Wednesday, May 14, 2014

Glantz Review Article is Little More than an Unscientific Hatchet Job on E-Cigarettes

A scientific review article on electronic cigarettes was published by Stan Glantz and colleagues this week in the journal Circulation.

(See: Grana R, Benowitz N, Glantz SA. E-Cigarettes: A Scientific Review. Circulation 2014; 129: 1972-1986.)

The article purports to review the scientific evidence of the use of e-cigarettes as a smoking cessation aid and it concludes that population-based studies have demonstrated that e-cigarettes inhibit quitting. Specifically, the article concludes as follows: "e-cigarette use in the real world is associated with significantly lower odds of quitting smoking cigarettes."

The article does mention that a clinical trial of e-cigarettes found that these products were as effective as the nicotine patch, but it then dismisses this result, concluding instead that: "e-cigarettes are not associated with successful quitting in general population-based samples of smokers."

The Rest of the Story

In my opinion, rather than being an objective scientific review of the literature, this article is little more than a hatchet job on e-cigarettes. The authors clearly have reached a pre-determined conclusion that e-cigarettes are not helpful in smoking cessation and they stretch science beyond recognition in trying to get the published scientific evidence to support this conclusion.

To illustrate this, let's consider the five studies which the authors cite as providing evidence that electronic cigarettes inhibit smoking cessation.

Presumably, these five studies examined the rate of quitting among smokers who used electronic cigarettes in an attempt to quit smoking.

Question: Of these five studies, how many examined the rate of smoking cessation among smokers who were trying to quit using electronic cigarettes?

A. Five
B. Four
C. Three
D. Two
E. One

Sadly, the answer is:

F. None of the above.

The correct answer is actually:

G. Zero.

The rest of the story is that none of these studies examined quit rates among smokers who were trying to quit using e-cigarettes. None of these studies were in fact designed to examine the role of e-cigarettes in smoking cessation in the first place.

Instead, these were all population-based studies of smoking and e-cigarette use that did not even ask smokers using e-cigarettes if they were using them regularly or if they were using them in an effort to quit smoking. Actually, one of the studies did ask smokers if they were using e-cigarettes to quit smoking and the overwhelming majority said that they were not. In other words, many of the smokers in this study were probably just experimenting with, or trying an e-cigarette, and were not regular users of these products.

Moreover, the users of e-cigarettes in the population were likely more addicted to nicotine, making the comparison of their quit rates with those of other smokers inappropriate.

To illustrate how inappropriate the use of these studies are to draw conclusions about the effectiveness of e-cigarettes for smoking cessation, let's look at two of these studies:

1. The Vickerman study

What Stan does not reveal in his review article is that instead of estimating cessation rates among a cohort of smokers who made quit attempts using these products, the Vickerman 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 study systematically sampled a group of quitline callers who were unsuccessful using electronic cigarettes. These people tried and failed using electronic cigarettes. How do we know they failed? Because they wouldn’t have had to call the quitline if they weren’t still smoking. This is clearly a harder core group of smokers and it is no surprise that their cessation rates were lower after 6-months than the comparison group. The study tells us nothing about the effectiveness of electronic cigarettes, other than that they do not work for everyone. In fact, this research is biased in favor of not finding an effect of electronic cigarettes on smoking cessation.

The truth is that the authors of this study did not intend to examine the effectiveness of e-cigarettes for smoking cessation. They have in fact explicitly stated that their results cannot and should not be used to draw conclusions about the effectiveness of e-cigarettes.

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."

Furthermore, 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." 

2. The Grana study

Stan also fails to reveal in his review that this study, too, does not examine the rate of successful smoking cessation among electronic cigarette users who want to quit smoking or cut down substantially on the amount that they smoke and who are using e-cigarettes in an attempt to accomplish this.

Instead, the study examines the percentage of quitting among all smokers who have ever tried electronic cigarettes - for any reason - in the past month.

A large proportion of the 88 smokers in this study who had tried an e-cigarette may have simply been trying these products to see what they are like. It is plausible, in fact probable, that many of these 88 smokers were not actually interested in quitting or trying to quit with electronic cigarettes. These products have become very popular and have gained widespread media attention and it is entirely possible that many of these smokers simply wanted to see what the big fuss is all about.

It is easy to see how this fatal flaw in the research destroys the validity of the authors' conclusion.

But that isn't the end of the story. If this were simply a bogus conclusion, then we could simply evaluate the article as being junk science, dismiss it as bogus, and leave it there. But unfortunately, it doesn't end there.

Why? Because it is quite apparent from the study itself that the authors knew that the overwhelming majority of the 88 electronic cigarettes "users" in their study had little or no interest in quitting and were not using these products as part of a quit attempt.

How do we know this? Because the authors tell us!

In the Table, the authors report that of the 88 e-cigarette "users," only 8.0% reported that they were trying to quit at that time (that is, within the next 30 days). And only 39.8% of the e-cigarette users had any intention of quitting in the next six months. This means that we actually know for a fact that the majority of e-cigarette users in this study were not using these products as part of a quit attempt.

What this indicates is that this is not simply junk science. Rather, it is a deliberate attempt on the part of the investigators to misuse data. They are using these data to draw a conclusion about whether electronic cigarettes are effective in helping smokers quit, yet they are knowingly drawing upon data from smokers who are using e-cigarettes for other reasons, who may have simply tried an electronic cigarette once, and who most definitely were not using these products as part of a current quit attempt.

In other words, 92% of the e-cigarette users in the study were not trying to quit. We know for a fact that 92% of the e-cigarette users were not making a quit attempt. And yet the study authors interpret the data as if these smokers were trying to quit using e-cigarettes, but failed!

Putting It All Together

Question: When you conduct a meta-analysis of junk science, what do you come up with?

A. A meaningful point estimate of the association between the exposure and the effect.

B. More junk science.

The answer is:

B. More junk science.

This is exactly what Glantz has done in this review. He has thrown together the results of five studies which provide no actual data on whether or not e-cigarettes are effective in quitting smoking. He has misinterpreted the results of these studies, using them to support an apparently pre-determined conclusion that e-cigarettes are ineffective.

Interestingly, Glantz completely dismisses the results of the one study cited in his review which was actually designed to test the effectiveness of e-cigarettes: the Bullen study, which was a clinical trial of electronic cigarettes for smoking cessation. This study found that e-cigarettes were just as effective as the nicotine patch, which is widely recognized as being an FDA-approved, effective smoking cessation aid. However, Glantz simply dismisses this result, which he apparently does not like, in favor of the findings from the five studies which don't actually examine the relevant research question. He twists these studies to produce data which he does like.

It would be a tragedy if policy makers use the conclusions of this "scientific review" to draw conclusions about the effectiveness of electronic cigarettes for smoking cessation purposes.

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