Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol.

Toxicokinetic modelling provides a powerful tool in relating internal human exposure (i.e., assessed through urinary biomarker levels) to external exposure. Chemical specific toxicokinetic models are available; however, this specificity prevents their application to similar contaminants or to other routes of exposure. For this reason, we investigated whether a generic physiological-based kinetic (PBK) model might be a suitable alternative for a biokinetic model of deoxynivalenol (DON). IndusChemFate (ICF) was selected as a generic PBK model, which could be fit for purpose. Being suited for simulating multiple routes of exposure, ICF has particularly been used to relate the inhalation and dermal exposure of industrial chemicals to their urinary excretion. For the first time, the ICF model was adapted as a generic model for the human biomonitoring of mycotoxins, thereby extending its applicability domain. For this purpose, chemical-specific data for DON and its metabolites were collected directly from the literature (distribution and metabolism) or indirectly (absorption and excretion) by fitting the ICF model to previously described urinary excretion data. The obtained results indicate that this generic model can be used to model the urinary excretion of DON and its glucuronidated metabolites following dietary exposure to DON. Additionally, the present study establishes the basis for further development of the model to include an inhalation exposure route alongside the oral exposure route.

Lifetime cost-effectiveness and equity impacts of the Healthy Primary School of the Future initiative.

BACKGROUND: This study estimated the lifetime cost-effectiveness and equity impacts associated with two lifestyle interventions in the Dutch primary school setting (targeting 4-12 year olds). METHODS: The Healthy Primary School of the Future (HPSF; a healthy school lunch and structured physical activity) and the Physical Activity School (PAS; structured physical activity) were compared to the regular Dutch curriculum (N = 1676). An adolescence model, calculating weight development, and the RIVM Chronic Disease Model, calculating overweight-related chronic diseases, were linked to estimate the lifetime impact on chronic diseases, quality adjusted life years (QALYs), healthcare, and productivity costs. Cost-effectiveness was expressed as the additional costs/QALY gained and we used €20,000 as threshold. Scenario analyses accounted for alternative effect maintenance scenarios and equity analyses examined cost-effectiveness in different socioeconomic status (SES) groups. RESULTS: HPSF resulted in a lifetime costs of €773 (societal perspective) and a lifetime QALY gain of 0.039 per child versus control schools. HPSF led to lower costs and more QALYs as compared to PAS. From a societal perspective, HPSF had a cost/QALY gained of €19,734 versus control schools, 50% probability of being cost-effective, and beneficial equity impact (0.02 QALYs gained/child for low versus high SES). The cost-effectiveness threshold was surpassed when intervention effects decayed over time. CONCLUSIONS: HPSF may be a cost-effective and equitable strategy for combatting the lifetime burden of unhealthy lifestyles. The win-win situation will, however, only be realised if the intervention effect is sustained into adulthood for all SES groups. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02800616 ). Registered 15 June 2016 - Retrospectively registered.

The Relationship Between Internal and External Dose: Some General Results Based on a Generic Compartmental Model.

Statements on how the internal-to-external-dose (IED) relationship looks like are often based on qualitative toxicokinetic arguments. For example, the recently proposed kinetically derived maximum dose (KMD) states that the IED relationship must have an inflection point, due to saturation of underlying processes like metabolism or absorption. However, such statements lack a solid quantitative foundation. Therefore, we derived expressions for the IED relationship for a number of scenarios based on a generic compartmental model involving saturation. The scenarios included repeated or single dose, and saturable metabolism or saturable absorption. For some of these scenarios, an explicit expression for the IED relationship can be derived, for others only implicit expressions can be established, which need to be evaluated numerically. The results show that saturable processes will lead to an IED relationship that is nonlinear over the whole dose range, ie, it can be approximated by a linear relationship at the lower end, whereas the approximation will become gradually poorer with increasing doses. The finding that saturation does not lead to an inflection point in the IED relationship, as assumed in the KMD, implies that the KMD is not a valid approach for selecting the top dose in toxicological studies. An additional use of our results is that the derived explicit expressions of the IED relationship can be fitted to IED data, and, possibly, for extrapolation outside the observed dose range.

You Only Die Once: Accounting for Multi-Attributable Mortality Risks in Multi-Disease Models for Health-Economic Analyses.

Mortality rates in Markov models, as used in health economic studies, are often estimated from summary statistics that allow limited adjustment for confounders. If interventions are targeted at multiple diseases and/or risk factors, these mortality rates need to be combined in a single model. This requires them to be mutually adjusted to avoid 'double counting' of mortality. We present a mathematical modeling approach to describe the joint effect of mutually dependent risk factors and chronic diseases on mortality in a consistent manner. Most importantly, this approach explicitly allows the use of readily available external data sources. An additional advantage is that existing models can be smoothly expanded to encompass more diseases/risk factors. To illustrate the usefulness of this method and how it should be implemented, we present a health economic model that links risk factors for diseases to mortality from these diseases, and describe the causal chain running from these risk factors (e.g., obesity) through to the occurrence of disease (e.g., diabetes, CVD) and death. Our results suggest that these adjustment procedures may have a large impact on estimated mortality rates. An improper adjustment of the mortality rates could result in an underestimation of disease prevalence and, therefore, disease costs.

Projecting the COPD population and costs in England and Scotland: 2011 to 2030.

We aimed to estimate the prevalence, healthcare costs and number of deaths among people with chronic obstructive pulmonary disease (COPD) in England and Scotland 2011-2030. We adapted the Dutch COPD Model by using English and Scottish demographic, COPD incidence, COPD prevalence, smoking prevalence and mortality data to make projections. In England, the prevalence of COPD was estimated to be 1.79% (95% uncertainty interval 1.77-1.81) in 2011, increasing to 2.19% (1.85-2.33) by 2030. In Scotland, prevalence was 2.03% (1.96-2.10) in 2011 increasing to 2.20% (1.98-2.40) in 2030. These increases were driven by more women developing COPD. Annual direct healthcare costs of COPD in England were estimated to increase from £1.50 billon (1.18-2.50) in 2011 to £2.32 (1.85-3.08) billion in 2030. In Scotland, costs increased from £159 million (128-268) in 2011 to £207 (165-274) million in 2030. The deaths in England were estimated to increase from 99,200 (92,500-128,500) in 2011, to 129,400 (126,400-133,400) by 2030. In Scotland, in 2011 there were 9,700 (9,000-12,300) deaths and 13,900 (13,400-14,500) deaths in 2030. The number of people with COPD will increase substantially over the coming years in England and Scotland, particularly in females. Services need to adapt to this increasing demand.

Tobacco control policies specified according to socioeconomic status: health disparities and cost-effectiveness.

INTRODUCTION: Little is known about the cost-effectiveness of tobacco control policy for different socioeconomic status (SES) groups. We aimed to evaluate SES-specific cost-effectiveness ratios of policies with known favorable effect in low-SES groups: a tobacco tax increase and reimbursement of cessation support. METHODS: A computer model of the adult population specified by smoking behavior (never/current/former smoker), age, gender, and SES simulated policy scenarios reflecting the implementation of a €0.22 tobacco tax increase or full reimbursement of cessation support, which were compared. Relating differences in costs to quality-adjusted life years (QALYs) gained generated cost-effectiveness ratios for each SES group. RESULTS: In a cohort of 11 million people, the tobacco tax increase resulted in 27,000 additional quitters after 5 years, who were proportionally divided among the SES groups. Reimbursement led to 59,000 additional quitters, with relatively more quitters in higher-SES groups. The number of QALYs gained were 3,400-6,200 among the various SES groups for the tax increase and 6,300-14,000 for the reimbursement scenario. For both interventions, favorability of the cost-effectiveness ratios increased with SES: costs per QALY decreased from €6,100 to €4,500 for the tax increase and from €21,000 to €11,000 for reimbursement. CONCLUSIONS: The reimbursement policy produced the greatest overall health gain. Surprisingly, neither tax increase nor reimbursement reduced health disparities. Differences in use were too small to compensate for improved health gains per quitter among higher-SES groups. Both policies qualified as cost-effective overall, with more favorable cost-effectiveness ratios for high-SES than for low-SES groups.

Potential effect of salt reduction in processed foods on health.

BACKGROUND: Excessive salt intake has been associated with hypertension and increased cardiovascular disease morbidity and mortality. Reducing salt intake is considered an important public health strategy in the Netherlands. OBJECTIVE: The objective was to evaluate the health benefits of salt-reduction strategies related to processed foods for the Dutch population. DESIGN: Three salt-reduction scenarios were developed: 1) substitution of high-salt foods with low-salt foods, 2) a reduction in the sodium content of processed foods, and 3) adherence to the recommended maximum salt intake of 6 g/d. Health outcomes were obtained in 2 steps: after salt intake was modeled into blood pressure levels, the Chronic Disease Model was used to translate modeled blood pressures into incidences of cardiovascular diseases, disability-adjusted life years (DALYs), and life expectancies. Health outcomes of the scenarios were compared with health outcomes obtained with current salt intake. RESULTS: In total, 4.8% of acute myocardial infarction cases, 1.7% of congestive heart failure cases, and 5.8% of stroke cases might be prevented if salt intake meets the recommended maximum intake. The burden of disease might be reduced by 56,400 DALYs, and life expectancy might increase by 0.15 y for a 40-y-old individual. Substitution of foods with comparable low-salt alternatives would lead to slightly higher salt intake reductions and thus to more health gain. The estimates for sodium reduction in processed foods would be slightly lower. CONCLUSION: Substantial health benefits might be achieved when added salt is removed from processed foods and when consumers choose more low-salt food alternatives.

[Societal costs of asthma, COPD and respiratory allergy]. / Maatschappelijke kosten van astma, COPD en respiratoire allergie.

OBJECTIVE: To estimate the societal costs of asthma, COPD and respiratory allergy for the year 2007 and future healthcare costs for the period 2007-2032. DESIGN: Descriptive study. METHODS: Representative registries were used to estimate the healthcare costs of asthma, COPD and respiratory allergy for the year 2007. A simulation model for asthma and COPD and a demographic projection for respiratory allergy were used to determine future healthcare costs. Production losses due to sick leave and work incapacity were calculated using the friction-cost method. RESULTS: Total healthcare costs for asthma, COPD and respiratory allergy in 2007 were estimated at 287, 415 and 103 million euros respectively; on average 530, 1400 and 170 euros per patient with asthma, COPD and respiratory allergy. Average costs of sick leave for asthma were on average 1200 euros and for COPD 1900 euros per employee per year. The costs of work incapacity of an employee with COPD were 1200 euros. There is expected to be an increase in the number of patients from 443,000 in 2007 to 567,000 in 2032 for asthma and from 335,000 to 600,000 for COPD. The number of patients with a respiratory allergy are expected to remain approximately stable at 625,000 patients. The healthcare costs for respiratory allergy are expected to rise by 73%, those for asthma to double, and those for COPD to triple. CONCLUSION: Patients with asthma and COPD have high healthcare costs. Sick leave makes up a large part of the costs of asthma and COPD. In addition, the costs of work incapacity for employees with COPD are high. The number of patients with asthma and COPD will rise in the coming decades, as well as the healthcare costs for these diseases.

The DYNAMO-HIA model: an efficient implementation of a risk factor/chronic disease Markov model for use in Health Impact Assessment (HIA).

In Health Impact Assessment (HIA), or priority-setting for health policy, effects of risk factors (exposures) on health need to be modeled, such as with a Markov model, in which exposure influences mortality and disease incidence rates. Because many risk factors are related to a variety of chronic diseases, these Markov models potentially contain a large number of states (risk factor and disease combinations), providing a challenge both technically (keeping down execution time and memory use) and practically (estimating the model parameters and retaining transparency). To meet this challenge, we propose an approach that combines micro-simulation of the exposure information with macro-simulation of the diseases and survival. This approach allows users to simulate exposure in detail while avoiding the need for large simulated populations because of the relative rareness of chronic disease events. Further efficiency is gained by splitting the disease state space into smaller spaces, each of which contains a cluster of diseases that is independent of the other clusters. The challenge of feasible input data requirements is met by including parameter calculation routines, which use marginal population data to estimate the transitions between states. As an illustration, we present the recently developed model DYNAMO-HIA (DYNAMIC MODEL for Health Impact Assessment) that implements this approach.

Cost-effectiveness of counseling and pedometer use to increase physical activity in the Netherlands: a modeling study.

BACKGROUND: Counseling in combination with pedometer use has proven to be effective in increasing physical activity and improving health outcomes. We investigated the cost-effectiveness of this intervention targeted at one million insufficiently active adults who visit their general practitioner in the Netherlands. METHODS: We used the RIVM chronic disease model to estimate the long-term effects of increased physical activity on the future health care costs and quality adjusted life years (QALY) gained, from a health care perspective. RESULTS: The intervention resulted in almost 6000 people shifting to more favorable physical-activity levels, and in 5100 life years and 6100 QALYs gained, at an additional total cost of EUR 67.6 million. The incremental cost-effectiveness ratio (ICER) was EUR 13,200 per life year gained and EUR 11,100 per QALY gained. The intervention has a probability of 0.66 to be cost-effective if a QALY gained is valued at the Dutch informal threshold for cost-effectiveness of preventive intervention of EUR 20,000. A sensitivity analysis showed substantial uncertainty of ICER values. CONCLUSION: Counseling in combination with pedometer use aiming to increase physical activity may be a cost-effective intervention. However, the intervention only yields relatively small health benefits in the Netherlands.

Developing and applying a stochastic dynamic population model for chronic obstructive pulmonary disease.

OBJECTIVES: To develop a stochastic population model of disease progression in chronic obstructive pulmonary disease (COPD) that includes the effects of COPD exacerbations on health-related quality of life, costs, disease progression, and mortality and can be used to assess the effects of a wide range of interventions. METHODS: The model is a multistate Markov model with time varying transition rates specified by age, sex, smoking status, COPD disease severity, and/or exacerbation type. The model simulates annual changes in COPD prevalence due to COPD incidence, exacerbations, disease progression (annual decline in the forced expiratory volume in 1 second as percentage of the predicted value), and mortality. The main outcome variables are quality-adjusted life years, total exacerbations, and COPD-related health care costs. Exacerbation-related input parameters were based on quantitative meta-analysis. All important model parameters are entered into the model as probability distributions. To illustrate the potential use of the model, costs and effects were calculated for 3-year implementation of three different COPD interventions, one pharmacologic, one on smoking cessation, and one on pulmonary rehabilitation using a time horizon of 10 years for reporting outcomes. RESULTS: Compared with minimal treatment the cost/quality-adjusted life year was €8,300 for the pharmacologic intervention, €10,800 for the smoking cessation therapy, €8,700 for the combination of the pharmacologic intervention and the smoking cessation therapy, and €17,200 for the pulmonary rehabilitation program. The probability of the interventions to be cost-effective at a ceiling ratio of €20,000 varied from 58% to 100%. CONCLUSIONS: The COPD model provides policy makers with information about the long-term costs and effects of interventions over the entire chain of care, from primary prevention to care for very severe COPD and includes uncertainty around the outcomes.

Targeted versus universal prevention. a resource allocation model to prioritize cardiovascular prevention.

BACKGROUND: Diabetes mellitus brings an increased risk for cardiovascular complications and patients profit from prevention. This prevention also suits the general population. The question arises what is a better strategy: target the general population or diabetes patients. METHODS: A mathematical programming model was developed to calculate optimal allocations for the Dutch population of the following interventions: smoking cessation support, diet and exercise to reduce overweight, statins, and medication to reduce blood pressure. Outcomes were total lifetime health care costs and QALYs. Budget sizes were varied and the division of resources between the general population and diabetes patients was assessed. RESULTS: Full implementation of all interventions resulted in a gain of 560,000 QALY at a cost of €640 per capita, about €12,900 per QALY on average. The large majority of these QALY gains could be obtained at incremental costs below €20,000 per QALY. Low or high budgets (below €9 or above €100 per capita) were predominantly spent in the general population. Moderate budgets were mostly spent in diabetes patients. CONCLUSIONS: Major health gains can be realized efficiently by offering prevention to both the general and the diabetic population. However, a priori setting a specific distribution of resources is suboptimal. Resource allocation models allow accounting for capacity constraints and program size in addition to efficiency.

Co-occurrence of diabetes, myocardial infarction, stroke, and cancer: quantifying age patterns in the Dutch population using health survey data.

BACKGROUND: The high prevalence of chronic diseases in Western countries implies that the presence of multiple chronic diseases within one person is common. Especially at older ages, when the likelihood of having a chronic disease increases, the co-occurrence of distinct diseases will be encountered more frequently. The aim of this study was to estimate the age-specific prevalence of multimorbidity in the general population. In particular, we investigate to what extent specific pairs of diseases cluster within people and how this deviates from what is to be expected under the assumption of the independent occurrence of diseases (i.e., sheer coincidence). METHODS: We used data from a Dutch health survey to estimate the prevalence of pairs of chronic diseases specified by age. Diseases we focused on were diabetes, myocardial infarction, stroke, and cancer. Multinomial P-splines were fitted to the data to model the relation between age and disease status (single versus two diseases). To assess to what extent co-occurrence cannot be explained by independent occurrence, we estimated observed/expected co-occurrence ratios using predictions of the fitted regression models. RESULTS: Prevalence increased with age for all disease pairs. For all disease pairs, prevalence at most ages was much higher than is to be expected on the basis of coincidence. Observed/expected ratios of disease combinations decreased with age. CONCLUSION: Common chronic diseases co-occur in one individual more frequently than is due to chance. In monitoring the occurrence of diseases among the population at large, such multimorbidity is insufficiently taken into account.

Estimating and comparing incidence and prevalence of chronic diseases by combining GP registry data: the role of uncertainty.

BACKGROUND: Estimates of disease incidence and prevalence are core indicators of public health. The manner in which these indicators stand out against each other provide guidance as to which diseases are most common and what health problems deserve priority. Our aim was to investigate how routinely collected data from different general practitioner registration networks (GPRNs) can be combined to estimate incidence and prevalence of chronic diseases and to explore the role of uncertainty when comparing diseases. METHODS: Incidence and prevalence counts, specified by gender and age, of 18 chronic diseases from 5 GPRNs in the Netherlands from the year 2007 were used as input. Generalized linear mixed models were fitted with the GPRN identifier acting as random intercept, and age and gender as explanatory variables. Using predictions of the regression models we estimated the incidence and prevalence for 18 chronic diseases and calculated a stochastic ranking of diseases in terms of incidence and prevalence per 1,000. RESULTS: Incidence was highest for coronary heart disease and prevalence was highest for diabetes if we looked at the point estimates. The between GPRN variance in general was higher for incidence than for prevalence. Since uncertainty intervals were wide for some diseases and overlapped, the ranking of diseases was subject to uncertainty. For incidence shifts in rank of up to twelve positions were observed. For prevalence, most diseases shifted maximally three or four places in rank. CONCLUSION: Estimates of incidence and prevalence can be obtained by combining data from GPRNs. Uncertainty in the estimates of absolute figures may lead to different rankings of diseases and, hence, should be taken into consideration when comparing disease incidences and prevalences.

To die with or from heart failure: a difference that counts: is heart failure underrepresented in national mortality statistics?

AIMS: Mortality attributed to a disease is an important public health measure of the 'burden' of that disease. A discrepancy has been noted between the high mortality rates associated with heart failure (HF) and the share of deaths ascribed to HF in official mortality statistics. It was our main aim to estimate excess mortality associated with HF and use the estimates to better understand the burden of HF. METHODS AND RESULTS: Excess mortality was defined as the difference in mortality rates between individuals with and those without HF. An epidemiological model was formulated that allowed deriving age-specific excess mortality rates in HF patients from HF incidence and prevalence. Incidence and prevalence were estimated from yearly collected cross-sectional data from four nationally representative General Practice registries in the Netherlands. The year 2007 was chosen as a reference. Next, excess mortality rates were used to calculate numbers of deaths among HF patients and compare the figures with national cause-of-death statistics. The latter were found to be more than three times smaller than the former (roughly 6000 vs. 21 000). Further, by applying HF prevalence and mortality rates to a life table of the Dutch population, average numbers of life years lost due to HF were calculated to be 6.9 years. CONCLUSION: National mortality statistics strongly underestimate the number of deaths associated with HF. Moreover, the high mortality rate in HF patients amounts to a remarkably large number of life years lost given the advanced age of disease onset.

Economic evaluation and the postponement of health care costs.

The inclusion of medical costs in life years gained in economic evaluations of health care technologies has long been controversial. Arguments in favour of the inclusion of such costs are gaining support, which shifts the question from whether to how to include these costs. This paper elaborates on the issue how to include cost in life years gained in cost effectiveness analysis given the current practice of economic evaluations in which costs of related diseases are included. We combine insights from the theoretical literature on the inclusion of unrelated medical costs in life years gained with insights from the so-called 'red herring' literature. It is argued that for most interventions it would be incorrect to simply add all medical costs in life years gained to an ICER, even when these are corrected for postponement of the expensive last year of life. This is the case since some of the postponement mechanism is already captured in the unadjusted ICER by modelling the costs of related diseases. Using the example of smoking cessation, we illustrate the differences and similarities between different approaches. The paper concludes with a discussion about the proper way to account for medical costs in life years gained in economic evaluations.

Association between lung function and exacerbation frequency in patients with COPD.

PURPOSE: To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD. METHODS: We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo. Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization. The association between the mean forced expiratory volume in one second (FEV(1))% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects. The regression equations were applied to the mean FEV(1)% predicted for each GOLD stage to estimate the frequency per stage. RESULTS: Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations. Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD. Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively. For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively. Study duration or type of study (cohort versus trial) did not significantly affect the outcomes. CONCLUSION: This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes.

Long-term effectiveness and cost-effectiveness of smoking cessation interventions in patients with COPD.

BACKGROUND: The aim of this study was to estimate the long-term (cost-) effectiveness of smoking cessation interventions for patients with chronic obstructive pulmonary disease (COPD). METHODS: A systematic review was performed of randomised controlled trials on smoking cessation interventions in patients with COPD reporting 12-month biochemical validated abstinence rates. The different interventions were grouped into four categories: usual care, minimal counselling, intensive counselling and intensive counselling + pharmacotherapy ('pharmacotherapy'). For each category the average 12-month continuous abstinence rate and intervention costs were estimated. A dynamic population model for COPD was used to project the long-term (cost-) effectiveness (25 years) of 1-year implementation of the interventions for 50% of the patients with COPD who smoked compared with usual care. Uncertainty and one-way sensitivity analyses were performed for variations in the calculation of the abstinence rates, the type of projection, intervention costs and discount rates. RESULTS: Nine studies were selected. The average 12-month continuous abstinence rates were estimated to be 1.4% for usual care, 2.6% for minimal counselling, 6.0% for intensive counselling and 12.3% for pharmacotherapy. Compared with usual care, the costs per quality-adjusted life year (QALY) gained for minimal counselling, intensive counselling and pharmacotherapy were euro 16 900, euro 8200 and euro 2400, respectively. The results were most sensitive to variations in the estimation of the abstinence rates and discount rates. CONCLUSION: Compared with usual care, intensive counselling and pharmacotherapy resulted in low costs per QALY gained with ratios comparable to results for smoking cessation in the general population. Compared with intensive counselling, pharmacotherapy was cost saving and dominated the other interventions.

If you try to stop smoking, should we pay for it? The cost-utility of reimbursing smoking cessation support in the Netherlands.

BACKGROUND: Smoking cessation can be encouraged by reimbursing the costs of smoking cessation support (SCS). The short-term efficiency of reimbursement has been evaluated previously. However, a thorough estimate of the long-term cost-utility is lacking. OBJECTIVES: To evaluate long-term effects of reimbursement of SCS. METHODS: Results from a randomized controlled trial were extrapolated to long-term outcomes in terms of health care costs and (quality adjusted) life years (QALY) gained, using the Chronic Disease Model. Our first scenario was no reimbursement. In a second scenario, the short-term cessation rates from the trial were extrapolated directly. Sensitivity analyses were based on the trial's confidence intervals. In the third scenario the additional use of SCS as found in the trial was combined with cessation rates from international meta-analyses. RESULTS: Intervention costs per QALY gained compared to the reference scenario were approximately euro1200 extrapolating the trial effects directly, and euro4200 when combining the trial's use of SCS with the cessation rates from the literature. Taking all health care effects into account, even costs in life years gained, resulted in an estimated incremental cost-utility of euro4500 and euro7400, respectively. In both scenarios costs per QALY remained below euro16 000 in sensitivity analyses using a life-time horizon. CONCLUSIONS: Extrapolating the higher use of SCS due to reimbursement led to more successful quitters and a gain in life years and QALYs. Accounting for overheads, administration costs and the costs of SCS, these health gains could be obtained at relatively low cost, even when including costs in life years gained. Hence, reimbursement of SCS seems to be cost-effective from a health care perspective.