Wednesday, May 06, 2009

Anti-Smoking Advocate Commits Science-by-Press Release to Influence FDA Tobacco Bill; But "Science" Turns Out to Be Nothing But Pure Speculation

A prominent anti-smoking researcher and advocate has released conclusions of a non-peer-reviewed study to the media - without making the actual study available - in an admitted attempt to influence the FDA tobacco legislation which will be heard by a U.S. Senate committee on Tuesday.

The story was reported yesterday in an article in the New York Times. According to that article: "For three decades, Dr. David M. Burns has written and edited some of the seminal work on tobacco science and the hazards of modern cigarettes: surgeon general’s reports, National Cancer Institute monographs, World Health Organization studies. ... with the Senate just weeks away from a vote on landmark legislation to regulate tobacco, Dr. Burns, 61, is now willing to sidestep the protocols of peer-reviewed science. ... Dr. Burns says he has new information, based on two years of study, indicating that cigarettes — even the supposedly safer ones — pose a much higher risk of lung cancer than before the surgeon general first declared them a health hazard in 1964. He said the risk of a smoker’s developing lung cancer may be twice as high as it was then, even though tar and nicotine have been reduced."

"Last Thursday, Dr. Burns presented a “late-breaking abstract” — a summary of his findings — in Dublin at a meeting of the Society for Research on Nicotine and Tobacco. And the Campaign for Tobacco-Free Kids, a Washington advocacy group, has been promoting his work to journalists. His thesis has not yet been reviewed by a panel of experts, such as the sort who would vet his research if he were to submit it to a medical publication like The New England Journal of Medicine, where his work has been published in the past. He says he plans to submit an article. But that process can take months — long after the vote on the tobacco bill... . ... Dr. Burns notes that the way much tobacco is cured in the United States increases the level of dangerous compounds called nitrosamines. In the past in this country, and in places like Australia, tobacco was cured in the open air. But many American growers now speed it up with nitrogen fertilizers and propane heaters, leading to the formation of nitrosamines. They are among the 47 known animal or human carcinogens in cigarette smoke."

The Research

The research is described in an abstract and poster from the Dublin conference. Basically, what the study did was estimate the expected lung cancer mortality over the past five decades based on relative risk data from the American Cancer Society's CPS-I study, using actual data on cigarette consumption. The main finding was that while squamous cell lung cancer rates were accurately predicted, there was a substantial (about 50%) underestimate of the adenocarcinoma rates. This finding suggests that the actual relative risk for adenocarcinoma of the lung has increased over time (compared to the mid-1960s), while the relative risk for squamous cell carcinoma of the lung has remained relatively steady. The study also noted that data for Australia indicate that the proportion of lung cancers that are adenocarcinoma has increased to much less of an extent during the past five decades than in the United States.

The Conclusion

Therefore, it follows naturally, the researcher concludes, that the increased risk of lung cancer is due to the curing of tobacco indoors rather than outdoors, which has resulted in increased levels of nitrosamines in cigarettes.

If that conclusion seemed to jump at you from out of nowhere, you're not alone.

There is no basis - and certainly nowhere close to a sufficient basis - to conclude that the explanation of the increased adenocarcinoma rates observed in smokers over time is that the curing process has led to increased nitrosamines.

We have a scientific term for offering that type of explanation: it is called pure speculation.

That explanation is certainly one possibility among many. Another plausible explanation is that the greatly reduced nicotine levels in cigarettes have resulted in very different smoking behavior patterns. It may be that smokers are inhaling more deeply, and that the tar is being delivered into more distal parts of the lung, where adenocarcinoma is more common.

While it may be true that curing processes are one thing that has changed since the mid-1960s, there are many other factors that have changed as well. A huge one is the introduction of filters and the greatly reduced delivery of tar and nicotine.

This researcher is selectively choosing one potential explanation as being the one and only correct reason, but there is absolutely no solid evidence to support this particular conclusion. It is, indeed, pure speculation.

The Rest of the Story

The rest of the story is that rather than being a new scientific finding, this is actually pretty old news. We have known for well over a decade that adenocarcinoma risks have increased among smokers and that the proportion of adenocarcinoma to total lung cancers has been increasing. And there has in fact been an extensive discussion in the scientific literature about the reasons for this phenomenon. A number of plausible explanations have been offered, of which the change in tobacco curing is just one (in fact, it doesn't even appear in the prior literature).

Turn the clock back to November 1995 (fourteen years ago). At that time, the renowned tobacco scientist Ernst Wynder and his colleague - Joshua Muscat - published an article in the journal Environmental Health Perspectives which was specifically intended to address the possible reasons for the increasing risk of adenocarcinoma among smokers (see: Wynder EL, Muscat JE. The changing epidemiology of smoking and lung cancer histology. Environmental Health Perspectives 1995; 103(suppl 8).

In that article, Wynder and Muscat wrote: "In this overview we discuss the steeper increase during recent decades of lung adenocarcinoma incidence compared with squamous cell carcinoma of the lung. In 1950, the ratio of these two major types of lung cancer in males was about 1:18; today it is about 1:1.2-1.4. This overview discusses two concepts that are regarded as contributors to this change in the histological types of lung cancer. One factor is the decrease in average nicotine and tar delivery of cigarettes from about 2.7 and 38 mg in 1955 to 1.0 and 13.5 mg in 1993, respectively. Other major factors for the reduced emission of smoke relate to changes in the composition of the cigarette tobacco blend and general acceptance of cigarettes with filter tips; the latter constitute 97% of all cigarettes currently sold. However, smokers of low-yield cigarettes compensate for the low delivery of nicotine by inhaling the smoke more deeply and by smoking more intensely; such smokers may be taking up to 5 puffs/min with puff volumes up to 55 ml. Under these conditions, the peripheral lung is exposed to increased amounts of smoke carcinogens that are suspected to lead to lung adenocarcinoma. Among the important changes in the composition of the tobacco blend of the U.S. cigarette is a significant increase in nitrate content (0.5% to 1.2-1.5%), which raises the yields of nitrogen oxides and N-nitrosamines in the smoke. Furthermore, the more intense smoking by the consumers of low-yield cigarettes increases N-nitrosamines in the smoke 2- to 3-fold. Among the N-nitrosamines is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a powerful lung carcinogen in animals that is exclusively formed from nicotine. This organ-specific tobacco-specific nitrosamine (TSNA) induces adenocarcinoma of the lung. All of these factors, the more intense smoking, the deeper inhalation of the smoke, and the increased yields of N-nitrosamines in the smoke of low-yield cigarettes, are considered major contributors to the drastic increase in lung adenocarcinoma among cigarette smokers in recent years."

As you can see, Wynder and Muscat did not attribute the increased risk of adenocarcinoma to changes in the curing process. They did, however, attribute this phenomenon largely to the decreased yields of cigarettes, which led to deeper inhalation and deeper penetration of the smoke constituents into the periphery of the lung, an area which is more susceptible to adenocarcinoma.

The Important Lesson

If there is one thing we have learned, or should learn, from the precise type of research being released through the newspaper yesterday, it is that it is extremely difficult - if not impossible - to predict the effects on human cancer risk of changes in the design and composition of cigarettes.

For many years, public health advocates warned of the dangers of high-tar cigarettes and urged cigarette companies to develop lower yield products. Everyone thought that this innovation would result in decreased morbidity and mortality from cigarette-related diseases. Instead, it turned out that cigarette smokers changed their behavioral patterns in response to the decreased delivery of nicotine and other constituents. As a result, the predicted health gains were never realized (and the situation may actually have been made somewhat worse).

The issue of predicting the precise risk of a particular change in cigarette design and composition is an extremely difficult one. It is not so easy as saying that if we reduce the level of a particular component, the lung cancer rates will decline. In fact, when cigarette companies went along with public health authorities and greatly reduced the yields of every major smoke component, the end result was the absence of any health protection. This is too complex a business for a researcher to come along and tell the New York Times that he has a solution that will prevent 50% of lung cancer deaths.

A number of cigarette companies have experimented with products in which the levels of particular smoke constituents are significantly reduced. The result? It turns out that while the levels of these constituents went down, the levels of other constituents went up. The cigarettes were not any safer.

If the curing process for tobacco were changed, we simply do not know what the effect would be on cancer rates. There are more than 50 carcinogens, of which nitrosamines are just a few. You need to understand the entire profile of carcinogenesis before you can definitively draw conclusions about actual human risk. And you also need to know the way in which the altered product is going to change actual human smoking behavior.

We don't know this, with respect to nitrosamines or any other component, and these researchers from the UCSD School of Medicine have no business touting themselves as holding the solution to preventing 50% of lung cancer deaths from smoking when there has been absolutely zero clinical testing of such a product.

Perhaps the most troublesome aspect of this story, to me, is the damage that it could do. It is a very deceptive and inappropriate public action for a researcher to take. The study has not been peer reviewed, nor is it being released publicly, yet its conclusions - which amount to pure speculation - are being disseminated worldwide in an attempt to influence policy. It is the classic strategy of science by press release.

In conclusion, what we have here is a thinly-disguised (as science) attempt to influence the FDA tobacco legislation, at the last moment, by manipulating the media. Under the guise of science, a researcher has presented what essentially amounts to pure speculation and dressed it up so that it appears to be real science. I can assure my readers that it is nothing of the sort. It is pure correlation. Pure speculation.

In fact, there are equally plausible alternative explanations for the "new" study's findings which involve not only the cigarette design, but also the behavior of smokers. There is nothing new and nothing startling about the phenomenon being presented as a startling new finding. We have known about this for well over a decade and Ernst Wynder himself opined that a primary reason for the increased adenocarcinoma risk associated with lower yield cigarettes is the deeper inhalation and deeper delivery of tar into the more susceptible periphery of the lung.

Rather than argue for the FDA regulation of the design of cigarettes, today's news argues instead that the FDA legislation is a huge public ruse. Under the propaganda that FDA regulation will result in a safer cigarette, the bill to be considered by a Senate committee on Tuesday will actually ensure that truly safer cigarettes do not enter the market. This will protect Philip Morris - the bill's primary supporter - from competition.

If you possess 50% of the cigarette market and your biggest potential competition could come from a novel, reduced risk product, the thing you desire most is to block such products from the market. The FDA legislation does just that by putting insurmountable obstacles in the way of the introduction of safer cigarettes.

Instead, the legislation protects the existing cigarettes on the market. And even worse, it creates the false public perception that the FDA now has the ability to require safer cigarettes when the truth is that the FDA is no more capable than Joe the Plumber of designing a safer cigarette. The only difference is that while Joe the Plumber is not approving cigarettes for public consumption, the FDA - on behalf of the federal government - will be doing just that if this legislation is enacted.

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