Economic gains of transitioning towards reduced-risk products: evidence from Mexico

Abstract

Unhealthy behaviors such as poor diet and tobacco use contribute to disease burden and escalating healthcare costs. This paper evaluates potential savings from people adopting reduced risk behaviors in Mexico. Using the Preventable Risk Integrated Model, we compare actual consumption in 2016 (baseline) to optimal intake following WHO guidelines (counterfactual) for salt, fiber, fruit/vegetables, and fat to estimate reductions in coronary, cerebrovascular, cancer, diabetes and hypertensive diseases. We also model 50% of smokers switching to e-cigarettes/heated tobacco with 65–97% lower disease risk. Results indicate over 650,000 preventable cases annually, mostly from diet changes (fruits/vegetables, fat, salt). Healthcare cost savings reach $3.4 billion USD; $2.8 billion from nutrition and $0.3 billion from smoking substitution. Fruit/vegetable intake and reduced fat confer over $1 billion savings each. Salt and fiber also contribute significantly. Adding smoking transitions provides further savings. Shifting Mexicans towards healthier diets and alternative nicotine products could substantially lower disease burden and healthcare costs. These findings underscore the economic imperative of promoting reduced-risk behaviors through public health policies.

1 Introduction

Addictions and high-risk behaviors encompass a wide range of actions that can potentially endanger a person's health or well-being. Unhealthy eating habits, excessive alcohol intake, and tobacco use stand out among these. They not only pose a threat to public health, leading to numerous deaths each year, but also impose a substantial burden on the healthcare sector and on society at large.

Scientific evidence emphasises the health benefits of a diet rich in whole grains, vegetables, fruits, legumes, and nuts, while limiting salt, free sugars, and fats, especially saturated and trans-fats. Establishing a healthy diet early in life is crucial, with positive impacts on education, productivity, and lifelong health. However, accessing healthy diets remains challenging, particularly in low- and middle-income countries with high food insecurity rates. Globally, about 3 billion people lack access to safe, nutritious food [1]. The prevalence of highly processed foods, driven by aggressive marketing, rapid urbanization, and changing lifestyles, contributes to unhealthy dietary habits marked by increased energy intake and excessive free sugars, salt, saturated fats, and trans fats [2]. Alcohol consumption, particularly in excessive amounts, is associated with various adverse consequences, serving as a risk factor for diseases, criminal activities, road incidents, and, for certain individuals, alcohol dependence. On a global scale, alcohol consumption contributes to 2.8 million premature deaths, annually [3]. Tobacco smoking stands as one of the most significant health challenges globally, leading to millions of individuals experiencing compromised health. Researchers estimate that each year, approximately 8 million people succumb to premature deaths attributable to smoking. This issue has persisted as a major health concern for several decades [4]. Throughout the entire twentieth century, roughly 100 million people experienced premature mortality due to smoking, with the majority of cases occurring in wealthy countries [5]. Some projections indicate that as many as one billion individuals could face death attributed to tobacco use over the course of the twenty-first century [6, 7]. In England, smoking alone is responsible for over 60,000 deaths, annually. A recent report from the charity Action on Smoking and Health estimated the associated cost at £49.2 billion, covering lost productivity, service expenses, and an additional £25.9 billion in quality-adjusted life years due to premature deaths. When considering only direct costs, the Department of Health has estimated £2.5 billion for the National Health Service (NHS). A recent study suggests that the NHS could save approximately half a billion pounds annually if English smokers transitioned to low-risk alternatives like e-cigarettes and heated tobacco [8]. Another study focusing on Italy estimated that promoting a shift toward reduced-risk products such as vaping, combined with increased physical exercise and a reduction in excessive alcohol intake, could potentially save the Italian NHS €1 billion every year [8].

In this paper, we explore potential savings from adopting reduced-risk behaviors in Mexico, using data from the year 2016. These behaviors involve decreasing excessive salt, fats, and alcohol consumption, increasing the intake of fibers, fruits, vegetables, and alcohol and transitioning from conventional cigarettes to e-cigarettes and heated tobacco. To investigate this, we employed the NCDprime [9] Preventable Risk Integrated Model (PRIME). PRIME serves as a publicly accessible scenario modeling instrument specifically designed to evaluate how changes in noncommunicable disease risk factors influence mortality rates. We adopt this modelling approach to estimate the reduction in preventable disease cases and the related costs that occur when shifting from current to recommended intake levels of fibers, fruits, vegetables, and alcohol and when transitioning from traditional cigarettes to e-cigarettes and heated tobacco. Our findings indicate that Mexican government could achieve savings of approximately $3.4 billion annually associated to over 654,000 preventable disease cases.

The reminder of the paper is structured as follows. Section 2 reviews the literature, Sect. 3 describes data sources and methods, Sect. 4 comments on estimation results and Sect. 5 concludes.

2 Background literature

2.1 Health risk behaviors and their impact on healthcare costs

Direct costs in healthcare specifically pertain to the immediate expenses related to treating a specific medical condition, such as hospital stays and medication. Conversely, indirect costs encompass the broader economic impact of the condition, extending to lost productivity and premature death [10, 11]. Notably, in the context of unhealthy goods and habits like smoking and obesity, these costs can be substantial, with indirect costs often outweighing direct costs [12, 13].

Malnutrition emerges as a significant factor influencing healthcare costs, as identified in a review of nutrition economics by [14]. This study found that malnutrition can escalate healthcare costs, while nutrition interventions have the potential to lower them. Public health strategies targeting unhealthy diets and physical inactivity have proven to be cost-effective in several countries, including Brazil, China, India, Mexico, Russia, South Africa, and England [15]. However, the adoption of healthy diets faces barriers, particularly for low-income households where the cost of nutritious foods becomes a deterrent [16, 17]. Also, Moscone [18] for Italy investigates regional disparities in avoidable mortalities and hospital discharges due to high-risk behaviors like excessive alcohol consumption, smoking, and inadequate physical activity, finding that reductions in these behaviors can result in substantial cost savings for the healthcare system and improved health outcomes. These insights primarily stem from studies conducted in Europe, the USA, Canada, and Australia.

Research from New Zealand highlights the effectiveness of food taxes and subsidies, especially those on salt, sugar, and unhealthy products, in yielding significant health gains and cost savings [19]. Similar findings were reported in the UK, where diets aligning with dietary recommendations are associated with higher food costs [20]. Moreover, Reeve [21] and Hyseni [22] underscored the potential for reformulating unhealthy products high in salt and sugar to reduce intake and improve health outcomes. This is particularly relevant in the UK and the USA, where high salt and sugar consumption significantly contributes to healthcare costs. Supporting this notion, Hashem [23] found that product reformulation can effectively reduce sugar intake and body weight, although the evidence quality is noted to be low. Thus, while there is potential for reformulation to reduce healthcare costs, further research is required to confirm its effectiveness. In fact, the effectiveness of these interventions may vary across countries, with a lack of evidence from middle and low-income countries [24].

Research on the healthcare costs of alcohol consumption and unhealthy products yields mixed results. Nelson [25] discovered that changes in alcohol taxes and prices had selective effects on various harms, with positive outcomes observed for liver disease and older persons in Finland and Russia. Rehm [26] estimated that the costs associated with alcohol consumption exceeded 1% of the gross national product in high-income and middle-income countries, with social harm costs constituting a significant proportion. Norström [27] identified a significant relationship between per capita alcohol consumption and mortality from liver cirrhosis, other alcohol-related diseases, accidents, homicide, and all-cause mortality. Barlow [28] found that participation in US and EU Free Trade Agreements was associated with a reduced likelihood of implementing WHO-recommended tobacco and child food marketing policies, based on studies conducted in various countries, including the United States, Australia, Denmark, Finland, Hong Kong, Iceland, Russia, Sweden, Switzerland, Canada, and the EU.

The economic burden of smoking is substantial, incurring significant healthcare costs in both high-income and low- and middle-income countries. In 2012, the global healthcare expenditure due to smoking-attributable diseases was estimated at a staggering $467 billion, contributing to a total economic cost of $1852 billion [29]. Latin America, for instance, grapples with smoking-related expenditures, accounting for 6.9% of health budgets and 0.6% of GDP, with tax revenues covering only 37% of health expenditures [30]. A 50% increase in cigarette prices through taxation could potentially avert deaths, reduce healthcare spending, and increase tax revenues [30]. In seven Latin American countries, smoking is responsible for 0.7% of the region's GDP and 8.3% of its health budget, with tax revenues covering only 37% of smoking-attributable health expenditures [31]. These findings underscore the need for stronger tobacco control measures or shifting toward lower-risk alternatives to address the healthcare costs of smoking.

Some recent research suggests that transitioning from smoking to reduced-risk products, such as vaping and non-combustible products, could have potential benefits for both individual health and healthcare costs [8]. For example, regular vaping may reduce the risk of respiratory infections and pneumonia [32]. While the upfront costs of vaping products may be higher than cigarettes, the long-term costs are generally lower, making vaping an attractive alternative to smoking [33]. Also, Arredondo et al. [34] and Levy et al. [35] present crucial insights into the economic and public health implications of smoking and the potential benefits of transitioning to reduced-risk products. Arredondo et al. [34] illustrate the financial strain of smoking-related diseases in middle-income countries like Mexico, emphasizing the need for effective prevention and control measures. On the other hand, Levy et al. [35] provide a decision-theoretic model that quantifies the potential positive impact of vaporized nicotine products (VNPs) on reducing smoking-attributable deaths and life years lost. These studies collectively underscore the importance of targeted policies and interventions to mitigate the health and economic burdens of smoking and promote the adoption of reduced-risk alternatives. However, it is crucial to note that the long-term health effects of these products, especially in chronic obstructive pulmonary disease (COPD) patients, remain unclear and necessitate further research [36]. This ongoing exploration is essential for a comprehensive understanding of the potential health and economic implications associated with these alternatives (for further discussion on reduced-risk products, see also appendix section A.3).

2.2 The Mexican context

Mexico is a typical Latin American Country in terms of risky behaviors and health care systems. While alcohol consumption remains below the OECD average, amounting to 5.1 L alcohol per capita in 2021, Mexico reports one of the fastest growth trend in alcohol consumption by 1 L between 2011 and 2021 [37]. Regarding dietary intake, Mexico performs substantially worse than the OECD average and than many Latin American countries [38]. Only 51% of the population consumes vegetables daily in 2021 and more than 70% of Mexicans can be considered as obese or overweight. This makes Mexico the number one country in terms of unhealthy dietary intake among all OECD and Latin American countries, and results in an overweight-related GDP loss of 5.3% until 2050 [39]. Although Mexico became the first Latin American country to ratify the WHO FCTC in 2004, the country accounts for 17 million smokers in 2019, expected to further rise due to demographic growth [40, 41]. This high number of smokers is responsible for 48 thousand smoking-related death cases. Despite a moderate smoking prevalence 14.9% of Mexican’s population in 2021, smoking prevalence remains high among male adults amounting to 23.4% [4].

At the same time, the Mexican government struggles to provide adequate health care access and service. Only 72% of the population is covered by health care (compared to the OECD average of 98%) and 41% of health care expenditures needs to be paid by patients out-of-pocket (compared to the OECD average of 18%) [37]. Moreover, the Mexican health system spends very little on healthcare (6% of GDP in 2021) and provides the fewest hospital beds (1 bed per 1000 inhabitants in 2021) among OECD countries.

Considering the combination of high-risk behaviors and a struggling public health system, there exists a need to alleviate pressure off the health care system. Latin America grapples with smoking-related expenditures, accounting for 6.9% of health budgets and 0.6% of GDP, with tax revenues covering only 37% of health expenditures. The 63% of health spending caused by smoking is therefore borne by Mexican society—and not by smokers responsible for these expenditures. The resulting need for reforms drives our estimations to costs of harmful substance use. Results should stir a policy debate in Mexico showing a reduction in harmful behavior could be an effective tool to mitigate health costs.

3 Methods

3.1 The PRIME model

This study evaluates the healthcare costs associated with excessive consumption of salt, fat, smoking, alcohol, and insufficient intake of fiber, fruits, and vegetables in Mexico in 2016, associated to the occurrence of specific diseases. Specifically, of one or more diseases focusing on few important classes of disease, namely cerebrovascular diseases, ischemic heart diseases, hypertensive diseases, diabetes, and chronic obstructive pulmonary diseases, and 12 types of cancers, namely lip, oral cavity and pharynx, stomach, pancreas, colorectum, breast, kidney cancer, liver cancer, cervix cancer, and bronchus and lung cancer.

We adopt the PRIME methodology to simulate the number of preventable disease cases under different consumption patterns of unhealthy products. Specifically, we compare real-world data from a given year (baseline scenario) with hypothetical scenarios derived from extensive meta-analyses (counterfactual scenario). We employ relative risk figures obtained from existing literature for each disease given by the PRIME model, by age group, and gender to assess potential reductions in incidences due to variations in risk factors. We refer to Table A in the Appendix for a list of references used to calculate the risk reduction by risk factor. Population attributable fractions (PAFs) are then calculated based on these relative risks, determining the number of disease cases avoidable under alternate risk factor scenarios [42]. After calculating the number of avoidable cases, we estimate the health costs that are avoidable when switching to healthy consumption, by multiplying the number of avoidable cases by the average annual direct treatment costs per illness. Costs include annual direct costs of acute and chronic diseases and are taken from multiple sources in the literature. We refer to Table 1 for a summary of costs per disease and the associated data source. For reasons of comparability, all annual costs per disease are converted to 2022 Mexican Pesos and then to 2022 US dollars.

Table 1 Direct health costs by disease case, and associated data source (in 2022 US Dollars)

For calculating the incidence of diseases, we use two approaches depending on the nature of different types of diseases. For acute diseases, such as cerebrovascular, ischemic heart, hypertensive diseases, diabetes, and chronic obstructive pulmonary diseases, the method follows a formula proposed by Pichon-Reviere et al. [31]:

$${I}_{d}= \frac{{M}_{d}}{{L}_{d}}$$

This formula calculates incidence based on the number of deaths and the lethality rate of the disease, where I_d, M_d, and L_d are the incidence, number of deaths and lethality of disease d, respectively. This approach is specific to acute diseases, focusing on immediate or short-term impacts.

In contrast, the calculation for cancer adopts a formula that exploits data spanning over a 10-year period. This method incorporates the number of new cases each year along with the survival rate, thus accumulating data over a decade. The rationale for using this approach is to account for the fact that the incidences for cancer disease is an accumulation of the cancer survivors and new cases per-year. The formula for cancer diseases is:

$${Total \,I}_{c,n}={I}_{c}+{(Total \,I}_{c,n-1}*{SR}_{c})$$

where Total I_c,n is the total incidence (absolute risk) for cancer c observed in time period n, I_c is the number of new cases per year for cancer c, SR_c denotes the yearly survival rate derived from the survival rate per cancer and n is the total number of past years that we wish to include in the calculation.¹ Pichon-Riviere et al. [30] emphasizes the importance of this 10-year span for chronic diseases like cancer, due to their prolonged progression. The 10-year model is essential for providing a more accurate assessment of both the incidence and the healthcare costs associated with cancer. However, it operates under the assumption of a consistent decline in survival rates over the ten years and presumes that individuals are no longer affected by cancer after this period. This is crucial for healthcare policymakers, providers, and researchers to make better decisions and allocate resources effectively.

When evaluating the healthcare costs associated with excessive consumption of salt, fats, and alcohol, and insufficient intake of fiber, fruits, and vegetables we assume as baseline the observed scenario. As counterfactual we assume that for each age and sex group the population follows the guidelines set by the World Health Organization.² When evaluating the healthcare costs associated with smoking, as counterfactual we take some specific assumptions on the behaviour of smokers, as explained in the next Section.

3.2 Switching from cigarettes to less harmful products

In this paper we adapt the PRIME model to account for the possibility that people can switch from conventional cigarettes to reduced-risk Nicotine-Containing Alternatives (NCAs). The rationale behind such extension stems from acknowledging the health risks associated with smoking. While the World Health Organization aspires to a smoke-free world, this goal is seen as excessively idealistic. It is more realistic to assume that a segment of the population will continue to smoke due to nicotine addiction. However, research indicates that certain nicotine products are less harmful than cigarettes [48,49,50]. Therefore, aiming for a completely smoke-free society may be less feasible than encouraging smokers to switch to less harmful alternatives. Thus, we adopt a more practical approach, where a portion of smokers transition from conventional cigarettes to less harmful alternatives.

When evaluating the public health implications of smokers transitioning to alternative nicotine products, such as electronic cigarettes (e-cigarettes) or heat-not-burn tobacco products (HTPs), it is essential to quantify the impact of such transition on disease risk reduction. Recent studies suggest that switching from traditional cigarettes to reduced-risk products (RRPs) like electronic cigarettes or heat-not-burn (HNB) tobacco can offer significant health benefits, showing up to 97% reductions in harmful constituents specified by the World Health Organization and the US FDA. Forster et al. [48] compared the emissions of RRPs to traditional cigarettes, finding substantial decreases in toxicants. Mallock et al. [49, 51] highlighted the lowered health risks of HNBs compared to traditional smoking but emphasized the need for thorough regulation and monitoring due to uncertainties about their long-term health impacts. Surveys among primary care physicians indicate a belief in the efficacy of e-cigarettes for smoking cessation and in lowering disease risk. A notable example is a discrete choice experiment and survey amongst Florida primary care physicians, where a majority acknowledged the effectiveness of e-cigarettes in lowering disease risk by 65% [52]. For our model, we assume a risk reduction factor of 80%. This value falls within the range of 65-97% reported in the literature. In addition, our model takes into consideration a quitting rate of 10% to represent the fraction of individuals who decide to quit.

In this paper we assume as counterfactual scenario that 50% of the smoking population transitions to these alternatives, leading to a risk of developing smoking-related illnesses reduced by 65–97%. To calculate how such reduced risk translates into a reduction in disease incidence, we use the formula:

$${N}_{switcher}={N}_{smoker}*[1-\left({r}_{switch}*{r}_{reduction}\right)]$$

where N_switcher is the estimated number of smokers potentially affected by smoking-related diseases after the transition to alternative products, N_smoker denotes the total initial population of smokers, r_switch is the rate of smokers switching to alternative products, r_reduction indicates the relative risk reduction in disease incidence for smokers who switch to alternative products. Using this formula, a 50% switch rate coupled with an 80% reduction in risk of developing smoking-related illnesses equates to a 40% reduction in the overall number of smokers. This calculation arises from the substantial risk reduction associated with switching, which mirrors the health benefits of a significant portion of smokers quitting entirely. In scenarios where the risk reduction is as high as 97%, the impact is even more pronounced, highlighting the public health advantages of encouraging smokers to adopt lower-risk alternatives. This methodology provides a tangible metric for assessing the health impact of such transitions, making it a valuable tool for policy discussions and healthcare planning.

4 Data

The PRIME model requires three sets of input data: the age and gender distribution of the population, NCD mortality rates categorized by age and gender for a specific year, and information on risk factor behavior among the population categorized by age and gender.

We obtained population data by age and gender from the Proyecciones de la Población de México y de las Entidades Federativas (CONAPO), and disease-specific hospital admission data by age and gender from the Dirección General de Información en Salud (DGIS) as well as mortality data by age and gender from the Instituto Nacional de Estadística y Geografía (INEGI) for the year 2016.

We gather data on the average daily intake of fibre, fat, salt, fruit and vegetables, split by gender and age groups for the year 2016 from the Encuesta Nacional de Salud y Nutrición (ENSANUT). We observe that salt consumption is underreported in the ENSANUT survey, as data only include added salt during cooking, while salt within industrialized products is omitted. To adjust for this issue, we have added to the salt consumption figure from the survey the salt intake coming from processed food calculated by Vargas et al. [53], based on an extensive food database along with the ENSANUT survey.

We have collected data on the proportion of current, former and non-smokers from the Encuesta Nacional de Consumo de Drogas, Alcohol y Tabaco (ENCODAT) for the year 2016. From the same sources we have gathered data on daily alcohol consumption, and in particular on the number of drinks per day, under the assumption that a standard drink contains 15g of alcohol.

5 Results

Figures 1, 2 illustrate the cases that could be prevented³ by transitioning from the baseline to the counterfactual scenario. A significant total of 654,000 cases could be averted yearly, with the majority attributed to improvements in diet: fruits and vegetables (208,000 cases), fat (182,000 cases), salt (142,000 cases), and fibers (75,000 cases). Additionally, moving away from smoking would avert over 50,000 cases yearly.

Fig. 1

First three diseases causing most of avoidable incidence cases when switching from baseline to counterfactual scenario

Fig. 2

Number of avoidable incidence cases for other diseases when switching from baseline to counterfactual scenario (Fat is not associated with any of the listed diseases in Fig. 2 and thus not included.)

Table 2 reports costs, expressed in US Dollars, that can be averted when switching from baseline to counterfactual scenario. Switching to an optimal consumption of salt, fats, alcohol, fiber, fruits, and vegetables could result in $3.1 billion avertable healthcare costs, which represents about 32.43% of Mexico's total health expenditure for 2022 [54]. More specifically, adhering to the recommended guidelines could lead to avertable healthcare costs of $750 million when focusing on salt and fiber levels, over 1 billion for fat, and over 1.2 billion for fruit and vegetables. Adjusting alcohol consumption, at least for Mexicans, does not seem to have a significant effect on cost savings.

Table 2 Avoidable costs by consumption good (in 2022 US dollars)

Shifting from conventional cigarettes to low-risk alternatives such as e-cigarettes and heated tobacco contributes an additional avertable cost of over $342 million.

Finally, in the appendix section A.2 a few sensitivity analyses are presented. The analyses, discussed there, underscore the reliability and consistency of the primary results. Therefore, these robustness checks present further evidence and support the main results. First, a substantial portion of the model's outcomes relies on the risk-reduction factor, which has been applied with an uncertainty band from 65 to 97%. This range is supported by literature (sources of the studies available in the appendix). Additionally, the factor is integrated linearly into the model, ensuring a linear relationship with the costs of smoking or the number of avertable disease cases. Second, the PRIME model incorporates a Monte Carlo (MC) simulation, providing a robustness check for the results. The simulation, which includes 5,000 replications, offers insights into a wide range of potential outcomes. A detailed table in the appendix section presents the results, including incidences averted or delayed by cause, and by behavioral risk factors, with values at the 2.5th, mean, and 97.5th percentiles.

6 Concluding remarks

Promoting reduced smoking and healthier dietary habits not only enhances individual well-being but also eases the burden on the healthcare system. This involves reducing excessive salt, fats, and alcohol intake, increasing consumption of fibers, fruits, and vegetables, and transitioning from conventional cigarettes to e-cigarettes and heated tobacco. To address this concern, we have adopted and tailored the PRIME model from Oxford. The findings indicate that following WHO recommended guidelines on consumption and allowing consumers to shift from high-risk to reduced-risk products could yield $3.4 billion in avertable costs, which could be reinvested to bolster Mexico's health system resilience against economic and health challenges. With the total healthcare expenditure in Mexico estimated at approximately $40.59 billion, the potential reduction in healthcare costs represented by the $3.4 billion in avertable costs would equate to about 8.37% of the overall healthcare spending. This substantial reduction underscores the potential impact of adopting measures to promote healthier behaviors and reduce high-risk consumption patterns.

The estimated 8.37% reduction in total healthcare costs from improving diet and reducing smoking is quite significant. To put this in perspective, this potential cost savings is greater than many other public health interventions. For example, a systematic review found that workplace wellness programs reduce healthcare costs by about 1.5% on average [51]. Our model shows dietary and smoking changes can yield much larger savings, suggesting these should be a top priority from a cost perspective.

Adopting optimal consumption patterns for salt, fats, alcohol, fiber, fruits, and vegetables could result in an annual savings of $3.1 billion. Specifically, adhering to recommended guidelines could lead to avertable costs of $750 million for salt and fiber, over 1 billion for fats, and over 1.2 billion for fruits and vegetables. Interestingly, adjusting alcohol consumption, particularly for Mexicans, does not appear to significantly impact cost savings. Furthermore, making the shift from conventional cigarettes to low-risk alternatives like e-cigarettes and heated tobacco contributes an additional yearly saving of nearly $342 million.

The substantial cost savings estimated from diet changes and tobacco harm reduction point to clear policy implications. Specifically, Mexico should strongly consider implementing public health campaigns and programs aimed at promoting the dietary and smoking changes modeled in this study. Given the strain on the healthcare system, investing in interventions to drive these behavioral changes could pay significant dividends in terms of cost savings and financial sustainability.

Acknowledging that individuals frequently tend to partake in risky behaviors, the goal should be to alleviate the disproportionate harm they inflict upon themselves. Promoting reduced smoking, and improved diet would enhance individual well-being. Additionally, it would substantially alleviate the financial burden on our healthcare systems. Recognizing the inherent inclination of individuals towards high-risk behaviors, the objective should be to minimize resultant harm.

Appendix

1.1 Summary of literature

See Table 3 here.

Table 3 Associated literature for different risk factors

1.2 Sensitivity analyses

• 1. Risk-reduction factor (provided in the paper)

I have applied an uncertainty band to the main assumption of risk reduction that is quite large: 65% and 97% both backed by literature. Sources also applying a prediction band:

• Modeling the Population Health Impact of Introducing a Modified Risk Tobacco Product into the U.S. Market (2018): 70%; 90%

• A novel approach to assess the population health impact of introducing a Modified Risk Tobacco Product (2015): 70%; 90%

• Does switching from tobacco to reduced-risk products free up hospital resources? (2023): 70%;

• An economic evaluation of the use of non-combusted alternatives using a cost of illness approach: The Philippine case (2023): 70% (28.81%, 97%)

Additionally, in the risk reduction factor, there are no uncertainties in the estimates. The factor itself is linearly integrated into the model, leading to a linear relation with costs of smoking or avertable disease cases.

• 2. Sensitivity analysis on relative risk estimates

The PRIME model includes a Monte-Carlo (MC) simulation. A result table for the MC simulation is provided below with 5000 replications.

	2.5th	Mean	97.5th
Incidences averted or delayed by cause
Cardiovascular disease	511,476	618,136	719,556
Coronary heart disease	407,293	490,336	565,586
Stroke	41,545	53,916	64,695
Heart failure	1512	3552	5575
Aortic aneurysm	58	137	220
Pulmonary embolism	57	171	345
Rheumatic heart disease	84	292	605
Hypertensive disease	31,085	69,899	103,572
Diabetes	837	22,047	43,772
Cancer	17,405	23,294	28,890
Mouth, larynx and pharynx	964	1566	2106
Oesophagus	480	933	1322
Stomach	98	1135	2256
Lung	5180	8560	11,762
Pancreas	366	695	1036
Colorectum	3371	7813	12,118
Breast	19	31	44
Endometrium	− 297	− 144	7
Gallbladder	0	0	0
Kidney	128	749	1410
Bladder	0	0	0
Liver	− 455	77	580
Cervix	716	1,870	3,133
Chronic obstructive pulmonary disease	3802	14,196	24,542
Kidney disease	0	0	0
Liver disease	686	1856	3584
Incidences averted or delayed by behavioral risk factor
Diet (excluding obesity)	421,242	496,781	565,967
Fruit and vegetables	137,380	206,077	262,567
Fiber	44,401	77,582	108,582
Fats	151,148	181,671	199,039
Salt	62,615	142,375	213,809
Alcohol consumption	− 7248	− 4858	− 2197
Smoking	41,032	53,217	65,520

1.3 Further discussion on cigarettes and e-cigarettes

To the best of our knowledge most health organizations, governmental institutions and respected research institutions agree either on the fact that e-cigarettes and HTPs pose a lower risk compared to combustible tobacco or conclude that this question cannot be answered yet. However none of these institutions can evidence-based defend the thesis that e-cigarettes and HTPs pose the same health risks compared to combustible products—the statement implied by the reviewer.

The WHO FCTC decision (22) the reviewer explicitly mentions noted that “there is currently limited guidance to guide Parties on the classification and regulation of heated tobacco products” (WHO FCTC, 2018). Consequently the WHO FCTC requests more “evidence on novel and emerging tobacco products, in particular heated tobacco products, regarding their health impacts” and advises an “adequate classification of novel and emerging tobacco products such as heated tobacco products to support regulatory efforts and the need to define new product categories”.

The European Parliament goes further and acknowledges that “for heated tobacco products, the presence of certain harmful substances in the emissions of these products can be lower by around 80 to 90% compared to tobacco cigarettes” (European Parliament, 2023). Considering this risk reduction level cannot be equally translated to a reduction in health risks, the European Parliament currently evaluates health risks and adverse events. Nevertheless, the European Parliament aims to develop “a science base for harm reduction strategies” and applies a different regulatory scope to novel tobacco products compared to combustible tobacco products.

Several other governmental institutions agree on a high risk reduction level of e-cigarettes and HTPs. The UK Committee on Toxicity showed a reduction of harmful and potentially harmful compounds (HPHCs) in the aerosol generated by HTPs by 50 to 90% and concludes that “it is likely that there is a reduction in risk, though not to zero, to health for smokers who switch completely to heat-not-burn tobacco products” [55]. Researchers from the Dutch National Institute for Public Health and the Environment (RIVM) determine the risk-reduction levels of HTPs at 90 to 96% and assume “consuming HTPs instead of cigarettes will be associated with a substantial increase in life expectancy, for the subgroup of smokers who would die from cancer” [49]. The German Federal Institute for Risk Assessment (BfR) states that “the herein confirmed reductions of relevant toxicants by about 80–99% are substantial, leading to the relevant question of putatively reduced health risks” [56, 57]. Even more decisive, the U.S. Food and Drug Administration (FDA) accepts IQOS (Philip Morris’ HTP product) as Modified Risk Tobacco Product (MRTP) in 2020 [58]. This means the FDA assumes IQOS “is expected to benefit the health of the population as a whole”.

All of these institutions therefore reflect a precautionary approach to novel tobacco products, advising to collect more evidence on health risks. Nevertheless, they recognize the current state of research, which provides ample evidence of reduced emissions from e-cigarettes and HTPs (more of this in Statement 2). More importantly, they agree HTPs and e-cigarettes have a positive health impact compared to combustible tobacco. Our assumption that e-cigarettes and HTPs are less harmful therefore corresponds to the current state of research. Doubting this assumption would only be backed up by a weak minority.

Quantifying the risk-reduction level of HTPs and e-cigarettes, compared to conventional cigarettes remains an ongoing research topic. Novel tobacco products show a reduction in emissions, but it remains unclear how this translates into a reduction in the health effects caused by cigarette smoke. The following table provides a small excerpt of the large database that assesses the reductions in emissions applying different methodologies.

Author(s)	Toxicological risk reduction of HTPs/ e-cigarettes compared to cigarettes (%)
Forster et al. [48]	97
Nutt et al. [59]	96
Slob et al. [49]	90–96
Mallock et al. [57]	80–99
Bekki et al. [65]	Max. 95
Auer et al. [60]	84
Jaccard et al. [61]	90
Li et al. [62]	80
Farsalinos et al. [63]	Max. 95
Stephens [64]	98

Considering the novelty of these products, there exist no longitudinal large-sample epidemiological study. These so-called nested prospective case–control studies are required to exclude confounding factors, which are particularly pertinent for consumer products, but are also lengthy and very costly. Thus, while our toxicological risk reduction factor of 80% is indeed justified by literature manifold, the epidemiological translation to mortality and morbidity cannot be justified by literature yet. While some government institutions and researchers interpret the magnitude of reduced health impact from reduced emissions, some researchers simply apply a prediction band based on reduced emission levels derived from literature.