More Conflicts of Interest Being Hid by Electronic Cigarette Opponents: Funding of their Organization by Big Pharma Not Disclosed

Two days ago, I pointed out a strong bias against electronic cigarettes in the response of Drs. Nathan Cobb and David Abrams to a commentary I co-authored with Drs. Ted Wagener and Belinda Borrelli in the September issue of Addiction. After pointing out the bias, I posed the question of whether there may be a potential explanation for this strong apparent bias against a potentially effective new smoking cessation product that might compete with the mainstays of current treatment: smoking cessation drugs and cessation quitlines and web sites.

Yesterday, I revealed that there is indeed a possible explanation: financial conflicts of interest of both authors with companies which produce products used in smoking cessation treatment (cessation web sites and cessation drugs).

Specifically, I revealed that:

• Dr. Cobb is a paid consultant to a company that makes its profits based on an internet smoking cessation site which heavily promotes smoking cessation drugs: "Dr Cobb is a consultant to Healthways Inc, the current owner of the QuitNet system." Thus, he is conflicted because to the extent that the use of electronic cigarettes presents a different pathway to cessation than the traditional one - the use of a smoking cessation internet site, medication, online support, etc. - e-cigarettes may represent a threat to the profits of Healthways. 


• Dr. Abrams has received grant funding from multiple pharmaceutical companies that have investigated or manufactured smoking cessation drugs, including Eli Lilly, Dupont Merck, Glaxo-Wellcome, SmithKline Beecham, Sano Corporation, Bristol-Myers Squibb, Knoll Pharmaceuticals, and Pfizer. Dr. Abrams also reports having served as a senior scientific advisor for Johnson & Johnson. It is difficult to find a pharmaceutical company involved in smoking cessation drugs that Dr. Abrams has not had an association with over the years. 

None of these conflicts were disclosed in the article, which reported that the authors had nothing to disclose.

The Rest of the Story

The conflicts of interest with Big Pharma go far deeper than I revealed yesterday. The conflicts I revealed yesterday relate to personal conflicts of the co-authors. But there is also an institutional conflict of interest.

Both authors are with the Schroeder Institute for Tobacco Research and Policy Studies at the American Legacy Foundation.

What these authors did not disclose in the article is that the American Legacy Foundation receives funding from Big Pharma - specifically, from Pfizer, which is the maker of Chantix, a smoking cessation drug which stands to lose severely if electronic cigarettes become more and more popular. Thus, the Foundation's receipt of funding from Pfizer is a conflict of interest that I believe should have been revealed in the article.

What is the evidence for a financial connection between Pfizer and the American Legacy Foundation? Although you won't easily find any disclosure of this connection on the Legacy web site, Pfizer is transparent in reporting its donations to the American Legacy Foundation:

• In the first quarter of 2011, Legacy received $150,000 from Pfizer for a "Quitting Smoking Public Opinion Initiative."


• In the third quarter of 2011, Legacy received $150,000 from Pfizer for a "Quitting Smoking Public Opinion Initiative."


• In the first quarter of 2009, Legacy received $260,500 from Pfizer for a "Smoking Cessation Awareness and Benefit Survey."


• In addition, Pfizer is listed as a contributor to the 2009 American Legacy Foundation Honors event.


• Pfizer is not the only pharmaceutical company from which Legacy has taken money. The Foundation also admits to receiving funding from GlaxoSmithKline, Novartis Consumer Health, and Schering-Plough between 2008 and 2010.

The rest of the story is that these substantial conflicts of interest were not revealed in the article, thus hiding from readers the fact that these authors work at an organization which receives substantial funding from multiple companies that manufacture smoking cessation drugs and stand to lose tremendously if electronic cigarettes become more popular. I think that readers deserve to have this information and I therefore think these conflicts, along with the personal conflicts of interest I revealed yesterday, should have been disclosed.

Electronic Cigarette Opponents Fail to Disclose Relevant Conflicts of Interest to the Public

Yesterday, I pointed out a strong bias against electronic cigarettes in the response of Drs. Nathan Cobb and David Abrams to a commentary I co-authored with Drs. Ted Wagener and Belinda Borrelli in the September issue of Addiction. After pointing out the bias, I posed the question of whether there may be a potential explanation for this strong apparent bias against a potentially effective new smoking cessation product that might compete with the mainstays of current treatment: smoking cessation drugs and cessation quitlines and web sites.

The first thing that should cross the mind of regular readers of this blog is the possibility of a conflict of interest among the authors. 

However, in the published response, the authors deny having any conflict of interest. The declaration of interests statement reads: "Declarations of interest: None."

The Rest of the Story

Dr. Cobb is a paid consultant to a company that makes its profits based on an internet smoking cessation site which heavily promotes smoking cessation drugs: "Dr Cobb is a consultant to Healthways Inc, the current owner of the QuitNet system." Thus, he is conflicted because to the extent that the use of electronic cigarettes presents a different pathway to cessation than the traditional one - the use of a smoking cessation internet site, medication, online support, etc. - e-cigarettes may represent a threat to the profits of Healthways.

Dr. Abrams has received grant funding from multiple pharmaceutical companies that have investigated or manufactured smoking cessation drugs, including Eli Lilly, Dupont Merck, Glaxo-Wellcome, SmithKline Beecham, Sano Corporation, Bristol-Myers Squibb, Knoll Pharmaceuticals, and Pfizer. Dr. Abrams also reports having served as a senior scientific advisor for Johnson & Johnson. It is difficult to find a pharmaceutical company involved in smoking cessation drugs that Dr. Abrams has not had an association with over the years.

According to the guideline for authors on the Addiction web site: "Authors are also required to declare any financial conflict of interest arising from involvement with organisations that seek to provide help with or promote recovery from addiction."

It is difficult to see how Healthways, through its ownership of the QuitNet system, is not an organization that seeks to provide help with or promote recovery from addiction.

It is also difficult to see how the many pharmaceutical companies from which Dr. Abrams has received funding are not organizations that seek to provide help with or promote recovery from addiction.

Dr. Cobb's financial interest in Healthways appears to be current, since he disclosed that interest in a 2011 Archives of Internal Medicine paper.

Dr. Abrams' financial relationship with the pharmaceutical companies is in the past, as his most recent grant from Big Pharma appears to have been in 2003.

In my opinion, both of these conflicts of interest are relevant to readers' assessment of the validity of the opinions in the response and therefore they should have been disclosed.

One might ask the question of whether a financial interest dating back to 2003 is still relevant in 2012. In a previous post, I provided a detailed explanation of why I think past conflicts are relevant. I wrote that "past conflicts of interest are indeed critical for readers to know about. Just because Professor X and Professor Y had nothing to disclose during the past three years does not indicate that they have no financial conflicts of interest that need to be disclosed in their current publications, the journal's requirements notwithstanding. Furthermore, it would be hypocritical and inconsistent to argue that past conflicts are only relevant when it comes to tobacco. If past conflicts are relevant, then past conflicts are relevant. Therefore, it is my feeling that researchers do need to disclose their past conflicts (albeit briefly). A financial conflict of interest does not disappear simply because the conflict is no longer active. ... Clearly, past conflicts of interest are relevant and I believe that researchers have the obligation to disclose past conflicts that are related to the research in question."

It seems to me that Dr. Cobb's financial interest ought to have been disclosed both because of the journal's requirement for disclosure and because readers deserve to know about that conflict. While Dr. Abrams' conflicts of interest may not have needed to be disclosed under the journal's policies (it is unclear because no time frame is provided for conflicts), I nevertheless believe that it still should have been disclosed because readers deserve to know about these past conflicts in order to make informed judgments about the opinions expressed in the article.

The rest of the story is that this is yet another example of the failure of electronic cigarette opponents to disclose relevant conflicts of interest to readers and to the public.

Commentary and Responses in Addiction Consider the Potential Role of Electronic Cigarettes in Smoking Cessation and Harm Reduction

This month's issue of the journal Addiction features a detailed consideration of the potential role of electronic cigarettes in smoking cessation.

In a commentary, Drs. Ted Wagener, Belinda Borrelli and I argue that in the previous literature, the potential harms of electronic cigarettes have been exaggerated or over-emphasized relative to the benefits and that these products could play a role in smoking cessation. We write: "Concerns have been raised that the advent of electronic cigarettes (e-cigarettes) may be harmful to public health, and smokers have been advised by important agencies such as the US Food and Drug Administration not to use them. This paper argues that, while more research is needed on the cost–benefit equation of these products and the appropriate level and type of regulation for them, the harms have tended thus far to be overstated relative to the potential benefits. In particular: concern over repeated inhalation of propylene glycol is not borne out by toxicity studies with this compound; risk of accidental poisoning is no different from many household devices and chemicals available in supermarkets; concern that e-cigarettes may promote continued smoking by allowing smokers to cope with no-smoking environments is countered by the observation that most smokers use these products to try to quit and their use appears to enhance quitting motivation; concerns over low nicotine delivery are countered by evidence that the products provide significant craving reduction despite this in some cases; and e-cigarettes may help reduce toxin exposure to non-smokers."

In the first response, Dr. Peter Hajek supports our perspective, suggesting that electronic cigarettes or a product similar to them could eventually be a viable competitive alternative to conventional cigarettes. Hajek writes: "The consideration of EC [electronic cigarettes] as a consumer product is even more exciting. If a harmless nicotine delivery device appeared which would be capable of competing with tobacco products in the market-place, the public health benefit would be enormous. I personally do not think that the current versions of EC are as yet up to the task of replacing CC [conventional cigarettes], but they can be seen as a trial run of a hugely promising new development. The first evidence is emerging that perhaps 20% of smokers who try EC become regular users [3]. Our reaction to this first dawn of a credible non-tobacco consumer nicotine product is likely to influence future developments profoundly. If we ban EC or make them jump through hoops and choke them in red tape, the deadly CC will continue to rule unchallenged. ... EC are the first sign that such a product can be commercially viable. The public health community should support this development."

In the second response, Dr. Linda Bauld suggests that electronic cigarettes show promise but that more rigorous evaluation studies are needed. She writes that "the limited evidence we have about e-cigarettes suggests that users are treating them as a replacement for tobacco smoking and are using them to cut down and to quit, as outlined by Wagener and colleagues. This evidence should be treated with some caution, as it is drawn largely from surveys that may attract those who are positive rather than negative about the products. However, if it can be confirmed in larger population studies or trials then these products may have a role to play in reducing smoking prevalence."

In the third response, Dr. Jean Francois-Etter recommends that while further research is a priority, based on the existing evidence, clinicians might consider recommending electronic cigarettes to some patients: "Clinicians should inform users about the scarcity of relevant data on safety and efficacy, but they should also tell users that the risks are lower than for smoking. If users say that e-cigarettes help them to quit smoking, counsellors should focus on smoking cessation rather than on e-cigarette cessation. Advising smokers to stop using e-cigarettes might be deleterious in many situations, in particular in people who failed to quit with other treatments. Hopefully, the timely paper by Wagener et al. will stimulate research and debate."

In the fourth and final response, Drs. Nathan Cobb and David Abrams accuse us of arguing that electronic cigarettes should remain completely unregulated, setting the clock back on the history of public health protection and the FDA's role in ensuring a safe drug supply. They write: "In 1906, in an effort to end the sale of unsafe and ineffective patent medicines, the US Congress passed the Food and Drug Act, bringing regulation to what had been a chaotic and dangerous laissez-faire market-place. Thirty years later mass poisonings from a diethylene glycol antibiotic solution led to the subsequent creation of the Food and Drug Administration (FDA), and a move to proactive monitoring and oversight. Wagener, Siegel & Borrelli appear to be in favor of turning back the clock... ."

In a final reply from the authors, we thank Drs. Hajek, Bauld, and Francois-Etter for their thoughtful comments on our piece and their additional insights on the electronic cigarette issue. However, we then point out that in contrast, Drs. Cobb and Abrams completely misrepresent our position, falsely claiming that we oppose the regulation of e-cigarettes and would therefore turn the clock back more than a century. There is not a shred of truth to this claim. This is a straw man argument that we would ourselves beat down if anyone were senseless enough to propose that these products continue on the market without any regulation.

We write: "We believe that our thesis was misconstrued by Cobb & Abrams. The main goal of our article was a call for a more balanced perspective regarding the potential utility of e-cigarettes by researchers, tobacco control experts and the FDA. The current FDA website, for example, does not cite any of the potential promise of e-cigarettes and overstates some of the data on risk. We concluded our initial commentary by stating that the ‘initial evidence suggests that e-cigarettes offer more promise than peril’ and we called for future discussion to be ‘based on a balanced view of the available science rather than an ideology that opposes harm reduction’. At no point in the article did we call for ‘turning back the clock’ on the FDA and public health or an e-cigarette market ‘unfettered by national regulatory agencies’. We are strongly in favor of FDA regulation of e-cigarettes under the Family Smoking Prevention and Tobacco Control Act (FSPTCA) through the Center for Tobacco Products (CTP). ... What we were disputing was Cobb & Abrams presentation of the scientific information regarding the potential effectiveness of these products, concerns over repeated propylene glycol inhalation, and risks of potential child or adult overdose of nicotine liquid or ‘e-juice’—selecting pieces of information from studies that supported their hypotheses while ignoring information that did not."

The Rest of the Story

It appears to me that Cobb and Abrams have such a strong bias against electronic cigarettes that they are unable to debate the merits of a substantive argument supporting the potential role of these products in smoking cessation. Instead of dealing with the actual argument, they instead misrepresent our position, setting up a straw man argument to then beat down.

Is there a potential explanation for this strong apparent bias against a potentially effective new smoking cessation product that might compete with the mainstay of current treatment: quitlines and smoking cessation drugs? (Stay tuned until tomorrow.)

Author of Article Attacking E-Cigarettes Appears to Have Failed to Disclose Significant Financial Conflict of Interest

An article published in the March issue of the journal Nursing Clinics of North America reviews electronic cigarettes as potential harm reduction devices and makes recommendations to nurses about the advice they should give patients regarding the use of these products.

(See: Riker CA, Lee K, Darville A, Hahn EJ. E-cigarettes: Promise or peril? Nursing Clinics of North America 2012; 57:159-171.)

In this article, the authors make a shocking claim: 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.


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 and more than 60 known carcinogens 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.

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. 

Also striking is the review article's failure to report the levels of chemicals detected in electronic cigarette cartridges and vapor. For example, the article warns about the finding of tobacco-specific nitrosamines in e-cigarettes, without informing readers that only trace levels were found, that these levels are comparable to those found in the nicotine patches and nicotine gum which the authors recommend later in the article, and that these levels are orders of magnitude lower than in tobacco cigarettes (providing direct evidence, therefore, that e-cigarettes are indeed safer than tobacco cigarettes - evidence which they later deny exists at all).

While the article expresses concern that the tobacco-specific nitrosamines, present in trace levels, in electronic cigarettes render them inappropriate for use by smokers until future research determines their long-term cancer potential, the authors do not similarly warn nurses about the fact that nicotine replacement products approved by the FDA and recommended in the article have also been found to contain carcinogens. Neither do they suggest that nurses hold off on recommending nicotine gum and patches until future research determines the long-term cancer risk associated with the use of these products.

In other words, the anti-electronic cigarette/pro-NRT and Chantix bias in this article is profound. Keep in mind that electronic cigarettes are a potential threat to the profitability of companies manufacturing and marketing nicotine replacement therapy and Chantix. Pfizer is the company that manufacturers Chantix, and it stands to lose substantially if electronic cigarettes gain significantly in the smoking cessation market. In other words, Pfizer (among other Big Pharma companies) produce a drug that is a direct competitor to the product being reviewed in this article.

The Rest of the Story

According to the conflict of interest disclosure published in the article: "The authors have nothing to disclose."

It therefore came as a surprise to me when I read the September-October 2008 issue of the University of Kentucky College of Nursing's Office of Research and Scholarship, which reported the award of a $5,000 grant to Dr. Ellen Hahn from Pfizer, entitled "Reducing Secondhand Smoke Exposure: An Innovative Approach to Promoting Cessation." This grant was announced as being awarded by Pfizer to Dr. Hahn and Dr. Karen Butler for fiscal year 2009.

It also came as a surprise to me when I read the disclosure statement for the authors of an American Heart Association working group in 2010 which disclosed that Dr. Hahn either served on a speaker's bureau for, or received an honorarium or honoraria from Pfizer.

If these disclosures are accurate - and I have no reason to believe they would not be since both seem like reliable sources of information on these facts - then it is my opinion that these financial relationships with Pfizer should have been disclosed in the article. These financial interests would certainly appear to represent conflicts of interest since the article reviews and makes national recommendations about a product which is a direct competitor to a product manufactured and marketed by Pfizer, the company with which the investigator appears to have a financial interest.

While I would argue that this financial conflict of interest should have been disclosed whether required by the journal or not, I did note that the journal asks authors to "DISCLOSE ANY RELATIONSHIP with a commercial company that has a direct financial interest in the subject matter or materials discussed in the article or with a company making a competing product."

I think it is quite clear that Pfizer has a direct financial interest in the subject matter (electronic cigarettes, a potential competing product for the smoking cessation market) and that Pfizer makes a competing product (Chantix). Thus, any relationship with Pfizer would appear to need to be disclosed. There is no time limit noted in the instructions, so it would not appear that only current financial relationships are being sought. This request for disclosure of conflicts of interest is a broad one.

There is direct evidence from the actions of pharmaceutical companies that they view alternative smoking products as direct threats to their profits. For example, according to an article in the Wall Street Journal, the pharmaceutical company GlaxoSmithKline urged the FDA to remove dissolvable tobacco products from the market.

According to the article: "GlaxoSmithKline PLC called for the U.S. government to remove so-called dissolvable smokeless-tobacco products from the market, a move that shows emerging battle lines between pharmaceutical and tobacco companies aiming to sell alternatives to cigarettes. GlaxoSmithKline, which markets quit-smoking aids such as Nicorette gum, said Monday that it urged the Food and Drug Administration to take oral dissolvable tobacco products from store shelves until companies that make such products, including tobacco giant Reynolds American Inc., 'can demonstrate to the FDA that their marketing is appropriate for the protection of public health.'"

This story demonstrates that Big Pharma views alternative tobacco products - such as dissolvable smokeless tobacco and electronic cigarettes - as a threat to its profits because such products may be used as an alternative to nicotine replacement therapy among smokers who want to quit or cut down on their smoking and reduce their health risks.

Further evidence of the degree to which electronic cigarettes represent a potential threat to the profits of pharmaceutical companies comes from financial analysts, such as Bonnie Herzog of Wells Fargo Securities.

According to a CS/P article: "Use of electronic cigarettes could overtake consumption of traditional cigarettes within 10 years, Bonnie Herzog, New York City-based managing director of beverage, tobacco and consumer research for Wells Fargo Securities LLC, speculated in a research note. "While difficult to predict, we think it is possible that consumption of e-cigarettes could outpace traditional cigarettes over the next decade, especially given the rapid pace of innovation and consumers' demand for reduced harm products," Herzog said. ... Herzog's bottom line: "We believe e-cigs are more than just a fad and most of our industry trade contacts agree. Considering both [Lorillard and Reynolds American] have dipped their toes in the e-cig waters, the next move is [Altria's], and we expect it to be big."

The rest of the story is that if the author's financial relationships with Pfizer - as reported by the University of Kentucky and by the American Heart Association - are accurate, then there is a significant conflict of interest that I believe should have been reported in the article. Given the subject matter of the article, it is important that readers be informed of these conflicts of interest so that they can make an informed judgment of the validity of the article's conclusions and recommendations.

Finally, given the unsupported claim that there is no evidence that cigarette smoking is any more harmful than vaping, as well as the biased reporting of the significance of the presence of tobacco-specific nitrosamines in electronic cigarettes, it certainly creates an appearance that the bias in this review could be related (subconsiously) to the conflict of interest. This makes it especially important that the conflict of interest be disclosed, or - if the University of Kentucky and American Heart Association have inaccuracies on their web sites - to have these mistakes corrected immediately.


(Note: Dr. Hahn is a colleague of mine. We have worked together in the past to help research and educate the public about the health effects of secondhand smoke and to promote smoke-free bars and restaurants. I have the utmost respect for Dr. Hahn's work, especially all that she has done to promote the cause of smoke-free workplaces and to promote smoking cessation. The state of Kentucky has made tremendous progress in tobacco control, in a difficult political climate, specifically because of Dr. Hahn's presence and efforts in the state. This is therefore an uncomfortable commentary for me to write. It is not intended to be personal, but to draw attention to the larger issue of conflicts of interest in tobacco control research and the importance of disclosure of these conflicts. I emphasize that there is nothing wrong with a conflict, nor is there anything wrong with a conflict that produces a bias. In fact, my argument is that these biases are automatic - arising subconsciously - and do not mean that the conflicted researcher has intentionally misrepresented information. I am merely arguing that where conflicts are present, it is important that these conflicts be disclosed. Also, out of respect to Dr. Hahn as a colleague, I wrote to her - prior to preparing this commentary - and asked her to confirm whether or not the financial interests with Pfizer reported by the University of Kentucky and the American Heart Association are accurate. I also wrote to Dr. Butler to confirm whether the University of Kentucky was accurate in reporting the grant from Pfizer. Unfortunately, neither one responded. I assume that if there were inaccuracies, they would have hastened to correct them. My readers should understand that if by some strange occurrence, both the University of Kentucky and the American Heart Association have inaccurately reported these relationships with Pfizer, then my comments above on the conflicts of interest are of course not relevant. But without having received a response, I have to assume that these reputable web sites are correct. Nor do I feel that this issue is trivial enough that I can let it rest until receiving a response, which is most likely not forthcoming).

U.S. Court of Appeals Upholds District Court's Invalidation of FDA's Proposed Graphic Cigarette Warning Labels

On Friday, the U.S. Court of Appeals for the District of Columbia upheld the District Court's decision that overturned the FDA's proposed graphic warning labels for cigarettes on the grounds that these warnings violate the First Amendment.

Although the appeals court applied a different standard than the district court, it still found that under that less stringent standard, the proposed warning labels do not pass constitutional muster as they do not satisfy the third prong of the Central Hudson criteria for commercial speech: that the restriction of free speech must directly advance the government's stated interest (and the government must provide substantial evidence to support this contention). In this case, that interest is in promoting smoking cessation. The appeals court found that the FDA did not provide sufficient evidence to support the contention that the graphic warning labels will cause smokers to quit.

The Rest of the Story

There are two key findings in the decision. The first relates to the appropriate level of scrutiny to evaluate the First Amendment claims, and the second relates to whether the warning labels pass muster under that level of scrutiny.

The FDA argued that a very lenient level of scrutiny is appropriate (a level defined in the Zauderer case) because the proposed warning labels are merely an uncontroversial statement of the facts regarding the effects of smoking. The district court ruled that a high level of scrutiny (sometimes called "strict scrutiny") was the appropriate standard, and under that high level of scrutiny, the warning labels do not even come close to passing constitutional muster.

Interestingly, the appeals court took the middle ground, ruling that an intermediate level of scrutiny is appropriate because:

1. The case involves commercial speech, and is not subject to strict scrutiny that might be required of non-commercial speech; and

2. The warning labels go far beyond disclosing uncontroversial, factual information and therefore the low Zauderer level of scrutiny is not appropriate.

The Court writes: "this case raises novel questions about the scope of the government's authority to force the manufacturer of a product to go beyond making purely factual and accurate commercial disclosures and undermine its own economic interest - in this case, by making 'every single pack of cigarettes in the country a mini-billboard' for the government's anti-smoking message. ... the graphic warnings do not constitute the type of 'purely factual and uncontroversial' information ... to which the Zauderer standard may be applied. ... the graphic warnings are not 'purely' factual because - as FDA tacitly admits - they are primarily intended to evoke an emotional response, or at most, shock the viewer into retaining the information in the text warning." ...

"In fact, many of the images do not convey any warning information at all, much less make an 'accurate statement' about cigarettes. For example, the images of a woman crying, a small child, and the man wearing a T-shirt emblazoned with the words "I QUIT" do not offer any information about the health effects of smoking. And the "1-800-QUIT-NOW" number, when presented without any explanation about the services provided on the hotline, hardly sounds like an unbiased source of information. These inflammatory images and the provocatively-named hotline cannot rationally be viewed as pure attempts to convey information to consumers. They are unabashed attempts to evoke emotion (and perhaps embarrassment) and browbeat consumers into quitting. ... While none of the images are patently false, they certainly do not impart purely factual, accurate, or uncontroversial information to consumers. Consequently, the images fall outside the ambit of Zauderer.

The appeals court thus decides that the appropriate standard of scrutiny in this case is an intermediate level of scrutiny, as set forth in Central Hudson. Under Central Hudson, the government must demonstrate (with substantial, scientific evidence) that the graphic warning labels will advance the government's stated interest in reducing smoking by encouraging smokers to quit and thus reducing smoking rates.

After reviewing the scientific evidence put forward by the FDA, the Court finds that the evidence is not at all compelling (the FDA does not even provide a "shred of evidence" to support its position), and therefore, the regulations do not pass muster under Central Hudson.

The Court writes: "FDA has not provided a shred of evidence - much less the 'substantial evidence' required by the APA - showing that the graphic warnings will 'directly advance' its interest in reducing the number of Americans who smoke. FDA makes much of the 'international consensus' surrounding the effectiveness of large graphic warnings, but offers no evidence showing that such warnings have directly caused a material decrease in smoking rates in any of the countries that now require them. ... FDA's Regulatory Impact Analysis (RIA) essentially concedes the agency lacks any evidence showing that the graphic warnings are likely to reduce smoking rates. ... The Rule thus cannot pass muster under Central Hudson."

In a dissenting opinion, Judge Rogers rules that only the "1-800-QUIT-NOW" aspect of the warning labels is unconstitutional. That aspect of the warning, he argues, falls outside of the reach of Zauderer, thus forcing a stricter level of scrutiny under Central Hudson. And under that intermediate level of scrutiny, the warning label fails because the "1-800-QUIT-NOW" requirement has not been shown to be the least stringent requirement necessary to advance the government's interest in reducing smoking (the fourth prong of the Central Hudson test).

Putting it All Together

What does this all mean?

What it means is that the anti-smoking movement's use of shoddy science has finally caught up to it. While the lack of rigor in its recent use of science to support its policy positions may be good enough to convince policy makers, it is not good enough to convince the courts.

The Court did not fall for the argument that studies have demonstrated an effect of graphic warning labels on smokers' attitudes about quitting. The Court wanted to see studies showing that these labels actually led to smokers quitting, but such evidence was not forthcoming. The Court essentially laid bare the lack of scientific evidence behind the "international consensus" that graphic warning labels are effective.

The Court agreed with the argument I have advanced for some time that the FDA's own evidence, as well as evidence from a host of other studies, does not support its case.

These previous posts lay out my argument:

Even the FDA Itself Concludes that Graphic Warning Labels Will Have Minimal Impact, and Perhaps No Impact, on Cigarette Smoking - August 29, 2011

FDA Analysis Shows that Graphic Cigarette Warning Labels Increased Cigarette Smoking in Canada from 2001-2008 - August 30, 2011

New Study Shows No Effect of Graphic Warning Labels in England on Smoking Behavior - August 22, 2011

Yet Another New Study Suggests Likely Ineffectiveness of Graphic Cigarette Warning Labels - April 25, 2012

Data from Other Countries Show No Effect of Graphic Warning Labels on Cigarette Consumption - August 14, 2011

Research Firm Report Estimates that Graphic Warning Labels Will Reduce Cigarette Consumption by No More than 1% - July 11, 2011

Experimental Study Demonstrates that Graphic Cigarette Warning Messages Invoke Defense Response; May Explain Observed Lack of Effect of Warning Labels - August 23, 2011

Study Shows Carotid Artery Plaque Screening Does Not Promote Smoking Cessation; Provides Further Evidence that Graphic Warning Labels Will Not Work - February 1, 2012

More New Research Suggests that Graphic Cigarette Warning Labels Will Not Be Effective in Deterring Smokers - July 13, 2011

This story also exposes the gross distortions of the scientific evidence by the FDA and the Department of Health and Human Services in over-hyping the significance of the graphic warning labels:

Health Agencies Boast of Dramatic Impact of New Cigarette Warning Labels - November 15, 2010

Finally, the story shows that the FDA and the health groups which filed an amicus brief in the case undermined the FDA's position by making it very clear that the intended purpose of the warning labels was to reduce smoking, not merely to warn smokers of the health effects. Because of this, the agency had to provide evidence that the warning labels would reduce smoking, rather than merely provide evidence that the warning labels would warn smokers. In addition, these arguments made it more difficult to argue that Zauderer was the correct standard. Thus, the arguments put forward by the FDA and the health groups undermined the government's case both for the Zauderer standard and for validity under the Central Hudson standard:

FDA and DHHS Harm their Own Case by Pushing Political Propaganda and Over-hyping Significance of Graphic Warning Labels on Cigarettes - March 5, 2012

Amicus Brief Submitted by Anti-Smoking Groups Undermines Case for Graphic Cigarette Warning Labels - September 25, 2011

The rest of the story is that the loss of scientific rigor in the anti-smoking movement - the lack of a clear link between science and policy - has now come back to hurt the movement. While anti-smoking groups may have pulled the wool over the eyes of politicians and policy makers in convincing them that regulating the "safety" of tobacco products and instituting graphic warning labels were effective methods of standing up to Big Tobacco, their weak scientific support for this agenda did not fool the D.C. Appeals Court.

In my view, the graphic warning labels are now dead in the water. Even if the FDA appeals to the Supreme Court, it is not going to be successful. In fact, such an appeal will likely result in even more of an embarrassment for the agency.

Electronic Cigarette Opponents Now Making Up, Not Just Lying About Evidence

In a USA Today article on electronic cigarettes, Dr. David Abrams - executive director of the Shroeder Institute and a staunch opponent of electronic cigarettes - was quoted as stating that many electronic cigarette users would have quit smoking if not for their e-cigarette use.

"'Many people use them as a bridge product' to avoid smoke-free laws — and as a result, they delay or avoid quitting, says David Abrams, executive director of the Shroeder Institute, operated by the anti-tobacco group Legacy. He co-authored a study in the same issue of the public health journal that found 70% of Americans believe e-cigarettes are less harmful than regular cigarettes."

In other words, Dr. Abrams is claiming that there is evidence to support the contention that electronic cigarettes are preventing many smokers from quitting. If not for their use of electronic cigarettes, they would have quit smoking.

The Rest of the Story

First, and most importantly, there is simply no evidence to support this contention. It is essentially "manufactured" evidence. There is no study which has shown that electronic cigarettes are preventing smokers from quitting: that is, that without electronic cigarette use a substantial number of vapers would have instead quit smoking.

Second, the existing evidence actually suggests the exact opposite. Rather than preventing smokers from quitting, electronic cigarettes are helping many smokers to either quit smoking completely or to cut down substantially on the amount they quit. In the Polosa study, which was conducted among smokers unmotivated to quit, 54% of the smokers either quit or cut down by more than half on their smoking when they initiated use of electronic cigarettes.

There are multiple surveys which have documented that a large number of smokers have been able to quit smoking using electronic cigarettes. Most other electronic cigarette users have been able to cut down substantially on the amount they smoke. Very few electronic cigarette users report that they have continued to smoke cigarettes at the same level as before they started vaping. And no evidence supports the contention that any substantial proportion of vapers who still smoke would have quit smoking completely if they had not begun vaping. In fact, most vapers make it very clear that if not for electronic cigarettes, they would most certainly still be cigarette smokers.

In other words, there is abundant evidence that the truth is exactly the opposite of what Dr. Abrams claims to be the case. He is essentially making up evidence that does not exist in order to try to convince the public not to use these innovative harm reduction products.

There is certainly room for an honest debate on the appropriate role of electronic cigarettes as part of a national smoking cessation strategy, and as a part of efforts to promote smoking cessation among individuals. But there is no room for researchers to make up evidence that doesn't exist in an effort to try to make their case.

Tobacco-Free UK Declares that Electronic Cigarettes Cause Cancer

A poster on the University of Kentucky campus sponsored by Tobacco-Free UK warns the campus community that electronic cigarettes cause cancer.

The text of the poster states:

"E-cigarettes. 3 Strikes. You're out.

1. In Your Brain
You think e-cigs help you quit real cigarettes. There's no evidence of this.

2. In the Vapor
Acetone and Xylene. Nail polish remover and paint thinner? You're going to breathe that? Really? And what about the friends next to you?

3. In the Cartridge
Nitrosamines. Known carcinogens. That means it causes cancer.
Formaldehyde. Highly toxic to all animals, including you. Good for embalming dead bodies. Causes cancer."

The Tobacco-Free UK organization appears to be a UK Tobacco-Free Task Force, which is headed up by Ellen Hahn, the professor who has made misleading claims about electronic cigarettes and apparently, has also 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.

The Rest of the Story

This poster contains a host of misleading statements, a scientific claim without any evidence, and an outright lie, as well as extremely damaging and irresponsible medical advice.

The Outright Lie

The poster asserts that there is "no evidence" that electronic cigarettes can be helpful in smoking cessation. This is untrue, as it ignores the Polosa et al. clinical trial, which reported a six-month smoking cessation rate of 22.5% among smokers who were not even motivated to quit smoking. This certainly provides evidence that electronic cigarettes may be useful in smoking cessation.

If Tobacco-Free UK had asserted that the effectiveness of electronic cigarettes in smoking cessation has not been proven, that would be fine. But to claim that there is no evidence that electronic cigarettes may be helpful in smoking cessation is simply a lie. 

The Misleading Statements

The poster claims that the vapor exhaled by vapers contains significant levels of acetone and xylene, and that the levels of these chemicals poses a risk to innocent bystanders. There is no evidence to support this statement. The poster also claims that electronic cigarettes contain nitrosamines. However, it fails to inform the viewer that the levels of these nitrosamines are extremely low, that the levels are about 1000 times lower than in cigarettes, and that the level of nitrosamines in electronic a

The Tobacco-Free UK poster is equivalent to a poster warning smokers not to use nicotine replacement therapy because nicotine gum and the nicotine patch contain carcinogens and are therefore carcinogenic. Would Dr. Hahn claim that the nicotine patch causes cancer? Would she warn smokers who might want to quit by using the nicotine patch that they should avoid the patch because it contains nitrosamines that cause cancer?

Remember that all nicotine-containing products are going to have trace levels of tobacco-specific nitrosamines because the nicotine is derived from tobacco. If the evidence is sufficient to claim that electronic cigarettes cause cancer, then it is also sufficient to claim that NRT causes cancer. But I don't see Tobacco-Free UK warning the campus community about the cancer risks associated with NRT. Why not?

But the most misleading aspect of this communication is that it fails to provide any context. It fails to put the risks of electronic cigarette use in the context of the risks associated with tobacco cigarettes. That is the comparison which is relevant, since these products are intended as a safer alternative to cigarettes for smokers who want to quit or cut down on their cigarette consumption in order to improve their health.

What the poster fails to inform the UK campus community is that electronic cigarettes have much lower levels of nitrosamines than regular cigarettes, have much lower levels of formaldehyde, acetone, and xylene, and contain essentially none of the other thousands of chemicals and scores of carcinogens in tobacco smoke.

The Scientific Claim without Any Evidence

The claim that electronic cigarettes cause cancer is without scientific evidence. While it is true that trace levels of tobacco-specific nitrosamines have been detected in electronic cigarettes, similar trace levels are also present in nicotine gum and nicotine patches. If electronic cigarettes can be said to cause cancer, then so can nicotine replacement therapy.

There is simply no scientific evidence that NRT causes cancer, because it is unclear that the trace levels of tobacco-specific nitrosamines in these products have any clinical significance, are capable of inducing cancer, or that there has ever been a human case of cancer caused by NRT.

Similarly, there is simply no scientific evidence that electronic cigarettes cause cancer, because it is unclear that the trace levels of tobacco-specific nitrosamines in these products have any clinical significance, are capable of inducing cancer, or that there has ever been a human case of cancer caused by electronic cigarettes.

The Extremely Damaging and Irresponsible Medical Advice

The poster is essentially providing the following medical advice to smokers: Do not try to quit using electronic cigarettes.

And it is providing the following medical advice to ex-smokers who have quit by virtue of electornic cigarettes: Stop using the electronic cigarettes (which means, for most vapers, going back to cigarette smoking).

This is irresponsible advice because it asserts that the many electronic cigarette users who have quit successfully using these devices should discontinue their use and take their chances with NRT or Chantix. But because a large proportion of these ex-smokers are vaping specifically because they tried NRT or Chantix and failed, this advice is tantamount to urging these ex-smokers to return to cigarette smoking. It is difficult to imagine more irresponsible medical advice.

In fact, many vapers have reported dramatic improvement in their health, such as increases in lung function and physical stamina. Discontinuing electronic cigarette use and returning to smoking is the last thing in the world these individuals should be encouraged to do. Returning to smoking will undoubtedly harm the health of these individuals and perhaps even ruin what would have been a great opportunity to keep them off cigarettes permanently.

Putting it All Together

I find this poster, and the campaign it represents, to be extremely dangerous and damaging to the public's health. If the campaign is successful, it is going to discourage ex-smokers from continuing to stay smoke-free because it will scare them into thinking they are going to get cancer (as if they are less likely to get cancer from smoking Marlboros!). And it is going to discourage current smokers from making quit attempts using electronic cigarettes - smokers who might otherwise have joined thousands of other vapers in finding the tremendous advantages of these products for smoking cessation or smoking reduction.

To make matters worse, it appears that Dr. Hahn may have a financial conflict of interest, as a disclosure was apparently made that she has either served on a speaker's bureau or received honoraria from Pfizer (the maker of Chantix), a company which stands to lose severely if electronic cigarettes continue to rise in popularity. If accurate, then this conflict should have been disclosed in the poster because the advice is apparently coming from a conflicted researcher. The public has a right to know this.

To be sure, more research needs to be conducted on electronic cigarettes to more clearly define their effectiveness in smoking cessation and to more fully understand their precise health effects. However, notwithstanding the need for more research:

(1) It is incorrect to state that there is no evidence that these devices are useful in smoking cessation or reduction. Clinical trial evidence suggests that these products could be very useful, even among smokers with little motivation to quit.

(2) It is deceptive to scare people by asserting that electronic cigarettes deliver carcinogens, without noting the level of those carcinogens and the fact that the same carcinogens are also present in nicotine replacement products.

(3) It is imperative that researchers giving national advice on electronic cigarettes disclose significant financial conflicts of interest, so that the public has the ability to take this into consideration when evaluating the validity of that advice.


Finally, it is important that public health campaigns not lie to the public. The false and misleading information in this hatchet job on electronic cigarettes not only does the public a disservice because the advice is medically irresponsible, but it also threatens the credibility of public health practitioners.


(Thanks to Bill Godshall for the tip.)

In Calling for Ban on Flavored Cigars, Senator Lautenberg Reaches a New Record Level of Hypocrisy

Last week, Senator Frank Lautenberg (D-NJ) reiterated his call for a ban on flavored cigars. These products were not included in the Congressional ban on flavored cigarettes, which covers all candy and fruit flavorings such as strawberry, banana, acai, lemon, and pineapple, but exempts menthol.

According to his press release: "U.S. Senator Frank R. Lautenberg (D-NJ) today reiterated his call for a ban on flavored cigars, which are surging in popularity among children and young adults. The 2011 National Youth Tobacco Survey released today by the Centers for Disease Control and Prevention (CDC) reports that cigar smoking remains popular among high school students, even as overall tobacco use has declined. ... “Flavored cigars are designed to attract young adults, and the new CDC report indicates Big Tobacco is succeeding in its mission,” said Lautenberg.  “The federal government must use its full authority over the tobacco industry and ban flavored cigars before the next generation of tobacco users are hooked. The increase in cigar use is troubling, and we must continue to do everything we can to keep our kids healthy and safe.” The Family Smoking Prevention and Tobacco Control Act of 2009 banned flavored cigarettes; however, some companies are avoiding the ban by marketing their products as flavored cigars, which are not prohibited by law."

The Rest of the Story

The exemption of flavored cigars is hardly the only, or the most important loophole in the Tobacco Act as it relates to the banning of flavored tobacco products that may appeal to children. The most important loophole is the exemption of menthol cigarettes, which - unlike the cherry, pineapple, banana, and raspberry cigarette flavorings which were banned - are actually smoked by a substantial proportion of youth smokers, about 50% to be exact.

This exemption of menthol cigarettes in the Tobacco Act is largely a result of Senator Lautenberg's efforts, as he was one of the champions of the negotiations between the Campaign for Tobacco-Free Kids and Philip Morris which led to the Act. Senator Lautenberg, along with the health groups, was opposed to an amendment which would have removed the menthol exemption. Apparently, he isn't as committed to banning products that attract youth and hook the next generation of tobacco users as he claims to be.

If Senator Lautenberg were truly committed to banning products that "are surging in popularity among children and young adults," then certainly he would be including in his demand to the FDA an insistence that the agency also ban menthol cigarettes, since these are flavored cigarette products with widespread appeal to youth smokers and which have been demonstrated to play a significant role in the smoking initiation process by making early smoking experiences more pleasant (menthol is an anaesthetic which soothes the airways and decreases the harshness and irritation produced by smoke, which is especially important in not turning youth away during their initial experiences with cigarettes).

While I am not necessarily arguing here that menthol cigarettes should be banned, I am pointing out that once a politician stands up and argues that he is a champion for the public's health because he is committed to getting rid of flavored tobacco products that appeal widely to young people, that politician is a complete hypocrite if he does not also push for the removal of menthol-flavored cigarettes from the market.

Moreover, why is Senator Lautenberg not calling on the FDA to ban Marlboro, Camel, and Newport cigarettes? After all, if the criterion for justifying the banning of a tobacco product is that it should be banned if it appeals widely to young people, then certainly Marlboro, Camel, and Newport should be the very first products to go since they account for about 90% of the cigarettes smoked by youth. These three brands are overwhelmingly popular among youth, have widespread appeal among these young smokers, and clearly "are surging in popularity among children and young adults," just as Senator Lautenberg claims flavored cigars are doing.

Remember that this is the same Senator who in March 2009, announced that he wanted the FDA to take electronic cigarettes -- which deliver essentially pure nicotine (with no tar or other tobacco constituents) -- off the market. At the same time, his legislation went into effect, which provided special protection to actual tobacco-containing cigarettes and ensured that this most toxic variety of cigarettes always remains on the market and continues to kill hundreds of thousands of Americans each year.

Senator Lautenberg's call for removing the electronic cigarette from the market, as well as for providing special protection - and government approval - for the much more toxic actual tobacco-containing cigarettes - was endorsed by the American Heart Association, American Lung Association, American Cancer Society, and the Campaign for Tobacco-Free Kids.

What Senator Lautenberg and the health groups tried to do is ban a much less harmful type of cigarette but give an official government seal of approval to the much more toxic one that we know is killing hundreds of thousands of Americans each year. The logic of these actions completely escapes me.

Of note, The Ashtray Blog pointed out that Senator Lautenberg is the recipient of more than $128,000 from pharmaceutical companies (in 2008 alone).

The only real threat that electronic cigarettes pose is not to the public's health, but to the profits of the pharmaceutical companies, which manufacture competing products (nicotine replacement therapy). If lots of smokers turn to electronic cigarettes, rather than pharmaceuticals, in order to try to quit smoking, then the pharmaceutical companies stand to lose lots of money. So perhaps it is not surprising that Senator Lautenberg is standing up to protect the financial interests of the pharmaceutical companies over the interests of the public's health.

Electronic cigarettes pose a threat to pharmaceutical smoking cessation aids precisely because the pharmaceutical aids are so dismally ineffective. The rates of successful smoking cessation with these pharmaceuticals is less than 10%. Thus, the overwhelming majority of smokers who try to quit using pharmaceutical aids are unsuccessful. Accordingly, there is a huge potential market for a nicotine delivery system (such as an electronic cigarette) that will be more popular with smokers. The fact that the e-cigarette system is similar to a cigarette may make it much more effective and popular for use among smokers who are trying to quit smoking.

Senator Lautenberg is already a member of the Colonel Benjamin Church Hypocrisy Hall of Shame. His call for a ban on flavored cigars, while at the same time he supported an exemption for menthol cigarettes, simply solidifies his position in the Hall.

New Study on Effectiveness of Smoking Cessation Medications is Really a Retrospective, Rather than Prospective Cohort Study; Bias in Defining Exposure Groups Threatens Validity of Results

Yesterday, I reported on a new study published online ahead of print in the journal Addiction which presented survey data purporting to show that quit attempts using medication were more successful than unaided attempts. The study used data from an international survey conducted in the United Kingdom, Canada, Australia and the United States to study smoking and quitting behavior.

I criticized the study on the basis of a number of biases towards finding an effect of smoking cessation drugs, coupled with a financial conflict of interest of one of the study authors, who has served as a paid pharmaceutical consultant and speaker, writing: "the study introduces two sources of potential bias, both of which would bias the results toward finding a higher rate of effectiveness of medication. The more troubling of the two is the exclusion of medication users based on a question, asked retrospectively, about the reasons for their use of stop smoking medication. In my view, once you start excluding certain users of medication, you are no longer playing fair. Smoking cessation drugs are smoking cessation drugs and to exclude failures based on smokers retrospectively reporting that they actually didn't have the desire to completely quit smoking is not a fair and balanced analytic approach."

Today, I comment on a less important but interesting aspect of the study - namely, what type of study was it? According to the article, this was a "prospective cohort" study. However, as I will argue, the study design was really more of a retrospective cohort study.

The Rest of the Story

A cohort study is one in which subjects are grouped by their exposure to the variable of interest and then followed over time to determine an outcome of interest and its relationship to the exposure. In this study, the exposure variable is making a quit attempt with medication versus making a quit attempt without medication. The outcome is successful cessation for one month or six months. Thus, there is no question that it is a cohort study. Groups are defined based on their exposure (medication or no medication) and then quit rates are estimated and compared between the two groups.

The key to distinguishing a prospective versus a retrospective cohort study is whether subjects with the exposure were identified before or after the follow-up period began to determine their outcomes.

For example, suppose we conduct a longitudinal survey, following a group of 1000 smokers over two years. We interview them at baseline and then again two years later. Of course, some of them will have quit after the two years. We are interested in examining the differences in quit rates for smokers who quit using medication and for those who quit unassisted.

There are two possibilities for how this study can be conducted:

#1: We can determine the exposure variable prior to starting the follow-up period. In other words, we can take the 1000 smokers and divide them into two groups. One group is instructed to try to quit using medication. Another groups is instructed to try to quit without medication. Since the exposure is determined prior to the follow-up period (subjects are enrolled into exposure groups prior to the follow-up period), this is a prospective cohort design.

This design does not require that we instruct subjects whether to use medication or not. They could, instead, make their own decisions about how they choose to quit. But to be a prospective cohort study, the determination of which exposure group they are in needs to be made prior to the observation period of the outcome.

#2: Suppose we do not know which smokers will try to quit. Since our interest is only in comparing smokers who try to quit using medication and those who try to quit without medication, we cannot identify our exposure groups at the start of the study. We have to wait until the study is concluded and the second wave of data have been collected to define the exposure groups. Specifically, in the wave 2 survey, we would ask subjects if they made a quit attempt between waves 1 and 2, and if so, we would then assess what method they used to try to quit.

Because we are assessing the exposure after the observation period, this is a retrospective cohort design.

The study of interest is a bit more complicated because there are multiple waves of data, but essentially it is like a combination of mini-studies, each consisting of a two-wave follow-up study as per the above example. The key point is that exposures are being assessed only after the subjects have been followed up and the observation period has begun.

In any given wave, we do not know who is going to try to quit and whether they will use medication or not. Thus, exposures are not known prior to the observation period. The way that the investigators determine exposure to form the groups is to retrospectively assess (in the following wave) which subjects made a quit attempt and if so, what method they recall using to quit.

Because the exposure assessment is being made retrospectively - after the observation period has begun - this study is most accurately described as a retrospective cohort study.

Why This is So Important

The reason this is important is that it has major implications for the introduction of bias into the study.

If the study were conducted using a true prospective cohort design, there would be much less opportunity to introduce bias into the classification of exposure (i.e., whether or not someone was in the medication group or the non-medication group). Just prior to, or at the time of their quit attempts, subjects could easily be separated into groups based on the mode being used to quit. The assessment of the mode of quitting would be quite accurate as it would not depend at all upon recall.

However, with the retrospective cohort design of the present study, there is ample opportunity for the introduction of bias, and in fact, that is exactly what happened.

For one, the study re-defined what subjects were to be included in the exposure group after the fact. So rather than including all attempting quitters who reported using medication in their quit attempt, the study decided to throw out subjects who - retrospectively - reported that their original intention was not actually to quit completely.

Second, the study most likely misclassified exposure because at wave 5 and earlier, the study classified users of medication based on whether they had used any smoking cessation medication since the previous survey, not necessarily whether they used medication in their most recent quit attempt. The method used to quit during the most recent quit attempt does not appear to have been ascertained in the survey until wave 6. Therefore, it seems entirely possible that for wave 5 and earlier, a person might have tried and failed a few times to quit using NRT and then decided to go cold turkey for their most recent quit attempt. But because this person is not asked to report the method used in their most recent quit attempt, they would be classified as a medication user. If they were successful in their cold turkey attempt, that would go down in the results as a success for the use of drugs, not a success for unassisted quitting.

Third, because exposure is being assessed via recall (that is, retrospectively), it opens the door to the very bias that the study argues is operating here: differential recall of quit attempts based on whether the attempt was medication-assisted or unassisted. Were this a prospective cohort study as claimed by the article, then there would be no recall bias because exposure would have been determined at baseline, prior to the follow-up or observation period. It is precisely because the study uses a retrospective cohort design that there is a perceived need to control for recall bias.

Finally, the retrospective determination of the exposure groups allowed the study to introduce another source of bias: the inclusion of unaided quitters who tried to quit by cutting down gradually (a method known to be much less effective than abrupt, cold-turkey quitting).

A contrast to the current study is the study recently reported by the UK National Health Service. In that study, callers to a national quitline were assigned to receive or not receive medication and then followed up to observe their cessation rates. The results, as I reported last week, showed no significant advantage to the use of smoking cessation drugs. The advantage of this truly prospective cohort design is that exposure was determined more accurately as it did not depend on recall. In addition, the assessment of exposure status was not subject to bias. It was quite clear whether or not a client was receiving medication. No recall was required. The study could not retroactively drop a huge portion of the medication users out of the study by arguing that they didn't really intend to quit completely.

The rest of the story is that:

1. The retrospective nature of this cohort study opens it to substantial exposure classification bias.

2. There are indeed several aspects of substantial bias present in the exposure classification, each of which would lead to an overestimate of the relative efficacy of medication-assisted compared to unassisted and cold turkey quitting.

3. The presence of a significant financial conflict of interest of one of the study authors - who has been a paid consultant and served on the speakers bureau of pharmaceutical companies that manufacture smoking cessation drugs - creates the appearance that the biases introduced may be attributable to the conflict of interest (although I do not believe they were consciously introduced; conflicts of interest usually create bias subconsciously).

New Study Reports Effectiveness of Smoking Cessation Medication But is Biased Towards Finding an Effect; Financial Conflict of Interest Present

A new study published online ahead of print in the journal Addiction reports survey data purporting to show that quit attempts using medication were more successful than unaided attempts. The study uses data from an international survey conducted in the United Kingdom, Canada, Australia and the United States to study smoking and quitting behavior.

The study methods are described as follows: "A total of 7436 adult smokers (18+ years) selected via random digit dialing and interviewed as part of the International Tobacco Control Four Country Survey (ITC-4) between 2002 and 2009. Primary analyses utilized the subset of respondents who participated in 2006 or later (n = 2550)." The main outcome of interest was successful quitting at either 1 month or 6 months from the quit attempt.

The chief results of the paper were reported as follows: "Among participants who recalled making a quit attempt within 1 month of interview, those who reported using varenicline, bupropion or nicotine patch were more likely to maintain 6-month continuous abstinence from smoking compared to those who attempted to quit without medication [adjusted odds ratio (OR) 5.84, 95% confidence interval (CI) (2.12–16.12), 3.94 (0.87–17.80), 4.09 (1.72–9.74), respectively]; there were no clear effects for oral NRT use."

The study concludes as follows: "Consistent with evidence from randomized controlled trials, smokers in the United Kingdom, Canada, Australia and the United States are more likely to succeed in quit attempts if they use varenicline, bupropion or nicotine patch. Previous population studies that failed to find an effect failed to control adequately for important sources of bias."

The Rest of the Story

This is a complicated study and there are many aspects to the rest of the story, so let me take them one at a time. The study procedures are extremely complex because of its retrospective design, so I will do my best to explain these important flaws.

1. Many Medication Users Were Thrown Out of the Study

The most important aspect of the study for readers to understand is that its methods were biased so as to find a higher effectiveness of smoking cessation drugs. How was this achieved?

It was achieved by throwing out from the study a significant proportion of medication users, but not using any similar procedure to exclude non-medication users, all of whom were included in the study.

Any time that you treat the intervention group different than the control group, you introduce a bias into the study and in this case, that bias works towards finding medication use to be more effective.

Specifically, here is what happened in the study: Rather than simply including all medication users (that is, reporting the quit rates for all smokers who used medication in their most recent quit attempt), the study excluded certain smokers who used medication based on their response to a question about their reasons for using smoking cessation medication.

The study explains this exclusion as follows: "During each survey wave, respondents were asked to recall their use of medications since the last survey, and those who reported using medications were asked a series of questions regarding the medications indicated, including: ‘What was the main reason you used [the medication]?’. Only those who reported using medication in an attempt to stop smoking completely were considered to be medication users for the purpose of these analyses."

In other words, the study did not define medication users as being "medication users." Instead, it defined medication users as subjects who, after having tried medication to try to quit smoking and potentially failed, retrospectively report their use of medication was to intended to help them quit smoking.

Remember that the only indicated purpose for the use of smoking cessation drugs is to quit smoking. These drugs are not approved for any other purpose. So why exclude anyone who reported using smoking cessation medications? And if you are going to exclude smoking cessation medication users based on their intended purposes (reported after the fact), then why not also exclude unassisted quitters based on their reported intentions, also after the fact?

The way the human mind works, people are likely to alter their perceptions of why they used a particular approach after they observe the result of that approach. For example, suppose I am a two pack-per day smoker and I try to quit using NRT. I fail. Instead, I am able to cut down a little. Then, a few months later, I am asked to report the reason I used the NRT. To save face, I might (subconsciously) decide that the real purpose of my using the NRT was to cut down on the amount I smoke, rather than to quit completely.

Importantly, the same phenomenon might occur with a non-medication user. A person might initially decide that they are going to try to quit (without medication). But they might find it too difficult. So instead, they decide to just cut down. When asked a few months later why they decided to make a "quit" attempt, they might respond that they were actually trying to cut down rather than to try to stop smoking completely.

The effect of this procedure would be to systematically exclude smokers who have used smoking cessation medication unsuccessfully. In other words, this procedure would artificially bolster the observed smoking cessation rate for medication users.

To make matters worse, the question about the purpose of using smoking cessation drugs referred to any use of these drugs in the past year, not to the most recent quit attempt. Therefore, someone might have used NRT to try to cut down about six months ago and then used NRT to try to quit more recently. But they might still answer the question about the use of NRT as indicating that their intent was not necessarily to quit completely.

The bottom line is that smoking cessation medications are smoking cessation medications. Any study which excludes users of smoking cessation medications from the analysis, especially retrospectively, is going to bias the results towards finding an artificially high cessation rate for medication users.

2. Cold Turkey Quitters May Have Been Included in the Medication Group

For wave 5 and earlier of the survey, the study classified users of medication based on whether they had used any smoking cessation medication since the previous survey. However, it does not appear to have assessed the method used to quit during the most recent quit attempt. This question does not appear to have been added to the survey until wave 6. Therefore, it seems entirely possible that for wave 5 and earlier, a person might have tried and failed a few times to quit using NRT and then decided to go cold turkey for their most recent quit attempt. But because this person is not asked to report the method used in their most recent quit attempt, they would be classified as a medication user. If they were successful in their cold turkey attempt, that would go down in the results as a success for the use of drugs, not a success for unassisted quitting.

While the study describes itself as a "prospective cohort" study, it really is a "retrospective cohort" study because the assignment of exposure status is being made after the fact.

What might be the effect of this misclassification of exposure? If it were true that cold turkey quitting is more effective than NRT use, then this misclassification would mask that effect. It would result in successful quit attempts going down as being attributed to medication when they are really due to an unaided quit attempt.

In my view, the inability of the study to determine definitively the method used for the most recent quit attempt makes it suspect. Much more useful would be true cohort studies in which the classification of exposure is meaningful. An example of such an approach is the study reported by the UK National Health Service. In that study, callers were assigned to receive or not receive medication and then followed up to observe their cessation rates. The results, as I reported last week, showed no significant advantage to the use of smoking cessation drugs.

3. The Study Results Depend on the Exclusion of Anyone Other than Those Making Quit Attempts in the Past Month or Two

The study finds that the effectiveness of medication greatly increases among subjects who report having made their most recent quit attempt in the past month or two. When all quit attempts are considered, there is no significant effect of nicotine gum, the nicotine patch, or buproprion.

The study justifies the exclusion of the bulk of its data on the premise that unsuccessful cold turkey quitters are more likely than unsuccessful medication quitters to forget that they have attempted to quit smoking. On its face, this seems implausible. Would not a person making a cold turkey attempt remember that they made such an attempt? More importantly, the data purported to demonstrate this effect fail to do so.

The premise that failed cold turkey quit attempts are not remembered as easily as failed medication quit attempts is based on the finding that failed quitters who used medication are more likely to report a greater time since their quit attempt than failed quitters who did not use medication. The assumption is that the medication users made additional attempts to quit without medication more recently but forgot about those quit attempts. However, the paper provides no evidence to back up this assertion. It only demonstrates that those failed quitters who used medication reported more remote failed quit attempts than failed quitters who did not use medication.

There is a very reasonable alternative explanation for this finding, which is that when medication users fail in their quit attempts, they are very discouraged from making additional quit attempts. In contrast, cold turkey quitters do not face the same discouragement because they can always rationalize that they can do things differently. But if medication fails, it may be more likely to lead to a sense of hopelessness, which could well deter quit attempts for quite some time.

4. Non-Cold Turkey Quitters Were Included in the Unassisted Cessation Group

The real question of interest is not simply whether medication-assisted quitting is more effective than unassisted quitting, but whether medication-assisted quitting is more effecting than unassisted cold turkey quitting. I am not aware of anyone advocating for unassisted quitting using a gradual reduction approach. The question of interest is how an abrupt attempt at smoking cessation that is unassisted compares with medication-assisted quit attempts.

Unfortunately, this study does not report the effectiveness rates for cold turkey, unassisted quitting. Instead, it lumps together all unassisted attempts to quit, even those in which the smoker cut down gradually, an approach that has been shown to be ineffective and which no one is advocating. By including these attempts and reporting them in the unassisted quitting figures, the study again biases the results towards finding a greater effectiveness of medication-assisted quitting.

The comparison which nobody seems to want to make is smoking cessation drugs versus cold turkey quitting without drugs. But that is the relevant research question.

Importantly, a large proportion of the "unaided" quitters in the ITC Four-Country Survey used a gradual reduction, rather than a cold turkey approach. In fact, approximately one-third of smokers used a gradual reduction approach. Therefore, the inclusion of these subjects creates a substantial bias which artificially lowers the reported effectiveness rate of unassisted quitting, or at least fails to provide the key data of interest to the research question.

Putting it All Together

It strikes me that those who are trying to explain away the consistent finding that drugs do not appear to be much better than cold turkey quitting in population based studies (outside the context of clinical trials) are now grasping at straws, making valiant efforts at reasoning away the clear findings of these population-based studies.

Here, the study has created a premise for the entire analysis (that there is differential recall of failed cold turkey vs. medication quit attempts), a premise which is based not on the demonstration that cold turkey quit attempts tend to forget their quit attempts, but on the observation that medication users recall more remote failed quit attempts than unassisted quit attempters. Not considered is the possibility that the findings are real (rather than based on memory defects). Is it not possible that failed smoking cessation attempts are likely to deter further quit attempts for a longer period of time than failed unassisted quit attempts?

Furthermore, the study introduces two sources of potential bias, both of which would bias the results toward finding a higher rate of effectiveness of medication. The more troubling of the two is the exclusion of medication users based on a question, asked retrospectively, about the reasons for their use of stop smoking medication. In my view, once you start excluding certain users of medication, you are no longer playing fair. Smoking cessation drugs are smoking cessation drugs and to exclude failures based on smokers retrospectively reporting that they actually didn't have the desire to completely quit smoking is not a fair and balanced analytic approach.

Perhaps the most telling fact about this study is that, as you might expect based on the various biases in the study, one of the co-authors has a significant financial conflict of interest with companies that manufacture smoking cessation drugs.

According to the study's disclosure statement, one of the study investigators: "has served as a paid consultant on smoking cessation to Pfizer and Novartis, [and] has received payment from Pfizer and GlaxoSmithKline for lectures on smoking cessation to health professionals."

I am not suggesting that there is any conscious bias but subconsciously, these kinds of financial connections are going to influence the slant with which one conducts, analyzes and reports results. In this case, there is ample evidence from an analysis of the study that there is indeed bias towards finding an effect of smoking cessation medications. There is nothing wrong, since the conflict was appropriately disclosed. However, readers should take this conflict into account when interpreting the study results.

UK National Health Service Data Show that NRT is No More Effective than Unassisted Quitting on a Population Level

A report released yesterday by the Health and Social Care Information Centre of the UK National Health Service assesses the smoking cessation rates of clients offered services through the NHS Stop Smoking Services during the period April 2011 through March 2012. The cessation rates refer to 4-week quit rates (defined as not having smoked for 2 weeks at the 4 week mark post-quit date). Data are based on 400,955 successful quitters at the 4-week mark among 816,444 people who set a quit date with NHS Stop Smoking Services.

Because some of the clients were offered and received pharmacotherapy and others received no medication, we are able to compare 4-week cessation rates of the clients with and without pharmacotherapy. Here are the results, showing 4-week quit rates by type of treatment:

Drugs: 49.6%
No drugs: 50.5%

Based on this finding, then, there was no improvement in the effectiveness of smoking cessation treatment with the use of medication.

The results by type of medication varied slightly but the overall patterns showed little difference between various types of drugs and unassisted quitting:

NRT: 45.6%
Zyban: 52.9%
Chantix: 60.2%
NRT and Zyban: 44.8%
NRT and Chantix: 46.6%

This finding that smoking cessation drugs do not improve smoking cessation rates on a population level in the setting of a national smoking cessation service provider is further supported by data on trends in 4-week cessation. Although the proportion of clients who were prescribed drugs increased from 84% in 2001/02 to 93% in 2011/12, the rate of successful quitting actually decreased slightly from 53% to 49%.

In 2006/07, when the use of NRT peaked at 83%, the proportion of 4-week quitters was 53%, no different from the start of the study period when only 63% of clients received NRT.

Prior to the availability of Chantix, the 4-week cessation rates ranged from 53% to 57%. Since the availability of Chantix, when use rates were as high as 26%, the 4-week cessation rates have ranged from 49% to 52%.

The Rest of the Story

These data indicate no benefit from offering smokers drugs in an effort to help them quit smoking in the setting of provision of national smoking cessation services on a population basis.

The data conflict with those from clinical trials, where smokers are generally offered a smoking cessation drug or a placebo. There is evidence that these trials are not successfully blinded. Smokers who receive placebo can often tell that they are not receiving a study medication. This could well explain the lower observed rates of smoking cessation with placebo and could indicate that the observed "effectiveness" of these drugs in clinical trials is a result of what one might call the opposite of a placebo effect.

While these results should not be interpreted as suggesting that NRT or other drugs should not be prescribed by physicians as treatment for specific patients who are trying to quit, they do suggest that on a population basis, in the setting of a national smoking cessation strategy, pharmacotherapy simply does not appear to be effective in increasing smoking cessation rates.

Keep in mind as well that these are only 4-week success rates. The long-term effectiveness of unassisted quitting might be expected to exceed that of drug therapy based on these short-term findings, as the benefits of medication often diminish over time and NRT in particular is only intended to be taken for a limited period of time.

This report demonstrates why it is so problematic that anti-smoking organizations such as the North American Quitline Consortium have severe financial conflicts of interest with pharmaceutical companies. Quitline service decisions should be based on an objective view of the scientific evidence, but this is not possible when the group making these decisions is financially conflicted.