the Chantix trials because what remains unknown is the the length of time that a heart risk may appear after treatment ends. “We were learning from the Vioxx issues. With Vioxx, heart risks didn’t climb until long after people were taken off the drug. She assumes the potential CV risk is due to direct effect of the drug being in the body, so when the drug is out the risk should go away. I’m making a very different assumption. I don’t know how the drug is increasing heart risk, so I’ll count data through the end of a study and some lasted up to a year,” he says. “Which world do you live in? She’s assuming she knows how the drug causes CV risks and I’m assuming I don’t know. And those are the kinds of studies that are needed.”"

Dr. Singh makes a critical point. Since we don't know how Chantix increases heart attack risk, if it does increase that risk, then it is imperative not to assume that the effects must occur within 30 days of drug use. The assumption that the conflicted researcher makes is a perfect example of the kind of bias that can easily be introduced into research by a financial conflict of interest.

Tuesday, May 29, 2012

Anti-Smoking Groups Calling On Family Dollar, But Not Other Stores, to Stop Selling Tobacco Products

In a move that I find quite strange due to its selectivity, a large number of anti-smoking groups last week called on Family Dollar, but not other retail stores, to reverse its decision to sell tobacco products. The coalition of anti-smoking groups argued that Family Dollar should "put consumer health ahead of profits."

According to a press release issued by the American Legacy Foundation: "Approximately a dozen national public health and advocacy organizations are urging Family Dollar to reconsider its decision to sell tobacco products in its stores nationwide. In a letter today to the CEO of Family Dollar, the groups said the announcement “comes as a dire disappointment to the nation’s public health community.”
Family Dollar’s decision to sell tobacco goes up against the company’s commitment ‘to improve the quality of life of [its] customers and Team Members’, given that tobacco is the No. 1 cause of preventable death in the United States,” said Cheryl G. Healton, DrPH, President and CEO of Legacy®. “Selling tobacco at Family Dollar could heavily impact the lives of those Americans who already suffer disproportionately from tobacco’s economic and health consequences,” she added."

"For years, the tobacco industry has deliberately marketed tobacco brands to low socio-economic and minority youth and adults. Smoking is greatest among adults with working class jobs, low educational levels, low income, and those who are unemployed – groups that comprise the very communities Family Dollar serves. Since Family Dollar stores mainly operate in neighborhoods with low-income and middle income families, the company has the potential to increase access to the nation’s deadliest consumer product."

Among the organizations who signed on to the letter and press release are the American Legacy Foundation, American Academy of Pediatrics, Association of State and Territorial Health Officials, Citizens’ Commission to Protect the Truth, National Association of County and City Health Officials, National Association of Chronic Disease Directors, National Association of Local Boards of Health, North American Quitline Consortium, and the Smoking Cessation Leadership Center, UCSF Department of Medicine.

The Rest of the Story

Is Family Dollar the only retail store that has decided to sell cigarettes? Is Family Dollar the only store to operate in low-income and middle-class neighborhood to sell tobacco products? Why does the sale of tobacco products at Family Dollar heavily impact the lives of those Americans who "already suffer disproportionately from tobacco’s economic and health consequences," but the sale of the very same tobacco products at other stores in these same neighborhoods not impact those lives? Why is the sale of tobacco products at Family Dollar a "dire disappointment" to the nation's public health community, but the sale of tobacco products at a host of other retail stores not a dire disappointment?

What sense does it make for these anti-smoking groups to send a letter of complaint to Family Dollar, but not to send similar letters of complaint to all the other discount stores that target low- and middle-income families and sell cigarettes?

Why are the American Legacy Foundation, American Academy of Pediatrics, Association of State and Territorial Health Officials, Citizens’ Commission to Protect the Truth, National Association of County and City Health Officials, National Association of Chronic Disease Directors, National Association of Local Boards of Health, North American Quitline Consortium, and the Smoking Cessation Leadership Center, UCSF Department of Medicine seemingly unconcerned with the hundreds of discount stores that fail to put "consumer health ahead of profits" by refusing to sell tobacco products?

Apparently, the sale of tobacco products to low- and middle-class smokers who already suffer disproportionately from tobacco's economic and health consequences is perfectly acceptable as long as you were already in the business in April 2012. But if you go into the very same business after that time you are putting profits above consumer health. I take it that the many hundreds of other discount stores that sell tobacco products are not putting profits above consumer health.

There is no evidence that Family Dollar's decision to sell cigarettes will "increase access to the nation’s deadliest consumer product." There are plenty of places where smokers can currently get cigarettes and there is no reason to believe that the availability of cigarettes at Family Dollar will cause anyone to start smoking who would not have started anyway. What the decision would do is simply to shift the sale of cigarettes from some other stores to Family Dollar.

Regulating or interfering with the distribution of profits from the sale of tobacco to different stores does not seem to me to be a legitimate public health concern. Saving lives from tobacco-related disease and death is the public health concern, but this action by these anti-smoking groups will do nothing to save lives. All it does is mis-frame the issue of tobacco as being a problem only when sold by certain types of stores.

These groups should be working to significantly reduce tobacco use, not merely to shift around the distribution of which stores profit from it.

Friday, May 25, 2012

Anti-Smoking Researchers Seem to Be Losing Basic Scientific Reasoning Skills Due to Ideology; Researchers Claim there is No Evidence that Cigarettes are Any More Hazardous than Electronic Cigarettes

In a shocking, public claim, anti-smoking researchers at the Kentucky Center for Smoke-free Policy have published a statement asserting that there is no scientific basis to argue that cigarettes are any more harmful than non-tobacco-containing electronic cigarettes that merely vaporize nicotine from a solution containing nicotine, glycerin, and propylene glycol.

(See: Riker CA, Lee K, Darville A, Hahn EJ. E-cigarettes: Promise or peril? Nursing Clinics of North
2012; 47:159-171.)

In their review article regarding electronic cigarettes, these authors assert that despite the fact that electronic cigarettes contain no tobacco and involve no combustion, produce no smoke, and do not contain most of the tens of thousands of chemicals in tobacco smoke, there is no scientific basis to claim that tobacco cigarettes are any more harmful than electronic ones.

The article states that: "no scientific basis currently exists for making claims of ... reduced harm ... for e-cigarettes."

Of course, asserting that there is no scientific basis for making claims that e-cigarettes are less harmful than cigarettes is the same as asserting that there is no scientific basis for making claims that cigarettes are any more harmful than e-cigarettes.

The Rest of the Story

It is shocking to me that in 2012, despite all we know about the dangers of cigarettes, despite the fact that more than 400,000 Americans die each year from smoking, despite the fact that cigarettes contain tens of thousands of chemicals, including more than 60 known carcinogens, despite the fact that cigarette smoke itself contains propylene glycol, despite the fact that electronic cigarettes contain no tobacco whatsoever and produce no smoke, and despite the fact that more than 2 million Americans are currently using electronic cigarettes without any reported health effects (other than one battery explosion), these authors could publicly assert to nurses throughout the country that there is no scientific reason to believe that cigarette smoking is any more hazardous than using an electronic cigarette.

It appears to me that an ideology - some sort of entrenched opposition to any behavior that looks like smoking - is intruding upon sound scientific reasoning. How can a device which delivers vaporized nicotine with a few other chemicals (including propylene glycol) and trace levels of carcinogens (TSNAs) possibly be more hazardous than a device that delivers nicotine plus thousands of other chemicals (including propylene glycol) and more than 60 carcinogens (including high levels of TSNAs, about a thousand times higher than in e-cigarettes)?

Can you imagine if any cigarette company made the same claim? We would be mauling them from all sides. How could this cigarette company dare to suggest to the public that smoking is no more hazardous than vaping? Anti-smoking groups would be attacking the company to no end.

That at least one of these authors is losing sound scientific reasoning to ideology is evidenced by an email that she apparently wrote to several colleagues, in which she falsely claimed that Professor Brad Rodu, a harm reduction proponent at the University of Louisville, is on the Board of Directors of U.S. Tobacco. I know Brad, and although he has received research funding from the smokeless tobacco industry, he has never shared with me the information that he served on the Board of Directors of U.S. Tobacco. To write a potentially libelous email like this without first checking to make sure the facts about Dr. Rodu were accurate seems to me to show a sort of ideologic zealotry that is over-riding rigorous scientific and evidence-based, careful reasoning.

The most unfortunate part of this story is that nurses might believe the statement in the article and advise their patients that cigarette smoking is no more hazardous than vaping, which would be terribly misleading advice and could have serious repercussions for patients who might otherwise consider quitting smoking using these devices or staying smoke-free using these devices.

By the way, I have no problem with the authors of this article disagreeing with me about the potential promise or peril of electronic cigarettes. They are entitled to their opinions and debate over the promise or peril of these products is much needed and appropriate. But the debate should be based on some semblance of scientific reasoning and argumentation. To make blind ideological statements like: "There is no scientific basis for claiming that electronic cigarettes are any safer than tobacco cigarettes" does not add anything useful to the debate, and in fact, significantly detracts from it by misleading potentially thousands of health practitioners about the demonstrable scientific facts.

Thursday, May 24, 2012

In Embarrassing Ironic Twist, Lorillard Promotes Smoking Cessation While Anti-Smoking Groups Do Not

In an irony of epic proportions that is an embarrassment to the anti-smoking movement, the Lorillard Tobacco Company is now promoting smoking cessation among thousands of consumers using electronic cigarettes, while most anti-smoking groups are not.

Believe it or not, here is the actual advice that Lorillard and anti-smoking groups are giving - publicly - to current smokers who are thinking of quitting smoking using electronic cigarettes:

Lorillard: Do.
Anti-Smoking Groups: Don't.

And here is the advice that Lorillard and anti-smoking groups are giving - publicly - to ex-smokers who have successfully quit using electronic cigarettes:

Lorillard: Continue to stay off tobacco cigarettes by using the electronic ones.
Anti-Smoking Groups: Do not use the electronic cigarettes.

This advice from the anti-smoking groups is tantamount to saying: "Return to cigarette smoking rather than use a product whose risk profile is not 100% documented."

The Rest of the Story

Through its acquisition of blu ecigs®, Lorillard is now officially in the business of harm reduction and it is devoting a substantial amount of resources to promoting smoking cessation via the use of electronic cigarettes. On the other hand, anti-smoking groups are largely opposed to the use of electronic cigarettes and have called for their removal from the market. They, along with the FDA, are actively discouraging smokers from trying to quit using these products and are scaring smokers who have quit using electronic cigarettes into discontinuing the use of these devices and instead, returning to smoking.

In addition to being a strange but true ironic twist, I view this as being a major embarrassment for the anti-smoking movement.

Is it not unfortunate that we in tobacco control are the last to adopt the idea of harm reduction to help protect the health of millions of smokers who - let's face it - are not going to quit smoking? Is it not a disgrace that Big Tobacco is now promoting a form of smoking cessation that we in tobacco control are discouraging?

I had the opportunity to meet Lorillard CEO Murray Kessler earlier this week at the TMA Annual Meeting and to hear him discuss the acquisition of blu. Ecig Advanced has also published an interview with Kessler in which he explains the company's commitment to promoting the electronic cigarette industry. While some might be skeptical about the motivation behind a tobacco company purchasing an electronic cigarette company and might assume that the purpose is to sabotage the e-cigarette industry, it is clear to me after speaking with and listening to both Jason Healy at blu (who I have known for several years) and Murray Kessler that this is not the case at all. Lorillard is committed to developing a thriving business for its blu product, and that means a willingness to promote smoking cessation via blu cigs.

Knowing Jason, I can assure my readers that if Lorillard was even in the slightest way not committed to supporting blu fully, he would not have agreed to the acquisition. Moreover, the choice of blu shows that Lorillard is committed to building an industry segment that can compete successfully in a difficult regulatory environment. Blu ecigs has been a leader in the industry in terms of quality control:
  • Blu was one of the first companies to move to in-house (domestic) production of its juice, ensuring tighter quality control over the contents of its cartridges;
  • Blu was one of the first companies to document the levels of nicotine in its products through analytic testing;
  • Blu wisely made a decision to rely upon glycerin as an excipient, rather than propylene glycol, thus avoiding health concerns related to the long-term inhalation of propylene glycol and eliminating any worries about the respiratory irritant effects of propylene glycol (even though these are obviously minor compared to tobacco cigarettes).
While I have to admit that initially I thought the entrance of a tobacco company into the electronic cigarette market might undermine the development of this industry, I now believe it is the opposite. There are three reasons for this:

1. The entrance of Lorillard into the electronic cigarette space now means that a substantial amount of resources - not previously available - can be devoted to marketing the product and making the public aware of electronic cigarettes, something which has previously been quite slow to develop. It is unfavorable for the e-cigarette industry that even four years after introduction of this product, consumers are still largely unaware of the very existence of the product. Even tobacco control experts are confused about the differences between a cigarette and an electronic cigarette.

2. The entrance of Lorillard into the electronic cigarette space now means that the industry has the resources to conduct the types of studies that may be required in order to obtain FDA approval for various important marketing claims that will ultimately be pivotal for the industry. While it is unclear whether the FDA will apply section 911 to electronic cigarettes (I have urged the agency not to do so), if it does there is no chance that any of the smaller electronic cigarette companies could possibly produce the research required to meet the heavy burdens of that statute. At least there is now a chance. But more importantly:

3. The entrance of Lorillard into the electronic cigarette space creates a formidable force that the FDA must now deal with and which has the resources to apply pressure to the agency to promote a reasonable approach to electronic cigarette regulation. It is not clear to me that the smaller e-cigarette companies, on their own, have the experience or political power to interact with the FDA in a way that would influence the agency's decisions. That is no longer the case.

4. Finally, the entrance of Lorillard into the electronic cigarette space helps the entire industry by establishing an entity that can introduce the most stringent and appropriate quality control measures and help address concerns such as:
  • the presence of diethylene glycol in some cartridges;
  • unpredictable delivery of nicotine;
  • inaccurate nicotine levels on cartridges;
  • exploding batteries;
  • leaky cartridges, etc.
I hate to steal Jacob Sullum's analogy again, but it is the best expression of the rest of the story. The anti-smoking groups are essentially telling survivors of a shipwreck who are submerged in the ocean not to use the ship's lifeboats because they have not been FDA tested and approved. Instead, they are telling the drowning passengers to stick to the "tried and true" method: treading water.

The difference, of course, is that in the case of electronic cigarettes, these "lifeboats" have actually been tested quite extensively and we know that for literally thousands of ex-smokers, they work. Even among unmotivated smokers, these products allow more than 50% of smokers to either cut down substantially (by more than half) on the amount they smoke or to quit altogether.

For the better part of two years, I have been struggling to figure out why anti-smoking groups are so hesitant to embrace even the possibility that electronic cigarettes may be helping many smokers to improve their health. It is now clear to me that the primary reason for their hesitance is this:

It is simply not in the anti-smoking mindset, given the dogma of the movement, to condone a behavior that looks like smoking. Ironically, the very factor that makes electronic cigarettes so effective for cessation - the fact that they simulate smoking - is precisely the factor that prevents anti-smoking advocates from embracing the strategy, despite its obvious public health advantages.

The rest of the story is that the anti-smoking groups are going to be the last on board in the recognition that, as Murray Kessler himself said, non-tobacco-containing, nicotine-delivering devices of some sort are going to be the wave of the future. I find it to be an embarrassment that a major tobacco company is now promoting smoking cessation using this new technology while most anti-smoking groups are still discouraging smokers from trying to quit using what may be the single most effective method available to them.

Wednesday, May 23, 2012

Nu Mark Test-Marketing a New Nicotine Disc as a Smoking Alternative; How Will the FDA Handle This and Other Reduced Risk Products?

Nu Mark, an Altria company, has announced that it is now test-marketing (in limited distribution in Virginia) a new tobacco product in the form of mint-flavored discs. These discs contain nicotine that is derived from tobacco; however, there is no tobacco per se in the product. Obviously, these are non-combustible products. They are chewed by the user. The product is called VERVE™.

According to the VERVE™ Fact Sheet: "Nu Mark, an Altria company primarily focused on responsibly developing and marketing innovative tobacco products for adult tobacco consumers, is introducing VERVE discs. This is a new kind of tobacco product designed to appeal to adult smokers interested in innovative types of spit-free tobacco product alternatives to cigarettes. Based upon our research, we believe that approximately 30% of adult smokers are interested in such alternatives. Adult tobacco consumers put the product in their mouth, chew on it and should properly dispose of it when they are done. Primary ingredients are tobacco-derived nicotine, non-tobacco cellulose fibers, flavorings and a polymer. ... Each VERVE disc contains approximately 1.5 mg of nicotine. The amount of nicotine an adult consumer receives depends on how the consumer uses it, including how hard the product is chewed and the amount of time it is kept in the mouth. The amount of nicotine in a VERVE disc is lower than the range of nicotine typically found in pouched smokeless tobacco products currently on the market."

To protect from youth access to the product, it is sold in child-resistant packaging. The package also displays a prominent warning to keep it away from children. It is directed to be sold only to adults, and only in a clerk-assisted transaction (i.e., not through a self-service display).

Because this is a tobacco product as defined under the Tobacco Act (it is derived from nicotine), it will -- when introduced for interstate commerce -- most likely be subject to FDA regulation as a novel type of smokeless "tobacco" product. While the FDA has not yet promulgated regulations for these "middle-ground" products (including electronic cigarettes) that meet the definition of a tobacco product but are not cigarettes or smokeless tobacco products as defined by the Tobacco Act, the agency is expected to release its regulatory plan for such products this summer.

Given the fact that VERVE contains no tobacco and that the only significant exposure is to nicotine, the product is clearly much safer than cigarettes. But here's the key question: Will Altria be allowed to inform consumers that the product is safer than cigarettes? And if not, what will the company have to do in order to be able to provide such (obviously) truthful information to consumers?

The Rest of the Story

The answer depends on how the FDA chooses to handle the application of modified risk tobacco product issues to these innovative non-cigarette, non-smokeless tobacco products such as electronic cigarettes, which deliver tobacco-derived nicotine but do not contain tobacco.

Let me just state at the outset that the worst thing the FDA could do is issue a deeming regulation that treats these "non-tobacco, tobacco products" (i.e., VERVE, electronic cigarettes) the same way as traditional tobacco products. Most importantly, FDA must not make these products subject to the provisions of section 911 (the modified risk tobacco product provisions) of the Act.

If products like VERVE and electronic cigarettes are made subject to section 911, it will place a nearly insurmountable barrier in front of the successful marketing of these products as truly reduced risk products that could potentially save many lives by transitioning smokers off of cigarettes.

In this commentary, I discuss the reason why section 911 would be a death knell for both VERVE and electronic cigarettes. I refer mainly to VERVE here since that is the topic at hand, but the argument applies equally well to electronic cigarettes.

In order to be approved as a modified risk product under section 911, Altria would have to demonstrate the likelihood that the marketing of VERVE will: (1) cause smokers who would otherwise have quit to use VERVE instead; and (2) cause nonusers of tobacco to start using VERVE (especially youth), which could then lead to nicotine addiction and subsequent tobacco use. 

How can one find out whether the marketing of VERVE as a reduced risk product would cause smokers who would otherwise have quit to use VERVE instead of quitting? The only way to do this scientifically is to actually market VERVE as a reduced risk product and then observe what happens. Importantly, one would have to conduct a clinical trial with a control group that does receive VERVE in order to know what the cessation rates would have been in the absence of VERVE. This would require a huge sample size.

But the study is impossible to carry out in the first place. Why? Because the only way to observe the effects of marketing VERVE as reduced risk product would be to actually market VERVE as a reduced risk product. But Altria could not do that until it received approval from the FDA. And to receive that approval, it would first have to present the evidence of a trial in which VERVE was marketed as a reduced risk product.

In other words, this is a catch-22 situation. If section 911 were applied to VERVE, then Altria could not market the product as a reduced risk product until it received FDA approval, but could not receive FDA approval until it marketed the product as a reduced risk product.

What about the "reduced exposure" provisions of section 911? Could Altria market VERVE not as a reduced risk product, but as a reduced exposure product? No - not if the FDA applies section 911 in its current form to these intermediary products. In fact, one could argue that Altria would not even be allowed to inform consumers that VERVE is free of tobacco, as that would be considered a "reduced exposure" claim under the statute.

In order to have such a reduced exposure claim approved by the FDA, Altria would first have to demonstrate that consumers do not interpret the absence of tobacco as an indication that the product is safer. But that's preposterous. First of all, no consumer in their right mind is going to fail to consider a product safer than other "tobacco" products when informed that it contains no tobacco. But more importantly, even if they did, consumers are not going to buy the product if they don't think it is any safer. How can a company market a product which is a safer alternative to cigarettes without being able to have consumers think that it is a safer alternative to cigarettes?

Again, section 911 creates a catch-22. You can only market a product as reduced exposure if consumers will not believe it is any safer. But if consumers will not believe it is any safer, then what is the value of marketing the product?

As expected, the Campaign for Tobacco-Free Kids has reacted negatively to the introduction of VERVE, warning the public about the potentially risky contents of this new product. The Campaign was quoted as stating: "In the absence of FDA review of the contents of the product, the American public is essentially being asked to be human guinea pigs."

It is not the contents of the product that are of concern. After all, there are only four: nicotine, cellulose, polymer, and mint? Which of these four products does the Campaign believe needs to be immediately reviewed by the FDA for use among smokers who are otherwise going to be inhaling upwards of 10,000 chemicals and 60 carcinogens in each puff?

No, the concern is not about the contents of VERVE, it is about the potential effects on the behavior of current smokers and nonsmokers. Will smokers who might otherwise have quit decide to use VERVE along with their cigarettes? Will youths be attracted to VERVE and then become addicted to nicotine and advance to cigarette use? These questions can be answered, but they do require a natural experiment (i.e., the introduction of VERVE into the market).

The Campaign for Tobacco-Free Kids and other anti-smoking groups are so protectionist about allowing new entries onto the market that they are essentially protecting the most hazardous known tobacco product (cigarettes) from competition from what are certainly safer products (i.e., electronic cigarettes and other non-tobacco nicotine-delivering products, like VERVE).

Hopefully, the FDA will decide not to apply section 911 to non-tobacco products that fall under the jurisdiction of the Tobacco Act by virtue of their use of tobacco-derived nicotine. A more reasonable approach would allow the use of much less stringent scientific evidence requirements than outlined in section 911.

The rest of the story is that while section 911 is touted as being necessary to prevent tobacco companies from making dishonest representations to consumers, the application of section 911 to electronic cigarettes and other non-tobacco, nicotine-containing products like VERVE will actually force companies to do that very thing: misrepresent the truth about a product by failing to communicate the most essential aspect that the consumer needs to know: the fact that the product contains no tobacco and involves no combustion of tobacco and is therefore much safer than cigarette smoking.

Tuesday, May 22, 2012

Cal State Fullerton Bans Smoking, Smokeless Tobacco Use, Alcohol Use, Binge Drinking, Unprotected Sex, and Junk Food Consumption on Campus; Actually, Just Smoking and Smokeless Tobacco Use

In an act of selective paternalism, the California State University at Fullerton has banned all tobacco use on campus, including smoking in cars and all smokeless tobacco use. The reason for the ban? According to the president of the Academic Senate: "Shouldn't the university be about health?"

The Rest of the Story

I call this selective paternalism because while the policy bans some unhealthy personal behaviors - smoking and smokeless tobacco use - it does not prohibit others, such as alcohol use, binge drinking, unsafe sex, and excessive junk food consumption.

Although some apparently defended the policy as being necessary to protect the campus community from secondhand smoke, that explanation could obviously not justify a policy that bans smokeless tobacco use since chewing tobacco produces no secondhand smoke and threatens no one else.

The apparent purpose for the policy, then, is to control personal health decisions that students make. This is classic paternalism. However, it is a selective form of paternalism as it only addresses one specific unhealthy behavior - tobacco use - while leaving many others untouched.

I find it highly hypocritical for the university to claim that it is about health and then to selectively ban tobacco use without touching alcohol use. Before boasting about how the university is all about health, perhaps Cal State Fullerton should first examine its tremendous alcohol problem. The university readily admits that 28% of its students drink alcohol excessively.

I find the university to be full of hypocrisy, as well as cowardice, to ban students from stuffing tobacco in their cheeks but continue to allow them to drink alcohol and get drunk on campus.

The hypocrisy of self-righteous actions like this is troubling. If you are willing to justify controlling student behavior to protect them from themselves, then how could you not protect them from the most imminent and severe health threat they face on campus: excessive alcohol use?

After all, shouldn't the university be about health?

Monday, May 21, 2012

"Safe and Effective?" Not the Correct Standard for Electronic Cigarettes

A number of anti-smoking groups have called for the removal of electronic cigarettes from the market until such time as they have been shown to be "safe and effective." For example, the Association for the Treatment of Tobacco Use and Dependence (ATTUD) issued a press release to promote a ban on the sale of electronic cigarettes in the United States. The press release highlighted a letter written from the organization to the FDA requesting that the Agency remove electronic cigarettes from the market.

The press release stated: "The Association for the Treatment of Tobacco Use and Dependence (ATTUD), the premier professional organization of tobacco treatment specialists, today announced its support of the FDA ban on so-called "electronic" or e-cigarettes. The letter ... stated that there is no scientific evidence that the e-cigarettes are safe and effective." As tobacco treatment professionals we are concerned that smokers desperate to quit will place their faith in unproven therapies," said John Hughes, MD, President-elect of ATTUD and professor of psychiatry at the University of Vermont College of Medicine."

The letter to the FDA stated: "The Association of Tobacco Use and Dependence (ATTUD) is a non-profit organization of providers dedicated to the promotion of and increased access to evidence-based tobacco treatment for the tobacco user. As such, we are writing to support the Food and Drug Administration (FDA) enforcement action against manufacturers of “electronic cigarettes”. These products should be removed from the market until and unless they are proven safe and effective."

As another example, the prestigious Mayo Clinic has strongly advised smoking patients against using electronic cigarettes to try to quit, stating: "If you're looking for help to stop smoking, there are many FDA-approved medications that have been shown to be safe and effective for this purpose."

Similarly, the American Legacy Foundation has published a policy statement which also calls for the removal of electronic cigarettes from the market until they have been shown to be "safe and effective." According to the statement, which is entitled "The FDA Should Take Electronic Cigarettes Off The Market Until It Is Satisfied That They Are Safe and Effective," the electronic cigarette must be taken off the market because it has not been shown to be either safe or effective: "While e-cigarettes are viewed by some as a less dangerous alternative to cigarettes or a potential smoking cessation aide, there had been no publicly available independent research on the critically important questions of safety and efficacy. With regard to safety, that has now changed with the FDA’s release on July 22, 2009 of extremely troubling laboratory findings regarding the constituents and manufacturing standards of some e-cigarettes now on the market. There continues to be no scientific support for the anecdotal claims that e-cigarettes are an effective smoking cessation aid."

More broadly, all of the major national anti-smoking groups, including the Campaign for Tobacco-Free Kids, American Heart Association, American Lung Association, American Cancer Society, Action on Smoking and Health, American Academy of Pediatrics, and the American Legacy Foundation, have called for an immediate ban on electronic cigarettes because they claim we are not sure whether these products are safe and effective for use as smoking cessation devices.

The Rest of the Story

The problem with all of these calls for a ban on electronic cigarettes is that the "safe and effective" standard is no longer the appropriate standard that the FDA must use in regulating these products. The District of Columbia Court has ruled that electronic cigarettes are a "tobacco product" under the Tobacco Act and that in the absence of therapeutic claims by a particular manufacturer, they may be regulated under the Tobacco Act as tobacco products, but not under the Food, Drug, and Cosmetic Act as drugs, devices, or drug/device combinations. While the "safe and effective" standard is appropriate for FDA to use in evaluating applications for new drugs to enter the market, is is not appropriate for FDA to use in deciding whether electronic cigarettes - an alternative tobacco product - should be allowed to remain on the market.

In the absence of a specific therapeutic claim by a manufacturer, essentially the only standard that the FDA may use to decide whether an electronic cigarette is whether or not it is an "established product" by virtue of having been in interstate commerce in the U.S. as of February 15, 2007. I don't think there is any doubt that these products were being marketed in the U.S. in 2007, and thus, that they are established products that are grandfathered in by the Family Smoking Prevention and Tobacco Control Act.

The second question is whether new brands of electronic cigarettes, which may have been introduced subsequent to 2007, are "substantially equivalent" to the electronic cigarettes on the market in 2007. Hopefully, the FDA will interpret the term "substantially equivalent" quite liberally with respect to electronic cigarettes. Otherwise, it will create an absolute regulatory nightmare. Certainly, the spirit of the law supports such a liberal designation, since virtually all electronic cigarettes share basic risk profiles that put them in a completely separate ballpark from regular cigarettes.

Assuming that the FDA does apply the substantially equivalent standard liberally to electronic cigarettes, there will be no means by which to remove these products from the market. The interesting issue will then become: will these products be subject to the modified risk provisions of the Act, and if so, how stringently will those provisions be enforced with respect to electronic cigarettes.

Under the current guidance that the FDA has offered regarding the modified risk provisions, it would be virtually impossible for electronic cigarettes to be marketed as reduced risk products because the research evidence required would be monumental. The manufacturer would have to conduct a long-term clinical trial, demonstrate that the product reduces health risks in both the short-term and long-term, demonstrate that it does not induce smokers who would have quit to instead use e-cigarettes, and demonstrate that the benefits outweigh any costs related to new users who start vaping, in particular, youths.

This research burden is so strong that it is unlikely to be met in a setting where you don't have a few large e-cigarette companies. Instead, you have hundreds of small distributors. No single company has the money to conduct the research that would be necessary. It would take many years and in the mean time, companies could not tell their consumers that the product is any safer than regular cigarettes. That seems absurd to me.

Therefore, it is my hope that the FDA will not make electronic cigarettes subject to section 911's modified risk tobacco product provisions, or else, that the FDA will outline a separate procedure for electronic cigarettes to achieve modified risk status that is far less burdensome.

The rest of the story is that the "safe and effective" standard is not appropriate for electronic cigarettes, which have been deemed by the courts to be an alternative tobacco product, not a drug. The key question is not whether these devices are "safe and effective," but whether they are relatively safe and effective. In particular, are they relatively safe compared to tobacco cigarettes and are they relatively effective in keeping people off cigarettes compared to nicotine replacement therapy?

The answer to the first question is unequivocally yes. And the answer to the second is not yet clear. However, early signs, including abundant anecdotal and experimental evidence and the results of an initial clinical trial suggest that the answer may well be yes as well. Electronic cigarettes must continue to be available to smokers and ex-smokers while this research is conducted. The worst scenario would be to follow the anti-smoking groups' advice and remove these products from the market because they have not been proven to be "safe and effective."

Thursday, May 17, 2012

Further Analysis of FDA Warning on Electronic Cigarettes: What is the Agency Saying to Smokers Who Have Quit Using E-Cigs and Tried NRT Unscuccessfully in the Past?

One of the hallmarks of a national recommendation by a public health agency is that it applies to all persons unless qualified as to relate only to a sub-group of the population. Thus, the FDA's recommendations regarding the use of electronic cigarettes, which I highlighted yesterday, can be inferred as being meant to apply to the whole population, not only to smokers who have not yet tried electronic cigarettes.

Today, let's consider what the FDA is saying specifically to this sub-group of the population, which consists of thousands: ex-smokers who have quit successfully with the help of electronic cigarettes and who have tried NRT unsuccessfully in the past. In fact, the failure of NRT was the reason why most of these smokers decided to try electronic cigarettes in an attempt to quit smoking.

To remind readers, the FDA warns the public against the use of electronic cigarettes because their risk profile and chemical constituents have not been definitively characterized, because they may interest some kids in smoking, and because they may not deliver nicotine at precisely defined quantities.

The Rest of the Story

To the specific subgroup of ex-smokers who have quit by using electronic cigarettes and who are successfully maintaining themselves smoke-free with the help of electronic cigarettes, the FDA is saying: stop using your electronic cigarettes because we do not know how unsafe they are. Instead, throw away your e-cigs and switch to a known entity -- FDA-approved NRT products.

However, the truth is that these are a population of people who have already tried NRT products and found them to be unhelpful in aiding their quit attempts. Many of these ex-smokers have tried NRT multiple times and failed every time. Clearly, if everyone in this population took the FDA's advice, threw away their electronic cigarettes, and switched to NRT, the majority of them would be smoking regular cigarettes by week's end. And by month's end, most of the rest would also be smoking. By year's end, the overwhelming majority of these smokers would have returned to cigarette smoking.

Some recommendation.

Why can't the FDA make a recommendation that makes more sense from both a scientific and a public health perspective? Something like:

"If you have successfully quit smoking using electronic cigarettes, congratulations! You have succeeded in the most important action you can take to improve your health. Because the long-term risks of electronic cigarettes are not completely understood, you may want to consider efforts to wean yourself off electronic cigarettes, or if that is not possible, to wean yourself from a high to a low nicotine cartridge and then down to a zero nicotine cartridge if possible. But in no case should you return to regular cigarettes. You are an ex-smoker and we want you to stay that way for the sake of your health. The FDA has made it an urgent priority to study the safety and efficacy of electronic cigarettes and should we gain any new information which alters the above advice, we will share it promptly. We will be issuing regulations this summer to make sure that the quality control processes used by electronic cigarette distributors are as solid as they can and should be."

No. Instead, the message being sent to these ex-smokers is:

"e-Cigarettes may contain ingredients that are known to be toxic to humans, and may contain other ingredients that may not be safe. Additionally, these products may be attractive to young people and may lead kids to try other tobacco products, including conventional cigarettes, which are known to cause disease and lead to premature death."

"Because clinical studies about the safety and efficacy of these products have not been submitted to FDA, consumers currently have no way of knowing

  • whether e-cigarettes are safe for their intended use,
  • what types or concentrations of potentially harmful chemicals are found in these products, or
  • how much nicotine they are inhaling when they use these products."
The FDA might as well just tell these vapers (i.e., ex-smokers) to throw away their electronic cigarettes and return to regular cigarette smoking. After all, that is the practical effect of the agency's advice to these ex-smokers.

Tuesday, May 15, 2012

FDA Warns Smokers Against Using Electronic Cigarettes Because Unlike Tobacco Cigarettes, Their Risks are Not Precisely Known

On its web site, the FDA is warning smokers against the use of electronic cigarettes because - in contrast to the known hazards of tobacco cigarettes - the risks of electronic cigarettes are not precisely known.

The FDA's electronic cigarette warning reads as follows:

"e-Cigarettes may contain ingredients that are known to be toxic to humans, and may contain other ingredients that may not be safe. Additionally, these products may be attractive to young people and may lead kids to try other tobacco products, including conventional cigarettes, which are known to cause disease and lead to premature death."

"Because clinical studies about the safety and efficacy of these products have not been submitted to FDA, consumers currently have no way of knowing
  • whether e-cigarettes are safe for their intended use,
  • what types or concentrations of potentially harmful chemicals are found in these products, or
  • how much nicotine they are inhaling when they use these products."
The web page closes by urging smokers to use FDA-approved smoking cessation methods, such as nicotine replacement drugs.

The Rest of the Story

As a service to my readers, I will now provide a translation of what the FDA is really saying to U.S. smokers, using Google's convenient "lay person translation" application. Here is the translation:

"We urge smokers not to use electronic cigarettes because unlike regular cigarettes, it is not known whether e-cigarettes are safe for their intended use, it is not known what types of potentially harmful chemicals are found in these products, and it is not known how much nicotine they are inhaling when using these products. Thus, with electronic cigarettes, you get a bunch of unknowns. But with regular cigarettes, you get a sure thing. We know exactly how unsafe these products are for their intended use. We also know thousands of the harmful chemicals that are found in cigarettes. And to boot, the consumer knows exactly how much nicotine he or she is getting because those levels are tightly controlled by the tobacco industry.

We urge smokers not to take risks with their health. Don't substitute electronic cigarettes - with their many question marks - for the well-known and well-characterized risks you get with your normal cigarettes. Do you really want to be inhaling a vapor that could potentially contain some harmful chemicals, when instead, you could be inhaling smoke whose harmful constituents have already been neatly categorized and classified?

We also urge smokers not to take risks with the amount of nicotine they may be getting from electronic cigarettes. Why take a chance that you may be getting a lower amount of nicotine than you get with your usual Marlboros, Camels, Newports, Winstons, and Kools? With these tobacco cigarettes, you can count on the tobacco companies to provide you with a carefully regulated dose of nicotine in each puff. They have spent years perfecting the carefully titrated and consistent delivery of nicotine. But with electronic cigarettes, you're dealing with amateurs. They really don't know what they're doing and there's no way to be sure that you're getting the precise amount of nicotine that they say you're getting. Why take a chance when you can get a known amount of nicotine?

Additionally, there is the risk that electronic cigarettes may be attractive to young people and might lead kids to try smoking. With your regular cigarettes, it is a known fact that your using the product will attract kids to smoking. Why take a risk on an unknown when you can be sure that your smoking has known effects on the youth population?

While a preliminary clinical trial demonstrated a 22.5% six-month cessation rate among unmotivated smokers who used electronic cigarettes to try to quit, why take a risk that the true quit rate among highly motivated smokers is lower than that? Why not stick with the reliable and well-documented 8% long-term quit rate that has been demonstrated with the use of approved nicotine replacement therapy? And if you are one of the many electronic cigarette users who tried those products specifically because you failed with NRT, all we can say is: try and try again. Why take a risk on an unknown when you can use a product that has a very high known failure rate?"

Monday, May 14, 2012

Cohasset May Ban Vaping in Public Places to Protect Kids from Seeing People Trying to Quit Smoking

The Cohasset (MA) Board of Health is considering regulations to ban vaping (use of electronic cigarettes) in public places that are subject to no-smoking rules.

According to an article in the Boston Globe: "In an interview, Dr. Michael Siegel, a tobacco control specialist at Boston University School of Public Health, ...had concerns about lumping electronic cigarettes with other tobacco products when regulating public smoking because “there’s no scientific evidence that the exhaled vapor poses any health hazard to bystanders.” The battery-operated devices, which were introduced in China in 2003, look like cigarettes but produce nicotine-laced vapors that are usually far less potent than the real thing. Studies have shown the e-cigarettes are effective in helping smokers kick the habit, Siegel said. While Lawrence [a Board of Health member] acknowledged that the health effect of e-cigarettes was unclear, he said their similarity to cigarettes was unsettling. 'From my perspective, using [them] models a child to a smoking behavior that can be easily turned into the real deal,' he said. 'I may be out on the fringe, but my responsibility is to look out for the health of the citizens in the town where I live.'"

The Rest of the Story

It appears that the Cohasset Board of Health wants to outlaw vaping in public places because they don't want children to see people using electronic cigarettes. In other words, they don't want children to see people trying to quit smoking.

Apparently, the Board of Health seems to misunderstand the most basic fact about electronic cigarettes: these products are being used primarily by smokers who want to quit smoking or cut down substantially in order to protect their health. Why would this be something that we wouldn't want children to see?

In fact, it might be that if children were to see how many smokers want to quit, it would actually decrease their perceptions of the glamor of smoking.

While opponents of vaping in public argue that it may lead children to start smoking, I think the opposite may be true. Such a view is, I believe, very short-sighted. While it may be true that if a child sees, for the first time, someone use an electronic cigarette, the child may be confused and think it is a real cigarette. But surely, over time, children will come to recognize electronic cigarettes and to understand that they are being used by smokers who are trying to quit because they are concerned about the health effects of smoking. This will help to de-glamorize smoking by teaching children that many smokers are unhappy that they started smoking and now want to quit. This could actually serve as an anti-smoking, rather than a pro-smoking phenomenon.

The second major argument against banning vaping in public places is that there is no evidence that exhaled electronic cigarette vapor is hazardous to bystanders. I believe that it undermines the justification for banning smoking in public places if health boards and city councils ban a behavior for which there is no evidence of harm. The reason why I believe workplace smoking bans are justified is that there is solid scientific evidence that secondhand smoke exposure is a significant health hazard for nonsmoking employees. If health boards start to ban behaviors without evidence of health hazards, then it undermines the seriousness of their responsibility to regulate behaviors for which there is evidence of health harm to others.

The article also noted that the Cohasset Board of Health is considering banning the sale of tobacco products in pharmacies because it "would do anything to reduce the amount of tobacco products being used." The problem is that banning the sale of tobacco in pharmacies will not reduce tobacco use. It will simply shift the sale of tobacco away from pharmacies and towards other types of stores, such as gas stations and convenience stores.

Thursday, May 10, 2012

Story of Biased Chantix Study by Pfizer-Funded Author Gets Worse; Article Violates FDA Recommendations, Excludes Heart Attack and Stroke Events, and Doesn't Adequately Consider Low Power of Studies

Monday, I discussed the results of a re-analysis of a previous study that showed an increased risk of adverse cardiovascular events among patients receiving Chantix. The new study concludes that Chantix is perfectly safe for use in patients in terms of cardiovascular risk. One of the authors of the new study is a recipient of grant funding from Pfizer, the manufacturer of Chantix, and therefore has a significant financial conflict of interest. I have previously argued that: "The bias present in the study has the appearance of being a result of this conflict of interest."

Today, I reveal several more dimensions of this story.

First, as Dr. Sonal Singh points out in his rapid response to the re-analysis, it appears that the authors excluded from their analysis several severe adverse cardiovascular events that have already been reported, including by the FDA itself. As Dr. Singh notes: "For example, in the largest clinical trial, the Rigotti study, the authors recorded 10 events in each treatment arm. In contrast, the updated FDA label, which contains warnings about an increase in cardiovascular risk associated with varenicline in patients with cardiovascular disease, notes several more treatment-emergent cardiovascular events during 30 days in varenicline than placebo [in this same study]: “These include treatment emergent events (on treatment or 30 days after treatment of angina pectoris (13 patients in varenicline arm vs 7 in placebo arm), and the serious cardiovascular events of non-fatal MI (4 vs 1) and nonfatal stroke (2 vs 0).”"

These exclusions presumably occurred because the authors did not count any adverse events that happened more than 30 days after discontinuation of the drug. However, the FDA-mandated clinical trial to assess the cardiovascular risks associated with Chantix required that follow-up of treated patients for adverse cardiovascular outcomes must continue out to at least one year. Thus, the study violates the FDA's recommendation that a one-year follow-up period is necessary. Apparently, the FDA is concerned that adverse effects of Chantix could occur well after discontinuation of the drug.

And well they should be. We all know about the severe cardiovascular adverse events associated with Vioxx use. Vioxx was in fact pulled from the market because of these effects. It is critical to note that these adverse cardiovascular effects of Vioxx persisted up to one year after discontinuation of the drug. How does it make any sound scientific sense, then, to exclude events occurring more than 30 days, but less than one year, after discontinuation of Pfizer.

This dimension of the story seems to make the apparent bias of the study even more striking.

Second, I do not believe that the article appropriately considers the lack of power in the clinical trials to detect a significant increase in a rare, serious adverse event such as heart attacks. These studies were powered to detect differences in smoking cessation between treatment arms, not to detect differences in rare adverse events. Pfizer itself notes that these clinical trials should not be used for conclusive evidence on whether the drug poses cardiovascular risks. Speaking about one clinical trial, Pfizer notes: "The study was powered for assessing efficacy (ie quit rates) but not for assessing differences in the occurrence of serious CV events between CHAMPIX and placebo. Therefore, the study was not large enough to allow conclusions regarding the difference in the incidence of CV events reported in the two arms."

In this light, it is difficult to understand how the paper could conclude not only that there was no statistically significant increase in risk, but also that there was no clinically significant increase. As I pointed out yesterday, even a 0.27% absolute increased risk would translate into thousands of adverse events because of the large number of patients being treated with the drug. And if the drug is not particularly effective in achieving smoking cessation, then the risk-benefit analysis could easily tip towards the risk side.

Even if one accepts the results of the article at face value, the upper end of the confidence interval for the risk difference was 0.63%. This means that because of the small sample sizes in the clinical trials, this meta-analysis cannot rule out an effect as large as a risk difference of 0.63%. With 1.8 million annual prescriptions for Chantix, however, this excess risk of 63 events per 10,000 treated patients would be quite significant. To conclude definitively that there is no clinically significant cardiovascular risk associated with Chantix based on the meta-analysis thus appears to be quite biased.

Finally, while the article does not provide details of the purpose for which the conflicted author is receiving funding from Pfizer, it turns out that this funding is for a clinical trial of Chantix among hospitalized smokers. In my opinion, this makes the conflict of interest even stronger.

Clearly, the verdict is not yet in and an investigator who has a conflict of interest by virtue of taking money from Pfizer for a clinical trial of Chantix should not draw a conclusion at this point in time, based on the existing under-powered clinical trials, that the drug has no clinically significant cardiovascular risks.

Wednesday, May 09, 2012

Study Conclusion on Adverse Effects of Chantix Suggests Bias Which Has Appearance of Being Related to Financial Conflict of Interest

Monday, I discussed the results of a re-analysis of a previous study that showed an increased risk of adverse cardiovascular events among patients receiving Chantix. In this new study, the authors failed to find any significant effect of Chantix on cardiovascular event risk and they conclude: "Our meta-analysis of treatment emergent, cardiovascular serious adverse events, with attention to bias and critical design issues, indicates that the risk of these events associated with varenicline use is small, and statistically and clinically insignificant."

As I pointed out: "one of the authors of the new study is a recipient of grant funding from Pfizer, the manufacturer of Chantix, and therefore has a significant financial conflict of interest." I argued that: "The bias present in the study therefore has the appearance of being a result of this conflict of interest, rather than as a result of the desire to ensure the rigor of reported scientific findings."

Today, I discuss two aspects of the study which, upon further thought, lead me to more seriously question both the apparent bias in the article and the apparent influence of the conflict of interest in shaping this bias.

The Rest of the Story

The first issue that I find particularly troubling is the study's exclusion of any adverse cardiovascular events that occurred more than 30 days after discontinuation of Chantix. This might be justifiable if the effects in question were acute effects that could occur only in the presence of the drug in the bloodstream. For example, if one were studying the effects of a drug on sedation, it would be implausible that the drug would have an effect after a period of more than about five or six half-lives, because the drug is out of the system and any sedation effects would have ceased by that point. However, the hypothesized effect of the drug is not solely due to its presence in the bloodstream. The effect may be due to long-term changes in blood vessels, which do not simply disappear immediately after withdrawal of the drug.

For example, when a smoker quits smoking, her risk of cardiovascular events does not immediately drop to the level of a nonsmoker. In fact, it takes about two years - at least - before cardiovascular risk returns to normal. This is because smoking induces long-term atherosclerotic changes and vessel disease which are not immediately reversible. If one excluded events occurring more than 30 days after smoking cessation in a study of the adverse effects of smoking, one would obtain an incorrect, and substantially lower than accurate estimate of the magnitude of smoking's cardiovascular effects.

Since the adverse effect in question is related to the atherosclerotic process, rather than to some acute phenomenon, it seems inappropriate to exclude any events that occurred more than 30 days after drug withdrawal.

The second issue that I find troubling is the study's conclusion that based on this meta-analysis, Chantix has no "clinically significant" cardiovascular effects. Due to the extremely small sample sizes in the studies and to the rare nature of the events in question, the meta-analysis has limited power to detect a statistically significant effect of Chantix on cardiovascular event risk. Importantly, the meta-analysis, even with its exclusion of some adverse events, found a 0.27% excess absolute risk of adverse events among patients treated with Chantix.

This represents 27 adverse events among every 10,000 treated patients. Approximately 1.8 million patients per year receive Chantix prescriptions. If the risk difference reported in the meta-analysis is correct, then this translates into approximately 4800 adverse cardiovascular events among treated patients due to Chantix. This number hardly seems "clinically insignificant."

A judgment of the clinical significance depends further upon an evaluation of the number of treated patients who will quit smoking, and thus gain substantial health benefits. Assuming that 10% of treated patients will quit long-term because of the drug and that 10% of these patients will be saved from a severe adverse cardiovascular effect because of quitting, the drug will prevent adverse events among 18,000 people. However, this comes at the expense of causing severe harm to 4800 people. In other words, for every four smokers who are "saved" by the drug, one will be seriously harmed by it.

These numbers are of course estimates, but my point is simply that one needs to conduct an analysis like this before one can opine about the clinical significance of an observed 0.27% absolute risk increase of serious adverse cardiovascular events associated with Chantix.

The most important point, however, is that the sample sizes in the studies were so small that one should not - at this point - draw any conclusion that Chantix has no clinically significant adverse effects based on the current meta-analysis. These studies were powered to determine whether Chantix helps people quit smoking, not to specifically determine whether the drug can increase the risk of rare outcomes such as heart attacks.

Dr. Singh, the author of the original study, points out this important fact in his rapid response to the re-analysis: "the authors provide no information on the optimal information size or the power of their meta-analysis. They conflate the lack of statistical significance in an underpowered meta-analysis as clinically insignificant. Despite the removal of cardiovascular events on varenicline, and a statistical approach that has limited powered to detect an effect there is an excess risk of cardiovascular events with varenicline in all five measures reported in their study. ... Since none of the trials evaluated cardiovascular events as a primary outcome or were powered to detect individual differences in cardiovascular outcomes between varenicline and placebo, adequately powered randomized controlled trials are needed. ... A post-marketing Study to Evaluate Cardiac Assessment following different treatments of smoking cessation medications in subjects with and without psychiatric disorder (CATS) comparing varenicline, placebo, bupropion and nicotine replacement therapy of approximately 8000 patients with major adverse cardiovascular events as a primary outcome has been requested by the FDA. After 24 weeks of treatment it will collect data on cardiovascular outcomes for an additional 28 weeks of non-treatment, for a total of 52 weeks. Unfortunately, the results will only be available in 2017, just in time for the patent expiry of varenicline. ... until the results of such outcome trials are available, clinicians need to consider the overall risks of varenicline. i. e., the serious cardiovascular risk and other serious risks such as suicide, depression and violence noted in the drug label. They need to balance these serious risks against its efficacy on abstinence, compared to placebo."

In other words, it is far too premature to draw the conclusion that Chantix has no serious cardiovascular adverse effects. Were that the case, then why would the FDA be requesting a study with 8000 patients.

The point is this: none of the existing studies has the power to detect a small, but significant increase in cardiovascular events due to Chantix. The large study, with 8000 patients, is necessary before any conclusion can be drawn. Certainly, physicians and researchers should refrain from disseminating to the public the conclusion that Chantix is perfectly safe in terms of its cardiovascular risk profile.

However, this is precisely what the authors of this study have done. Their conclusion that Chantix is safe - based on their study - is completely unwarranted and I believe, inappropriate. That this conclusion is based on a study conducted by an author with a substantial financial conflict of interest - receiving grant funding from the manufacturer of the drug in question - is, in my mind, not only unfortunate but unacceptable.

The public in general, and physicians in particular, need to be able to rely on the opinions of unconflicted researchers in order to make decisions regarding the clinical safety and effectiveness of medical treatments. While there is nothing wrong with a researcher carrying out a drug-funded study, that researcher should not place themselves in the position of making national recommendations for the use of a drug, or drawing overall conclusions regarding the safety of the drug.

The rest of the story is that this study is severely biased, as evidenced by biased methodology and by a heavily biased conclusion that Chantix is perfectly safe. The severe bias has the appearance of being related to the lead author's receipt of grant funding from the manufacturer of the drug in question. This is the type of bias that proper management of conflicts of interest is intended to prevent.

Tuesday, May 08, 2012

IN MY VIEW: Smoker-Free Workplace Policies are Moral Crusades, Not Public Health Measures

The Fort Worth City Council is considering a proposal that would preclude smokers from employment with the city.

According to an article from McClatchy newspapers: "While such a move would be rare for a city, employers everywhere are getting more involved in their employees' lifestyle decisions that affect health, experts say. Companies and some government agencies have crafted policies that range from banning smoking to charging penalties on the health care benefits of overweight workers. "Their ultimate goal is to make their employees healthier, and there is a direct correlation between that and reducing health care costs," said Danny Cooner, president of Safety First, a division of Behavioral Health Systems, a company that helps employers enact wellness and smoke-free campaigns."

The Rest of the Story

If the goal of these policies is to make employees healthier and to save money, then why is every employer who implements these policies restricting them to current smokers? Ex-smokers are at a significantly increased risk of disease. The risks of heart disease do not return to baseline levels for at least two years after smoking cessation and cancer risk remains elevated for as long as two decades after smoking cessation. Thus, ex-smokers are not as healthy as nonsmokers and employing them results in increased health care costs for the employer. Why, then, is every employer which is discriminating against smokers in hiring perfectly OK with hiring ex-smokers, despite their increased disease risk and their increased health care costs?

Furthermore, if these policies are all about creating a healthy workforce, then why is it that only one of the many companies which refuse to hire smokers has also applied the policy to current employees? Especially for a large company, refusing to hire smokers is not going to make much of a dent in the health of the workforce, since many current employees already smoke? Why not do what Weyco did and apply the policy to current workers, giving them a certain amount of time to quit smoking or else firing them? 

The answer to these questions, I believe, is that these policies are not actually about improving the public's health, but instead, are part of a moral crusade against smoking. The policies are about punishing smokers in order to show moral disapproval of one particular unhealthy behavior choice. They are not about creating a healthier workforce. They are about expressing moral disapproval of smoking and tobacco use.

Monday, May 07, 2012

Researchers Reanalyze Data from Previous Study Which Showed Cardiovascular Adverse Effects of Chantix and Find No Adverse Effect

A study published last week in BMJ presented a re-analysis of data from a previous meta-analysis of the potential adverse effects of the smoking cessation drug Chantix. The original study reported that the odds of serious cardiovascular events were 1.7 times higher among smokers treated with Chantix compared to those receiving placebo, using data from from 14 double-blind randomized controlled trials involving 8216 participants.

In the new study, the authors examined data from 22 randomized clinical trials of Chantix. The major differences in the two studies were:

1. The new study included 8 clinical trials in which there were no adverse cardiovascular events observed. Those studies were excluded from the original study.

2. The new study only included adverse cardiovascular events that occurred within one month of patients discontinuing Chantix. The original study included all observed cardiovascular effects in the clinical trials.

The authors failed to find any significant effect of Chantix on cardiovascular event risk. They conclude: "Our meta-analysis of treatment emergent, cardiovascular serious adverse events, with attention to bias and critical design issues, indicates that the risk of these events associated with varenicline use is small, and statistically and clinically insignificant."

The Rest of the Story

The authors of this study argue that the exclusion of trials in which there no adverse events leads to a bias away from the null hypothesis of no adverse cardiovascular events associated with Chantix. This is how they justify the inclusion of those trials. One could also argue, of course, that the inclusion of the trials with no observed adverse effects biases the results towards the null hypothesis (when one is using the absolute risk difference as the primary outcome measure). With no adverse effects observed, the risk difference has to be zero, because there can be no difference in absolute risk when the risk in both groups is zero.

The authors of this study also argue that the inclusion of adverse events occurring after the study drug was discontinued was inappropriate because the drug is no longer present in the person's system and thus can no longer have any effect. They write: "We conducted a systematic review and meta-analysis of treatment emergent, cardiovascular serious adverse events in all published, randomised controlled trials of varenicline for tobacco cessation. We defined these events as occurring during drug treatment or within 30 days of discontinuation. We chose a 30 day window because it was biologically relevant for detecting a drug toxicity effect, while still being conservative; the half life of varenicline is 24 hours, and any direct pharmacological effect should be gone within seven days."

However, one could easily argue that the exclusion of adverse cardiovascular events occurring more than 30 days after discontinuation of Chantix therapy is inappropriate because if the drug causes inflammatory processes that accelerate atherosclerosis or facilitate plaque formation, then the risk does not disappear immediately after the drug is withdrawn. For example, if studying the adverse cardiovascular effects of smoking, one would not exclude events occurring more than one month after smoking cessation.

So in a way, the exclusion of events occurring more than 30 days after discontinuation of Chantix therapy biases the results towards the null hypothesis and this procedure seems inappropriate for a study whose outcome is adverse cardiovascular events, where risk does not decrease immediately after discontinuation of an offending agent (such as tobacco smoke, hypertension, high cholesterol, or a pro-thrombotic or pro-atherogenic drug).

The point is that these authors are presenting a biased view of the relationship between Chantix and adverse cardiovascular events. It is almost as if they were not willing to accept the previous results and were searching for a way to negate the earlier findings. It may or may not be the case that they are correct, but the bias is apparent.

There would be no problem at all with that bias under normal circumstances. Every scientist looks at a problem with a particular bias, and that is generally a good thing. It ensures rigorous scientific consideration of hypotheses and study findings and generally enhances science.

However, the problem is that these are not "normal circumstances." In this case, one of the authors of the new study is a recipient of grant funding from Pfizer, the manufacturer of Chantix, and therefore has a significant financial conflict of interest. The bias present in the study therefore has the appearance of being a result of this conflict of interest, rather than as a result of the desire to ensure the rigor of reported scientific findings.

According to the study: "JJP [the lead author] is principal investigator on ... an Investigator Initiated Research award from Pfizer...".

The conflict of interest arises from this Pfizer funding. Because she receives funding from Pfizer, there is a financial conflict with her reporting the results of a meta-analysis of clinical trials on Chantix, because if she were to report an adverse effect of Chantix, this would obviously threaten any future funding she might receive from the pharmaceutical company.

I have serious concerns about a conflicted author making national recommendations like this about the safety of a drug, especially when other research has concluded otherwise, and when the FDA itself has forced the company to include a black box warning about the adverse cardiovascular effects of the drug. I believe that while it is fine for this author to conduct the study for which she has been funded by Pfizer, she should refrain from making national recommendations supporting the drug's use and minimizing its potential adverse effects, because those recommendations are by definition the results of a conflicted analysis, which is tarnished by a significant financial conflict of interest.

Thursday, May 03, 2012

Physician Urges Public Not to Use Electronic Cigarettes, Claiming that They Involve Combustion

In an article about electronic cigarettes at the KTLA (Los Angeles) web site, a physician is quoted as cautioning the public about the use of these products because they involve combustion.

According to the article: "some doctors say not enough is known about the cigarettes to determine if they pose a health risk. 'We don't know if they offer any potential health risk or not,' said Dr. Clark Fuller of Saint John's Health Center. 'What we do know is it involves a combustion and a release of a vapor that is inhaled in the lungs. The chemical makeup of that vapor is unknown.'"

The Rest of the Story

Wrong on both accounts.

First of all, electronic cigarettes do not involve combustion. The juice is heated with an electric element to vaporize the nicotine, but there is no combustion. You do not "light" an electronic cigarette. Since there is no combustion, there is no smoke. Most importantly, there is no tobacco involved.

Second of all, we do know the chemical makeup of electronic cigarette vapor. There are a number of laboratory studies in which the composition of electronic cigarette vapor was analyzed using gas chromatography mass spectrometry. I have summarized the major findings of these studies in the review article I co-authored with Zachary Cahn, which was published in the Journal of Public Health Policy.

This story illustrates two important points.

First, there remains a great deal of misinformation, even among health professionals, about electronic cigarettes. These products have now been on the market for more than four years. Much has been written about them, both in the lay press and in scientific journals. Yet so many health professionals are apparently so eager to criticize the product and discourage smokers from using it to quit that they have not taken the time to research the basic facts about electronic cigarettes.

Second, the story illustrates that many health care professionals have a deeply rooted bias against the idea of an alternative nicotine delivery system that resembles a cigarette, even if it may be much safer. Clearly, this physician has very little knowledge upon to which to make a statement to the media that will be carried internationally. He doesn't even know whether electronic cigarettes involve combustion or not, nor does he know, apparently, whether there are any laboratory studies on the composition of electronic cigarette vapor. Nevertheless, he is willing to make (factually incorrect) public statements to the media about the product. This suggests to me that he (and many other health care professionals) have an inherent bias against these products, and that their statements are being guided purely by ideology, and not by science.

This physician has made not one, but two factual errors in his statement to the press. In my opinion, you really should be an expert on an issue, or at least know a moderate amount about it, before you make public statements that could have national implications for the public's health. In this case, the implication could be to discourage people from using the product, and therefore to dissuade many smokers from quitting who might have otherwise been successful.

Wednesday, May 02, 2012

Defective Electronic Cigarette Battery Injures One Person; Defective but Legal Cigarette Lighters Injure 1000 Per Year

In February, an electronic cigarette battery exploded in a man's mouth, causing serious injuries. That one event led many to argue that electronic cigarettes are unsafe and some to state that they are not even safer than cigarettes. A number of anti-smoking groups, such as Americans for Nonsmokers' Rights, have linked to this story in an effort to convince the public of the dangers of electronic cigarettes (which will, of course, discourage them from trying to quit smoking using these products).

The explosion of this electronic cigarette battery emphasizes the need for the Food and Drug Administration to promulgate regulations to protect vapers -- most importantly, to ensure that appropriate quality control measures are used by all electronic cigarette companies. However, those who have responded to this story by scaring the public into thinking that these products are no safer than cigarettes may not be aware of the entire story.

The Rest of the Story
According to an article on the WFMY (Greensboro, NC) web site, cigarette lighters are responsible for about 1,000 injuries each year and an exploding lighter may have been the cause of one man's death. The article states: "the lighter had a defective seal. After it had been used, the defective seal allowed the butane to keep flowing. A small flame stayed lit, hidden by the wind guard. And when Bill put the lighter in his pocket, it exploded, giving him third degree burns. Bill was using an MK lighter made in China. The Consumer Product Safety Commission found that defective cigarette lighters caused nearly 1,000 injuries a year."

In other words, the rest of the story is that exploding cigarette lighters cause far more injuries (by at least two orders of magnitude) than electronic cigarettes. Thus, even ignoring the reduction in adverse health effects attributable to the fact that electronic cigarettes do not involve the combustion of tobacco, these products are far safer than cigarettes merely because there has only been one reported case of a battery explosion-related injury compared to a thousand annual injuries from cigarette lighters.

The lack of perspective displayed by many anti-smoking groups in warning the public about the dangers of electronic cigarettes is striking. So is the overwhelming bias in many of these groups' presentation of the scientific facts. For example, while Americans for Nonsmokers' Rights presents article after article scaring people about the potential, but un-demonstrated hazards of electronic cigarettes, it links to not a single scientific study which has demonstrated beneficial effects of using these products, including the only clinical trial conducted on electronic cigarettes, in which these products were associated with a 22.5% six-month smoking abstinence rate among unmotivated smokers.

It is becoming increasingly difficult for the public to get the full story about science and health issues from the anti-smoking groups. This is why I believe there is such a need for a source where the public can continue to get "the rest of the story."

Tuesday, May 01, 2012

UCSD Researchers Call Attention to Differences Between Science and Policy on National Smoking Cessation Strategy

Researchers at the University of California, San Diego School of Medicine are calling attention to a major discrepancy between the scientific evidence base and national policy on smoking cessation, according to a press release issued by the university. The researchers, led by Dr. John Pierce, are pointing out that while most smokers who have successfully quit have done so unaided, national cessation policy discourages unaided quitting and in fact insists that every smoker be treated with a drug, a strategy which the UCSD researchers say destroys smokers' confidence in their ability to quit and undermines smoking cessation in the long-run. This perspective is summarized in a review article published in the 2012 Annual Review of Public Health.

According to the review article: "While quit attempts have increased, widespread dissemination of these aids [pharmaceutical aids and quitlines] has not improved population success rates. Pharmaceutical marketing strategies may have reduced expectations of the difficulty of quitting, reducing success per attempt. Some policies actively discourage unassisted smoking cessation despite the documented high success rates of this approach. There is an urgent need to revisit public policy on smoking cessation."

According to the press release: "'For the past decade, attempts to quit smoking have increased, but the proportion of people who become successful quitters has gone down' said John P. Pierce, PhD, professor of Family and Preventive Medicine and director of Population Sciences at UC San Diego Moores Cancer Center. 'Widespread dissemination of cessation services has not led to an increase in the probability that a quit attempt will be successful.'" ... recent evidence suggests that part of the problem may lie in how cessation aids are marketed by pharmaceutical companies: many such ads suggest that quitting smoking may be as simple as putting on a patch. It appears that younger smokers in particular are now more likely to underestimate the amount of work needed in order to quit smoking successfully."

"Traditionally, the majority of smokers who quit successfully have done so without assistance, and recent data suggests that this has not changed.  However, current national policy discourages unassisted quitting, advising clinicians to make sure smokers who want to quit do so with pharmaceutical assistance.  This policy may undermine smokers’ belief in their ability to quit on their own."

The Rest of the Story

These are critical findings which must be considered by tobacco control practitioners and which should lead to a re-thinking of national smoking cessation strategies and policy.

One may ask why there is such a discrepancy between the scientific evidence base and national policy. I believe the answer is that many of the leading researchers and organizations that have developed and disseminated recommendations for a national smoking cessation strategy have strong financial ties to pharmaceutical companies which manufacture smoking cessation drugs. This conflict of interest has led to a systematic bias whereby these researchers and groups have not been able to objectively analyze and interpret the literature, but instead have, albeit subconsciously, slanted the research findings to fit a preconceived belief in the value of pharmaceutical aids.

Just last week I pointed out that the 2012 National Conference on Tobacco or Health is being sponsored by a pharmaceutical company (Pfizer). There is no way that this conference can undertake an objective consideration of the role of smoking cessation drugs as part of national tobacco control strategies. My call on the National Conference on Tobacco or Health to return Pfizer's money and to institute a policy of rejecting pharmaceutical company sponsorship of its conferences has apparently fallen on deaf ears. As a result, this conference can no longer claim to be an objective scientific conference which serves the purpose of undertaking an objective, evidence-based consideration of "the latest evidence on what works in tobacco control."

This is just one recent example of the way in which the tobacco control field has become systematically biased because of the receipt of pharmaceutical company funding.

Another example of this systematic bias is the fact that the chair of the expert panel which made the national smoking cessation treatment recommendation in the first place had access to up to $50,000 in annual resources from GlaxoSmithKline to support his educational, research, and policy activities. In addition, the panel chair has a history of doing outside consulting work for pharmaceutical companies which on an annual basis ranged between about $10,000 and $40,000 per year. In the past, he has has served as a consultant for, given lectures sponsored by, or has conducted research sponsored by Ciba-Geigy, SmithKline Beecham, Lederle Laboratories, McNeil Consumer Products, Elan Pharmaceutical, Pharmacia, and Glaxo Wellcome. In addition, he has lectured and consulted for Pfizer and has served as an investigator on research studies at the University of Wisconsin (UW) that were supported by GlaxoSmithKline, Nabi, Pfizer, and sanofi-aventis.

Another aspect of the problem is that the conflicted researchers and organizations do not seem to appreciate the magnitude of this conflict of interest or the degree to which it could potentially affect their objectivity. In some cases, the disclosure of these conflicts has not been forthcoming or completely transparent, as appears to be the case with this 2006 disclosure, in which the signer (the chair of the NIH expert panel on smoking cessation treatment) fails to disclose his history, within the past 5 years according to his sworn testimony, of receiving consulting income on the order of tens of thousands of dollars during the past 5 years. This testimony was given in 2005; thus, his testimony indicates that the period during which he received consulting income from Big Pharma corresponds to the 5-year period about which his 2006 disclosure inquires.

In his testimony, the panel chair states: "Separately, I have done some consulting work for pharmaceutical companies over the years. Over the past five years, my outside consulting work on an annual basis has ranged between about $10,000 and $30,000 or $40,000 per year." Yet his signed initial disclosure for the NIH panel the following year reveals only that: "In keeping with recent JAMA recommendations, Dr. Fiore does not accept honorarium nor do consulting work for the pharmaceutical industry." Since the form requires disclosure of all financial interests during the past 5 years, the interpretation of this disclosure statement is that Dr. Fiore does not currently do consulting work for the pharmaceutical industry, and has not done such consulting work for the past 5 years. Based on Dr. Fiore's testimony, this appears not to be true. Thus, this appears to be a bit dishonest or misleading, or at very least, a flawed and incomplete disclosure.

Moreover, there are other examples of scientific articles on the effectiveness of pharmaceutical aids for smoking cessation in which the conflicts of interest with Big Pharma are not adequately or completely disclosed. For example, in a 2009 nicotine gum study, the financial conflicts of interest of the study site principal investigators are not disclosed. I was able to find out about these financial conflicts only after hours of research using databases that are not publicly available. I think readers of this article would be shocked to find out, for example, that one of the study site principal investigators had consulted for GlaxoSmithKline, manufacturer of nicotine gum, as well as for 20 other pharmaceutical companies. This type of information, especially because it is not disclosed, really puts the validity of the study findings and conclusions in question.

As another example, in 2009, the Association for the Treatment of Tobacco Use and Dependence (ATTUD) issued a press release to promote a ban on the sale of electronic cigarettes in the United States. The press release highlighted a letter written from the organization to the FDA requesting that the Agency remove electronic cigarettes from the market. However, the press release and letter failed to reveal that Dr. John Hughes - who is one of the co-signers of the letter to the FDA - apparently has conflicts of interest by virtue of his having consultancies, honoraria, and research grants/contracts with pharmaceutical companies.

Elsewhere (Drug and Alcohol Dependence, Volume 98, Issue 3, 1 December 2008, Pages 169-178), Dr. Hughes has disclosed that: "In the last 3 years he has received research grants from the National Institute on Health and Pfizer Pharmaceuticals and Sanofi-Synthelabo Pharmaceuticals both of whom are developing smoking cessation treatments. In the last three years, he has accepted honoraria or consulting fees from the following profit or non-profit institutions regarding nicotine or other drug abuse topics: Academy for Educational Development, Acrux DDS; American College of Chest Physicians, Adelphi Consulting, Aradigm; Atrium, Baltimore Research, Campus Consulting, Cambridge Press, Cline, Davis and Mann; Concepts in HealthCare, Constella Group; Consultants in Behavior Change; Cowen Inc, Cygnus, Edelman, Fagerstrom Consulting; Free and Clear; Healthwise, Health Learning Systems, International Marketing Systems, Insyght; Johns Hopkins University; Maine Medical Center, McNeil, Medicus, Nabi, National Institutes on Health; NCI Consulting, Pfizer Pharmaceuticals; Pinney Associates; Research Triangle Institute, Shire Health London; Temple University of Health Sciences; University of Arkansas, University of Auckland; University of Cantabria; University of Greifswald; University of Kentucky, University of Memphis, Warner Pharmaceuticals, Wolters Press, Xenova, and ZS Associates."

Thus, Dr. Hughes is essentially a walking conflict of interest with Big Pharma. But none of this was disclosed in the letter to the FDA or the press release as they appeared on the internet.

The other co-signer of the letter to the FDA demanding a ban on electronic cigarettes - the current ATTUD president at the time - Dr. Michael Burke, had also apparently received honoraria from Pfizer Health Solutions, a subsidiary of the pharmaceutical company Pfizer, according to a disclosure posted on the ATTUD web site. This was also not disclosed in the letter to the FDA or the press release as they appeared on the internet.

The rest of the story is that there is a disconnect between the scientific evidence base and national policy on smoking cessation treatment. And the reason for this discrepancy is the existence of severe financial conflicts of interest among some of the leading researchers and organizations that have pushed for the current national cessation policy. The problem is rounded out by an apparent lack of regard for the importance of these conflicts of interest and the failure to disclose them in all statements making recommendations about national smoking cessation treatment policy.

Worst of all, there does not appear to be any interest in resolving the problem. My call for the divestment of the National Conference on Tobacco or Health from Big Pharma has fallen on deaf ears, as have similar appeals to several other major tobacco control organizations and conferences. There is, in fact, no resolution in sight.