Friday, June 28, 2013

Electronic Cigarette Opponent Grasps at Straws to Discredit New E-Cigarette Clinical Trial

As I correctly predicted yesterday based on his one-line email inquiry, electronic cigarette opponent (and my mentor, hero, and colleague) Stan Glantz was nonplussed with the clinical trial showing that electronic cigarettes achieved an almost miraculous 13% one-year quit rate among Italian smokers who had no interest in quitting. As I also correctly predicted, he quickly scrambled to try to discredit the study in order to support what I believe is a predetermined conclusion in his mind that electronic cigarettes are useless.

Today, he posted on his blog a critique of the study.

In his critique, Stan makes two main arguments:

1. "There is not a control group of people who were not using e-cigarettes that would allow assessment of spontaneous quit rates.  By not having a true control group that would account for spontaneous quitting without using e-cigarettes one cannot say anything about whether e-cigarettes affected quitting."

2. "The [second] problem is that the authors failed to include the required Yates correction in their calculation of the chi-square test statistic and associated p value.  Recalculating the test properly yields p = 0.07, which is no longer statistically significant.  Thus, the correct conclusion is that there is no statistically significant difference between the nicotine and non-nicotine e-cigarettes."

The Rest of the Story

Let's take each of these arguments in turn.

First, it is true that the study did not include any control group. However, that doesn't necessarily mean that we have no idea what the quit rate would have been for smokers with no interest in quitting in the absence of electronic cigarettes. We can simply examine the ample scientific evidence reporting one-year quit rates among smokers in the absence of intervention.

However, as I noted yesterday, what we really want is the one-year quit rate among smokers with no interest in quitting. To be conservative, we can use the one-year quit rate among smokers who do want to quit (and try to quit), which is about 3%.

Clearly, the quit rate observed in the high-nicotine electronic cigarette group (13%) is considerably larger than the 3% observed for the population of smokers who want to quit and make quit attempts. The natural quit rate among smokers with no desire to quit would be substantially lower than 3%.

In fact, the paper provides population-based data showing that in Italy, the spontaneous quit rate during the study period was a dismal 0.02%.

So this first argument does not invalidate the study's conclusion that electronic cigarettes did help achieve smoking cessation for some smokers. There is no scenario under which you would observe 13% of non-motivated smokers quitting within one year without any intervention.

It is also important to point out that the comparison group Stan requests is not possible. One could not ethically conduct a clinical trial of smoking cessation in which one group is assigned to receive no intervention.

What is really needed is a head-to-head comparison of electronic cigarettes compared to nicotine replacement therapy (NRT).

Stan's second argument is that the study conclusions are invalid because of failure to apply the Yates correction. This argument is invalid because it is a sort of sleight-of-hand. It is kind of like magic, where the magician can succeed in a trick by diverting the audience's attention away from the central event taking place.

Why is this argument a diversion? It is a diversion because there is no placebo in this trial. Had this study compared electronic cigarettes with a placebo, then the appropriate analysis would indeed be to statistically compare the cessation rates in the e-cigarette vs. placebo groups. But there was no placebo. The group receiving electronic cigarettes without nicotine was in fact an intervention arm. Even without nicotine, electronic cigarettes have been shown to reduce the craving to smoke. And in fact, in this trial, the most remarkable finding was that in the zero nicotine e-cigarette group, 14% either quit or cut down by more than half. This is remarkable for a group of smokers who had no intention to quit and who received no non-tobacco cigarette nicotine for an entire year.

The paper actually acknowledges the lack of statistical significance in quit rates between the three study arms at one year. But this doesn't mean the treatment wasn't effective. It reflects the small sample size of the study along with the fact that there was some effect among the 0 nicotine e-cigarette group.

Stan is absolutely right that the correct comparison to make to evaluate the results of the study is how the observed quit rate (about 9% for all three groups combined) compares to the spontaneous one-year quit rate among the population of smokers, except that one would have to restrict that to the population of smokers who have no interest in quitting.

If anyone can show me data demonstrating that more than 2% of smokers with no interest in quitting achieve smoking cessation over a one-year period, then I will retract my conclusion about this study. But short of that, it cannot be denied that the results achieved in this study are better than what one would have obtained with no intervention.

Thursday, June 27, 2013

Fox 25 News Segment on New Electronic Cigarette Clinical Trial

I was fortunate to be able to comment on the new electronic cigarette clinical trial this morning on Boston's Fox 25 news. We had been scheduled to go live yesterday morning but the Aaron Hernandez story displaced this one. Things quieted down so we were able to get the interview in today.

Contest: What is this Anti-Smoking Researcher Up To?

Tuesday, Stan Glantz sent out a one-line note on his announcement list, simply asking if anyone could provide a particular statistic in which he is interested.

Now I think I know my colleague and hero so well that I can guess exactly why he is looking for this  statistic.

So today's Rest of the Story is a contest to see if any of my readers can figure out what Dr. Glantz is up to (in my opinion) and why (in my opinion) he wants this particular statistic.

The announcement was entitled:

"Question about spontaneous unassisted quitting."

His query was as follows:

"I am looking for the one-year successful quit rate for people who quit unassisted. Results from Italy would be especially useful. ... as would supporting citations."

The Rest of the Story

I will review and evaluate all guesses and then later on, provide my answer.
Believe it or not, I think there is an important lesson here regarding the modern-day anti-smoking movement and its tactics.

Wednesday, June 26, 2013

First-Ever Clinical Trial of Electronic Cigarettes Finds 13% One-Year Quit Rate Among Smokers with No Interest in Quitting

A new study published yesterday in the journal PLoS One reports the results of the first-ever clinical trial of electronic cigarettes.

(See: Caponnetto P, et al. Efficiency and safety of an electronic cigarette as tobacco cigarettes substitute: A prospective 12-month randomized control design study. PLos One 8(6): e66317.)

In this study, a group of 300 smokers with no interest in quitting were randomized to one of three groups:

A: Electronic cigarettes with 7.2 mg nicotine cartridges for 12 weeks
B: Electronic cigarettes with 7.2 mg nicotine cartridges for 6 weeks, then 5.4 mg nicotine cartridges for 6 weeks
C: Electronic cigarettes with 0 mg nicotine cartridges

The subjects were followed for one year. Smoking cessation was verified with exhaled carbon monoxide measurements.

The follow-up rate ranged from 55% to 65%. Because of the loss to follow-up, an intent-to-treat analysis was used.

The major result was that the 12-month smoking cessation rate for group A was 13%. For all three groups combined, the cessation rate was 7.8%.

Surprisingly, of those who quit smoking, 70% also quit using electronic cigarettes.

The Rest of the Story

Opponents of electronic cigarettes can no longer argue that claims of the effectiveness of this product for smoking cessation are based solely on anecdotal or survey evidence. We now have clinical trial evidence that these devices can be useful in smoking cessation, even among a population of smokers which had no interest in quitting. Despite this worst-case scenario, a 13% cessation rate was achieved after one year with the group that received 7.2 mg nicotine cartridges for 12 weeks, and the overall cessation rate was 7.8%.

It is difficult to compare these figures to those observed with NRT because NRT clinical trials involved smokers who wanted to quit. However, as I noted in a recent article, the 12-month smoking cessation rate for NRT in clinical trials with biochemical confirmation of smoking cessation is on the order of approximately 12%. Thus, electronic cigarettes in this trial performed about as well among non-motivated smokers as NRT performed among highly motivated smokers. Thus, this trial provides preliminary evidence that electronic cigarettes are more effective than traditional NRT treatment.

Opponents of electronic cigarettes can also no longer argue that smokers who quit using electronic cigarettes are merely substituting one addiction for another. More than 70% of the smokers who quit using electronic cigarettes actually quit using e-cigarettes as well. It appears that switching to electronic cigarettes may facilitate the process of quitting nicotine use altogether. This lessens any concern that electronic cigarettes might maintain nicotine addiction among smokers who would otherwise have quit smoking and completely ended their nicotine use.

The use of electronic cigarettes in the ECLAT trial was also associated with a dramatic reduction in respiratory symptoms, including shortness of breath. Thus, this study provides the first rigorous scientific evidence that electronic cigarette use improves smokers' health.

Future research should refine ECLAT in two ways: (1) test electronic cigarettes among smokers who are motivated to quit; and (2) compare electronic cigarettes and NRT head-to-head.

Tuesday, June 25, 2013

Physician Who Opposes Electronic Cigarettes Fabricates Scientific Information to Deter their Use

On a television news segment that aired last Wednesday on WRAL-TV (Raleigh, NC), Dr. Adam Goldstein - director of the University of North Carolina's Tobacco Dependence Program - attacked electronic cigarettes by publicly claiming that they expose users to vapor that can be several thousand degrees when it hits the lungs.

The implication, of course, is that using an electronic cigarette is extremely dangerous because the scalding hot temperature of the inhaled vapor can damage the lungs.

The exact quote: "It [the vapor] can be several thousand degrees when it hits your lungs."

The Rest of the Story

If this were true, then the millions of electronic cigarette users throughout the country would be experiencing serious pulmonary effects from the continual burning of their airways. It would not be a pretty sight to see these millions of vapers breathing in vapor at a temperature of several thousand degrees.

Of course, the truth is that electronic cigarette vapor is not nearly this hot. In fact, one of the advantages of an electronic cigarette is that it propylene glycol vaporizes at a much lower temperature than water, therefore allowing a much lower level of heat. While a tobacco cigarette burns at between 600 and 900 degrees Celsius, an electronic cigarette is able to produce vapor at a much lower temperature - around 40 to 65 degrees.

Now, even if we convert this to the Kelvin scale, we still get a vapor temperature that is only 313 to 338 degrees.

So how did this electronic cigarette opponent come up with the scientific fact that electronic cigarette vapor hits the lung at a temperature of "several thousand degrees?"

Quite simple. Apparently, he just made it up.

In other words, he fabricated it.

Now, I'll be the first to admit that there are many complex issues involved in discussing policy issues related to electronic cigarettes. There is certainly a need for many different perspectives at the table. However, what is not needed is fabrication of scientific evidence or facts.

This is yet another example of the depths to which electronic cigarette opponents are sinking to try to sink the electronic cigarette ship. Apparently, they realize themselves that they have such a weak case that they need to make up facts in order to make their case.

But if you think this is where the story ends, think again.

After the segment aired, a number of viewers brought this obviously false assertion to the attention of the station. Dr. Goldstein was asked to back up his assertion. Apparently, his office replied by admitting that the statement was fabricated: "We can’t find any citations about the temperature of the vapor specifically...".

So Dr. Goldstein acknowledged that his public assertion had been completely fabricated. But interestingly, there was no apology or retraction. Instead, he tried to divert attention away from his provision of misinformation to the public.

While I certainly don't condone the fabrication of scientific information, especially when it relates to important medical decisions, I can understand that someone could make a mistake. But the failure to correct the mistake and apologize is not something I understand. Why not just admit that you fabricated the information, apologize to the public, and promise not to do it again?

It almost looks like there is some sort of ideological or other barrier that is preventing Dr. Goldstein from telling the truth. It almost seems like he must be financially conflicted. Otherwise, it seems difficult to explain this fabrication of scientific information and failure to retract the bogus information.

Well, in fact, I just found out that Dr. Goldstein is indeed a recipient of funding from a pharmaceutical company that makes a competing product to electronic cigarettes: Chantix. He has acknowledged funding from Pfizer. This is a financial conflict of interest that is very relevant to his offering an opinion on the medical risks of electronic cigarettes, and in my opinion, should have been disclosed to the news station.

Combined with yesterday's story, it sure looks like Big Pharma gets its money's worth when it funds anti-smoking researchers.

Monday, June 24, 2013

Big Pharma Gets Its Money's Worth: Study by Pharma-Funded Researchers Reports Invalid Data to Show that NRT Works When the Correct Study Data Show No Effect

A study published last month in the journal Tobacco Control purports to show that the provision of free nicotine replacement therapy (NRT) for 5 weeks to quitline callers produces a six-month quit rate of 18%, nearly twice that of smokers who do not receive free NRT.

(See: Zawertailo L, Dragonetti R,  Bondy SJ, Victor JC, Selby P. Reach and effectiveness of mailed nicotine replacement therapy for smokers: 6-month outcomes in a naturalistic exploratory study. Tobacco Control 2013;22:e4.)

The study compares six-month quit rates between two groups of smokers: (1) callers to an Ontario quitline which provided eligible smokers with free NRT for five months, in addition to telephonic counseling and referral services; and (2) a similar sample of participants in the Ontario Tobacco Survey who did not receive free NRT, matched by smoking behavior and motivation to quit.

The results are summarized as follows:

"Of those with complete follow-up data, the percentage reporting abstinence after 6 months in the treatment cohort was 21.4%, relative to 11.6% in the no-intervention cohort (rate ratio of 1.84; 95% CI 1.79 to 1.89), with the 30-day point prevalence of 17.8% and 9.8% for the intervention and no-intervention cohorts, respectively (rate ratio 1.81; CI 1.75 to 1.87)."

The paper concludes as follows:

"Provision of free NRT by mail following a brief telephone intervention is an effective strategy to reach and assist a large number of smokers making a quit attempt. ... This was a high-reach cost-effective public health measure and as such should be an integral part of comprehensive tobacco control programmes."

The Rest of the Story

This paper is a dream-come-true for the pharmaceutical industry. In it, the authors recommend that all comprehensive tobacco control programs purchase five months worth of NRT for all quitline callers. The financial implications of this advice are immense. If this advice were followed, NRT would become the main feature of smoking cessation programs throughout the world and sales of NRT would skyrocket.

There is nothing wrong with this, assuming that the study conclusion was valid and that the study did indeed demonstrate that the provision of NRT resulted in a six-month quit rate of 18%, nearly doubling the baseline quit rate of about 10% for similarly motivated smokers who do not receive free NRT.

The rest of the story, however, is that the study conclusion is not valid, the six-month quit rate was not 18%, and the NRT intervention was not demonstrated to be effective.


Because the authors reported (and based their conclusions on) the wrong data.

The study reports the quit rate among the smokers who were successfully followed up for six months. But we know from previous literature that smokers who are lost to follow-up are much more likely to be non-quitters. Thus, the proper number to report is that based on an "intent-to-treat" analysis, where subjects who are lost to follow-up are assumed to be non-quitters. In this study, the loss to follow-up was substantial (58%). Thus, failure to use an intent-to-treat analysis heavily biases the results.

Even in the heavily-biased 2008 Clinical Practice Guideline update, intent-to-treat analyses were exclusively relied upon in evaluating the effectiveness of NRT. The intent-to-treat analysis is also used in a new clinical trial which will be released later today that evaluates the effectiveness of electronic cigarettes. In fact, intent-to-treat analyses are the basis for all comparisons of the effectiveness of different smoking cessation medications and approaches.

So what are the actual results of this study, under an intent-to-treat analysis?

It turns out that under an intent-to-treat analysis, the 30-day point prevalence of quitting at six months in the free NRT group was only 9%, not 18%. This compares to a quit rate of just below 9% in the comparison group, resulting in a relative risk of quitting of 1.03 (not statistically significant) associated with the intervention. Thus, the truth is that this study fails to provide evidence that the provision of free NRT increased the smoking cessation rate. And it certainly fails to provide evidence that provision of free NRT will yield a cessation rate of 18% at six months.

The bottom line: in an intent-to-treat analysis (i.e., the correct analysis), this study documents only a 9% quit rate at six months for free NRT and finds that this intervention is not effective.

So why, then, do the authors choose to report the wrong results in the abstract and to base their conclusion on results from only 42% of the sample? Why do they choose to veer away from the standard reporting mechanism in hundreds of NRT clinical trials and to rely on a measure that is invalid on its face?

Unfortunately, the presence of significant financial conflicts of interest with Big Pharma create the appearance that the authors are being influenced (albeit subconsciously, perhaps) by these conflicts, which may have introduced investigator bias. In other words, the conflict of interest has the appearance of having biased the interpretation and reporting of the study findings.

What are the conflicts of interest? As reported in the paper (but apparently, not available unless you purchase the article): 
  • "L.Z. has received speaker honoraria from Pfizer Canada Inc. ... ."
  • "P.S. has received speaker's honoraria from Schering Canada, Johnson & Johnson Consumer Health Care Canada, Pfizer Canada Inc., Pfizer Inc. Sanofi-Synthelabo Canada, GlaxoSmithKline Canada Inc., Genpharm Canada, Prempharm Canada, NABI Pharmaceuticals, and consulting fees from Schering Canada, Johnson & Johnson Consumer Health Care Canada, Pfizer Canada Inc., Pfizer Inc., Sanofi-Synthelabo Canada, GlaxoSmithKline Canada Inc., Genpharm Canada, Prempharm Canada, NABI Pharmaceuticals, ... and AstraZeneca Canada Inc."
  • "R.D. has received speaker honoraia from Pfizer Inc."
Thus, three of the five authors have personal financial conflicts of interest by virtue of having accepted personal payments (honoraria or consulting fees) from Big Pharma companies, many of which are in the NRT/smoking cessation drug business. And the paper's senior author has apparently received personal payments (honoraria and/or consulting fees) from no fewer than 10 different pharmaceutical companies.

(Also see John Polito's response to the article. The response was cleverly entitled "Free NRT by mail an intent to treat defeat.)

Thursday, June 20, 2013

Study Concludes that Youth Access Laws Reduce Adult Smoking Rates, Even Though Laws Have Been Shown Not to Affect Youth; The Problems of Confounding and Multiple Comparisons

A new study published online ahead of print in the American Journal of Public Health concludes that state youth access laws (i.e., laws that reduce youth access to purchasing cigarettes) significantly reduce the rate of smoking when these youth are young adults.

(See: Grucza RA, Plunk AD, Hipp PR, et al. Long-term effects of laws governing youth access to tobacco. American Journal of Public Health. Published online ahead of print on June 13, 2013: e1-e7. doi: 10.2105/AJPH.2012.301123.)

The study examined the relationship between respondents' reports of their smoking status at age 18-34 at the time of a national survey conducted during the period 1998-2007 and the status of the youth access law in their current state of residence when they were less than 18 years of age.

The study examined three different outcomes: (1) ever smoking; (2) current smoking; and (3) heavy smoking. It examined results for all respondents, for just males, and for just females. It separately examined nine different types of youth access policies (e.g., bans on vending machines, ID requirements, signage requirements, inspection requirements, and free distribution restrictions). It also examined the effects of combinations of 4 selected policies and of all 9 policies together.

The study found that among males, there was no association between youth access policies and any of the measures of smoking status. Among females, there were significant associations between vending machine restrictions and all three smoking measures, between identification requirements and two smoking measures, and between repackaging restrictions, statewide enforcement authority, and free distribution restrictions on one smoking behavior.

The paper concludes: "Our findings suggest that restricted access to tobacco during adolescence is associated with reduced smoking prevalence in adulthood, but the association are observed only among women."

The study then goes on to claim that if all 9 youth access policies were in place, there would be a 14% reduction in smoking prevalence for women, and a 29% reduction in heavy smoking among ever smokers.

The Rest of the Story

The results of this study must be interpreted in light of the existing literature, which documents that youth access policies have no impact whatsoever on youth smoking rates. It is simply too easy for youth to access cigarettes and at least half of youth do not purchase their cigarettes in the first place. It has been well-documented that even in communities where compliance checks show high rates of compliance with youth access laws, young people have no problem accessing cigarettes.

So how does one explain the conflicting results of this study?

There are two major problems that threaten the validity of the study conclusions.

First, confounding is a severe problem. The enactment of youth access policies is not a random phenomenon. It is possible that policy enactment is related to levels of anti-smoking sentiment in a state. And anti-smoking sentiment may itself be strongly related to youth smoking. Thus, it might appear that the youth access laws are reducing youth smoking, when really it is the anti-smoking sentiment in the state which is associated with lower smoking rates.

In fact, in my own research, I found the above to be true at the local level in Massachusetts. We were able to control for anti-smoking sentiment at the local level by including a variable that reflected the proportion of a town's residents who voted for a state cigarette tax initiative. But we did find that passage of tobacco policies is strongly related to levels of local anti-smoking sentiment. Unfortunately, this study was not able to control for this confounding variable.

But there is a more obvious problem which, in my view, makes it very difficult to support the conclusions that the paper draws.

The problem is called multiple comparisons.

Think of it this way: You have a hypothesis that there are more boys than girls enrolled in your child's elementary school. To study this, you could simply take a random sample of students in the school. You could estimate the proportion of boys and use a 95% confidence interval to see if the proportion differs from 0.5 by chance alone (using a p-value of 0.05).

However, instead of proceeding as above, you decide instead to take a sample from each of the 100 classrooms in the school. Now suppose that the truth is that there are exactly 10 boys and 10 girls in each classroom. By chance alone, it is almost certain that you are going to find that at least one classroom contains more boys than girls, with a difference that is significant at a level of 0.05.

The point is that if you run enough different statistical tests, even if there is no true effect, you are bound to find a positive result by chance alone.

In epidemiology and biostatistics, this is called the problem of multiple comparisons. And that is the trap that this paper falls into.

The paper does not simply formulate a hypothesis and then test it with a model. Instead, it develops 81 different hypotheses and tests each one. There are:

  • 9 different policies;
  • 3 different smoking behaviors; and
  • 3 different gender breakdowns (male, female, and total).
Thus, the paper runs 81 different analyses, running 81 different statistical tests.

You can see that by chance alone, with 81 different tests, you are likely to find a few that are statistically significant at a p=0.05 level, even if there is no true effect of youth access policies. Thus, using a traditional significance level of 0.05 is not valid in this paper. But that is exactly the confidence level that the paper uses.

My mentor at Yale University School of Medicine - Dr. Alvan Feinstein - demonstrated how the problem of multiple comparisons resulted in a number of bogus conclusions being drawn in several epidemiologic studies. He wrote an excellent chapter about the problem in his book on medical statistics.

A mathemetician named Carlo Bonferroni developed a method to address the problem. Essentially, one raises the significance level by dividing the p-value by the number of comparisons being made. Thus, if one makes 81 comparisons, then instead of using a p-value of 0.05, one would use a p-value of 0.0006. Instead of a 95% confidence interval, one would need to use a 99.9% confidence interval.

If you look at the 95% confidence intervals for the "significant" findings in the paper, you'll see that all of them are very close to being non-significant, and it is very apparent that even a minor increase in the significance level would render all of these results non-significant. Certainly, applying the Bonferroni correction would invalidate all of the findings of this paper.

Essentially, this paper did what we sometimes call a "fishing expedition." That is, it tested out every possible hypothesis without any pre-existing rationale for why a particular policy would conceptually or empirically be expected to have an effect on the outcome. It is acceptable to do a fishing expedition, but one has to be aware that one cannot simply use the traditional 95% confidence level.

Incidentally, this is a problem that I see all the time among many of my students. Rather than develop one or two clear, conceptual-based hypotheses, they simply run every possible analysis of every possible variable. Invariably, they come up with some "significant" results. I explain to them that these results are not actually "significant" in statistical terms, because with so many comparisons, one would expect to find at least several "significant" results.

In fact, we can quantify the chances that this paper would have failed to find any significant relationship between at least one of the 9 policies and a smoking outcome if the truth were that there is no effect. Assuming no effect, if you do 81 comparisons,  using a p-value of 0.05, your chances of not finding any "significant" results is only 1.6%.

In other words, with 81 comparisons, there was a 98.4% probability that this study would find at least one "significant" result if there were absolutely no true relationship between youth access policies and smoking behavior.

As Dr. Feinstein explains, one has to be particularly careful with the problem of multiple comparisons when the conceptual foundation and/or empirical evidence relating to an association is suspect, as it is in this case (as the overwhelming scientific evidence leads us to conclude that there is no effect of youth access policies on youth smoking rates).

Wednesday, June 19, 2013

CASA Columbia Makes False Public Accusation; Needs to Get Its Facts Straight

In a letter to the editor published this week in the New York Times, CASA Columbia (formerly the National Center on Addiction and Substance Abuse at Columbia University) publicly accused Reynolds American and other tobacco companies of marketing flavored electronic cigarettes to children.

In the letter, the Center writes: "E-cigarettes are a very effective delivery system for the addictive drug nicotine. Nicotine is particularly dangerous for our children, since early use increases the risk of addiction involving both nicotine and other drugs. With its enthusiastic endorsement of e-cigarettes, the tobacco industry is once again marketing the disease of addiction to this most vulnerable customer base. ... Flavorings like chocolate, cherry and peach are clearly not aimed at the typical middle-aged consumer seeking to quit an addiction involving tobacco, and these products have not been proved to be effective in accomplishing that goal. More than one in seven Americans already have the disease of addiction. Are we prepared to knowingly stand by and allow Big Tobacco to increase that number in the name of profit yet again?"

The Rest of the Story

Unfortunately, CASA Columbia does not have its facts straight and its accusation is demonstrably false.

According to the Center, Big Tobacco is marketing electronic cigarettes in chocolate, cherry, and peach varieties in order to addict children. Well, Reynolds American is part of Big Tobacco, so let's examine a list of all of their chocolate, cherry, and peach electronic cigarette brands that are being marketed:

No, you didn't miss anything. Above is a complete list of the candy- and fruit-flavored electronic cigarettes marketed by Reynolds. There are none!

Vuse does not come in a chocolate flavor, nor a cherry flavor, nor a peach flavor. The truth is that it only comes in two flavors: original and menthol.

So CASA Columbia is obviously speaking nonsense when it accuses Reynolds American of marketing flavors like chocolate, cherry, and peach to youth.

While Lorillard's Blu cigs do come in several flavors, these flavors were available before the company was acquired by Lorillard and it would make no sense for the company to discontinue those flavors and lose most of its customers. Nevertheless, its disposable electronic cigarettes are only available in classic tobacco and menthol. If CASA Columbia were correct and Lorillard's true intention was to get children to become addicted to electronic cigarettes, then certainly it would offer some more interesting flavors than original tobacco and menthol.

The rest of the story is that the tobacco companies are not marketing electronic cigarettes to children and they are not going to do so. That would be stupid and would make no business sense. If electronic cigarettes do become popular among youth, it will be the end of the market. The FDA will step in quicker than a wink and put an end to the whole thing. The tobacco companies are being very careful not to market to youth. And they will continue to do so.

CASA Columbia doesn't appear to have a clue about what is going on in the real world. Its letter is pure ideological nonsense.

If the electronic cigarette companies were marketing to children, don't you think that after about seven years of this, surveys would be able to pick up more than zero nonsmoking youths who are regular electronic cigarette users? There is strong evidence that despite the marketing of these products for years, youth are not picking up the product for regular use. Addiction of children to electronic cigarettes is not occurring in the real world, although it is apparently the only purpose that electronic cigarettes serve in CASA Columbia's fantasy world.

This is yet another demonstration that the modern tobacco control movement has lost its scientific integrity. It is being driven by ideology, not science; by fantasy, not reality; and by false accusations and misrepresentations rather than by the plain truth.

Tuesday, June 18, 2013

Anti-Tobacco Advocate Argues that Cigarettes Should Remain More Freely Available to the Public than Fake Electronic Ones Without Any Tobacco

I remember years ago when a colleague was pressuring a chain of stores to stop selling candy cigarettes. While I certainly agreed that stores shouldn't sell candy cigarettes, I asked my colleague a question: "Why are you asking the store to stop selling the fake cigarettes but to continue selling the real ones?" That made no sense to me.

Now, in a story that is quite similar, an anti-tobacco advocate is arguing that steps should be taken to make sure that real, deadly, tobacco cigarettes remain much more readily available to the public than fake ones which have not been shown to cause any substantial harm and which are actually helping thousands of people to quit smoking.

In a commentary published in the journal Tobacco Control, Dr. Simon Chapman argues that electronic cigarettes are a tobacco industry ploy to keep people smoking, that reducing smoking has no health benefits, and that real cigarettes should remain more readily available to the public than the fake ones.

(See: Chapman S. Should electronic cigarettes be as freely available as tobacco cigarettes? No. Tobacco Control 2013; doi: Published 14 June 2013.)

One of the key arguments made in the commentary is that there is no health benefit to reducing the amount one smokes -- even if the reduction is substantial (e.g., greater than 50%). Chapman argues that: "importantly, cutting down cigarettes rather than quitting confers little if any health benefit, so dual use may be as bad as continued smoking in terms of health outcomes."

The Rest of the Story

If a physician made the same claim to a patient that Dr. Chapman is making, it would - in my opinion - constitute medical malpractice. Why? Because the statement is blatantly false and runs contrary to both medical science and widespread clinical experience. It is blatantly untrue that a major reduction in cigarette consumption confers no health benefits to a patient. In contrast, there are immediate and important health benefits.

Now obviously, cutting down is not nearly as beneficial as quitting entirely, but the statement made in this commentary is not that quitting is better than cutting down. The statement is that cutting down substantially has no health benefits.

But, wait, you say. Dr. Chapman cites research which found no health benefits associated with smoking reduction. Well, there are two problems. First, the paper did not look at all of the important health outcomes. For example, it does not report on whether smoking reduction improved patients' respiratory symptoms. In other words, did it improve their lives? Second, the paper did not have sufficient power to detect the health benefits that might accrue with smoking reduction. So even though some of the relative risks are not statistically significant, they are substantially less than 1.0 and probably represent an important health benefit. With a larger sample size, the study would likely have found these benefits to be statistically significant.

The first benefit that is unequivocally related to smoking reduction is an improvement in respiratory symptoms. That alone makes the statement false. Now the reduction in respiratory symptoms may not necessarily translate into a measurable improvement in lung function, but there is almost certainly a health benefit in terms of respiratory symptoms. This is an important health benefit because it improves people's lives. If they can actually climb up a flight of stairs, which they couldn't before, then how can one argue that they have not experienced any health benefit?

The second benefit that is almost certainly related to smoking reduction is a decreased risk of lung cancer. Even the research that the commentary cites as showing no health benefit actually shows that smokers who reduced their consumption were less likely to die of lung cancer. The relative risk was 0.66. This means that their lung cancer risk declined by one-third. That is a substantial decline. While the relative risk was not statistically significant, this was likely due to the low power of the study.

Importantly, other research - with a more appropriate sample size - has documented a reduction in lung cancer risk associated with smoking reduction. For example, a study published in the Journal of Clinical Oncology which had a sample size almost 10 times higher than the study which found the non-significant relative risk of 0.66 found a very similar reduction in lung cancer risk, but the reduction was statistically significant.

The study results were as follows: "For lung cancer, patients who reduced from heavy to moderate smoking and from heavy to light smoking (< 10 cigarettes/d) had significantly decreased risks based on multivariable-adjusted HRs (HR = 0.72, 95% CI, 0.49 to 0.89; HR = 0.63, 95% CI, 0.46 to 0.84, respectively)." This means that smokers who reduced their consumption were able to decrease their risk of lung cancer by one-third.

This is hardly evidence for a lack of any health benefit from smoking reduction.

This paper concludes that: "Smoking reduction was associated with a significant decrease in the risk of lung cancer...".

The third benefit that may be related to smoking reduction is a slowing of the progression of chronic lung disease. The research cited in the commentary did not even examine whether smoking reduction lowers the risk of death from chronic obstructive lung disease. So even from that research alone it is not appropriate to conclude that there are no health benefits associated with smoking reduction.

The upshot of this advice is that many patients who are unable to quit smoking but might well be able to reduce the amount that they smoke may decide that it's not worth the bother. If there are no health benefits, then why bother reducing consumption?

Well, perhaps the greatest health benefit of reducing cigarette consumption is that it makes it easier, ultimately, to quit smoking. There is no question that reducing smoking is often a behavior that lies along the pathway from heavy smoking to quitting. It is easier to quit smoking for someone who smokes a half pack per day than for someone who smokes three packs per day.

My point is not that smoking reduction should be the focus of tobacco control efforts. Readers will remember that last week I highlighted a recent chapter I wrote which emphasizes the importance of jolting smokers into spontaneous, cold turkey cessation. And in fact, I cited Dr. Chapman's important work in this area. He has been a pioneer in challenging the dogma of the tobacco control movement. I should make it clear that I have the greatest admiration for Dr. Chapman.

However, on this particular issue, I sense that there is some sort of ideological barrier that is slanting his take on the issue. The point of this post is to demonstrate that in opining about electronic cigarettes. Dr. Chapman has misrepresented the science on the benefits of smoking reduction. In doing so, he has negated any health value associated with switching from smoking to vaping for smokers who are not able to completely make the switch.

I challenge Dr. Chapman to actually speak to vapers who have made the switch, but are still maintaining some cigarette use, and ask them to report whether it is indeed true that they have not experienced any improvement in their respiratory symptoms. We know from speaking to many vapers that there is unquestionably a health benefit associated with switching from real cigarettes to fake ones, and that this benefit accrues even among those who are unable to achieve a 100% substitution of non-tobacco cigarettes for tobacco cigarettes.

The rest of the story is that once again, here is an example of an electronic cigarette opponent who seems more guided by ideology than by the facts. I understand that anti-tobacco advocates have a hatred for the act of cigarette smoking and for the tobacco companies. But we can't let that hatred blind ourselves to the scientific facts. And the fact is that vaping has improved the lives of hundreds of thousands of smokers and ex-smokers. To take this away from them, or even to make it more difficult for other smokers to experience these benefits, would be a public health tragedy.

At the end of the day, I would much rather that the public has easier access to fake cigarettes than to the real ones.

Monday, June 17, 2013

The Cleveland Clinic: Unethical By Its Own Standards

By its own standards, the Cleveland Clinic is acting unethically by supporting behavior that ultimately leads to death.

How is the Cleveland Clinic supporting behavior that leads to death?

Well, it's doing it in two ways:

1. By continuing to employ smokers, which increases health care costs, threatening our "sustainability as a nation."

2. By continuing to employ overweight individuals, which drives up health care costs, threatening our "sustainability as a nation."

The Rest of the Story

It is not me who opined that hiring employees who exhibit unhealthy behaviors is unethical. It is the Cleveland Clinic! In an op-ed piece, the physician who chairs the Wellness Institute at the Cleveland Clinic wrote:

"Is it ethical for employers to hire smokers? The practice fosters ill health and makes America less competitive in an international marketplace. The expense of healthcare in the United States represents more than 18 percent of the gross domestic product, more than in any other country. It threatens our sustainability as a nation, squeezing out education and defense. Therefore, we must do everything we can to bring down costs while improving quality. Tobacco use accounts for one in every five deaths each year in the U.S.To us, supporting a habit that ultimately leads to death would be unethical. In 2006, we began offering free smoking cessation to our employees; the following year we offered the same throughout Northeast Ohio. In 2008, we stopped hiring smokers, a natural progression."

So the Cleveland Clinic itself apparently believes that it is unethical to hire smokers. Well, then, the Cleveland Clinic is, by its own admission, engaging in unethical behavior because it employs smokers. In fact, 6% of its workforce smokes. Why is the Cleveland Clinic continuing to engage in this unethical behavior? Sure, the Cleveland Clinic has stopped hiring new employees who smoke, but ethics does not know the difference between an existing employee and a new one. If it is unethical to employ a smoker, then it is unethical to employ a smoker. There is nothing stopping the Cleveland Clinic from firing existing smokers who do not quit within a reasonable amount of time.

Moreover, by its own admission, the Cleveland Clinic is unethical in supporting another behavior that leads to death: overeating and under-exercising. Overweight and obesity are severe health risks that lead to billions of dollars in health care costs. To be sure, obesity is driving up health care costs in the same way as smoking. Some estimates put the costs of obesity as rivaling those of smoking.

So why is the Cleveland Clinic supporting these unhealthy behaviors which can lead to death by continuing to employ overweight and obese individuals?

While businesses that refuse to hire smokers can make a legitimate argument that they need to reduce health care costs. if they implement smoker-free policies for this reason then they are simply engaging in discrimination and bigotry. But the Cleveland Clinic is not just engaging in discrimination and bigotry. It is also engaging in the basest form of hypocrisy: telling the world that it has higher ethical standards than most, but not actually living up to the ethical standards it espouses.

The Cleveland Clinic tells us that it is unethical to employ smokers, but then it goes ahead and continues to employ smokers. The Cleveland Clinic tells us that hiring people who engage in unhealthy behavior is unethical, and then it goes ahead and continues to hire people who overeat and under-exercise to the point that their obesity threatens their health and lives.

The Cleveland Clinic is not just serving as a model for employment discrimination and bigotry. It is serving as a model for hypocrisy and political cowardice. They are not even willing to stand up for what they say they believe in.

This is politics, not public health.

The appropriate way for employers to deal with problems such as smoking and obesity is not to discriminate against smokers or overweight individuals in their hiring practices, but to offer comprehensive employee health and wellness programs with state-of-the-art initiatives to promote healthy behavior.

Worksite health promotion is a central aspect of public health. Employment discrimination is not.

Friday, June 14, 2013

Campaign for Tobacco-Free Kids Wants to Tie Childhood Education to Future High Levels of Smoking; Undermines National Tobacco Control Funding

In a destructive move that will have negative repercussions for future funding of tobacco control programs, the Campaign for Tobacco-Free Kids has turned its back on the state-of-the-art in tobacco control and instead, is pushing for a cigarette tax increase that will further reduce incentives for the government to reduce cigarette use.

In a letter to the editor published in the New York Times, the Campaign for Tobacco-Free Kids supports President Obama's proposal to increase the federal cigarette excise tax by 94 cents in order to fund early childhood education programs. The revenues would be used to help expand pre-school programs. None of this money would be allocated for tobacco control or even other health-related programs.

The Rest of the Story

The state-of-the-art in tobacco control is the use of cigarette tax increases to fund comprehensive tobacco control programs. This is precisely what California did in 1989, and this is specifically why California has been so successful in reducing smoking prevalence. Unfortunately, this model is not being used any more, largely because the Campaign for Tobacco-Free Kids turned its back on this model. Instead, the Campaign decided to, in knee-jerk reflex fashion, support any and all cigarette tax increases, regardless of their underlying purpose or the use of the resulting revenue.

Why is it that so few states are funding their anti-smoking programs at adequate levels? Part of the answer, believe it or not, is the actions of the Campaign for Tobacco-Free Kids.

In the late 1990s, the Campaign made a decision to support increasing state cigarette taxes without tying those tax increases to smoking-related spending. The Campaign initiated campaigns throughout the country to increase cigarette taxes, but did not insist that the revenues be allocated for treatment of smoking-related diseases, research to prevent or cure smoking-related diseases, or anti-smoking education and prevention programs.

As a result, numerous tax increases were enacted with no tie to smoking-related programs. Thus, the public learned to dissociate the two. The public also learned to distrust policy makers because they failed to see the tobacco revenues being used for smoking-related purposes. They saw the revenues simply being plopped into the general fund.

Largely because of this, it is now very difficult to pass any cigarette tax increase as the public trust is not there. Moreover, the idea of using cigarette taxes for smoking programs has all but disappeared.

It is my belief that in no small way, the Campaign for Tobacco-Free Kids is responsible for the devastation of statewide tobacco control in the United States. The low allocation of state budget resources - especially cigarette tax revenues - for anti-smoking programs is very much the Campaign for Tobacco-Free Kids' doing.

In addition to undermining funding for tobacco control programs, this policy has the disastrous effect of permanently tying the provision of pre-school education to continued high rates of cigarette smoking.

In the future, what would happen if smoking rates dramatically drop? The answer is that pre-school education programs would have to be cut because of declines in cigarette tax revenue. Thus, the President's proposal creates a situation in which the maintenance of pre-school education becomes dependent on continued high rates of cigarette smoking.

This has several perverse effects. One is that it takes away any incentive for the federal government to substantially cut cigarette smoking. Doing so would result in de-funding pre-school education and who would want to do that? A second effect is that it creates a government dependence on cigarette smoking for one of the most critical services that the government provides: pre-school education.

Essentially, this proposal would allow smokers to boast that it is thanks to them that our nation's 4 year-olds are being educated. Can you imagine bumper stickers like: "Support Pre-School Education: Smoke Early and Often," or "I Support Kids: I Smoke."

This is how perverse the effects of the proposed tax would be.

Should the Congress increase the cigarette tax? Well, it depends on the purpose of the tax increase. If the money is used to fund pre-school education, then no. It makes no sense, it makes this essential program dependent on continued high rates of smoking, it removes the incentive for the government to substantially reduce smoking rates, it undermines the principle of spending tobacco revenues on tobacco control, and it is unfair to smokers to have to shoulder the burden of funding pre-kindergarten education programs.

But if the money were to be used specifically for anti-smoking programs, then it would truly become a win-win situation. The tax would not only decrease cigarette consumption but would provide much-needed funding for tobacco control. It would be fair to smokers, because much of the revenue would be used to directly benefit smokers, such as finding more effective treatments for smoking-related diseases and providing specific services to smokers. Moreover, if the revenues decline over time, the program needs less money because there are fewer smokers.

This is what the Campaign for Tobacco-Free Kids should be supporting, not balancing our federal budget on the backs of smokers.

Thursday, June 13, 2013

New Article Reveals Massive Deception about Effectiveness of NRT, Need to Shift Toward Abrupt Cold Turkey Cessation Approaches

In a book chapter published last week by Future Medicine, I reveal how the public has been massively deceived about the true effectiveness of nicotine replacement therapy (NRT) and identify the need to shift focus toward the use of abrupt, cold turkey strategies for smoking cessation.

(See: Siegel M. Intervention for smoking cessation: from randomized controlled trial to real world. In: Polosa R, Caponnetto P, eds. Advances in Smoking Cessation. London: Future Medicine, 2013: 54-66.)

The chapter begins by citing a recent Cochrane review of the effectiveness of NRT for smoking cessation. It points out that in this "comprehensive" review, the pooled relative risk of smoking cessation associated with pharmacotherapy is given (1.8). The authors conclude that NRT and other drugs are effective for smoking cessation because they double quit rates compared to placebo.

However, what the review does not reveal is the absolute cessation rate achieved with NRT or other drugs. It turns out that the actual success rate - not provided in the article - was only 12.5% for studies that validated quitting biochemically. Thus, as my article states: "the treatment that this review recommends for all patients has a dismal 87.5% failure rate."

But the story does not end there. In real-life, as opposed to clinical trial settings, the quit rate associated with NRT use is only about 10%. I therefore conclude that: "Due to the low success rates for pharmacotherapeutic approaches to smoking cessation, the value of this strategy for smoking cessation is limited."

The article goes on to question a key theoretical assumption in the treatment of smoking dependence: that quitting smoking occurs in stages, according to the Transtheoretical Model (also called the Stages of Change model). I point out a number of studies which document that spontaneous, unplanned quitting is more effective than gradual, planned quit attempts. Some researchers, including Dr. Robert West, have called for the abandonment of the Transtheoretical Model for use in smoking cesation. Following West, I conclude that: "In practice and as supported by a growing body of literature, there is little support for the Transtheoretical Model as a valid description of typical smoking cessation behavior. ... Smoking cessation programs and policies therefore need to lessen their reliance upon the Transtheoretical Model and become open to alternative models which allow for sudden, spontaneous, unplanned behavior that does not require a gradual progression through various stages of change."

I cite the important work of Dr. Simon Chapman who has argued that there is too much of an emphasis in tobacco control on pharmacotherapy, to the almost complete neglect of cold turkey cessation: "Chapman and Mackenzie argue that the majority of successful quitters do so unaided or 'cold turkey,' without the help of pharmacotherapy. Furthermore, they argue that the tobacco control movement has become overly focused on the use of pharmaceutical approaches, neglecting the evidence base which consistently shows that the overwhelming majority of successful quitters have done so cold turkey."

The article also questions the assumption that smoking addiction is solely addiction to nicotine, arguing that the physical, behavioral, psychological, and social aspects of smoking contribute heavily to its addictiveness. This explains why NRT and other forms of pharmacotherapy are so ineffective and why electronic cigarettes represent such a promising approach: "They address not only the pharmacological, but also the physical and even the social aspects of smoking addiction. Placing a nicotine patch does nothing to simulate smoking behavior and there is no social aspect to the behavior. In contrast, electronic cigarettes closely mimic cigarette smoking and they can be used with other people in social settings. Future approaches to smoking cessation must treat smoking addiction more holistically, recognizing that it entails far more than merely a dependence on nicotine."

There are two major recommendations of my article:

1. "Rather than relying on the Transtheoretical Model and focusing on pharmacotherapy or counseling, the basis for an effective smoking cessation program should be an aggressive, hard-hitting, high exposure, anti-smoking media campaign that jolts smokers into quitting, regardless of their previous stage of readiness to quit."

2. "Instead of focusing solely on nicotine replacement, nicotine vaccines, or pharmacologic agents that bind to nicotine receptors, smoking cessation treatment approaches must address the behavioral aspects of smoking addiction in addition to its pharmacological component. The prototype for such a strategy is the electronic cigarette... ."

The Rest of the Story

I sincerely hope that this chapter will help to facilitate a paradigm shift in the tobacco control movement in terms of our strategies to promote smoking cessation.

Wednesday, June 12, 2013

A Changing World: All Three Major U.S. Tobacco Companies Have Now Entered the Electronic Cigarette Market

Reflecting massive changes in the U.S. tobacco space, all three major U.S. tobacco companies - Altria, Reynolds American, and Lorillard - have all entered the electronic cigarette market.

Lorillard had previously acquired Blu, but last week's announcement that R.J. Reynolds will introduce Vuse e-cigarettes in Colorado in July and this week's announcement that Altria will introduce MarkTen e-cigarettes in Indiana in August mean that all three companies will have entrants in the electronic cigarette market.

The Rest of the Story

There is now no question that the major cigarette companies are actively engaged in transforming the cigarette market, with a shift towards much less hazardous tobacco products. This shift has already resulted in a significant reduction in cigarette consumption, but the declines in smoking should grow as these alternative products begin to penetrate into brick-and-mortar retail stores, rather than just mall kiosks and the internet.

Ironically, the only groups which are opposing this transformation - which may result in a great reduction in cigarette-related morbidity and mortality - are the anti-smoking groups, which simply can't handle the fact that vaping looks like smoking and are not willing to actually examine the evidence that electronic cigarettes, in their seven years on the market, have not resulted in youth smoking initiation or even regular e-cigarette use among nonsmokers.

All three of the major tobacco companies are now officially in the business of harm reduction and are 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?

The entrance of the cigarette companies into the electronic cigarette market offers five distinct advantages that I believe in the long run will enhance the e-cigarette market:

1. The entrance of the tobacco companies 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 six years after introduction of this product, consumers are still largely unaware of the very existence of the product. Even tobacco control experts remain confused about the differences between a cigarette and an electronic cigarette. Already, the entrance of the tobacco companies into the market has resulted in substantial publicity and media attention which is helping to educate the public about these products. 

2. The entrance of the tobacco companies 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. Even if the FDA does not apply section 911 to electronic cigarettes, the entrance of tobacco companies into the market will help facilitate the conduct of important research into the safety and effectiveness of electronic cigarettes that can help inform the development of rational public policy regarding these products.

3. The entrance of the tobacco companies 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.

4. The entrance of the tobacco companies 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.
Anti-smoking advocates will no longer be able to argue that we have no idea what electronic cigarettes are or what they contain or how or where they are made. In addition, the tobacco companies will be able to educate the FDA and provide the agency with ideas about specific aspects of the manufacturing process that could be incorporated into sensible regulations that would help set high standards for the entire industry.

5. Perhaps most importantly, the entrance of the tobacco companies into the electronic cigarette space may help transform the market by shifting it from an internet and mall kiosk business into a more traditional retail store operation. Already, the cigarette companies have developed arrangements with retail stores to carry their products. This could potentially lead to a more traditional market in which these products are available at brick-and-mortar stores, not just on the internet or at mall kiosks.

Tuesday, June 11, 2013

New Study Shows that Electronic Cigarette Vapor is Much Less Cytotoxic than Cigarette Smoke

A new study from researchers in Italy and Greece, under the direction of senior author Dr. Konstantinos Farsalinos, reported last week in the journal Inhalation Toxicology that vapor from electronic cigarettes was found to be much less cytotoxic (damaging to cells) than tobacco smoke.

(See: Romagna G, Allifranchini E, Bocchieto E, Todeschi S, Esposito M, Farsalinos KE. Cytotoxicity evaluation of electronic cigarette vapor extract on cultured mammalian fibroblasts (ClearStream-LIFE): Comparison with tobacco cigarette smoke extract. Inhalation Toxicology 2013; 25(6):354-361.)

The study examined the effect of electronic cigarette vapor from 21 different brands compared to cigarette smoke on the growth of fibroblasts in cell culture. This is a laboratory test that detects whether or not a substance causes cell damage and therefore inhibits cell growth.

At the highest dilution, 20 of the 21 brands of electronic cigarette showed no signs of cytotoxicity. One brand showed evidence of cytotoxicity at the highest dilution but not at any lower dilutions. Even at this high dilution, the cytotoxicity was more than two orders of magnitude lower than that of cigarette smoke. In contrast, cigarette smoke was cytotoxic up until the third level of dilution.

The study reports the findings as follows:

"The main result of our study is that the vapor from only 1 of the 21 EC [electronic cigarette] liquids examined had cytotoxic effects on cultured fibroblasts according to protocol definition. CS [cigarette smoke] extract had significant cytotoxic effects, and fibroblast viability was significantly lower at all extract concentrations compared to EC vapor extracts."

The study concludes:

"This study indicates that EC vapor is significantly less cytotoxic compared to tobacco CS."

The Rest of the Story

This study adds further evidence that electronic cigarette use is much safer than cigarette smoking. There is absolutely no scientific basis for anti-smoking advocates to continue arguing that vaping is simply another form of smoking. This should put that argument to rest. Completely.

The one electronic cigarette brand that did show evidence of cytotoxicity was a "coffee-flavored" brand. Dr. Farsalinos and colleagues point out that it is quite likely that the cytotoxicity resulted from the flavoring, rather than the electronic cigarette liquid components generally used in most brands, as processing of coffee beans has been shown to lead to degradation products that exhibit cytotoxicity. They also point out that even for this brand, "the cytotoxic effect ... was found only at the highest extract concentration, and, even at this concentration, fibroblast viability was 795% higher compared to CS extract."

Nevertheless, the results do suggest that studies are necessary to make sure that flavorings or other additives in electronic cigarette liquids are not harm-producing. This is an area that the FDA could address in its regulatory oversight of these products.

The rest of the story is that we now have additional scientific evidence that vaping is much safer than smoking. We already knew that vaping greatly lowers the carcinogenic risk associated with cigarette smoking. Now we know that vaping greatly lowers cytotoxicity as well. There is strong evidence that vaping lowers both the carcinogenic risk and lung disease risks associated with cigarette smoking.

It is simply untenable for anti-smoking groups and policy makers to continue the argument that vaping is simply another form of smoking. There is a world of difference between the two. And that difference might just be that between life and death for hundreds of thousands of electronic cigarette users.

Monday, June 10, 2013

German Cancer Research Center Corrects Inaccurate Statement About Glycerine Causing Lipoid Pneumonia

In response to my blog post revealing an inaccurate statement in the German Cancer Research Center's report on electronic cigarettes, the Center has corrected the statement.

The original statement was: "Glycerine may cause lipoid pneumonia on inhalation." As I pointed out, this is not possible, because glycerine is an alcohol and lipoid pneumonia is associated with the aspiration of oils.

In response, the Center corrected this statement in its online version of the report to read: "Inhaled glycerine-based oils may cause lipoid pneumonia."

The Center also let me know that the incorrect statement was a mistake, rather than a deliberate attempt to mislead readers.

The Rest of the Story

I applaud the German Cancer Research Center for correcting this inaccurate statement. As I pointed out, the statement was particularly damaging, because it gave the impression that glycerin, which is widely used in almost every brand of electronic cigarettes, can potentially cause this serious adverse outcome. The effect could have been to discourage smokers from trying electronic cigarettes and potentially, to encourage governments to ban the product. So I thank the German Cancer Research Center for correcting this important mistake.

However, there is still a problem with the Center's conclusion, in my opinion. I simply do not think that a single case report is enough to justify a conclusion that electronic cigarettes pose any significant risk of lipoid pneumonia, especially when even this single case report was unable to document that the case was attributable to the use of an electronic cigarette.

To be very clear, I have no problem with the Center stating that there was a published case report in which the authors attributed a case of lipoid pneumonia to the use of an electronic cigarette. However, the report goes beyond this. It also includes a bullet point - which is essentially a summary or conclusion statement - that asserts to readers that electronic cigarettes can cause lipoid pneumonia because of the presence of "glycerine-based oils."

First, I believe it is misleading to use the term "glycerine-based" oils. By including the term "glycerine," I'm afraid that many readers will misinterpret the assertion to mean that glycerine itself may cause lipoid pneumonia. Why even include the word "glycerine"? Almost all oils are "glycerine-based" so the term is redundant and unnecessary. It creates confusion between the real potential cause - the possible presence of oils in some electronic cigarette brands - and the substance present in almost all electronic cigarettes which does not cause lipoid pneumonia: glycerine.

Second, I do not believe this conclusion is scientifically justified. It is based on just a single case report and if you carefully consider the details of the case report, it becomes clear that this report cannot definitively attribute the case to oils inhaled from an electronic cigarette.

The report does not document the specific brand of electronic cigarette used, nor does it document the ingredients of that electronic cigarette. Thus, it is not even clear whether the electronic cigarette brand contained oils as an ingredient or not. The author of the paper is not able to provide that information, so it is premature and inappropriate - I believe - to draw the conclusion that the case was attributable to something that we don't even know for sure was present in that particular brand of electronic cigarettes.

According to the paper: "Recent evaluation of the nicotine solution and vapor content of e-cigarettes found primary components of propylene glycol, glycerin, and nicotine. Other chemicals identified in trace amounts include N-nitrosamines, diethylene glycol, polycyclic aromatic hydrocarbons, anabasine, myosmine, and β-nicotyrine. ... Vegetable glycerin is often added to the nicotine solutions used in e-cigarettes to make the visual smoke when the solution is vaporized."

None of the chemicals mentioned in this case report could cause lipoid pneumonia. While I am not arguing that it is impossible that the presence of oils in some electronic cigarette brands could hypothetically cause lipoid pneumonia if aspirated, it seems clear that this report fails to even document that there were oils present in the specific brand of electronic cigarettes used by the patient.

In the absence of such documentation, I don't see how the report can definitively attribute the lipoid pneumonia to the use of electronic cigarettes.

There is even a third possibility. The patient in question reported that her home was fumigated with chemicals two weeks prior to her presentation in the hospital. Exposure to fumigation chemicals has been associated with the development of lipoid pneumonia, possibly because some of the fumigation chemicals used are oils or oil-based.

Again, I have no problem with the report speculating that the use of an electronic cigarette that may have used an e-liquid that contained oils could potentially have caused lipoid pneumonia in this particular patient. However, I do not believe this justifies a conclusion that electronic cigarettes cause lipoid pneumonia and I think that the use of the term "glycerine-based oils" is misleading.

Nevertheless, I applaud the German Cancer Research Center for correcting the mistake about the potential cause of lipoid pneumonia in a patient who used electronic cigarettes.

Friday, June 07, 2013

The Problem with the Tobacco Control Movement: Ideology Has Overtaken Science

According to a DNA India article, the health minister of France supported her call for a ban on vaping in public places and a ban on e-cigarette advertising by asserting that using an electronic cigarette is the same thing as smoking.

According to the article: "The Italian health ministry's top advisory body has recommended a ban on the smoking of electronic cigarettes in public places and their sale to pregnant women and minors. The recommendation by the ministry's Superior Health Council came after France's Health Minister Marisol Touraine said she was planning simiar restrictions. 'Smoking an e-cigarette is smoking,' she stated."

The Rest of the Story

Nothing could be further from the truth.

The truth is: "Smoking an e-cigarette is a step towards quitting smoking."

This is the bare fact that so few in the anti-smoking movement seem to appreciate.

The importance of this story is that it illustrates precisely what is wrong with today's anti-smoking movement. Instead of being driven by science, as it was in the past, it is now being driven by ideology. This ideology is so skewed that using a non-tobacco device resembling a pen that vaporizes a solution of nicotine and propylene glycol without any combustion or smoke production is considered equivalent to cigarette smoking.

That using an e-cigarette is considered to be the same thing as smoking is emblematic of the victory of ideology over science in today's anti-smoking movement. The science clearly tells us that vaping is not smoking and that in fact, vaping is a method of quitting smoking. But the ideology is telling many anti-smoking advocates that because it looks like smoking, vaping actually is smoking.

I explained yesterday how a tobacco control researcher - Dr. Glantz  - is so much guided by ideology instead of the science on this issue that he called a study which did not evaluate the effectiveness of e-cigarettes for smoking cessation a "good study" of the effectiveness of e-cigarettes for smoking cessation.

Apparently, the ideology against a behavior that looks like smoking is so strong that most anti-smoking advocates are incapable of condoning such a behavior, even if it is saving lives.

The upshot of this is that the anti-smoking movement is doing everything in its power to protect cigarette sales from the threat of e-cigarettes. Even the cigarette companies are hoping to shift some of the cigarette market toward e-cigarettes. Not so with the anti-smoking groups. And that's a tragedy.

Thursday, June 06, 2013

Researcher Continues to Use Bogus Data to Support Non-Efficacy of E-Cigarettes; Even Study Authors Admit Study Cannot Be Used to Evaluate E-Cig Efficacy

In my recent KQED radio discussion with Dr. Glantz about proposed California legislation to ban electronic cigarette use in public places, Dr. Glantz again cited data from a recent study by Vickerman et al. to support his contention that e-cigarettes are less effective than NRT for smoking cessation.

I have already explained in detail why the data from the Vickerman study cannot be used to assess the effectiveness of e-cigarettes for smoking cessation. Briefly, instead of estimating cessation rates among a cohort of smokers who made quit attempts using these products, the study analyzed cessation rates of a large number of smokers who had previously tried to quit using e-cigarettes but failed, and then called a quitline because they had failed and wanted to try again. Then, they compared the quit rate among these smokers to that among smokers without such a history of a failed quit attempt using electronic cigarettes.

In other words, this study did not estimate quit rates among smokers trying to quit using e-cigarettes. Instead, it estimated quit rates among many smokers who were not using e-cigarettes in their quit attempt at all!

The truth is that many of the electronic cigarette users in the study did not use electronic cigarettes in their quit attempts! According to data provided in the paper, a full 28% of the sample of electronic cigarettes did not use these products in their quit attempts.

It should be clear to readers that this study was poorly designed to investigate the efficacy of electronic cigarettes.

The Rest of the Story

Concerned that Dr. Glantz was misrepresenting the results of their study, the authors of the study - who are at Alere Wellbeing - publicly admitted that the study was never intended to assess the effectiveness of electronic cigarettes and that the data should not be used for this purpose.

The Alere Wellbeing blog states very clearly: "The recently published article by Dr. Katrina Vickerman and colleagues has been misinterpreted by many who have written about it. It was never intended to assess the effectiveness of the e-cig as a mechanism to quit."

Imagine that a tobacco company was concerned about the threat of electronic cigarettes to its profits and wanted to publicly disseminate a conclusion that electronic cigarettes are less effective than NRT for smoking cessation. A new study comes out, published in a reputable journal, that is not designed to evaluate the efficacy of electronic cigarettes for smoking cessation. It neither can nor should be used to gain information about the rate of successful cessation using e-cigarettes. But the tobacco company uses these data anyway, telling the public on a radio show that this study shows how ineffective electronic cigarettes are.

Without a doubt, anti-smoking advocates would view the behavior of this tobacco company as fraudulent. The company would be viewed as misleading the public, misrepresenting the results of research, and trying to pull the wool over the eyes of the people.

There is a reasonable discussion that can be conducted regarding the wisdom of banning vaping in public places. However, if we use bogus data to support a pre-determined position, this is no longer a scientific discussion.

It is clear to me that Dr. Glantz has a pre-determined opinion about electronic cigarettes and that this ideology is dictating his agenda, which is now blind to the actual scientific evidence. He is judging studies not based on their scientific rigor, but on whether their "findings" are "favorable" to his opinion. This is a perfect example of this. Here we have a study which, as the authors themselves admit, sheds no light whatsoever on whether electronic cigarettes are effective for smoking cessation. Yet Dr. Glantz used this study to publicly declare that e-cigarettes are less effective than NRT, a gross misrepresentation that deceives the public.

Dr. Vickerman herself explained that her results do not in any way indicate that electronic cigarettes are less effective than NRT, stating: "It may be that callers who had struggled to quit in the past were more likely to try e-cigarettes as a new method to help them quit. These callers may have had a more difficult time quitting, regardless of their e-cigarette use."

By the way, this is a study that Dr. Glantz called a "good study" on "the use of e-cigs for cessation."

Finally, I need to clarify another misrepresentation by Dr. Glantz. He stated on his blog that my main argument against the proposed California ban on vaping in public places is that this would harm vapers by decreasing electronic cigarette use. He states: "Mike's essential argument was that any restrictions on "life saving" e-cigarettes would discourage their use for smoking cessation."

This is not my argument. My argument is that the bill is not justified because there is no scientific evidence that vaping poses a substantial health risk for bystanders. My opinion is that we should not base coercive health legislation on pure speculation. I believe that we need solid scientific evidence of a public health hazard before we enact coercive legislation. 

Therefore, if there were evidence that vaping was harmful to bystanders, I would support a ban on vaping in public places, even if this would also discourage vapers from using these products to quit smoking. The point of my emphasizing this detrimental aspect of the legislation was simply to emphasize that while the bill offers no known benefits, it does create substantial harm. But I would support the legislation if there were known risks posed by passive vaping that would be minimized with such legislation.

Wednesday, June 05, 2013

French Government Would Rather that Smokers Continue to Smoke Instead of Switching to Electronic Cigarettes

Yesterday, I criticized a recently announced French policy that would ban vaping in public places. Today, I address a different aspect of the proposal: a ban on the advertising of electronic cigarettes.

According to the health minister, not only will vaping in public places be banned, but so will the advertising of electronic cigarettes. The new regulations include a "blackout on media advertising" of electronic cigarettes. Thus, the government will extend its current ban on tobacco advertising on television, radio, the internet, and print media to electronic cigarettes.

The Rest of the Story

By placing a ban on the advertising of electronic cigarettes, the French government is saying that it wants to put electronic cigarettes at a disadvantage in terms of recruiting customers. In other words, France is going to take an extreme, intrusive measure to protect tobacco profits. Obviously, this measure is going to reduce electronic cigarette use. Apparently, the French government would rather that people use real cigarettes that kill them instead of fake ones that cause little recognized harm and help thousands of French smokers to quit smoking and save their lives.

The most unfortunate part of this story to me is that anti-smoking advocates are supporting this measure. For example, Stan Glantz expressed his support for both aspects of the French policy on his blog. While I disagree with Stan's support of a ban on vaping in public places because there simply is no existing evidence that vaping poses a significant harm to bystanders, I can at least understand his position. However, I do not understand his support for a complete ban on the advertising of electronic cigarettes.

There is simply no valid basis to ban the advertising of electronic cigarettes at the current time. How anti-smoking advocates can place these devices in the same category as tobacco cigarettes is beyond me. With all due respect, this policy is going to result in increased disease and death. It is going to reduce the sales of electronic cigarettes and increase the consumption of tobacco cigarettes. What is the rationale for anti-smoking advocates to support a measure that is going to significantly harm the public's health?

Tuesday, June 04, 2013

French Health Ministry to Ban Electronic Cigarette Use in Public Places Based on Uncertainty and Pure Speculation

According to a Reuters article, France is set to ban electronic cigarette use in public places even though it is not aware of any scientific evidence that these products harm bystanders. Apparently, France will ban electronic cigarette use in these places simply because of uncertainty over the precise nature of potential, unproven risks.

The other justification given for banning vaping in public places is that it mimics smoking and COULD lead to smoking initiation: "'This is no orlarldinary product because it encourages mimicking and could promote taking up smoking,' said Touraine, who announced her plans at a news conference."

According to the article: "France will ban electronic cigarette smoking in public places by imposing the same curbs enforced since 2007 to combat tobacco smoking, Health Minister Marisol Touraine said on Friday. Amid mounting global concern over the public health implications of so-called e-cigarettes, Touraine said they faced the same fate as traditional ones: a ban on smoking in public spaces and sales to minors and a blackout on media advertising. ... The near-odorless electronic alternative - battery-driven devices that allow users inhale odorless nicotine-laced vapor rather than smoke - are gaining ground in no-go zones such as bars, cafes, trains, waiting rooms and offices. A government-commissioned report said this week that around 500,000 people in France had turned to e-cigarettes, which are designed to look like cigarettes although some come in different colors, and recommended a crackdown on public use."

The Rest of the Story 

My feeling is that the government should not use coercive interventions – such as bans – unless there is strong scientific evidence that a substantial public health problem exists. So far, I have seen no data to suggest that “passive vaping” represents any significant hazard. I think there needs to be more than just pure speculation for the government to take coercive action. The French government presents absolutely no evidence that secondhand vaping represents a public health threat.

The second justification given for the vaping ban is that it might encourage mimicking and could - hypothetically - promote smoking initiation. But again, there is absolutely no evidence that this is the case. Two large studies have had difficulty finding any substantial number of youth nonsmokers who regularly use electronic cigarettes, despite their presence on the market for at least six years and despite the fact that youth experimentation with this product has already occurred.

Pure speculation should not stand as a valid basis for coercive government action, in my opinion.
The same justification used by the French government - pure speculation - is also being used by Dr. Stan Glantz to promote a ban on electronic cigarette use in public places in California. On a KQED radio segment about California legislation to ban e-cigarette use in public places, Dr. Glantz defended the legislation by speculating that there "might" be a slight risk associated with these products. But he presented no evidence that as actually used, they pose any threat to bystanders.

In my opinion, these efforts to pass coercive legislation based on pure speculation - devoid of any scientific evidence of risk or harm - undermine the integrity of public health. What these anti-smoking advocates - such as Dr. Glantz - are admitting is that they would support 100% smoke-free laws even if there were no scientific evidence that secondhand smoke is harmful.

I'm not willing to adopt that position. My support for smoking bans is based on the substantial scientific evidence demonstrating that it is a significant public health hazard that is causing suffering, disease, and death.

Dr. Glantz' and others' support for banning vaping in public places without any evidence of risk or harm undermines the integrity of public health because it indicates that we would be willing to ban smoking in public places even in the absence of evidence that it is harmful. I believe that there needs to be a higher standard for coercive government action.

Monday, June 03, 2013

New Cochrane Review of Smoking Cessation Drugs Hides the Truth from Readers

A new, comprehensive, 51-page review of multiple meta-analyses summarizing the effectiveness of nicotine replacement therapy (NRT) and other drugs for smoking cessation concludes that these drugs are highly effective in helping smokers quit.

(See: Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.:CD009329.DOI: 10.1002/14651858.CD009329.pub2.)

The review was extensive, covering hundreds of studies and tens of thousands of subjects: "The authors combined the findings of existing Cochrane reviews on the subject, using all the available data from across the individual reviews. In total, they collected evidence from 267 studies, which together involved a total of 101,804 people. The studies covered a wide variety of licensed and unlicensed smoking cessation medications, comparing the treatments with placebo, and the three main treatments with each other. If a person stopped smoking for six months or longer, this was considered a successful quit attempt."

The study results were summarized - correctly - by one news outlet, as follows: "Participants were 80% more likely to quit when using a single NRT or taking bupropion compared to those using a placebo. Those using varenicline as well as an NRT had two to three times greater odds."

The Rest of the Story

If I gave my students an assignment to review the scientific evidence on the effectiveness of NRT and other drugs for smoking cessation and they handed in this comprehensive, 51-page review, I would not be able to give them a passing grade on the assignment.

Why not?

Because the article leaves out the single most important piece of information that the review should provide. It fails to answer the single most important research question:

What was the success rate for these products?

How could any review of this topic claim to be "comprehensive" when it doesn't answer the most basic question: What percentage of people who use NRT or other drugs to quit smoking are successful? If the paper doesn't provide the answer to that question, how can we consider it to be a solid review of the scientific evidence on this topic? That's why I would have to give a student passing in such a paper a failing grade.

This review reports only the relative risk of smoking cessation with NRT/drugs, not the absolute prevalence of abstinence following treatment. Knowing that the relative risk for cessation associated with NRT compared to placebo is 1.8 doesn't actually answer the question of whether these drugs are effective.

Suppose you went to the doctor for pneumonia. She prescribed an antibiotic and told you that the antibiotic is 500 times more likely than placebo to cure your infection. Sounds great, right? But suppose that the absolute cure rate with placebo for bacterial pneumonia is only 0.001%. That would mean that this antibiotic has a success rate of 0.5%. This means it will work only 5 out of 1,000 times. Your proper course of action is not to fill your prescription for this antibiotic with a relative risk of 500 compared with placebo but to head to your lawyer's office to file malpractice papers.

Well, sadly, this is the precise error that this review commits. It reveals the relative risk of treatment but hides from the reader any information about the absolute success rates. In other words, it doesn't actually tell us whether these treatments work or not!

The truth is that placebo success rates are only about 5%, so at best, use of NRT in real world settings produces about a 10% long-term quit rate.

How can a treatment with a 90% probability of complete failure be considered effective?

Instead of concluding that "Participants were 80% more likely to quit when using a single NRT or taking bupropion compared to those using a placebo," the review could have just as easily concluded that "Participants using NRT or taking bupropion had a 90% chance of failing to quit smoking."

To me, a 90% failure rate is not the hallmark of an "effective" medication.