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PLOS ONE logoLink to PLOS ONE
. 2020 Aug 28;15(8):e0237967. doi: 10.1371/journal.pone.0237967

Health burden and economic costs of smoking in Chile: The potential impact of increasing cigarettes prices

Marianela Castillo-Riquelme 1,*,#, Ariel Bardach 2,3,#, Alfredo Palacios 2, Andrés Pichón-Riviere 2,3,4,#
Editor: Stanton A Glantz5
PMCID: PMC7454964  PMID: 32857819

Abstract

Background

Globally, tobacco consumption continues to cause a huge burden of preventable diseases. Chile has been leading the tobacco burden ranking in the Latin American region for the last ten years; it has currently a 33. 3% prevalence of current smokers.

Methods

A microsimulation economic model was developed within the framework of a multi-country project in order to estimate the burden attributable to smoking in terms of morbidity, mortality, disability-adjusted life-years (DALYs), and direct costs of care. We also modelled the impact of increasing cigarettes’ taxes on this burden.

Results

In Chile, 16,472 deaths were attributable to smoking in 2017, which represent around 16% of all deaths. This burden corresponds to 416,445 DALYs per year. The country’s health system spends 1.15 trillion pesos annually (in Dec 2017 CLP, approx. U$D 1.8 billion) in health care treatment of illnesses caused by smoking. If the price of tobacco cigarettes was to be raised by 50%, around 13,665 deaths and 360,476 DALYs from smoking-attributable diseases would be averted in 10 years, with subsequent savings on health care costs, and increased tax revenue collection. In Chile, the tobacco tax collection does not fully cover the direct healthcare costs attributed to smoking.

Conclusion

Despite a reduction observed on smoking prevalence between 2010 (40.6%) and 2017 (33.3%), this study shows that the burden of disease, and the economic toll due to smoking, remain high. As we demonstrate, a rise in the price of cigarettes could lead to a significant reduction of this burden, averting deaths and disability, and reducing healthcare spending.

Introduction

In 2017, 7.1 million deaths and 182 million disability-adjusted life-years (DALYs) were attributed globally to tobacco [1]. Well above the global average of 25% prevalence for current smoking, Chile continues leading with the highest prevalence of smoking in Latin America, at 33.3% in 2017 (38% in men and 29% in women) [2]. Prevalence is high despite the reduction observed in the 2017 National Health Survey (NHS) in comparison to the 2010 and the 2003 NHS. In the latter, adult prevalence peaked at 43.5%. Likewise, according to the Global Youth Tobacco Survey (GYTS)–in which Chile was included for the first time in 2000 –the country has continued to show high rates of adolescent smoking, with an important feminization phenomenon where adolescent female consumption is higher than consumption in adolescent males [3].

Chile initiated a public policy against tobacco consumption with the subscription to the 2003 World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) [4], which was ratified by the country in 2005. In 2008, the Chilean Ministry of Health (MoH) estimated through its Burden of Disease study [5] that one out of eleven deaths were directly attributable to smoking. In addition, they reported 61,093 DALYs: 37,976 due to disability and 23,117 due to premature death [5]. In 2010, a cost-effectiveness study, also mandated by the MoH [6], reported that smoking-cessation interventions (e.g. individual/group counseling, and nicotine replacement therapy), were very cost-effective, with an incremental cost-effectiveness ratio (ICER) of less than one Gross Domestic Product (GDP) per capita per DALY avoided. However, there was considerable uncertainty associated with the effectiveness data available at that time.

The legislative road map in the fight against tobacco began in Chile in 2006 with amendments [7] to National Law 19,419 [8], which regulates tobacco-related activities. The first modifications to the law aimed at gradually implementing smoke-free areas and banning advertising. Since 2013, through Law 20,660 [9], advertising tobacco products is totally prohibited, as well as smoking in enclosed spaces. The structure of cigarette taxes was also modified, by increasing the specific component of the excise tax. These changes also led to the prohibition of the promotion and sponsorship of tobacco, both directly and indirectly.

According to the MPOWER strategy promoted by WHO in the context of the FCTC, Chile has progressed favorably in four out of the five areas of action that this policy package defines, lagging behind only in the action involving “offering help to quit tobacco use” [10]. Regarding taxation, in 2016 taxes accounted for more than 75% of the final price of the most sold cigarette pack [3, 11], reaching 82.5% in 2019 [10]. According to WHO, since 2017 Chile stands out as one of the 33 countries to fulfill the taxes prerogative [12]. However, the final price of a cigarette packet (around $4 US dollars) remains affordable for most Chileans and, therefore, there is still room for higher price increases with a double potential impact of curtailing demand and increasing tax collection. There is recent national evidence that household tobacco expenditure displaces disposable income for health care as well as for education [13]. Therefore, efforts to reduce tobacco consumption should also encompass treatment for highly dependent individuals. In this regard, several Pan American Health Organization (PAHO) and WHO reports [3, 10, 12] highlight that treatment of smoking dependence in primary health care, community services or hospitals, is not yet available in Chile. Although in some private practices smoking cessation therapies are prescribed, these are not covered or reimbursed by the health care system.

Increasing tobacco taxes has been considered the most effective way to reduce consumption [14, 15]. Higher tobacco taxes raise the price of a cigarette pack, prompting individuals to reducing its demand in line with the “price elasticity”. A national study on price-elasticity revealed a value of -0.45, implying that a 10% price increase in a pack of cigarettes would lead to a 4.5% decline in the demand [16]. Chile has a mixed tobacco tax structure, with a fix 30% ad valorem tax and a specific tax of 0.0010304240 unidades tributarias mensuales (UTM) per unit of cigarette in the package (approx. U$D 0.07). UTM is a unit of account used in Chile for tax and fines purposes, updated monthly according to inflation. In Chile the value added tax (VAT) is 19%, which is estimated on top of manufacturing costs plus specific taxes. The relative importance of these taxes changed in 2013, when the specific tax suffered an increase in relation to the ad valorem tax. However, to date there is not a minimum price policy, and price dispersion (that is, cheapest brand price divided by premium brand price × 100) reaches 58%, which is low, and thus provides opportunities for brand substitution [10]. Therefore, although modifications to the tax regimen had an impact on increasing the final price of the cigarettes pack, they seem insufficient, and further price increases should make cigarettes less affordable in Chile. Tax increases should target the specific tax component, which does not depend on the manufacturing cost, thus limiting the tactics manufacturers employ to reduce the production costs in order to minimize the tax burden.

The extent to which current control policies for tobacco control in Chile have been paying off, as well as the potential to deepen implementation, are important questions for policymaking. The present study is part of a collaborative research coordinated by the Department of Evaluation of Health Technologies and Health Economics of the Institute of Clinical and Healthcare Effectiveness (IECS) of Argentina. A team of more than 40 researchers and health decision makers from universities, research centers, and public institutions in Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Honduras, Mexico, Paraguay, Peru, and Uruguay conducted the broader project.

Aggregated results are available for the region [17], as well as for some specific countries such as Argentina [18], Perú [19], Paraguay [20], and Brazil [21]. For Chile, this initiative represents the first attempt to quantify the economic cost of smoking-attributable diseases using country-specific data. The application of the model to the Chilean population was first published in 2014 as grey literature [22], where data corresponded mostly to the year 2010. Here, we present an updated analysis based on the most recent information regarding smoking prevalence [2], tobacco-related mortality (for 2016), and population structure from the 2017 census [23]. However, we refer to the previous results for comparison purposes, when this seems relevant from a policy-evaluation perspective.

In this paper, our objective is twofold: to report the tobacco-related burden on disease, mortality and direct medical costs for Chile, and to estimate the health and financial impact of different levels of cigarettes price increase through increasing tobacco excise taxation.

Methods

Model development

A mathematical model was used to estimate the probabilities of people becoming ill or dying for each of the conditions associated with smoking. The detailed description of the model, as well as its calibration process, can be found in another study [24]. The model, programmed in Excel (Microsoft® Office Excel Professional Edition 2003) with Macros in Visual Basic (Microsoft Visual Basic® 6.3), corresponds to a first order Monte Carlo simulation, which carries out the analysis of a hypothetical cohort, along a discrete time period.

This model uses a prevalence-based approach to simulate a static cohort for one year. However, to estimate disease incidence, quality of life, health outcomes and healthcare costs for each sex and age strata in Chile for smokers, ex-smokers and never smokers we used the microsimulation model. In this way, we obtain aggregated population health outcomes and direct healthcare costs. In this cross-sectional approach all individuals by age and sex are considered, and smoking-related events are estimated through specific disease equations, which incorporate epidemiological and demographic data derived from the evidence and national healthcare statistics.

The health conditions analyzed were: coronary and non-coronary heart disease; cerebrovascular disease; chronic obstructive pulmonary disease (COPD); pneumonia; lung, mouth, larynx, pharynx, esophagus, stomach, pancreas, kidney, bladder and cervix cancer; and leukemia.

The model allows cohort follow-up according to age and sex, based on the annual risk of occurrence of the events and according to whether individuals are smokers, never-smokers or ex-smokers. We considered a cohort of people of 35 years of age and older living in Chile in 2017. We used probabilities that reflect the risk of occurrence of acute and chronic events based on the relative risks (RR) of never-smokers (baseline incidence) against those of smoking status. Risk of death was defined according to the events and conditions that individuals suffered, including general mortality (by sex and age). Finally, using previously determined parameters of quality of life and unit costs, we estimated the costs and quality-adjusted life-years (QALYs) for the overall survival time of the cohort.

The study used the DALY approach to decompose years of life lost due to premature mortality (YLL) and years lost due to disability (YLD). However, DALYs were not age-weighted, and for the base-case scenario values, they were not discounted either.

To estimate YLD, we used utility values identified through an extensive literature searching, where disability weights equal 1 –utility, while YLL were derived from Chilean life tables.

An analysis of the differences in events, deaths, and associated costs was conducted, in order to quantify the smoking-attributable disease burden. We did this initially by simulating a hypothetical Chilean cohort without smokers or ex-smokers, and then by running a cohort to which the prevalence of smokers and ex-smokers were incorporated. The evaluation platform allows for the simulation of the effect of different strategies aimed at preventing and controlling tobacco consumption, such as increasing cigarette taxes. The model was validated and used to estimate the burden of disease attributable to smoking and the potential impact of different interventions [1721, 25].

We explored three scenarios for price increase assuming policies for cigarette tax increase that resulted in generating 25%, 50% and 75% total price increase. The effect of these price increases on the prevalence of smoking was calculated as:

Prevalence=PrevB+(Ed*ΔP*Iρ*PrevB)

Where PrevB is the baseline prevalence of smoking before price increase; Ed is the price elasticity of demand (-0.45); ΔP is the per cent price variation for each scenario (25%, 50% or 75%); and Ip is the proportion of the variation on cigarette consumption expected to impact on smoking prevalence. Ip was assumed to range from 0.11 for a 25% price increase to a maximum of 0.34 for a 75% price increase. The reduction in prevalence assumedly affects all ages and to both sexes proportionally. The model assumes that smokers who quit become ex-smokers in the first two scenarios, while only in the third scenario do some ex-smokers adopt a risk similar to that of never-smokers.

Data sources

Regarding epidemiological data, local sources of good quality were the first choice; when not available, we used international sources as a second option provided we could consider them ‘transferable’. Thirdly, if none of the previous options were available, an estimate was derived based on the best available data for the country. The probability of acute events, the incidence of chronic diseases and its progression, as well as mortality rates associated with the conditions analyzed for each age and sex group, were drawn mainly by combining estimations from the Global Burden of Cancer (Globocan) for Chile, and MoH’s Department Statistics and Information on Health (DEIS). For COPD and some types of cancer, corrections were made for under-registration of cases and deaths. Taking into consideration ill-defined deaths, projections were modelled with the best estimates, but these were contrasted with the national registry for stroke and acute myocardial infarction (AMI). Epidemiological parameters for lung cancer were calibrated through a Markov model considering country-specific data on diagnosis and survival.

Since the model does not assess the consequences of passive smoking directly, the estimate of deaths, years of life lost, and costs associated with passive smoking was incorporated using approximations made in studies from the US, which can be considered conservative, since the US has been implementing smoking regulation long before Chile. Indeed, an additional burden of 13.6% in men and 12% in women over direct estimations was applied, based on studies of the U.S. Department of Health and Human Services [26]. Table 1 shows an overview of the main input parameters and its sources, grouped by type.

Table 1. Overview of main sources for model input parameters, by type.

Parameter type Description Source Ref
Demographics • Population structure: adults 35–100 years of age • Chile 2017 Census [23]
Epidemiology • Smoking prevalence (by sex and age group) • 2016–2017 National Health Survey [2]
Epidemiology • Mortality due to acute and chronic conditions (by sex and age group) • 2016 Deaths registry (DEIS) Health statistics—Ministry of Health [28]
• p>Globocan [22]
Epidemiology • Incidence, prevalence, and hospital care of acute and chronic conditions • Systematic Review [27]
• Health statistics—Ministry of Health [28]
• Use of specific equations • Globocan [22]
Epidemiology • Relative risks of mortality for smokers, ex-smokers, and never-smokers • Cancer prevention study II. U.S. Department of Health and Human Services [26]
Epidemiology • Passive smoking • Cancer prevention study II. U.S. Department of Health and Human Services [26]
Economics • Treatment costs for annual and acute events of conditions • AUGE Study of verification of the mean individual cost per beneficiary [29]
• Empirical study of costs in the public sector by FONASA [30]
• Delphi exercise with clinical experts done in Argentina [18]
• Chilean cost-effectiveness study [6]
Utilities • Several international sources reporting utilities in a 0–1 scale for the construction of QALYs • Systematic evaluation of various international sources for each of the conditions analyzed See Table 4
Economics • Tobacco, cigars, and cigarettes tax collection • 2017 Financial Treasury Report prepared by the General Treasury of the Republic of Chile [31]
Economics • Price elasticity of cigarette demand [- 0.45] • Study: “Tobacco control economics in Mercosur nations and associated countries: Chile” [16]

Treatment cost estimates

The costing methodology combined micro and macro costing techniques. The direct costs of treatment of the 17 conditions analyzed are presented in annual costs for chronic diseases, and as per event for acute conditions. In Chile, the national program of explicit guarantees in health (called AUGE) provides cost estimates for legally granted services. The study of ‘verification of the mean expected cost per beneficiary’ (EVC) corresponds to a detailed micro-costing exercise for each of the diseases guaranteed, and considers the stages of diagnosis, treatment, and follow-up. These estimations weigh the cost of treatment in the public and private sector, according to population affiliation. In Chile, nearly 75% of the population is affiliated to the national health fund (FONASA) while around 15% is affiliated to the ISAPRES (private insurers). The remaining 10% comprises other institutional arrangements for healthcare, including a low proportion corresponding to the uninsured population.

Since AUGE is a mandatory program covering both subsystems, private and public costs were weighted in the calculation. We applied a general weighting of 70% public and 30% private to obtain mean annual costs, however there were some adjustments to this weighting for services provided mainly for the private sector or conversely for the public system [22]. We prioritized the EVC as the main source of costing for pathologies covered through AUGE. Consequently, some costs were obtained from the EVC study [29]; however, we made adjustments in most cases to correct for the underestimation of public unit costs. To do this, we used an empirical health care service costing study for the public sector, commissioned by FONASA [30]. As AUGE does not cover all conditions involved in this study, we estimated the cost of some treatments from scratch, or based on other studies. The cost of lung cancer (not covered in AUGE before 2019) was taken from the national cost-effectiveness study that had considered this condition among others [6]. The cost for other cancers was estimated using relative proportions in costs obtained from an Argentinian study [18]. In this study, a Delphi exercise with local clinical experts was implemented, based on the cost of treating lung cancer, which was obtained by micro-macro costing. The experts estimated the likely proportion of some less frequent types of cancer in relation to lung cancer. All monetary values were in Chilean pesos (CLP) from December 2017 and were also converted to US dollars (U$D), using the mean observed exchange rate published by the Chilean Central Bank for 2017 (1 U$D = 649.33 CLP).

Results

We completed the search and selection of all parameters needed to populate the model. A summary of the smoking prevalence in Chile for the age groups of interest is shown in Table 2, while “S1 Table” shows the prevalence and population, for single age (35 years to 100) and sex.

Table 2. Smoking prevalence by age range, sex and smoking status (National Health Survey 2017).

Males prevalence Females prevalence
Age group Smokers Ex- smokers Smokers Ex- smokers
35–44 49,51% 23,59% 35,72% 23,61%
44–65 31,30% 36,78% 29,84% 23,67%
> = 65 15,69% 45,68% 9,05% 32,65%

The direct costs of treating the conditions studied in the Chilean healthcare systems are shown in Table 3, while the utility values assigned to each condition are presented in Table 4.

Table 3. Direct medical costs estimated in CLP of December 2017 and U$D*.

Disease events (annual) Cost CLP Cost U$D Method/source
Acute myocardial infarction (AMI) 3,015,985 4,645 AUGE- FONASA study
Non-AMI ischemic event 2,065,883 3,182 AUGE–FONASA study
CHD follow-up (annual) 1,104,263 1,701 AUGE–FONASA study—Delphi
Stroke 3,388,256 5,218 AUGE–FONASA study
Stroke follow-up (annual) 1,163,564 1,792 AUGE—FONASA—Delphi
Pneumonia/influenza 179,618 277 AUGE—FONASA
Mild COPD (annual) 191,223 294 Microcosting & OS
Moderate COPD (annual) 422,257 650 Microcosting & OS
Severe COPD (annual) 4,689,113 7,221 AUGE—FONASA–OS
Lung cancer 1st year 16,613,003 25,585 Cost-Effectiveness Study
Lung cancer 2nd year 21,480,916 33,082 CE Study & Delphi
Mouth cancer 1st year 11,961,362 18,421 Costing based on the proportions to lung cancer, as found in Delphi exercise in Argentina
Mouth cancer - 2nd year onwards 8,162,748 12,571
Esophageal cancer 1st year 13,954,922 21,491
Esophageal cancer - 2nd year onwards 9,451,603 14,556
Stomach cancer 1st year 13,622,662 20,980
Stomach cancer - 2nd year onwards 10,310,840 15,879
Pancreatic cancer 1st year 11,296,842 17,398
Pancreatic cancer - 2nd year onwards 7,733,130 11,909
Kidney cancer 1st year 11,961,362 18,421
Kidney cancer - 2nd year onwards 8,377,557 12,902
Laryngeal cancer 1st year 13,622,662 20,980
Laryngeal cancer - 2nd year onwards 9,881,221 15,218
Leukemia 1st year 17,942,043 27,632
Leukemia - 2nd year onwards 20,621,679 31,758
Bladder cancer 1st year 11,296,842 17,398
Bladder cancer - 2nd year onwards 10,310,840 15,879
Cervical cancer 1st year 10,300,062 15,863
Cervical cancer - 2nd year onwards 5,578,040 8,590

AUGE: national program of explicit guaranties in health, COPD: chronic obstructive pulmonary disease, CHD: coronary heart disease, FONASA: National Health Fund, OS: Other sources

*Exchange rate per dollar is the 2017 observed mean value, published by the Chilean Central Bank: 649,33 CLP.

Table 4. Utilities values used in the model.

Disease health state Utility Source
Acute myocardial infarction (AMI) 0,800 [32]
Non-AMI ischemic event 0,800 [33]
Coronary heart disease (CHD) 0,939 [33]
Stroke 0,641 [32]
Stroke follow-up (annual) 0,740 [34]
Pneumonia/influenza 0,994 [35, 36]
Mild COPD (annual) 0,935 [32]
Moderate COPD (annual) 0,776 [37]
Severe COPD (annual) 0,689 [37]
Lung cancer 0,500 [38]
Esophageal cancer 0,630 [39, 40]
Stomach cancer 0,550 [41]
Pancreatic cancer 0,550 [42]
Kidney cancer 0,780 [43]
Laryngeal cancer 0,890 [44]
Leukemia 0,800 [45, 46]
Bladder cancer 0,780 [43]
Cervical cancer 0,940 [47]

AMI: acute myocardial infarction, COPD: chronic obstructive pulmonary disease, CHD: coronary heart disease.

Relative risks for smokers and ex-smokers in reference to never-smokers, which, as explained earlier, were taken from the Cancer prevention study II [26], are contained in the S2 Table, where we provide a detail by tobacco-related condition and sex.

Mortality, morbidity, and costs of smoking

In Chile, we estimate 16,742 deaths attributable to smoking annually, a number that represents around 39% of deaths from smoking-related diseases (43,322) and about 16% of all cases of death. Among the diseases analyzed, nearly 180,000 events are expected each year, of which 85,000 (47%) are attributable to cigarette consumption. In terms of costs, these conditions burden the Chilean healthcare system with nearly U$D 3.4 billion, of which U$D 1.8 billion (52%) are smoking-attributable treatment costs. We show the main results drawn from modeling the burden attributable to cigarettes consumption in Table 5.

Table 5. Smoking-attributable deaths, events, and directs costs for the healthcare system for 2017.

Tobacco-related conditions Total deaths Smoking- attributable deaths Total events Smoking- attributable events Total costs (in millions) Smoking- attributable costs (millions)
n % row % col n % row % col CLP U$D* CLP U$D* % row % col
Cardiovascular diseases 12 948 2 220 17 13.3 37 578 11 386 30 13.4 561 646 865 170 045 262 30 14.8
Acute myocardial infarction 6 248 1 304 21 7.8 37 439 11 330 30 13.3
Non-AMI ischemic event 3 1 20 0.0 139 56 40 0.1
CV death of non-ischemic cause 6 696 916 14 5.5 NA NA NA NA
Stroke 6 356 923 15 5.5 28 666 4 761 17 5.6 322 410 497 57 649 88. 8 18 5.0
Lung cancer 3 673 3 076 84 18.4 4 409 3 712 84 4.4 262 309 404 222 488 342. 6 85 19.4
Pneumonia/influenza 3 198 573 18 3.4 18 675 4 352 23 5.1 3 354 5 782 1. 2 23 0.1
COPD 6 400 5 041 79 30.1 75 528 55 209 73 65.1 413 046 636 321 525 495. 2 78 28.0
Other cancers 8821 1926 34 17.8 14 784 5 401 37 6.4 632 369 974 242 435 373.0 38 21.1
Mouth and pharyngeal cancer 353 246 70 1.5 997 695 70 0.8
Esophageal cancer 861 590 69 3.5 1 152 795 69 0.9
Stomach cancer 2 145 517 24 3.1 2 853 693 24 0.8
Pancreatic cancer 2 121 562 26 3.4 2 378 631 27 0.7
Kidney cancer 837 240 29 1.4 1 813 543 30 0.6
Laryngeal cancer 370 310 84 1.9 804 677 84 0.8
Leukemia 977 176 18 1.1 1 166 216 19 0.3
Bladder cancer 591 259 44 1.5 2 058 916 44 1.1
Cervical cancer 566 83 15 0.5 1 563 236 15 0.3
Second-hand smoking (SHS) and other causes
SHS and other causes 1 926 1 926 100 11.5 NA NA NA NA NA NA 131 940 203.0 100 11.5
Total 43 322 16 742 39 100.0 179 640 84 821 47 100.0 2195 134 3 381 1146 863 1 766 52 100.0

AMI: acute myocardial infarction, CLP: Chilean pesos, COPD: chronic obstructive pulmonary disease, CV: cardiovascular, NA: not applicable, U$D: US dollars

* Exchange rate per dollar 1 U$D = 649,33 CLP.

Chronic obstructive pulmonary disease (COPD) represents the top cause of smoking-attributable mortality (30.1%), followed by lung cancer (18.4%), passive smoking (11.5%), acute myocardial infarction (7.8%), stroke (5.5%), and cardiovascular deaths of non-ischemic cause (5.5%). When aggregating by disease group, COPD (30.1%) and lung cancer (18.4%) are followed by the group of nine other cancers (17.8%), and the cardiovascular disease group (13.3%).

In terms of smoking-attributable morbidity, considering that these events are heterogeneous for comparison, COPD holds the top place with 55,209 events (65% of the total), followed by AMI (13.4%), stroke (5.6%), pneumonia/influenza (5.1%), and lung cancer (4.4%). Finally, the economic burden for the healthcare system attributed to smoking is distributed among COPD (28%), the group of nine other cancers (21.1%), lung cancer (19.4%), cardiovascular diseases (14.8%), and passive smoking (11.5%).

DALYs (premature mortality and disability)

Smoking causes a total of 416,445 DALYs (undiscounted and not age-weighted). Of these, DALYs due to premature mortality account for 69% of total, while the rest is due to disability. The DALY burden falls mainly on men (59%). Table 6 shows the distribution of DALYs by sex and disease group for the entire cohort analyzed, as well as the mean differential DALY for smokers and ex-smokers (in relation to never-smokers), when simulating a cohort of 35 years of age by its survival time.

Table 6. Years of life lost due to premature mortality and years of disability– 2017.

Disability-adjusted life-years (DALY) Women Men Total %
DALYS due to premature mortality (YLL) 114,227 173,164 287,392 69,0%
DALYS due to disability (YLD) 57,424 71,628 129,052 31,0%
Total DALY 171,652 244,792 416,444 100%
Years of Life Lost (YLL) by disease group
Cardiovascular disease 10,216 26,549 36,765 12.8%
Stroke 8,029 10,179 18,207 6.3%
Pneumonia /influenza 2,065 4,029 6,095 2.1%
COPD 42,561 37,314 79,875 27.8%
Lung cancer 20,883 36,093 56,976 19.8%
Other cancers 17,332 39,079 56,411 19.6%
Passive smoking /other causes 13,141 19,922 33,063 11.5%
Total DALY (YLL) 114,227 173,164 287,392 100.0%
Differential DALY per person in relation to a never-smoker
Smoking status Women Men
Smoker -5.9 -6.1
Ex- smoker -2.6 -2.9

COPD: chronic obstructive pulmonary disease, DALY: disability-adjusted life-years, YLL: years of life lost (YLL), YLD: years of life with disability

Costs, taxes and expenditure on health

Smoking generates a direct annual treatment cost of CLP 1.15 trillion (approx. U$D 1.8 billion), which is equivalent to 0.6% of the Chilean GDP in 2017, and 8.1% of the country’s annual healthcare spending. The tax collection on cigarettes sales (and other tobacco products) was around CLP 979 billion in 2017 [31], an amount that covers 85.3% of the direct expenses in the health system caused by smoking. Table 7 shows that increases in the final price of a cigarettes pack through different tax increases, would allow, in a ten-year period, for further reductions in deaths, health events, and DALYs, a fact which also comes with significant savings on treatment costs and higher tax revenue collection.

Table 7. Economic consequences of smoking and potential effects of price increase– 2017.

Category CLP (millions) U$D (millions) Source
Total health expenditure (THE) 14,220,119 21,900 WDI, WB
Gross domestic product (GDP) 180,211,290 277,534 WDI, WB
Tobacco-tax collection 978,696 1,507
Smoking-attributable direct costs of treatment 1,146,863 1,766 [31]
Treatment costs as % of GDP 0.64%
Treatment costs as % of THE 8.07%
% of costs recovered with taxes 85.34%
Scenarios for price increase: 10 years effect for different % increase
% increase in final price of a package 25% 50% 75%
Deaths prevented 6,833 13,665 20,498
Heart disease avoided 5,977 11,955 17,932
Number of Strokes avoided 3,804 7,607 11,411
New cases of cancer avoided 3,893 7,786 11,679
New cases of COPD avoided 17,248 34,496 51,743
DALYs avoided 180,238 360,476 540,713
Health costs avoided (millions of CLP) 471,252 942,504 1,413,756
Increase in tax collection (millions of CLP) 1,335,276 2,052,895 2,152,860
Total economic benefit (millions of CLP) 1,806,528 2,995,399 3,566,616
Health costs avoided (millions of U$D) 726 1,452 2,177
Increase in tax collection (millions of U$D) 2,056 3,162 3,316
Total economic benefit (millions of U$D) 2,782 4,613 5,493

CLP: Chilean pesos, DALY: disability-adjusted life-years, GDP: gross domestic product, THE: total health expenditure, U$D: US dollars, WB: World Bank, WDI: World Development Indicators

As can be seen from the table, a 50% increase in the final price of a cigarette package could prevent 13,665 deaths, 11,955 heart diseases, 7,786 new cancers and 7,607 strokes in ten years. In addition, financial resources could be generated for around U$D 4.6 billion, a figure that is derived from savings in health expenses (U$D 1.5 billion) and increase tax collection for cigarettes consumption (U$D 3.1 billion).

Discussion

This analysis shows that Chile faces an important burden associated with the habit of smoking. Annually, 16,742 deaths, 11,386 cases of AMI and other cardiovascular events, 4,761 strokes and 9,113 new cancer cases are attributable to smoking. A current smoker of 35 years of age is expected to lose around six years of disability-adjusted life, and an ex-smoker around 3 years in their lifespan, due to smoking. The health care system spends around U$D 1.8 billion per year in direct costs of care of smoking-attributable diseases, which represents 8.1% of the total health care budget. Despite the latest increases in cigarette taxes, revenues do not fully compensate for the healthcare system costs. We estimate that a further increase in cigarettes taxes that could drive-up the final price of the pack by 50% would have important accumulated benefits within the next 10 years, such as better health, healthcare savings, and further tax revenue collection. In Chile, tax increases should affect the specific tax component expressed in UTM, which does not depend on the production cost; this way one could avoid manufacturers’ well-known practice of reducing the net price to minimize tax burden.

Compared to the Burden of Disease Study commissioned by the MoH in 2008 [5], where the total annual DALY attributed to smoking was 61,093, our results are far above with 416,444 DALYs in 2017. However, we need to consider the time passed, epidemiological and demographic changes and various differences in methods: for example, passive smoking was not considered, a high discount rate was used (8%), and age was adjusted for in DALY calculation [5].

Our results do not differ much from those published in 2014, when 16,532 smoking-attributable deaths were estimated, equivalent to 18.5% of the country’s annual deaths. DALY, on the other hand, had been estimated at 428,588–3% more than the current study [22]. In a similar study, Perú estimated 396,069 smoking-attributable DALY for 2015 with an associated health expenditure that represented 5.3% of GDP and 61% of the overall public health expenditure [19].

Strong tax policies on tobacco are still not widely used in the region. Among its neighboring countries, Chile has a higher proportion of smoking-related health expenditure recovered by tobacco taxation revenues, reaching 85% in this analysis. Peru only collects 9% [19], Colombia 10% [25], Paraguay 20% [20], Brazil 25% [48] and Argentina 67% [18] of total smoking-attributable healthcare expenditure, through tobacco-taxes.

As percentage of GDP, Peru faces the highest burden in healthcare expenditure with a 5.3% [19], followed—far behind—by Argentina 0.75% [18], Chile 0.64% (this study), Colombia 0.59% [25] and Brazil 0.5% in 2011 [48].

In this analysis, we found that the impact of a 50% increase in the price of a pack of cigarettes would be a reduction of 13,655 deaths over ten years, a value that is less than our previous estimates of 20,502 deaths prevented in ten years [49]. However, this previous analysis used data for 2015 when there was a higher smoking prevalence. As pointed out before, the national smoking prevalence fell 6.5 percentage points in the 2017 NHS in relation to the 2010 NHS [2, 50], which can be the result of the regulations that have considerably limited the spaces were smoking is now permitted in Chile. These regulations were enforced with active supervision and control, and monetary fines were imposed to offenders [51].

The main strengths of this study are that the analysis uses a model platform that has been widely validated to assess tobacco burden in various Latin American countries [1721, 24], and that it incorporates the most updated information available. The latter includes smoking prevalence, mortality data, and the country population structure presented in the 2017 national census. In this way, this study provides a relevant source for policy guidance. In Chile, this is the first attempt to assess the economic and healthcare burden of tobacco consumption comprehensively.

Some of the potential weaknesses of the analysis are that indirect or productivity costs were not modeled, and that treatment costs were not re-analyzed but only updated to 2017 values, according to the consumer price index. Furthermore, while smoking is harmful in different ways, it entails various uncertain externalities, which make it difficult to assess the loss of productivity and other indirect costs at country-level appropriately. The study in Brazil shows that indirect costs can represent 30% of total smoking-attributable costs [21]. Our direct estimations fall short from representing the total smoking burden, which, ideally, should consider all the negative effects of smoking on people, their families, and society.

The second possible weakness of our study could be related to the cost structure of certain treatments that might have changed, as new pharmaceutical therapies come to the market every day. As new drugs are slowly incorporated in programs like AUGE, it is essential to review current treatments covered by AUGE, since omitting such review may lead to underestimation of costs; however, part of this underestimation can be compensated by other previously included expensive drugs, whose patents have already expired.

Regarding indirect costs, we did not consider smoking on pregnancy; a study using population-attributable fractions (PAFs) reported the negative impact of prenatal smoking on infant morbidity and mortality in Chile for the period 2008–2012 [52]. Using PAFs, the study estimated that between 5.5% and 12.3% of pre-term births (depending on cut-off point) and 27.4% of full-term low-weight births were attributable to prenatal smoking. Additionally, 11.9% of deaths caused by preterm-related causes, and 40% of deaths caused by sudden infant death syndrome were attributed to prenatal smoking.

The results published in the first report of this analysis in 2014 [22] played a key role as input information in the discussion of several policies and legislative changes regarding tobacco control in Chile. On the other hand, many of the regulations implemented since 2013 have already proven effective, even for this short time span. The 2017 NHS shows that people from all age strata experienced a reduction in their smoking, including those with less than eight years of schooling. There was also a reduction in the proportion of smokers with high tobacco dependence (those smoking within the first 60 minutes of waking up in the morning), which decreased from 33.2% (2010 NHS) to 22.3% (2017 NHS). Passive smokers prevalence fell from 31.0% to 15.2% during the same period [50].

A 2017 study [53] reported how the number of AMI declined immediately after smoking in public places was banned. In this analysis, the observed incidence of AMI showed an OR = 0.60 when comparing the first 30-month post law enforcement, against the 30-month prior to implementation. This study covered the main urban areas of the country [53].

Despite the recent progress regulating smoking in Chile, the implementation of free-of-charge cessation assistance programs is lacking. This pending task constitutes a moral imperative as limiting spaces (enclosed and open) to smoke together with increasing cigarettes prices lead to health and economic vulnerability, especially for those highly-dependent on tobacco use. The lack of coverage of these services, despite ample evidence on their cost-effectiveness [54], has been repeatedly pointed out by WHO reports that give account of country compliance of the MPOWER strategy [3, 10, 12]. A 2017 study shows how countries with less national income than Chile offer better coverage for smoking-cessation services [55].

Public policies should also address smoking by young women who are likely to be mothers in the future, to avoid the unacceptably high burden that this habit generates for newborns [52]. This seems even more relevant if we consider that there are far more adolescent females who are smoking than adolescent males in Chile [3].

Finally, policy-makers need to consider the possible regressive nature of tobacco taxes. A recent study [13] that analyzed expenditure patterns in Chilean household budgets found that those who spend more on tobacco, spend less on education and health, especially if they belong to lower socioeconomic groups.

In conclusion, sustained efforts and political will are necessary to deepen regulations and widen policy scope. We expect that this study will help raise awareness among government officials, policy makers, and other relevant stakeholders, about the negative public health and economic effects of smoking. At the same time, and despite the potential shortcomings of the study, we expect to have provided insight into appropriate policy options to continue tackling this problem.

Supporting information

S1 Table. Smoking prevalence and total population by single age and sex.

(DOCX)

S2 Table. Relative risks of mortality for smokers and ex-smokers for each tobacco-related condition, by sex (in reference to never-smokers).

(DOCX)

Acknowledgments

We thank the librarian Daniel Comandé of the Institute of Clinical and Healthcare Effectiveness for his important collaboration with the bibliographic searches. We are also indebted to Catherine De la Puente from the Chilean Ministry of Health for supporting this study by providing disaggregated data on the 2017 national health survey on smoking prevalence. Likewise, Luis Bustos Medina from La Frontera University (Temuco, Chile) helped us with the analysis of the country mortality database.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The International Development Research Center of Canada (IDRC) provided funding for this study in the form of a grant awarded to APR for the project "Empowering health care decision makers to achieve regional needs for tobacco control in Latin America" (107978-001). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

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2 Apr 2020

PONE-D-20-00908

Health burden and economic costs of tobacco in Chile: The potential impact of increasing cigarettes prices

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Reviewer #1: This study reported the authors’ estimates of the smoking-attributable (SA) deaths, DALYs, and healthcare costs in Chile, and the simulated impact of raising cigarette prices on SA deaths, DALYs, and healthcare costs. Because there is a paucity of literature on the evaluation of the economic burden of tobacco use in Latin American countries, this paper has a potential to contribute to the literature. However, there are several major problems in this paper.

1. The objectives of this study were not stated explicitly in the paper. If the goal is to estimate the SA deaths, DALYs, and healthcare costs, it is necessary to provide a literature review on these SA outcomes in the Background section, and provide a discussion to compare the SA estimates from this study with those from previous studies in Chile and other countries with similar tobacco use patterns and economic environment. If the goal is to simulate the impact of raising cigarette prices on SA outcomes, it is important to let the readers know how raising cigarette prices will change smoking prevalence, increase the number of quitters, and reduce smoking initiation in Chile. None of such information was provided in the paper. Also, in the Introduction and Discussion sections, the authors described many other tobacco control policies such as free-of-charge cessation programs without explaining their implications for the estimated smoking-attributable morbidity, mortality, and DALYs in Chile, causing distraction from the supposed theme.

2. This study used a mathematical model that was developed within the framework of a multi-country project to estimate the burden attributable to smoking. Many assumptions were made for the input parameters. Table 1 shows sources for this study’s input parameters. However, there is not enough detail about the assumption and methodology for estimating the SA morbidity, mortality, and healthcare costs.

a) Is this an incidence-based or prevalence-based approach? Because this study simulated the yearly outcomes for a hypothetical cohort aged 35 or older from 2017 through the cohort’s survival time, this study should be an incidence-based study. In this case, how were the annual SA estimates estimated for the year 2017?

b) What is the length of the time horizon? 60 years? 70 years?

c) During the time horizon, the study cohort will age and some of them would die; therefore, the population size of the cohort will decrease with time. Will those who newly become 35 years old be included in the cohort? Were the disease incidence rate, mortality rate, and healthcare costs assumed to be the same over the entire time horizon?

d) What were the smoking prevalence rates assumed in the model? Were they stratified by gender and age? If someone quit smoking in year 1, what was the risk of this person’s disease incidence, mortality, and healthcare cost in year 2, year 3, and so on? What was the assumption for the relapse rate? Because smoking prevalence is a key input variable, it deserves a separate table.

e) REF #25 does not contain the values of the RRs for smokers. The RRs derived from the Cancer Prevention Study II and cited by the SAMMEC and CDC were the RRs of disease-specific mortality for smokers relative to never smokers. Were the RRs of morbidity for smokers relative to never smokers and the RRs of healthcare cost relative to never smokers assumed to be the same as the RRs of mortality?

3. Individuals were classified into smokers, non-smokers, and ex-smokers. I suggest renaming these sub-groups as current smokers, never smokers, and ex-smokers. In the literature, “smokers” include current smokers and former smokers, while “non-smokers” usually refer to ex-smokers or never smokers.

4. In the Results section of the Abstract: “… 46 people die daily due to tobacco-related diseases…”, and “spends annually $1.15 trillion pesos… in health care due to tobacco-related illness”. The term “tobacco-related diseases” was used incorrectly in these sentences. This study used a disease-specific approach to quantify the amount of morbidity, mortality, and healthcare cost caused by tobacco-related diseases (including several cancers, cardiovascular diseases, and respiratory diseases) that can be attributable to smoking. The correct way is to say that “… die daily were attributable to smoking …”, and “… in health care attributable to smoking”. For example, Table 4 shows that in Chile, 43,322 deaths died annually due to tobacco-related diseases. Among these deaths, 16,742 were attributable to smoking.

5. The first sentence of the Conclusion in the Abstract was not justified by the results of this study.

6. The clarity of Table 4 can be improved by a) adding rows to show disease groups with sub-totals, and b) adding columns to show column percentages.

7. Table 5 indicates that the YLL per person was 5.9 (6.1) years for women (men) current smokers, and 2.6 (2.9) years for women (men) ex-smokers. These numbers do not look right. The YLL per person should be calculated by dividing the total YLL by the number of SA deaths. For both genders combined, the YLL per person is 17 years (= 287392/16742), an estimate which is more consistent with the literature. How did you estimate how many of the SA deaths (16742) were current smokers, and how many were former smokers?

8. Among the 55 references cited, more than half of them are in Spanish. Can the authors at least translate the titles of these articles in English?

Reviewer #2: This is one of the first comprehensive studies to quantify the economic costs of smoking in Chile using recent and updated data. The methods are sound and the results have important policy implications for tobacco control efforts in Chile. Overall, I think the study is well-done. However, the current version does have a few minor issues that need to be addressed.

1. In the Results section, it needs to be made clear the year for which the smoking-attributable deaths, events and costs were estimated. I assume it was 2017, but it needs to be clear stated in Table 4, 5, and 6.

2. In the Results section, the term “tobacco-attributable burden” was used many times. Given the analysis focused on smoking, I’d recommend replacing it with “smoking-attributable burden.”

3. What was the value of price elasticity of demand used in this study? For the simulation results for price in Table 6, did the author considered the recent research that shows price elasticity may increase as the price level increases? This could imply that the tax revenue collection could be much lower than estimated in Table 6 when the price increase was 50% and 75%.

4. Line 134, what was the rationale for not using age-weighted DALYs?

5. How were the differences in the treatment costs between public and private sectors accounted for? Using the 75% vs. 15% weights?

6. There are numerous grammatical errors throughout the entire manuscript. For example, line 164 “the CenterS for Disease Control and Prevention.” This paper would benefit from a thorough English-language check.

**********

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2020 Aug 28;15(8):e0237967. doi: 10.1371/journal.pone.0237967.r002

Author response to Decision Letter 0


14 May 2020

Answers to the review (general comments)

One of the reviewers asked that the titles of the Spanish references be translated into English. I think that this is a good idea. Please keep the original Spanish titles followed by English translations in brackets.

• All Spanish titles of national reports or grey literature are now followed by its English translation in brackets.

• For articles in Spanish, which are already indexed in PubMed with an English title, we used this translation as the title in brackets.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

We have made our best to follow closely the PLOS ONE's style requirements, we hope that we have not missed any instructions on style and file names.

2. Please ensure you have thoroughly discussed any potential confounding factors of this study within the Discussion section.

This study, which is based on modelling the effect of smoking on burden of disease, does not postulate any association or cause-effect, not already stablished in the literature, therefore confounding factors do not apply to this analysis. However, we have covered a wide range of factors in the discussion and we acknowledge some limitations that allow putting in context the results, and its external validity.

Answer to the Reviewers' comments:

Reviewer #1: This study reported the authors’ estimates of the smoking-attributable (SA) deaths, DALYs, and healthcare costs in Chile, and the simulated impact of raising cigarette prices on SA deaths, DALYs, and healthcare costs. Because there is a paucity of literature on the evaluation of the economic burden of tobacco use in Latin American countries, this paper has a potential to contribute to the literature. However, there are several major problems in this paper.

1. The objectives of this study were not stated explicitly in the paper. If the goal is to estimate the SA deaths, DALYs, and healthcare costs, it is necessary to provide a literature review on these SA outcomes in the Background section, and provide a discussion to compare the SA estimates from this study with those from previous studies in Chile and other countries with similar tobacco use patterns and economic environment. If the goal is to simulate the impact of raising cigarette prices on SA outcomes, it is important to let the readers know how raising cigarette prices will change smoking prevalence, increase the number of quitters, and reduce smoking initiation in Chile. None of such information was provided in the paper. Also, in the Introduction and Discussion sections, the authors described many other tobacco control policies such as free-of-charge cessation programs without explaining their implications for the estimated smoking-attributable morbidity, mortality, and DALYs in Chile, causing distraction from the supposed theme.

The objectives of the paper are stated in the abstract under “methods” and now a statement has been added at the end of the introduction section (lines 118-120) as follow:

“In this paper our objective is twofold: to report the tobacco-related burden on disease, mortality and direct medical costs for Chile, and to estimate the health and financial impact of different levels of cigarette’s price increase through tobacco taxation increase”.

Regarding the literature review mentioned, the scarce literature on the matter available for Chile is already described in the introduction (three studies commissioned for the Chilean Ministry of Health – refs 5 and 6). As we say later in the introduction (lines 122-123), to our knowledge, this is the first paper on the economic burden of tobacco in Chile to be published in a peer review journal.

Likewise, the introduction summarized the policies followed in Chile regarding tobacco control (lines 70-84) including cigarettes tax increase. A full systematic review was out of the scope for this study, where evidence on the impact of raising tobacco-taxes is published. In the introduction we mentioned ref 14 and added now ref 15. Drope J, Schluger N, Cahn Z, Drope J, Hamill S, Islami F, Liber A, Nargis N SM. The Tobacco Atlas. Atlanta: American Cancer Society and Vital Strategies. Published by the American Cancer Society, Inc; 2018.

Regarding how taxes on cigarettes will affect smoking behavior, we have now included a line explaining the mechanism of demand reduction, which depend on cigarette price elasticity (see lines 86-89 Introduction, and Methods section lines 161-171)

Regarding the discussion section, we have added a comparison of our results with the previous Burden of Disease country-study for DALY (ref 5) and with those obtained for neighboring countries in similar studies (Lines 324-338).

The WHO Framework Convention on Tobacco Control propose (and monitor) 5 strategies to address the tobacco problem across countries, being one of them taxation. This study, apart from measuring the burden of disease, explore taxation only, however we don’t see any harm in framing this analysis (in the introduction) within the wider scope of strategies, since a balanced approach is the WHO recommendation. That is why although we do not systematically show the evidence for each of these strategies, we try to describe the current state for the study country.

2. This study used a mathematical model that was developed within the framework of a multi-country project to estimate the burden attributable to smoking. Many assumptions were made for the input parameters. Table 1 shows sources for this study’s input parameters. However, there is not enough detail about the assumption and methodology for estimating the SA morbidity, mortality, and healthcare costs.

In the results we have included now a summary of national smoking prevalence by age group and sex (as Table 2).

Table 2: Smoking prevalence by age range, sex and smoking status

Males prevalence Females prevalence

Age group Smokers Ex- smokers Smokers Ex- smokers

35-44 49,51% 23,59% 35,72% 23,61%

44-65 31,30% 36,78% 29,84% 23,67%

>=65 15,69% 45,68% 9,05% 32,65%

We also include the value of price-elasticity on cigarette demand used. Additionally,

We are including two supplemental tables:

S1 Table. Smoking prevalence and total population by single age and sex

S2 Table. Relative risks for smokers and ex-smokers for each tobacco-related condition, by sex (in reference to never-smokers)

Other main assumptions used for the analysis, which were not explicit, were reviewed and clarified in the text.

a) Is this an incidence-based or prevalence-based approach? Because this study simulated the yearly outcomes for a hypothetical cohort aged 35 or older from 2017 through the cohort’s survival time, this study should be an incidence-based study. In this case, how were the annual SA estimates estimated for the year 2017?

This model uses a prevalence-based approach, covering the entire population of 35 years onwards, living in Chile in 2017. This represent a static cohort that is analyzed for the year 2017. The microsimulation model is used to estimate the disease incidence, quality of life, health outcomes and healthcare cost for each sex and age strata in Chile for smokers, ex-smokers and never smokers.

With this cross-sectional approach all individuals ages/sex are considered and smoking-related events are estimated using specific equations derived from the evidence and the burden observed in the country.

The disease burden was estimated as the difference in disease events, deaths and associated costs between the results predicted by the model for Chile under current smoking prevalence (status quo) and a hypothetical cohort of non-smokers.

These model characteristics has been made more explicit in the paper now (see lines 129-135)

b) What is the length of the time horizon? 60 years? 70 years?

As explained before it is one year, covering the entire country population of 35 years and older.

c) During the time horizon, the study cohort will age and some of them would die; therefore, the population size of the cohort will decrease with time. Will those who newly become 35 years old be included in the cohort? Were the disease incidence rate, mortality rate, and healthcare costs assumed to be the same over the entire time horizon?

Since the cohort is static, all values need to be valid for the year 2017. The costs for each condition/event were estimates for the year 2017, as explained in the methods section.

Disease rates and mortality rates were taken from national registries as explained in Table 1.

d) What were the smoking prevalence rates assumed in the model? Were they stratified by gender and age? If someone quit smoking in year 1, what was the risk of this person’s disease incidence, mortality, and healthcare cost in year 2, year 3, and so on? What was the assumption for the relapse rate? Because smoking prevalence is a key input variable, it deserves a separate table.

In the results we have included now a summary of national smoking prevalence by age group and sex. Additionally, we are including a table in “Supporting information”:

S1 Table. Smoking prevalence and total population by single age and sex.

During the year, we do not use assumptions on quitting or relapse rate. In other words, smoking status is kept fixed during the simulation year (2017).

For the scenarios of tax increase, the model assumes a hypothetical situation the reduction in prevalence is assumed to affect proportionally all ages and to both sexes. This has been now explained in the methods (lines 160-171)

e) REF #25 does not contain the values of the RRs for smokers. The RRs derived from the Cancer Prevention Study II and cited by the SAMMEC and CDC were the RRs of disease-specific mortality for smokers relative to never smokers. Were the RRs of morbidity for smokers relative to never smokers and the RRs of healthcare cost relative to never smokers assumed to be the same as the RRs of mortality?

Indeed, our RR come from the Cancer Prevention Study II. We have replaced ref#25 as this data is now contained in:

U.S. Department of Health and Human Services. The Health Consequences of Smoking: 50 Years of Progress. A Report of the Surgeon General. Atlanta: 2014. https://www.ncbi.nlm.nih.gov/books/NBK294316/

We are aware that this RR are relative to “never smokers”, in our model we use three smoking status and RR are for smokers as well as for ex-smokers in reference to never-smokers. See now Supporting information (S2 Table)

S2 Table. Relative risks for smokers and ex-smokers for each tobacco-related condition, by sex (in reference to never-smokers)

The RR for morbidity is derived from: mortality RR, lethality rates and other parameters that incorporate country data for observed events.

As for the costs, we don’t use RR since the differences in costs are the result of the differences in morbidity, expressed in less health care events.

3. Individuals were classified into smokers, non-smokers, and ex-smokers. I suggest renaming these sub-groups as current smokers, never smokers, and ex-smokers. In the literature, “smokers” include current smokers and former smokers, while “non-smokers” usually refer to ex-smokers or never smokers.

We have accepted this suggestion and we are referring now to:

• never-smokers,

• smokers, and

• ex-smokers

4. In the Results section of the Abstract: “… 46 people die daily due to tobacco-related diseases…”, and “spends annually $1.15 trillion pesos… in health care due to tobacco-related illness”. The term “tobacco-related diseases” was used incorrectly in these sentences. This study used a disease-specific approach to quantify the amount of morbidity, mortality, and healthcare cost caused by tobacco-related diseases (including several cancers, cardiovascular diseases, and respiratory diseases) that can be attributable to smoking. The correct way is to say that “… die daily were attributable to smoking …”, and “… in health care attributable to smoking”. For example, Table 4 shows that in Chile, 43,322 deaths died annually due to tobacco-related diseases. Among these deaths, 16,742 were attributable to smoking.

The reviewer is right. We have made the changes in the abstract and throughout the text to correct this ill redaction.

5. The first sentence of the Conclusion in the Abstract was not justified by the results of this study.

This is right. We have made a modification in the abstract, so that to clarify the conclusion coming from the study.

6. The clarity of Table 4 can be improved by a) adding rows to show disease groups with sub-totals, and b) adding columns to show column percentages.

We have added rows with sub-totals to differentiate disease groups and we added two columns for deaths and costs, with the relative importance across conditions (in percentages by col). Note that for clarity these changes were highlighted, as track-changes makes the table difficult to read.

7. Table 5 indicates that the YLL per person was 5.9 (6.1) years for women (men) current smokers, and 2.6 (2.9) years for women (men) ex-smokers. These numbers do not look right. The YLL per person should be calculated by dividing the total YLL by the number of SA deaths. For both genders combined, the YLL per person is 17 years (= 287392/16742), an estimate which is more consistent with the literature. How did you estimate how many of the SA deaths (16742) were current smokers, and how many were former smokers?

Table 5 portrait the mean DALY (YLL + YLD) difference for individual - men or woman - according to its smoking status. These values are the result of simulating three cohorts of 35 years until its death: 1. All smokers, 2. All ex-smokers and 3. All never-smokers. The numerator for 1 and 2 is the difference in DALY obtained with respect to the cohort 3 (all never-smokers) while the denominator is the number of people in the cohort. A line was added to explain this (282-284) and a correction was made in the title within table 6, for a clearer understanding.

The previous estimates do not relate to the total 16742 deaths estimated using the current mix of smoking prevalence in Chile. We used the prevalence data for age/sex (see table 2), which together with the specific RR for death in smoker and ex-smoker (S2 Table), contribute to modeling the total SA deaths (16742).

8. Among the 55 references cited, more than half of them are in Spanish. Can the authors at least translate the titles of these articles in English?

All original titles of national reports or grey literature are now followed by its English translation in brackets.

For articles in Spanish, which are already indexed in PubMed with an English title, we used this translation as the title in brackets.

Reviewer #2: This is one of the first comprehensive studies to quantify the economic costs of smoking in Chile using recent and updated data. The methods are sound and the results have important policy implications for tobacco control efforts in Chile. Overall, I think the study is well-done. However, the current version does have a few minor issues that need to be addressed.

1. In the Results section, it needs to be made clear the year for which the smoking-attributable deaths, events and costs were estimated. I assume it was 2017, but it needs to be clear stated in Table 4, 5, and 6.

Indeed, all results refer to the year 2017. We have added the year 2017 in the titles of tables 4, 5 and 6. Which are now 5, 6 and 7.

2. In the Results section, the term “tobacco-attributable burden” was used many times. Given the analysis focused on smoking, I’d recommend replacing it with “smoking-attributable burden.”

We have changed tobacco by smoking in the results and discussion sections.

3. What was the value of price elasticity of demand used in this study? For the simulation results for price in Table 6, did the author considered the recent research that shows price elasticity may increase as the price level increases? This could imply that the tax revenue collection could be much lower than estimated in Table 6 when the price increase was 50% and 75%.

We have added the price elasticity used in the method section (this is -0.45 and correspond to ref 16).

We see the point that the reviewer raises, however we did not assume any change in this value for different price increases. Mainly due to fact that we do not have data/evidence on this regard.

We have added the equation used to estimate changes in the prevalence, as a function of price increase and price-elasticity of cigarettes (see lines 161- 171, method section)

4. Line 134, what was the rationale for not using age-weighted DALYs?

We understand there has been controversy regarding DALYs age-weighting, where a universal agreement /consensus has not been reached.

However, we believe presenting unweighted DALYs is more frequent in published studies.

5. How were the differences in the treatment costs between public and private sectors accounted for? Using the 75% vs. 15% weights?

In general, total cost per event were weighted 70% public cost and 30% private cost. But there were some few exceptions for interventions that were mainly provided either in the public sector or conversely in the private sector. This is explained in detail in ref 22.

In this analysis we updated the costs estimated previously and detailed in ref 22, this fact is also acknowledged in the discussion (as a potential limitation).

Regarding costs weighting, we added a clarification line in the method section (lines 205-207).

6. There are numerous grammatical errors throughout the entire manuscript. For example, line 164 “the CenterS for Disease Control and Prevention.” This paper would benefit from a thorough English-language check.

We have asked a professional proof-reader to review the final version. However, we would be willing to carry out any further correction to improve the paper presentation and understanding.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Stanton A Glantz

22 Jun 2020

PONE-D-20-00908R1

Health burden and economic costs of tobacco in Chile: The potential impact of increasing cigarettes prices

PLOS ONE

Dear Dr. Castillo-Riquelme,

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors did a comprehensive response to reviewers’ comments, and the revision was well-done. I have no more major comments but have many editorial suggestions to further improve this manuscript.

1. In response to Review 2’s comment #2, the authors have replaced the term “tobacco-attributable burden” with “smoking-attributable burden” in the Results and Discussion sections given that this study focused on smoking. Given the same reason, I suggest revising the title by replacing the term “tobacco” with “smoking”.

2. In the Abstract, line 23 shows “ …. 33.4% prevalence of daily smokers”. This number was not reported elsewhere in the paper. Is this a typo? Given that the prevalence of current smokers in 2017 was 33.3%, how would it possible that the prevalence of daily smokers is greater than 33.3%?

3. In the Abstract, line 28: “46 people die daily from tobacco-related diseases caused by smoking”. This finding was not shown in the Results section of the main text. I suggest replacing it with “16,472 deaths were attributable to smoking in 2017”.

4. In the Abstract, the sentence shown on lines 38-39, “In Chile, the tobacco tax collection does not fully cover …”, should belong to the Results rather than the Conclusion. Moreover, the last sentence, “Additionally, …. Smoking-cessation …”, does not seem to be related to the findings reported above.

5. Line 94: “… an increased in relation to”. Is “increased” a typo of “increase”?

6. Line 171: “… some ex-smokers become non-smokers”. What do “non-smokers” mean in this sentence? In the response letter, the authors indicated that they have accepted the reviewer’s suggestion to change the term “non-smokers” to “never-smokers”. Does it imply that “non-smokers” referred in this sentence mean “never-smokers”?

7. In line 188, the meaning of “related regulation” needs to explained.

8. In Table 1: “relative risks for smokers, ex-smokers, …” Add “of mortality” after “relative risks”.

9. In Table 1, one of the cell in the last column says “See Table 2”. It should be corrected as “See Table 4”.

10. In Table 1, “Tobacco price elasticity of demand [- 0.45]” would be better changed to “Price elasticity of cigarette demand [- 0.45]”.

11. Lines 202-203: “In Chile, nearly 75% of the population is affiliated to the national health fund (FONASA) while around 15% is affiliated to the ISAPRES (private insurers).” Does this sentence suggest that 90% of the population is covered by public or private insurance, and 10% is uninsured?

12. Lines 257-262 contain the most important results from this study, namely, the estimated smoking-attributable health burden and economic costs of smoking. However, these estimates were not presented clearly enough and the distinction between “smoking-attributable” and “smoking caused diseases” still seems ambiguous. I suggest four editorial changes.

a. Line 256. Change the section title to “Mortality, morbidity, and costs of smoking”.

b. Lines 257-258. Change the sentence from “… around 16,742 people die annually due to pathologies caused by smoking, a number that represents around 16.3% of all deaths to “annually there are 16,742 deaths attributable to smoking, a number that represents around 39% of tobacco-related deaths (43,322) and 16.3% of all-cased deaths (xxx,xxx)“.

c. Lines 259-260. Change the sentence from “180,000 events are expected each year, of which 47% are attributable to tobacco consumption“ to “180,000 events are expected each year, of which 85,000 (47%) are attributable to cigarette consumption“.

d. Lines 261. Change the sentence from “U$D 3.4 billion, of which 52% corresponds to smoking-attributable treatment costs” to “U$D 3.4 billion, of which U$D 1.8 billion (52%) are smoking-attributable treatment costs”.

13. In Table 5, the last row’s label should not contain “tobacco attributable“. In other words, it should be just “Total”. For the “Smoking-attributable events” columns, the header, “%”, should be renamed as “% row”. Also, it would be helpful to add one more column to show the column percentage.

14. Line 188. Change “first cause” to “top cause”.

15. Line 281. Should “58%” be corrected as “69%” according to Table 6?

16. Line 308. Should “12,302 cases of AMI…” be corrected as “11,386 cases of AMI…” according to Table 5?

17. Line 310. Add “disability-adjusted “ before “life”.

18. Line 311. The number cited in the sentence “...spends around U$D 1.15 billion per year in direct costs of care of smoking..“ is incorrect.

19. Line 312. Is “8.3%” a typo of “8.1%”?

20. Lines 320-321. It is not clear what specific results of this study do not differ greatly from the estimates published in 2004 [22]. Are the authors referring to smoking-attributable deaths, DALYs, or costs of smoking? And, what are the estimates from reference #22?

21. Lines 329. Do the DALY and health expenditures cited here refer to “smoking-attributable” estimates?

22. Lines 340: “…is lower than our previous estimations [22]”. It is helpful to let the readers know what the previous estimates are.

**********

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Reviewer #1: No

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PLoS One. 2020 Aug 28;15(8):e0237967. doi: 10.1371/journal.pone.0237967.r004

Author response to Decision Letter 1


4 Aug 2020

Answer to the each of the editorial suggestions from Reviewer 1

Reviewer #1: The authors did a comprehensive response to reviewers’ comments, and the revision was well-done. I have no more major comments but have many editorial suggestions to further improve this manuscript.

1. In response to Review 2’s comment #2, the authors have replaced the term “tobacco-attributable burden” with “smoking-attributable burden” in the Results and Discussion sections given that this study focused on smoking. Given the same reason, I suggest revising the title by replacing the term “tobacco” with “smoking”.

Response: Thank you. This was implemented

2. In the Abstract, line 23 shows “ …. 33.4% prevalence of daily smokers”. This number was not reported elsewhere in the paper. Is this a typo? Given that the prevalence of current smokers in 2017 was 33.3%, how would it possible that the prevalence of daily smokers is greater than 33.3%?

Response: This was corrected. The percentage corresponds to current smokers (33.3%).

3. In the Abstract, line 28: “46 people die daily from tobacco-related diseases caused by smoking”. This finding was not shown in the Results section of the main text. I suggest replacing it with “16,472 deaths were attributable to smoking in 2017”.

Response: This was implemented

4. In the Abstract, the sentence shown on lines 38-39, “In Chile, the tobacco tax collection does not fully cover …”, should belong to the Results rather than the Conclusion. Moreover, the last sentence, “Additionally, …. Smoking-cessation …”, does not seem to be related to the findings reported above.

Response: Regarding the first sentence “In Chile, the tobacco tax collection does not fully cover …” we moved it to the results section as suggested by the reviewer.

Regarding the second point, we removed the sentence from the abstract.

We agree that there is no a direct link to the main analyses of our study. However, we believe that it is important to mention, that for Chile it is crucial to advance in all possible ways to reduce the burden of smoking. In addition to taxes, the country is lagging behind in terms of smoking cessation programs, which for ethical reasons should go hand in hand with other more restrictive measures, such as raising taxes, adopting plain packaging, and imposing smoke-free environments. Therefore, the lack of smoking cessation interventions was addressed in the introduction and in the discussion section.

5. Line 94: “… an increased in relation to”. Is “increased” a typo of “increase”?

Response: corrected – line 94

6. Line 171: “… some ex-smokers become non-smokers”. What do “non-smokers” mean in this sentence? In the response letter, the authors indicated that they have accepted the reviewer’s suggestion to change the term “non-smokers” to “never-smokers”. Does it imply that “non-smokers” referred in this sentence mean “never-smokers”?

Answer: Yes, it actually means never-smokers. We have re-written this sentence as:

“… while only in the third scenario do some ex-smokers adopt a risk similar to that of never-smokers”. line 171.

7. In line 188, the meaning of “related regulation” needs to explained.

Response: US has been implementing more strict smoking regulations for longer time (as compared to Chile), therefore indirect costs (taken in reference to US costs) are likely to be conservative when applied to Chile.

We modified the sentence, adding:

“…since the US has been implementing smoking regulation long before Chile”. Now in lines 188-189

8. In Table 1: “relative risks for smokers, ex-smokers, …” Add “of mortality” after “relative risks”.

Response: implemented

9. In Table 1, one of the cell in the last column says “See Table 2”. It should be corrected as “See Table 4”.

Response: corrected

10. In Table 1, “Tobacco price elasticity of demand [- 0.45]” would be better changed to “Price elasticity of cigarette demand [- 0.45]”.

Response: implemented

11. Lines 202-203: “In Chile, nearly 75% of the population is affiliated to the national health fund (FONASA) while around 15% is affiliated to the ISAPRES (private insurers).” Does this sentence suggest that 90% of the population is covered by public or private insurance, and 10% is uninsured?

Response: The remaining 10% comprises 1) other financial health care mechanisms, such as the Armed Forces and Police Department systems, 2) independent workers / professionals who cover their health expenses out-of-pocket, and 3) uninsured people (who is minimal).

We believe that this full explanation might not be necessary. However, we added a brief explanation, as follows:

“The remaining 10% comprises other institutional arrangements for healthcare, including a low proportion corresponding to the uninsured population" lines 205-207

12. Lines 257-262 contain the most important results from this study, namely, the estimated smoking-attributable health burden and economic costs of smoking. However, these estimates were not presented clearly enough and the distinction between “smoking-attributable” and “smoking caused diseases” still seems ambiguous. I suggest four editorial changes.

a. Line 256. Change the section title to “Mortality, morbidity, and costs of smoking”.

Response: implemented – line 258

b. Lines 257-258. Change the sentence from “… around 16,742 people die annually due to pathologies caused by smoking, a number that represents around 16.3% of all deaths to “annually there are 16,742 deaths attributable to smoking, a number that represents around 39% of tobacco-related deaths (43,322) and 16.3% of all-cased deaths (xxx,xxx)“.

Response: this recommendation was implemented, but we prefer not to add the total annual deaths at the end of the sentence. This is because, as our values are determined through modelling, absolute estimates do not always match the exact observed value. For total deaths, the model estimated slightly less (-0.031) deaths than the officially reported in Chile in 2017.

The new paragraph reads:

"In Chile, we estimate 16,742 deaths attributable to smoking annually, a figure that represents around 39% of deaths from smoking-related diseases (43,322) and about 16% of all cases of death" lines 259-260

c. Lines 259-260. Change the sentence from “180,000 events are expected each year, of which 47% are attributable to tobacco consumption“ to “180,000 events are expected each year, of which 85,000 (47%) are attributable to cigarette consumption“.

Response: this was implemented – lines 261-262

d. Lines 261. Change the sentence from “U$D 3.4 billion, of which 52% corresponds to smoking-attributable treatment costs” to “U$D 3.4 billion, of which U$D 1.8 billion (52%) are smoking-attributable treatment costs”.

Response: implemented – lines 263 -264

13. In Table 5, the last row’s label should not contain “tobacco attributable“. In other words, it should be just “Total”. For the “Smoking-attributable events” columns, the header, “%”, should be renamed as “% row”. Also, it would be helpful to add one more column to show the column percentage.

Response: implemented

14. Line 188. Change “first cause” to “top cause”.

Response: implemented - line 271

15. Line 281. Should “58%” be corrected as “69%” according to Table 6?

Response: yes, this was corrected - line 284

16. Line 308. Should “12,302 cases of AMI…” be corrected as “11,386 cases of AMI…” according to Table 5?

Response: corrected, and cases for stroke were added – line 310

17. Line 310. Add “disability-adjusted “ before “life”.

Response: added – line 312

18. Line 311. The number cited in the sentence “...spends around U$D 1.15 billion per year in direct costs of care of smoking..“ is incorrect.

Response: corrected to 1.8 – line 313

19. Line 312. Is “8.3%” a typo of “8.1%”?

Response: yes, this was corrected – line 314

20. Lines 320-321. It is not clear what specific results of this study do not differ greatly from the estimates published in 2004 [22]. Are the authors referring to smoking-attributable deaths, DALYs, or costs of smoking? And, what are the estimates from reference #22?

Response: this paragraph was rewritten as follows

"Our results do not differ much from those published in 2014, when 16,532 deaths attributable to smoking were estimated, equivalent to 18.5% of the country's annual deaths. DALY, on the other hand, had been estimated at 428,588 - 3% more than the current study [22] ". lines 327 -329

We also put this paragraph a little later, to maintain a chronological logic.

21. Lines 329. Do the DALY and health expenditures cited here refer to “smoking-attributable” estimates?

Response: Yes, we added “smoking-attributable” and “an associated health expenditure” to make this more explicit – line 330

22. Lines 340: “…is lower than our previous estimations [22]”. It is helpful to let the readers know what the previous estimates are.

Answer: This information has been provided and a reference has been added. The paragraph read now as follows:

"In this analysis, we found that the impact of a 50% increase in the price of a pack of cigarettes would be a reduction of 13,655 deaths over ten years, a value that is less than our previous estimates of 20,502 deaths prevented in ten years [49]. However, this previous analysis used data for 2015 when there was a higher smoking prevalence". lines 340-343

Attachment

Submitted filename: rebuttal letter_PONE-D-20-00908R1.docx

Decision Letter 2

Stanton A Glantz

7 Aug 2020

Health burden and economic costs of smoking in Chile: The potential impact of increasing cigarettes prices

PONE-D-20-00908R2

Dear Dr. Castillo-Riquelme,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Stanton A. Glantz

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Stanton A Glantz

19 Aug 2020

PONE-D-20-00908R2

Health burden and economic costs of smoking in Chile: The potential impact of increasing cigarettes prices

Dear Dr. Castillo-Riquelme:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Professor Stanton A. Glantz

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Smoking prevalence and total population by single age and sex.

    (DOCX)

    S2 Table. Relative risks of mortality for smokers and ex-smokers for each tobacco-related condition, by sex (in reference to never-smokers).

    (DOCX)

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: rebuttal letter_PONE-D-20-00908R1.docx

    Data Availability Statement

    All relevant data are within the manuscript and its Supporting Information files.


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