NOT PEER REVIEWED Funding: While this assessment was funded by RJ Reynolds Tobacco Company, it is the product of independent scientific thought, and it expresses solely the opinions of the authors. When data are lacking, models that simulate population health events under different exposure scenarios may serve to inform policy by providing the basis for decision making. In order for models to be used in this manner, their underlying assumptions must be as realistic as possible, and the data used to define the starting point, or "base case", must be accurate. If these criteria are met, then using the model to describe the potential effects of extreme scenarios (i.e., "worst case" and "best case") can provide useful information about the magnitude of effects to be expected for more reasonable scenarios. In a recent publication, Mejia et al. described a model using Monte Carlo simulations, to evaluate the population level health effect that might be expected if smokeless tobacco products were successfully promoted in the US as a safer alternative to cigarettes, resulting in substantial changes in the patterns of use of tobacco products (Mejia, Ling, et al. 2010). The authors concluded that "promoting smokeless tobacco as a safer alternative to cigarettes is unlikely to result in substantial health benefits at a population level". We investigated the methods described by Mejia et al. (2010), and evaluated their conclusion using three approaches: (1) critiquing the assumptions underlying the model and its input data; (2) comparing the published model estimates with estimates developed using the model as described, but with more realistic input data; and (3) using the original input data in a more realistic model, and comparing those results to the published model estimates. We used the results of this investigation to evaluate the utility of their model.

CRITIQUE OF MODEL ASSUMPTIONS AND INPUT DATA

Model transitions:

Mejia et al. (2010) describe their model as beginning with a hypothetical population of non-users of tobacco who are then allowed a very limited number of possible transitions between exposure states. People are allowed to initiate cigarette smoking or smokeless tobacco products, cigarette and smokeless tobacco initiators are allowed to continue use, quit use; switch to the other product, or to become users of both products ("dual users"). Return to cigarette smoking or smokeless product use after cessation, switching from continued cigarette use to a smokeless product or switching from continued smokeless product use to cigarette smoking are not modeled. The model also does not allow non- users of tobacco to initiate cigarette smoking.

Transition probabilities:

A crucial aspect of any model-based evaluation of the effectiveness of a health policy is the model input. Any data selected for the model, and the rationale for their selection, must be clearly documented for the model to be useful in evaluating the potential effectiveness of a proposed policy. In the tobacco harm reduction arena, model results depend heavily on the transition probabilities selected to describe movement between different tobacco exposure states that are expected to result from policy changes. For their base case scenario, Mejia et al. estimated transition probabilities based on multiple populations that differed with respect to age, calendar year and region, even though patterns of tobacco use have been shown to depend strongly on these factors (e.g. (CDC 2007; Gilpin, Pierce, et al. 1992; Nelson, Mowery, et al. 2006; Roth, Roth, et al. 2005; Tomar 2003). The estimated probabilities were applied to the entire hypothetical population, and did not account for age or gender. In addition, some transition probabilities were based on the estimated lifetime prevalence of ever use, others on the prevalence of current use, and yet others on the 2-year incidence of initiation, even though incidence and prevalence are not interchangeable measures or concepts. * The incidence of smokeless product initiation (4%) was based on the arithmetic average of: the prevalence of smokeless product use among adults in 2005 based on the National Survey on Drug Use and Health (3.3%) (NSDUH 2005); the prevalence of smokeless product use among adults (2.3%) based on data from the National Health Interview Survey (NHIS) conducted in 2000 (Nelson et al., 2006); and the prevalence of smokeless product use among 9-12th graders in 2003 (6.7%) based on NHIS data (Nelson et al., 2006). Mejia et al. (2010) averaged these prevalence estimates without taking the differences between the source populations into account.

* To estimate transition probabilities from smokeless tobacco use to other exposure states, Mejia et al. used data from Oregon boys in grades 7 and 9 who were followed for 2 years in the late 1990s. The implicit assumption was that the hypothetical population of smokeless product "initiators" (which in their example was the population of current smokeless product users) was like Oregon 7th and 9th grade boys in terms of their tobacco use patterns.

* The incidence of cigarette smoking initiation was assumed to be equal to the lifetime prevalence of ever smoking among US adults in 2006 (40%). Mejia et al (2010) then divided the group of cigarette "initiators" (i.e., ever smokers in 2006) into categories of continuing smokers, quitters, smokeless product users and dual users based on their motivation to quit smoking in future. The transition probabilities were chosen such that "the end state reflected the current smoking and smokeless use prevalence and quit ratio in the 2006 NHIS survey" (page 298), although the NHIS 2006 survey data were not used by Mejia et al. to provide estimates of smokeless use. The end state distribution of continuing smokers and quitters was approximately even (47% and 53%, respectively) based on the NHIS estimate that 50% of current smokers were able to quit smoking.

Discussion of the motivation to quit smoking in the future (will never quit; is health concerned; is affected by smoke-free regulations; and is price sensitive) comprised a substantial part of the Mejia et al. paper. However, motivation to quit is irrelevant to the stated purpose of the model, which was to estimate the population-level health effect to be expected under different distributions of cigarette smoking and smokeless tobacco use. The proportions of subjects in each motivation category were reportedly based on a study of adult smokers who had smoked for at least 5 years in 1987 (Gilpin, Pierce, et al. 1992). This cross-sectional study used data from the 1987 NHIS and reported the distribution of reported reasons for quitting smoking in the past 5 years among former smokers, and not motivation to quit smoking in the future among current smokers. The Gilpin et al. study did not consider a "smoke-free environment" category, it included a "health concerned and price sensitive" category because of considerable overlap between the two categories among their respondents, and it included several additional categories not considered by Mejia et al. (e.g., "lost interest" and "miscellaneous", among others). The proportion of the population of former smokers reporting reasons for quitting smoking that were not considered by Mejia et al. was almost 50% in the Gilpin et al. (1992) data. Further, according to Gilpin et al., the proportion of subjects that had never tried to quit smoking was 18% among ever smokers and 33% among current smokers, values that are very different from the 10% estimated by Mejia et al. (2010).

* Finally, Mejia et al. calculated the probability of remaining a non -user of tobacco (56%) as the remainder after accounting for the 40% of the population identified as smoking "initiators" and the 4% of the population identified as smokeless tobacco "initiators". The model allowed cigarette "initiators" (i.e., ever smokers) and smokeless product "initiators" (i.e., current users) to transition to other tobacco exposure states, but those initially defined as non-users of tobacco were not allowed to transition into tobacco use.

Tobacco-related health effects:

Mejia et al. created an artificial "tobacco-related health effects" variable to place the different tobacco exposure categories on a continuum of risk, where non-users of tobacco were at zero, former smokers, current smokeless product users and current dual users were log- normally distributed with means of 5, 11 and 90, respectively, and smokers were at 100. References to justify these values were only provided for smokeless product users; even in this case, the value of 11 (standard deviation = 5) was not directly derived from data but was a consensus estimate. Neither duration of use nor cessation was considered in estimating tobacco-related health risk.

Scenarios and results:

Mejia et al. modeled a number of scenarios to represent different levels of adoption of smokeless tobacco products due to varying hypothetical levels of successful smokeless product promotion. The modeled results under each of the scenarios produced wide posterior intervals that overlapped with one another and the base case scenario, indicating that none of the point estimates could be interpreted as demonstrating statistically significant differences in health risk resulting from differences in the exposure distributions. Under the "aggressive smokeless promotion" scenario considered by Mejia et al. to be the most extreme example, the transition probabilities and other assumptions in the model (e.g. that half the smokeless product users came from never tobacco users) were so unrealistic that even though a much lower health risk was assumed for smokeless product users than for cigarette smokers, the model suggested (statistically non-significant) net harm at the population level.

Mejia et al. acknowledged that their transition probabilities were less than ideal, but claimed that better data were unavailable. However, we found several examples that could have been used: Lundqvist et al. reported on patterns of tobacco use in a population of middle-aged Swedes that included initiation, cessation and rates of transition among cigarettes, smokeless tobacco and dual use over a ten year period (Lundqvist, Sandstrom, et al. 2009). Transitions between exposure states among adults in the United States, including cessation of smokeless tobacco and dual use, were provided by Zhu et al. in analyses of the Current Population Survey-Tobacco Use Supplement for 2002 and 2003 (Zhu, Wang, et al. 2009). Smoking initiation rates are available from the National Health Interview Survey (Escobedo and Peddicord 1997). The National Survey on Drug Abuse provides estimates of smoking initiation in the US (Office of Applied Statistics, 1998 and 1999); its successor, the National Survey of Drug Use and Health, provides estimates of cigarette and ST initiation for people aged 12 and older as recently as 2008 (http://oas.samhsa.gov/nsduh/2k8nsduh/2k8Results.pdf); and Davis et al. provided estimates of smoking initiation specifically for youth smokers (Davis et al., 2009). The study of Oregon teenagers that Mejia et al. relied on for smokeless tobacco product transition rates (Severson, Forrester, et al. 2007) also reported the probability of cigarette and smokeless tobacco initiation and the transition probabilities for those who used smokeless products at baseline, but these estimates were not used by Mejia et al.

From these alternative sources, we selected the three papers (Lundqvist et al., 2009; Severson et al., 2007 and Zhu et al., 2009) that provided the most complete sets of initiation, cessation and transition probabilities for comparison with the data used by Mejia et al. (2010). Compared to the probabilities presented by Lundqvist et al. (2009) for Swedish adults and the probabilities observed by Severson et al. (2007) among teenage boys in Oregon, Mejia et al. considerably underestimated the proportion of persons remaining non-tobacco users and greatly overestimated the smoking initiation probability among non-tobacco users. The estimate used by Mejia et al. (2010) was similar to that provided by Escobedo and Peddicord (1997) based on data from the early 1980s, but greater than that provided by Davis et al. (2009) based on students in grades 6-12 who participated in the ALLTURS study between 2000 and 2002. Further, contrary to evidence reported by Zhu et al. and Lundqvist et al. (2009), Mejia et al. (2010) assumed that (i) cessation of use was much lower among smokeless product users than cigarette smokers while initiation of dual use was much higher among smokeless product users; and (ii) switching from one product to the other was much more common among smokeless tobacco users than cigarette smokers.

Model validation:

Mejia et al. did not report any attempt to validate their model, although they did successfully replicate results, using similar model input, produced by another technique (Gartner, Hall, et al. 2007). Some problems underlying the model whose results Mejia et al. chose to replicate have been discussed elsewhere (Sulsky, Bachand et al., 2010)

SENSITIVITY ANALYSIS

Having identified problems with the data selected as model input by Mejia et al., we attempted to assess the model assumptions by using more defensible input and evaluating the difference in results. Although the authors provided the full model input, via a spreadsheet accessible to journal (Tobacco Control) subscribers through its web site, the spreadsheet does not perform any calculations. However, we had already used the WinBUGS computer program to create a simulation model that estimates mortality or morbidity for a hypothetical population of persons who have never used tobacco and who, as they age, may transition into and out of 33 possible tobacco exposure states, including current and former smoking or smokeless product use and recidivism for those who had quit. A brief description of this model is available (Bachand, Curtin, et al. 2010); a full description is currently being prepared for peer review. We were able to use the data documented in the spreadsheet provided by Mejia et al. in a simplified form of our simulation model to replicate their results. We then tested the sensitivity of their model by modifying the input documented by Mejia et al. and using it in the simplified form of our model.

Alternative results:

We simplified our model to restrict it to the transitions described by Mejia et al. (2010). After cigarette smoking initiation, only one change in tobacco exposure was allowed, and only one change was allowed after smokeless product initiation unless the subject switched to cigarettes; in this case, one additional change could be made. For transitions not modeled by Mejia et al., we used transition probabilities of 0. Using the model input specified by Mejia et al. (2010) was difficult to accomplish for several reasons: (i) Mejia et al. did not take age into account, while our model does; (ii) We did not use prevalence as an estimate of incidence in our model. Whenever their transition probabilities were prevalence estimates, we used incidence estimated from the National Household Survey on Drug Abuse (Office of Applied Studies, 1999), instead; and (iii) The proportions used by Mejia et al. to describe the distribution of motivations to quit were not useful for the stated purpose and were not based on reliable information; therefore, we calculated the weighted average of their transition probabilities for each of the four end states: quitting, continuing cigarette use, switching to a smokeless product and dual use. For this example, we used Mejia et al.'s comparison of the "aggressive smokeless promotion" scenario to their base case scenario. To approximate the input used by Mejia et al., we kept the ratios between the transition probabilities the same as the ratios between the "aggressive smokeless promotion scenario" and the transition probabilities in their base case scenario. It is important to keep in mind that their base case scenario assumed that 4% of the population used smokeless products while we assumed no form of tobacco use at baseline, but allowed proportions of the population to initiate cigarette or smokeless tobacco use at user-defined, age-specific rates. In our analysis, follow-up started at age 13, the youngest age at which a non-negligible proportion of tobacco users initiates use, and ended at age 72. The width of each age category was five years. To allow for validation of the model results against current mortality data accounting for adequate disease induction time, we based age category-specific smoking initiation rates on the 1980 National Household Survey on Drug Abuse (Office of Applied Studies, 1999). Age category-specific smoking cessation rates for 1980 were based on data from The California Tobacco Control Program's effect on adult smokers: (1) Smoking cessation (Messer K et al., 2007). More recent data could be used to model prospective future population health effects, if desired. For smoking initiation, we used 11.25%, 10%, 1.25% and 0.25% for age categories 13-17, 18-22, 23-27and 28- 32 years, respectively, and 0 for older age categories. For smoking cessation, we used 2.5% for age 13-17, 4.5 for the next 3 age categories, 5.0 for category 33-37 years, 5.5 for categories 38-42 and 43-47 years, 7.5% for category 48-52 years and 8.5% for the remaining 4 age categories. Mejia et al. used tobacco use patterns reported by 145 7th and 9th grade boys to estimate the transition probabilities for the whole population following the use of a smokeless product. Therefore, we also used the transition probabilities reported for the 7th and 9th grade boys for all ages in our model. Our model uses age-, years of smoking- and years of quitting-specific mortality rates based on the coefficients from a Poisson model estimated using data for men from the Kaiser Permanente Cohort study (Friedman, Tekawa, et al. 1997). The ratio of excess risks for current smokeless tobacco users versus smokers (0.08) was based on a consensus estimate reported by Levy et al. (Levy, Mumford, et al. 2004), and the ratio of excess risks for former smokeless product users versus smokers was set to 0.05. While Mejia et al. combined men and women in their analysis, we restricted our analysis to men because tobacco use patterns vary considerably between genders (see paragraph two of "Limitations", page 303 in Mejia et al. and reference numbers 5, 6, 12, 22, 29, 30, 31, and 36 from Mejia et al.).

Using data that replicated, as closely as possible, the flawed input and transition probabilities used by Mejia et al. to define a "worst-case" scenario of aggressive smokeless tobacco promotion, we, like them, observed statistically non-significant net harm. That is, there were more deaths estimated at the end of follow-up under the test scenario compared to the base-case, but the difference was not statistically significant.

We then made a slight change in the transition probabilities, such that the probabilities for transitions from smokeless tobacco use reported by Severson et al. for 7th and 9th grade boys were applied only to the youngest two age categories (13-<18 and 18-<23 years). For all other age groups, we used the transition probabilities reported by Lundqvist et al. or by Zhu et al. This change resulted in statistically significant net benefit , i.e., there were fewer deaths estimated at the end of follow-up under the test scenario compared to the base-case. Thus, running the model with only slightly more realistic input produced statistically significant estimates that suggested a benefit of aggressive smokeless tobacco promotion, rather than harm, at the population level.

As described above, the model used by Mejia et al. incorporated a very limited number of possible transitions between exposure states. Therefore, we wanted to determine the effect of using the flawed transition probabilities suggested by Mejia et al., but allowing all possible transitions in our model. For transitions not modeled by Mejia et al., we assumed that transition probabilities for "no change in tobacco use" were 95%, while transition probabilities for "changes in tobacco use" were 5%; when more than one type of change was possible, the transition probability of 5% was divided between them. For example, the probability of remaining a cigarette smoker (no change) after several previous changes in tobacco use was set to 95% while the probability of switching back to a smokeless product and the probability of quitting were set to 2.5% each. We repeated the analysis allowing a 25% probability for "change in tobacco use" while the transition probabilities for "no changes" were 75%. Allowing for a small degree (5%) of recidivism and switching from one to the other product after previous changes in tobacco use (while using Mejia et al.'s input, to the extent possible, for transitions considered in their model), we observed a net benefit (i.e., a reduction in mortality) at the population level. The benefit was statistically significant, based on the 95% posterior intervals, even when the transition probabilities for the 7th and 9th grade boys were applied to all ages. Allowing for a greater degree (25%) of recidivism and switching from one to the other product resulted in an even more pronounced, statistically significant, population benefit.

CONCLUSIONS

The model proposed by Mejia et al. model is overly simplistic in its use of only a limited number of exposure states and transitions: 56% of the starting population, identified as non-tobacco users at baseline, are not allowed to become tobacco users; no one who quits tobacco use is allowed to revert to a tobacco use state; the model uses the same initiation, cessation and transition rates for the whole hypothetical population, regardless of age or gender; and, the risk of tobacco related health outcomes "measured" by the health index is assumed to be the same regardless of duration of tobacco use or cessation.

The sources used by Mejia et al. (2010) to define the initial exposure distribution and the transition probabilities are difficult to justify. The authors mixed estimates for adult men and women, drawn from a nationally representative sample of current and former smokers, and for 145 7th and 9th grade boys who attended secondary school in one of a few towns in Oregon. The transition probabilities used by Mejia et al. incorrectly implied that smokeless tobacco users were very unlikely to quit (a beneficial transition) and very likely to switch to smoking or to initiate dual use (harmful transitions) while smokers were very likely to quit or to switch to smokeless tobacco (beneficial transitions) and unlikely to initiate dual use (a harmful transition).

The health index is of questionable validity, and does not seem to be based on empirical data. The data purportedly used to justify the values assigned to the health index comprised a mix of diseases and causes of death, measures of effect (incidence and prevalence), and exposures (product types). Furthermore, the Mejia et al. model assumes that risks associated with each type of tobacco product are the same for all users, i.e., the risk of experiencing a tobacco-related health outcome "measured" by the health index is assumed to be the same for males, females, all ages, and any duration of use or former use of tobacco. The results reported by Mejia et al. did not indicate statistically significant differences between exposure groups, yet the authors interpreted the results as showing no benefit of smokeless tobacco. An objective interpretation of their results is that the model provides no evidence for either benefit or harm to the population associated with increased promotion of smokeless tobacco use.

Due to the significant shortcomings of the methods employed by Mejia et al., their conclusion that "promoting smokeless tobacco as a safer alternative to cigarettes is unlikely to result in substantial health benefits at a population level" does not follow from the results. Small changes to Mejia et al.'s model input or assumptions led to the opposite conclusion. Because of its flaws, the simulation model proposed by Mejia et al. does not provide information that can be used in evaluating or setting tobacco control policy.

BIBLIOGRAPHY

Bachand AM, Curtin G, et al. 2010. Development of a dynamic simulation model to estimate population mortality effects resulting from the availability of smokeless tobacco products. Ann Epidemiol 20: P70. CDC. 2007. Cigarette smoking among adults--United States, 2006. MMWR Morb Mortal Wkly Rep 56: 1157-1161. Escobedo LG, Peddicord JP. 1997. Long-term trends in cigarette smoking among young U.S. adults. Addict Behav 22: 427-430. Friedman G, Tekawa IS, Sadler M, Sidney S. 1997. Smoking and mortality: the Kaiser Permanente experience. In: Shopland DR, Burns DM, Garfinkel L, Samet J, editors. Changes in Cigarette-Related Disease Risks and Their Implication for Prevention and Control. Rockville, MD: US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute.p 477-499. Gartner CE, Hall WD, et al. 2007. Assessment of Swedish snus for tobacco harm reduction: an epidemiological modelling study. Lancet 369: 2010-2014. Gilpin EA, Pierce JP, et al. 1992. Reasons smokers give for stopping smoking: do they relate to sucess in stopping? Tob Control 1: 256-263. Levy DT, Mumford EA, et al. 2004. The relative risks of a low-nitrosamine smokeless tobacco product compared with smoking cigarettes: estimates of a panel of experts. Cancer Epidemiol Biomarkers Prev 13: 2035-2042. Lundqvist G, Sandstrom H, et al. 2009. Patterns of tobacco use: A 10-year follow-up study of smoking and snus habits in a middle-aged Swedish population. Scandinavian Journal of Public Health 37: 161-167. Mejia AB, Ling PM, et al. 2010. Quantifying the effects of promoting smokeless tobacco as a harm reduction strategy in the USA. Tob Control 19: 297-305. Nelson DE, Mowery P, et al. 2006. Trends in smokeless tobacco use among adults and adolescents in the United States 7. Am J Public Health 96: 897-905. Roth HD, Roth AB, et al. 2005. Health risks of smoking compared to Swedish snus 4. Inhal Toxicol 17: 741-748. Severson HH, Forrester KK, et al. 2007. Use of Smokeless Tobacco is a Risk Factor for Cigarette Smoking. Nicotine Tobacco Research 9: 1331-1337. Tomar SL. 2003. Trends and patterns of tobacco use in the United States 1. Am J Med Sci 326: 248-254. Zhu SH, Wang JB, et al. 2009. Quitting Cigarettes Completely or Switching to Smokeless: Do U.S. Data Replicate the Swedish Results? Tobacco Control 18: 82-87.

Conflict of Interest:

Competing interests: The authors are preparing an alternative tobacco harm reduction model. This work was supported by RJ Reynolds Tobacco Company.

We are mildly flattered that Philip Morris found it worthwhile to have Peter Lee criticize our framework [1] for assessing the likely population effects of aggressive promotion of smokeless tobacco as a harm reduction strategy in the USA. Peter Lee is a longtime tobacco industry consultant who has a history spanning decades criticizing important studies demonstrating the harms of tobacco and secondhand smoke [2], including the landmark Hirayama study [3-5] and publishing papers or letters to the editor contesting the health effects of secondhand smoke on cardiovascular disease [6], cancer [7], SIDS [8] and more recently the health effects of smokeless tobacco [9, 10] and menthol [11]. Lee's role in industry efforts to discredit the Hirayama study has been well documented in the literature [12, 13]. As Lee notes, "one would intuitively expect a substantial benefit if increasing snus promotion led to many smokers switching to snus." The whole point of our analysis was to move beyond "intuition" and make predictions based on data in a way that explicitly accounts for the uncertainty in the data on tobacco use behavior and the associated health costs. The fact that the likely health cost ranges overlap is what leads to the conclusion that, accounting for this uncertainty, the market changes likely to accompany aggressive smokeless promotion would not confer population-level health benefits.

Lee, a statistician, simply ignores the uncertainty associated with the estimates that form the core of the model.

He criticizes the fact that we do not account for the temporal dynamics of changes in tobacco use behavior and the associated risks over time. He is correct that our model is a steady-state, not a dynamic, model. We considered a dynamic model, but doing so conflicted with our fundamental goal of basing the results on data rather than the rhetoric and "intuition" that have characterized the harm reduction debate to date. We were unable to find the data necessary to model the dynamics Lee seeks. It is noteworthy that Lee did not provide citations to the data that one could use to develop the model he desires.

Lee found the justification for the health cost we used for snus as 11 to be "unclear." In our paper, we clearly stated that this estimate came from an expert consensus panel estimate of the health effects, reference 9 in our paper [14]. As we noted in our paper, the estimate that this panel produced is probably low because subsequent research has found higher risks for heart disease, that are larger than those considered in this reference, a case that has only grown stronger as evidence has continued to accumulate [15]. If anything, we are almost certainly underestimating these risks.

Lee questions our assumption of a risk of 90 for dual use. He is correct that there is little data available on dual use (a subject worthy of study). The reason we assumed a modest reduction in risk was that there might be less exposure to cigarette smoke, which could lower cancer risk but would have little effect on heart disease risk because of the highly nonlinear relationship between smoking and heart disease risk, with most effect occurring at low levels of smoking.

Lee criticizes us for including what he sees as unacceptably high levels of dual use (i.e., concurrent use of smokeless tobacco and cigarettes) in our scenarios. (It is important to define "dual use" as use of either product on some days rather than both products on all days. This latter definition does not reflect actual dual use, particularly as the snus products are being promoted for use when one cannot "light up", and substantially underestimates dual use.) The base levels of dual use we used in our model are from surveys of actual use patterns in the USA. The fact that we model large increases in dual use reflects the actual marketing of smokeless products by the tobacco companies, who are promoting snus products as cigarette line extensions, packaging them together, and explicitly promoting dual use in their marketing. Dr. Lee could make a real contribution to the debate if he were to present an analysis based on the market targets that his client, in this case Philip Morris, has established for both Marlboro snus and dual use of Marlboro snus and cigarettes together.

Finally, we were surprised that Dr. Lee did not simply put the health costs he asserts are accurate into the model and present the results to demonstrate that his assertions are correct and supported by actual data. (The full model is available on the Tobacco Control website at http://tobaccocontrol.bmj.com/content/19/4/297/suppl/DC1, something we pointed out to him when he contacted us asking for a copy of the model.) The whole object of this enterprise is to move beyond the "intuitive" arguments Lee presents to making decisions based on quantitative estimates of likely population effects: Lee failed to provide credible estimates demonstrating that smokeless promotion would actually be likely to reduce harm on a population level.

Adrienne Mejia

Pamela M. Ling

Stanton Glantz

University of California, San Francisco San Francisco, CA 94143

REFERENCES

1. Mejia AB, Ling PM, Glantz SA. Quantifying the Effects of Promoting Smokeless Tobacco as a Harm Reduction Strategy in the USA. Tob Control. 2010 Aug;19(4):297-305.

2. Lee PN. Many Claims About Passive Smoking Are Inadequately Justified. BMJ. 1997 Feb 1;314(7077):371.

3. Hirayama T. Non-Smoking Wives of Heavy Smokers Have a Higher Risk of Lung Cancer: A Study from Japan. Br Med J (Clin Res Ed). 1981 Jan 17;282(6259):183-5.

4. Lee PN. "Marriage to a Smoker" May Not Be a Valid Marker of Exposure in Studies Relating Environmental Tobacco Smoke to Risk of Lung Cancer in Japanese Non-Smoking Women. Int Arch Occup Environ Health. 1995;67(5):287-94.

5. Ong E, Glantz SA. Hirayama's Work Has Stood the Test of Time. Bull World Health Organ. 2000;78(7):938-9.

6. Lee PN, Forey BA. Environmental Tobacco Smoke Exposure and Risk of Stroke in Nonsmokers: A Review with Meta-Analysis. J Stroke Cerebrovasc Dis. 2006 Sep-Oct;15(5):190-201.

7. Lee PN, Hamling J. Environmental Tobacco Smoke Exposure and Risk of Breast Cancer in Nonsmoking Women: A Review with Meta-Analyses. Inhal Toxicol. 2006 Dec;18(14):1053-70.

8. Lee PN. Passive Tobacco Exposure and Sudden Infant Death Syndrome. Pediatrics. 1993 Sep;92(3):505-6.

9. Lee PN, Hamling J. Systematic Review of the Relation between Smokeless Tobacco and Cancer in Europe and North America. BMC Med. 2009;7:36.

10. Sponsiello-Wang Z, Weitkunat R, Lee PN. Systematic Review of the Relation between Smokeless Tobacco and Cancer of the Pancreas in Europe and North America. BMC Cancer. 2008;8:356.

11. Werley MS, Coggins CR, Lee PN. Possible Effects on Smokers of Cigarette Mentholation: A Review of the Evidence Relating to Key Research Questions. Regul Toxicol Pharmacol. 2007 Mar;47(2):189-203.

12. Hong MK, Bero LA. How the Tobacco Industry Responded to an Influential Study of the Health Effects of Secondhand Smoke. BMJ. 2002 Dec 14;325(7377):1413-6.

13. Yano E. Japanese Spousal Smoking Study Revisited: How a Tobacco Industry Funded Paper Reached Erroneous Conclusions. Tob Control. 2005 Aug;14(4):227-33; discussion 33-5.

14. Levy DT, Mumford EA, Cummings KM, Gilpin EA, Giovino G, Hyland A, et al. The Relative Risks of a Low-Nitrosamine Smokeless Tobacco Product Compared with Smoking Cigarettes: Estimates of a Panel of Experts. Cancer Epidemiol Biomarkers Prev. 2004 Dec;13(12):2035-42.

15. Piano MR, Benowitz NL, Fitzgerald GA, Corbridge S, Heath J, Hahn E, et al. Impact of Smokeless Tobacco Products on Cardiovascular Disease: Implications for Policy, Prevention, and Treatment: A Policy Statement from the American Heart Association. Circulation. 2010 Oct 12;122(15):1520 -44.

Conflict of Interest:

None declared

INTRODUCTION Mejia et al1 argue that a harm reduction strategy based on promoting snus, the form of smokeless tobacco widely used in Sweden, is unlikely to result in any substantial health benefit to the US population. They divide the population into five tobacco groups (never tobacco users, former tobacco users, current cigarette smokers, current snus users, and current dual users), attaching to each group an estimate of the "tobacco-related health effect" (TRHE). By definition, TRHE is 0 in never smokers and 100 in current cigarette smokers, with other smoking groups having intermediate TRHE values, proportional to their relative excess disease risk. Mejia et al consider various scenarios (e.g. "aggressive smokeless promotion") which result in different predicted distributions by tobacco use, and hence different estimates of the overall average TRHE for the whole US population. For the "base case", with tobacco use distributions as they currently are, this is estimated as 24.2, and under the various scenarios considered the estimates lie between 19.2 and 30.5.

Their conclusion that snus promotion probably provides little health benefit seems surprising. Given the strong evidence that health risks from snus are much less than from smoking, one would intuitively expect a substantial benefit if increasing snus promotion led to many smokers switching to snus. It is useful therefore to look at the methodology used and assumptions made.

FAILURE PROPERLY TO ACCOUNT FOR PATTERNS OF TOBACCO USE

There are some deficiencies in the approach. First, there are clealy more than five relevant tobacco groups. Limiting attention to snus use and cigarette smoking, there are nine main groups, representing each combination of never, former and current use of each product. And within some combinations, there are subgroups by sequence of events. Why, for example, should TRHE be assumed similar in former tobacco users regardless of whether snus or cigarettes were previously used, or similar in current snus users who have or have not previously smoked cigarettes? Other deficiencies include failure to consider age, sex, amount used, and other tobacco products such as pipes or cigars. However, these are minor compared to the failure to account for time in its various guises - time since quit, time since switch, and time used snus or cigarettes. It is unsound to assume TRHE is the same for all former users of tobacco regardless of time quit, or the same for current snus users regardless of previous smoking history. Failure to consider time undermines the validity of the TRHE estimates for the different tobacco groups.

ESTIMATES OF TRHE BY SMOKING GROUP Quitters No justification is given for the TRHE estimate of 5 used by Mejia et al. It seems very low. Relative all-cause mortality rates for current, former and never smokers from the well- known CPS-II study2, indicates former smokers have about 40% of the excess all-cause mortality rate of current smokers, not 5%. The appropriate TRHE would be higher still for short- term quitters. Was the value of 5 intended to relate to long-term quitting?

Snus users The justification for the TRHE estimate of 11 is unclear. It is much too low, if applied to recent switchers from cigarettes, particularly following long-term smoking. However, if intended only to quantify effects of snus, it seems too high. Updates of published meta-analyses for snus use for heart disease3 and cancer4 (details available on request) suggest little or no increased risk, with combined relative risk (95% confidence interval) estimates of 1.01 (0.91-1.12) for ischaemic heart disease, 1.05 (0.95-1.15) for stroke, 0.97 (0.68-1.37) for oropharyngeal cancer, 1.10 (0.92-1.33) for oesophageal cancer, 0.98 (0.82-1.17) for stomach cancer, 1.20 (0.66-2.20) for pancreatic cancer, and 0.71 (0.66-1.76) for lung cancer. Given it is implausible that snus use might increase COPD risk, given the lack of confirmed reports of increased risks for other diseases, and given the much stronger relationships seen with smoking, the excess risk from snus use is probably no more than 2% of that from cigarette smoking and not as great as 11%.

Dual use The estimated TRHE of 90 derived from INTERHEART 5 is not relevant to snus, the smokeless tobacco use reported in that study being predominantly in Asian and African countries. Though data are lacking, one might imagine that if lifetime dual users get about half their required nicotine dose from each source, a TRHE of about 50 might be appropriate. Again, however, this would not apply to those changing from long-term smoking to dual use.

HIGH ESTIMATES OF DUAL USE The proportion of dual users predicted in some of the scenarios of up to about 20% seem implausibly high. Recent Swedish surveys (e.g.6,7 give estimates less than 3%. While adolescents in Sweden often try both products, adults usually only use one. Models based on studies in adolescents that do not take this into account may result in misleading predictions of the tobacco use distribution, especially when the data used8 relate to smokeless tobacco use, not snus.

SNUS AND INITIATION OF SMOKING Some Swedish retrospective studies9,10 claim snus users are less likely to initiate smoking than never tobacco users. While these claims are questionable (failing to adjust for time available to initiate), evidence that few Swedish smokers used snus before they started smoking9,10, and that most dual users started on cigarettes, suggest snus can be at most a minor determinant of smoking.

SNUS AND QUITTING SMOKING In theory snus use might discourage rather than encourage quitting. No published study in Sweden suggests discouragement, but many 9,11-15suggest encouragement. Although these studies have some limitations, concern regarding discouragement seems unjustified.

FURTHER THOUGHTS AND A SIMPLER APPROACH The approach of Mejia et al is complex and does not validly allow assessment of the effect on health of the various scenarios considered.

One problem is that promotion of snus cannot affect the risk resulting from past smoking (particularly so for those who quit before the promotion started), so that inclusion of this risk in the overall TRHE estimates obscures estimation of the effects of the various strategies discussed. It would seem better to compare the decline in risk for the given scenario of snus promotion with that in a comparable scenario where those assumed to switch to snus quit instead.

A second problem is that while their approach is complex, it ignores many factors, such as time quit or switched, age, sex, and quantity used. However, attempting to improve the model to account for these would likely be valueless, given the uncertainties involved.

Also Mejia et al do not define what they call a substantial health benefit. The strategy "aggressive promotion with most new users from smokers" reduces the overall TRHE from 24.2 to 19.2, i.e by about 20%. This seems quite substantial, especially so if it is a relatively short- term effect. Would strategies directly encouraging quitting do better?

To my mind, they have obscured a simple situation. Complete switching to snus seems likely to have a health effect virtually equivalent to quitting, with partial switching (dual use) having an intermediate effect. For smokers unwilling or unable to give up their nicotine, switching to snus is clearly a much better health alternative than continuing smoking. Promoting snus may produce some new tobacco users, but these will have little or no excess risk of disease, and be no more likely to take up smoking than are those who have never used tobacco.

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REFERENCES

1. Mejia AB, Ling PM, Glantz SA. Quantifying the effects of promoting smokeless tobacco as a harm reduction strategy in the USA. Tob Control 2010;19:297-305.

2. US Surgeon General. Reducing the health consequences of smoking. 25 years of progress. A report of the Surgeon General. Rockville, Maryland: US Department of Health and Human Services; Public Health Services; 1989. DHHS Publication No. (CDC) 89-8411. http://www.surgeongeneral.gov/library/reports/index.html

3. Lee PN. Circulatory disease and smokeless tobacco in Western populations: a review of the evidence. Int J Epidemiol 2007;36:789-804.

4. Lee PN, Hamling JS. Systematic review of the relation between smokeless tobacco and cancer in Europe and North America. BMC Med 2009;7:36:

5. Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet 2006;368:647-58.

6. Persson J, Sj?berg I, Johansson S-E. Bruk och missbruk, vanor och ovanor. H?lsorelaterade levnadsvanor 1980-2002 (Health related habits of life 1980-2002). Statistiska centralbyr?n; 2004, (Accessed Oct 2010). (Levnadsf?rh?llanden (Living conditions).) 105. http://www.scb.se/statistik/le/le0101/1980i02/le0101_1980i02_br_le105sa0401.pdf With additional data supplied by E H?gstorp, Statistiska centralbyr?n, 2005.

7. Wadman C. Levnadsvanor - Tobaksvanor. Statens Folkh?lsoinstitut; 2009, (Accessed Oct 2010). http://www.fhi.se/sv/Statistik- uppfoljning/Nationella-folkhalsoenkaten/Levnadsvanor/Tobaksvanor/

8. Severson HH, Forrester KK, Biglan A. Use of smokeless tobacco is a risk factor for cigarette smoking. Nicotine Tob Res 2007;9:1331-7.

9. Furberg H, Bulik CM, Lerman C, Lichtenstein P, Pedersen NL, Sullivan PF. Is Swedish snus associated with smoking initiation or smoking cessation? Tob Control 2005;14:422-4.

10. Ramstr?m LM, Foulds J. Role of snus in initiation and cessation of tobacco smoking in Sweden. Tob Control 2006;15:210-4.

11. Lindstr?m M, Isacsson S-O. Smoking cessation among daily smokers, aged 45-69 years: a longitudinal study in Malm?, Sweden. Addiction 2002;97:205-15.

12. Lundqvist G, Sandstr?m H, ?hman A, Weinehall L. Patterns of tobacco use: a 10-year follow-up study of smoking and snus habits in a middle-aged Swedish population. Scand J Public Health 2009;37:161-7.

13. Rodu B, Stegmayr B, Nasic S, Cole P, Asplund K. Evolving patterns of tobacco use in northern Sweden. J Intern Med 2003;253:660-5.

14. Gilljam H, Galanti MR. Role of snus (oral moist snuff) in smoking cessation and smoking reduction in Sweden. Addiction 2003;98:1183 -9.

15. Ramstr?m L. Is snus a model for harm reduction: the scientific evidence from Sweden. In: The 13th World Conference on Tobacco OR Health: Building capacity for a tobacco-free world, The 13th World Conference on Tobacco OR Health: Building capacity for a tobacco-free world. Washington DC, July 12-15 2006. 2006;

Conflict of Interest:

I am a long-term consultant to the tobacco industry, and this work was supported by Philip Morris

Snus is threatening not only for Sweden also other parts of Europe. We have anecdotal information that UK tourists in Sweden(who are smokers) are trying Snus quite frequently. Therefore, there is a threat of cross-border transmission of Snus addiction. Some of the reports claim that Snus is less injurious to health comparing smoking, but, the evidence shows there is a higher risk for the occurrence of oral cancer (OSCC) and development of Metabolic Syndrome [MS] (MS=Central Obesity, hypertriacylgycerolemia, low HDL cholesterol concentration, elevated BP and fasting glucose concentration). To date, a couple of studies have been published on Quid chewing related metabolic syndrome (1-3). Therefore, we cannot ignore the similar potential consequences of Snus consumption. Again, the claim regarding an antioxidant effect of wet- Snus to prevent cancer is misleading information. Obviously, such information is again misleading for a person who wants to consume Snus, and that needs to be stopped by removing the vested information deliberately quoted by the manufacturers to promote their Snus business in Europe, and probably extending to the other parts of the world. Therefore, any form of the Smokeless Tobacco (SLT) whether it's Indian/Chinese/Taiwanese/Japanese- is a major public health concern today. It needs to be mentioned that in 2010 Japan started marketing a new form of SLT: 'Zerostyle mint' targeting adolescents. And also for the smokers who wants to switch from smoking to 'Zerostyle Mint'- a refillable cartridge (4). It may be incorrect to say that Quid Chewing, Snus consumption or Zerostyle mint will be less injurious than smoking, because it is established that any form of SLT may contribute to the higher risk of oral and oro-pharygeal cancer and Metabolic Syndrome (MS). Therefore, Chewing Quid, Zerostyle Mint or Swedish Snus needs to be properly controlled under the WHO FCTC framework convention (5). We have undertaken an interventional study on Quid/Snus consumption and development of metabolic syndrome especially among the cases suffering from Quid induced oral sub-mucosal fibrosis (OSF)- a cause of high rate of morbidity and mortality in the risk group population. References. 1. Amy Ming-Fang Yen, Yueh-Hsia Chiu et al. A population-based study of the association between betel-quid chewing and the metabolic syndrome in men. Am. J Clin Nutr. 2006; 83:1153-60. 2.Boucher BJ, Mannan N. Metabolic effects of consumption of Areca catechu. Addiction Biol 2002;7: 103-10. 3. Boucher BJ, et al. Betel nut (areca catechu) consumption and induction of glucose intolerance in adults CD 1 mice and in their F1 and F2 offspring. Diabetologica 1994;37: 49-55. 4. JT to Launch New Style of Smokeless Tobacco Product "Zerostyle Mint" http://www.jt.com/investors/media/press_releases/2010/0317_01/index.html 5. WHO Framework Convention on Tobacco Control http://www.who.int/fctc/en/

Link/Contact: Professor Chitta R Choudhury, PhD, MPH, FFDRCS, FRSPH, BDS, DND Lead : OPCL/OSF study team

International Centre for Tropical Oral Health, PHT NHS Dept Max Fac, England & Oral Biology, Genomic Studies, Nitte University, Mangalore, India. President, Institute of Health Promotion & Education (IHPE), UK cr_choudhury@yahoo.co.uk

Conflict of Interest:

None declared

Joel L Nitzkin and Elaine Keller did an excellent job of identifying problems with this study so I shall not endeavor to duplicate their suggestions. Instead I wish to speak as a 43 year, at the end 2 to 3 pack, smoker who used Swedish snus 6 months ago to completely stop smoking.

I attempted smoking cessation for over 30 years using just about every NRT product except Chantix. I tried hypnosis twice, group and individual, and herbal remedies. Nothing worked. I was persuaded by my girlfriend to purchase an electronic cigarette over a year ago. That immediately got me down to a half dozen cigarettes a day plus the ecig. However, I was unable to stop smoking completely.

If it had not been for an electronic cigarette forum, I would never have tried any smokeless tobacco product. I was told decades ago that these were no better than smoking. In addition, the only vision I had of smokeless tobacco was the type that you had to spit the juices which I still would not do. That being said, I'm sure that there are many that would even consider that form of smokeless if they didn't feel it was just as dangerous as smoking.

Even after being directed to Swedish snus, I had serious doubts ingrained from bad science and worse publicity. It wasn't until I started investigating on my own that I realized what most of the 44 million smokers in the US don't know. Smokeless is anywhere between 90 and 99% safer than smoking. I was shocked and angry that I might have quit a quarter century ago if this information was provided by those that were supposedly trying to get people to stop smoking.

In her response, Elaine Keller wrote, "What if the government changed the warning labels to read "THIS PRODUCT IS NOT A 100% SAFE ALTERNATIVE TO SMOKING"? See what a difference one tiny change can make? This would lead folks to ask, "Well if it's not 100% safe, how much safer is it?" "

I shall take her thought one step further. How about a warning 25 years ago that read "THIS PRODUCT IS ONLY 95% SAFER THAN SMOKING", or whatever the right percentage is. Six months ago I had my first portion of Swedish snus. Six months ago I had my last cigarette with absolutely no desire to smoke since. For me, the electronic cigarette is still useful in certain circumstances, but it currently sits mostly unused as about four portions of Swedish snus have replaced cigarette smoking entirely.

Now you produce a modeling study using parameters that draw a conclusion that selling the idea of smokeless won't make a difference in the smoking rate. Had the industry been honest 25 years ago, your study wouldn't have needed to be done. We'd have the answer. My guess is that the number of smokers would have seriously been reduced. Of course that would not have aligned well with the goal of Big Pharma in providing the answer and that makes me angry.

How the industry and the "health" associations could continue to push products that have a success rate only a couple percent better than cold turkey after a year is beyond my comprehension. I know that 25 years less smoking would have improved my odds health wise in the future and that does not make me happy.

My last point is that the only snus mentioned was the American versions that have come out over the last year or so. These are not Swedish snus. I have difficulty even accepting that they can be considered snus. Whether it's nicotine content or the other tobacco alkaloids that are missing, I'm not sure. The product has to be adequate to fulfill the needs of the smoker.

Conflict of Interest:

I hold quite a few shares of Pharmaceutical shares, many with companies that sell NRT products.

In this paper, Mejia et al run a number of Monte Carlo simulations based on a set of totally unrealistic assumptions to reach the conclusion that promoting smokeless tobacco as a safer alternative to cigarettes is unlikely to result in substantial health benefits at a population level. In their analysis, Mejia et al do not consider the potential impact on the current adult smokers who will account for virtually all of the tobacco- related illness and death in the United States over the next 20 years. While recognizing that smokeless tobacco is far less hazardous than cigarettes, they fail to consider the health consciousness of American smokers that have led almost half to light cigarettes in recent decades, and failed to consider the potential impact of honestly informing the American public about the difference in risk posed by smokeless tobacco products, as compared to cigarettes. All of their data on switching rates in the United States is conditioned on the warning on smokeless tobacco products, in place in the USA since 1984, that this product is not a safe alternative to cigarettes. This purposely misleading warning has left over 80% of American smokers with the incorrect impression that smokeless tobacco products present the same risk of tobacco-related illness and death as cigarettes. Elimination of this warning, followed by honest and effective health education could transform American attitudes toward smokeless tobacco, especially among smokers unable or unwilling to quit. I find the following points problematic in the Mejia paper: 1. Harm reduction, by definition, means encouraging current users to use a less toxic product. In this study, Mejia et al do not consider the potential benefits to current smokers. 2. In the scoring of health effects, cigarettes are set at an arbitrary figure of 100. Smokeless tobacco products to be used for harm reduction should be scored at a level of 0.1 to 2.0, not 11 as in this study.1 3. For dual users, the score is arbitrarily set at 90, anticipating very little substitution of the lower risk product for cigarettes. A range of figures between 20 and 50 would have been more reasonable for the Monte Carlo simulations. 4. In their transition models for persons who initiate smoking, their transition rates to smokeless tobacco products, by scenario range from zero to 20.4% (to 30.1% when dual use is considered). All things considered, if the misleading warning is eliminated and effective health education follows, a range of 20% to 50% would be more reasonable; up to 80% if dual use is considered. Given all of these factors, the Tobacco Control Task Force of the American Association of Public Health Physicians (AAPHP), after an extensive literature review and policy analysis1 concluded the following: 1. The possibility now exists to save the lives of 4 million of the 8 million current adult American smokers who will otherwise die of a tobacco -related illness over the next 20 years (400,000 per year times 20 years). The harm reduction policy based on encouraging smokers to switch to selected low risk smokeless tobacco products should also eliminate the vast majority of the 40,000 deaths per year attributed to environmental tobacco smoke. Such a policy is likely to result in a situation 20 years from now in which tobacco-related deaths, now in excess of 440,000 per year will be less than 40,000 per year in the United States, with most of the remaining deaths among persons who still chose to continue smoking conventional cigarettes. 2. The only feasible way to achieve this public health benefit will be to honestly inform current smokers who are unable or unwilling to quit that they could cut their risk of tobacco-related illness and death by 98% or better by switching to one of a number of very-low-risk smokeless tobacco products or E-cigarettes. Such an approach constitutes a harm reduction policy based on commercially available smokeless tobacco and other non- pharmaceutical nicotine delivery products. 3. The impact such a harm reduction policy would have on the numbers of teens initiating tobacco use would depend on how the policy is implemented. FDA regulation of marketing of tobacco products under the new law, in collaboration with public health educational programming by FDA and others, should make it possible to implement the harm reduction policy as recommended above without increasing, and possibly while decreasing, the numbers of teens initiating tobacco use. 4. The currently available science gives us very good reason to believe on a basis of far more likely than not, that such a harm reduction initiative will achieve the desired public health benefits among smokers. 5. The studies needed to definitively prove such benefits are impossible to conduct by any means other than implementing the policy and carefully tracking booth process and outcomes. Requiring such proof in advance is both scientifically untenable and will predictably result in such a policy never being implemented. 6. The best that can be hoped from current FDA and other federal agency tobacco control policies is very small changes in annual tobacco-related death rates and very small reductions in teen smoking rates.

Reference 1. Nitzkin JL, Rodu B. AAPHP Resolution and White Paper: The Case for Harm Reduction for Control of Tobacco-related Illness and Death [http://www.aaphp.org/special/joelstobac/20081026HarmReductionResolutionAsPassed1.pdf] . In: AAPHP Tobacco Issues, 26/October, 2008. 3Aug2010.

Conflict of Interest:

None declared

How might those estimates change if we all told smokers the truth?

What if the government changed the warning labels to read "THIS PRODUCT IS NOT A 100% SAFE ALTERNATIVE TO SMOKING"? See what a difference one tiny change can make? This would lead folks to ask, "Well if it's not 100% safe, how much safer is it?"

The way the message is worded now, 85% of the people who read it conclude it means that smokeless tobacco products cause just as much disease and premature deaths as smoking. [1] We know it isn't true. But smokers don't know that.

And then what if the American Cancer Society, American Heart Association, American Lung Association, American Medical Society, and the Centers for Disease Control and Prevention informed smokers that their excess risk of lung disease would be totally eliminated if they switched from smoking to smokeless? What if they provided comparisons between smoking and smokeless of the odds of developing various types cancers, having a heart attack or a stroke?

We know that users of smokeless tobacco products have a lower mortality rate from all these diseases than continuing smokers. [2,3] We know that for most diseases, the Swedish snus user's mortality risks are reduced to the level of those who gave up all use of tobacco. [4] We know all that. But the smokers do not know that.

Most smokers do not read medical journals. They rely on the popular press and information provided by respected organizations that claim to have public health as a mission.

Curiously, most physicians are just as misinformed as their smoking patients. What if the doctors were to learn that their patients could reduce their risk of developing a smoking-related disease by 90 to 99% if they switch completely to a smokeless form of tobacco? Might not more smokers give snus a try if their own doctor told them it was safer than smoking?

What if the FDA required the tobacco companies to develop and conduct advertising campaigns aimed at convincing smokers to switch to smokeless products?

What if we did all these things? What effect would that have on the number of U.S. smokers who switch and consequently on the smoking-related morbidity and mortality rates? Factor in truth-telling and run those Monte Carlo simulations again.

References:

[1] Phillips, C.V. et al. You might as well smoke; the misleading and harmful public message about smokeless tobacco. BMC Public Health 2005, 5:31doi:10.1186/1471-2458-5-31.

[2] Accortt, N.A., et al. Chronic Disease Mortality in a Cohort of Smokeless Tobacco Users. American Journal of Epidemiology 2002; 156:730- 737

[3] Roth, H.D. et al. Health Risks of Smoking Compared to Swedish Snus. Inhalation Toxicology, 17:741-748, 2005.

[4] Gartner C.E, et al., Assessment of Swedish snus for tobacco harm reduction: an epidemiological modeling study. Lancet. 2007 Jun 16;369(9578):2010-4

Conflict of Interest:

None declared

Glantz et al conclude that "Promoting smokeless tobacco as a safer alternative to cigarettes is unlikely to result in substantial health benefits at a population level."

Obviously Glantz is not up to speed on Sweden. It has the lowest incidence of lung cancer in the developed world because so many smokers have switched to snus.

"Results: There were 172,000 lung cancer deaths among men in the EU in 2002. If all EU countries had the LCMR of men in Sweden, there would have been 92,000 (54%) fewer deaths." In conclusion it further adds "This study shows that snus use has had a profound effect on smoking prevalence and LCMRs among Swedish men. While it cannot be proven that snus would have the same effect in other EU countries, the potential reduction in smoking-attributable deaths is considerable. " This study says "the health risks associated with snus are lower than those associated with smoking. Specifically, this is true for lung cancer (based on one study), for oral cancer (based on one study), for gastric cancer (based on one study), for cardiovascular disease (based on three of four studies), and for all-cause mortality (based on one study)."

The consequences in Sweden are that in the UK LC is running at 64.7 persons per 100,000 and in Sweden it is 30, with 50% of Swedish men switching to snus. Ergo half the LC. My provenance is indeed the anti smoking Cancer Research.

The concusions of your paper are wrong.

http://www.ncbi.nlm.nih.gov/pubmed/16195209

http://no-smoking.org/dec03/12-26-03-2.html

http://sjp.sagepub.com/cgi/content/short/37/5/481

http://info.cancerresearchuk.org/cancerstats/types/lung/incidence/

Conflict of Interest:

None, I do not get a penny from tobacco or pharmaceutical companies.