Household Surveys in the General Population and Web-Based Surveys in IQOS Users Registered at the Philip Morris International IQOS User Database: Protocols on the Use of Tobacco- and Nicotine-Containing Products in Germany, Italy, and the United Kingdom (Greater London), 2018-2020.

BACKGROUND: Philip Morris International (PMI) has developed a novel heat-not-burn tobacco product, Tobacco Heating System (THS), which is marketed under the brand name of IQOS with HEETS (IQOS). The aerosol generated by THS has substantially fewer toxicants than combustible cigarette smoke, although the extent of the reduction of harmful and potentially harmful constituents reported varies between studies. To evaluate the potential harm reduction associated with IQOS use, the assessment of the uptake and continued use of IQOS in the context of all other tobacco- and nicotine-containing products is crucial. In March 2018, PMI launched cross-sectional surveys in Germany, Italy, and the United Kingdom (Greater London) to estimate the prevalence and use patterns of IQOS and other tobacco- and nicotine-containing products use in these 3 markets following the commercialization of IQOS. This study describes the protocol of the surveys. OBJECTIVE: The objectives of these surveys are to estimate the prevalence of tobacco- and nicotine-containing products use; describe past and current patterns of use; and explore their associations with self-reported health, motivation to use, risk perceptions, and perceived aesthetic changes. METHODS: The overall design of the surveys is similar in all 3 countries. Repeated cross-sectional surveys are being conducted annually over 3 consecutive years (2018 to 2020) and in 2 samples: a representative sample of the general population and a sample of IQOS users. A total of 6085 adults per year will be selected from the general population for each survey through multistage stratified sampling, and participants will respond to face-to-face computer-assisted personal interviews. In addition, 1404, 1384, and 1246 IQOS users per year in Germany, Italy, and Greater London, respectively, will be randomly selected from the PMI IQOS user database and will be invited to complete the Web-based survey using computer-assisted self-interviews. The Smoking Questionnaire is used to assess the tobacco use patterns of the participants. RESULTS: The recruitment of the general population sample began in March 2018 and that of the IQOS user sample began in April 2018. The data collection is ongoing, and the results of the first year data analysis are expected to be available by June 2019. CONCLUSIONS: As the design of the 3 surveys is similar, the results will allow for cross-countries comparison of the prevalence of IQOS and other tobacco- and nicotine-containing products use as well as patterns of use and associated factors. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12061.

Modeling the Population Health Impact of Introducing a Modified Risk Tobacco Product into the U.S. Market.

Philip Morris International (PMI) has developed the Population Health Impact Model (PHIM) to quantify, in the absence of epidemiological data, the effects of marketing a candidate modified risk tobacco product (cMRTP) on the public health of a whole population. Various simulations were performed to understand the harm reduction impact on the U.S. population over a 20-year period under various scenarios. The overall reduction in smoking attributable deaths (SAD) over the 20-year period was estimated as 934,947 if smoking completely went away and between 516,944 and 780,433 if cMRTP use completely replaces smoking. The reduction in SADs was estimated as 172,458 for the World Health Organization (WHO) 2025 Target and between 70,274 and 90,155 for the gradual cMRTP uptake. Combining the scenarios (WHO 2025 Target and cMRTP uptake), the reductions were between 256,453 and 268,796, depending on the cMRTP relative exposure. These results show how a cMRTP can reduce overall population harm additionally to existing tobacco control efforts.

Quantifying the risk-reduction potential of new Modified Risk Tobacco Products.

Quantitative risk assessment of novel Modified Risk Tobacco Products (MRTP) must rest on indirect measurements that are indicative of disease development prior to epidemiological data becoming available. For this purpose, a Population Health Impact Model (PHIM) has been developed to estimate the reduction in the number of deaths from smoking-related diseases following the introduction of an MRTP. One key parameter of the model, the F-factor, describes the effective dose upon switching from cigarette smoking to using an MRTP. Biomarker data, collected in clinical studies, can be analyzed to estimate the effects of switching to an MRTP as compared to quitting smoking. Based on transparent assumptions, a link function is formulated that translates these effects into the F-factor. The concepts of 'lack of sufficiency' and 'necessity' are introduced, allowing for a parametrization of a family of link functions. These can be uniformly sampled, thus providing different 'scenarios' on how biomarker-based evidence can be translated into the F-factor to inform the PHIM.

Estimating the effect of differing assumptions on the population health impact of introducing a Reduced Risk Tobacco Product in the USA.

We use Population Health Impact Modelling to assess effects on tobacco prevalence and mortality of introducing a Reduced Risk Tobacco Product (RRP). Simulated samples start in 1990 with a US-representative smoking prevalence. Individual tobacco histories are updated annually until 2010 using estimated probabilities of switching between never/current/former smoking where the RRP is not introduced, with current users subdivided into cigarette/RRP/dual users where it is. RRP-related mortality reductions from lung cancer, IHD, stroke and COPD are derived from the histories and the assumed relative risks of the RRP. A basic analysis assumes a hypothetical RRP reduces effective dose 80% in users and 40% in dual users, with an uptake rate generating ∼10% RRP and ∼6% dual users among current users after 10 years. Sensitivity study changes in tobacco prevalence and mortality from varying effective doses, current smoking risks, quitting half-lives and rates of initiation, switching, re-initiation and cessation. They also study extreme situations (e.g. everyone using RRP), and investigate assumptions which might eliminate the RRP-related mortality reduction. The mortality reduction is proportional to the dose reduction, increasing rapidly with time of follow-up. Plausible increases in re-initiation or dual users' consumption, or decreased quitting by smokers would not eliminate the drop.

A novel approach to assess the population health impact of introducing a Modified Risk Tobacco Product.

Based on the Food and Drug Administration's Modified Risk Tobacco Product (MRTP) Application draft guideline, Philip Morris International (PMI) has developed a Population Health Impact Model to estimate the reduction in the number of deaths over a period following the introduction of an MRTP. Such a model is necessary to assess the effect that its introduction would have on population health, given the lack of epidemiological data available prior to marketing authorization on any risks from MRTPs. The model is based on publicly available data on smoking prevalence and on the relationships between smoking-related disease-specific mortality and various aspects of the smoking of conventional cigarettes (CCs), together with an estimate of exposure from the MRTP relative to that from CCs, and allows the exploration of possible scenarios regarding the effect of MRTP introduction on the prevalence of CC and MRTP use, individually and in combination. By comparing mortality attributable in a scenario where the MRTP is introduced with one where it is not, the model can estimate the mortality attributable to CCs and the MRTP, as well as the reduction in the deaths attributable to the introduction of the MRTP.

Systematic review of the relation between smokeless tobacco and cancer of the pancreas in Europe and North America.

BACKGROUND: Recent reviews claiming smokeless tobacco increases pancreatic cancer risk appear not to have considered all available epidemiological evidence; nor were meta-analyses included. We present a systematic review of studies from North America and Europe, since data are lacking from other continents. Risk is also difficult to quantify elsewhere due to the various products, compositions and usage practices involved. METHODS: Epidemiological studies were identified that related pancreatic cancer to use of snuff, chewing tobacco or unspecified smokeless tobacco. Study details and effect estimates (relative risks or odds ratios) were extracted, and combined by meta-analyses. RESULTS: Nine North American and two Scandinavian studies were identified. Reporting was limited in four studies, so only seven were included in meta-analyses, some providing results for never smokers, some for the overall population of smokers and non-smokers, and some for both. Giving preference to study-specific estimates for the overall population, if available, and for never smokers otherwise, the random-effects estimate for ever smokeless tobacco use was 1.03 (95% confidence interval 0.71-1.49) based on heterogeneous estimates from seven studies. The estimate varied little by continent, study type, or type of smokeless tobacco. Giving preference to estimates for never smokers, if available, and overall population estimates otherwise, the estimate was 1.14 (0.67-1.93), again based on heterogeneous estimates. Estimates varied (p = 0.014) between cohort studies (1.75, 1.20-2.54) and case-control studies (0.84, 0.36-1.97). The value for cohort studies derived mainly from one study, which reported an increase for never smokers (2.0, 1.2-3.3), but not overall (0.9, 0.7-1.2). This study also contributed to increases seen for snuff use and for European studies, significant only in fixed-effect analyses. The studies have various weaknesses, including few exposed cases, reliance in cohort studies on exposure recorded at baseline, poor control groups in some case-control studies, and lack of a dose-response. Publication bias, with some negative studies not being presented, is also possible. CONCLUSION: At most, the data suggest a possible effect of smokeless tobacco on pancreatic cancer risk. More evidence is needed. If any risk exists, it is highly likely to be less than that from smoking.

Occupational acrylonitrile exposure and lung cancer: a meta-analysis.

The present work summarizes the currently available published studies on lung cancer and occupational acrylonitrile exposure. Meta-analytic methods were used to estimate the overall risk. To adjust for the healthy worker effect, rate ratio estimates based on regression analyses and ratios of standard mortality ratios were aggregated. Overall effect estimates were 0.95 (95% CI 0.86 to 1.06) and 1.25 (95% CI 1.10 to 1.43) before and after adjustment for the healthy worker effect, respectively. Therefore, a 25% increase in lung cancer risk attributable to occupational acrylonitrile exposure is suggested. Possible contribution of smoking confounding the increased risk cannot be fully excluded.