Health economic modeling to assess short-term costs of maternal overweight, gestational diabetes, and related macrosomia - a pilot evaluation.

BACKGROUND: Despite the interest in the impact of overweight and obesity on public health, little is known about the social and economic impact of being born large for gestational age or macrosomic. Both conditions are related to maternal obesity and/or gestational diabetes mellitus (GDM) and associated with increased morbidity for mother and child in the perinatal period. Poorly controlled diabetes during pregnancy, pre- pregnancy maternal obesity and/or excessive maternal weight gain during pregnancy are associated with intermittent periods of fetal exposure to hyperglycemia and subsequent hyperinsulinemia, leading to increased birth weight (e.g., macrosomia), body adiposity, and glycogen storage in the liver. Macrosomia is associated with an increased risk of developing obesity and type 2 diabetes mellitus later in life. OBJECTIVE: Provide insight in the short-term health-economic impact of maternal overweight, GDM, and related macrosomia. To this end, a health economic framework was designed. This pilot study also aims to encourage further health technology assessments, based on country- and population-specific data. RESULTS: The estimation of the direct health-economic burden of maternal overweight, GDM and related macrosomia indicates that associated healthcare expenditures are substantial. The calculation of a budget impact of GDM, based on a conservative approach of our model, using USA costing data, indicates an annual cost of more than $1,8 billion without taking into account long-term consequences. CONCLUSION: Although overweight and obesity are a recognized concern worldwide, less attention has been given to the health economic consequences of these conditions in women of child-bearing age and their offspring. The presented outcomes underline the need for preventive management strategies and public health interventions on life style, diet and physical activity. Also, the predisposition in people of Asian ethnicity to develop diabetes emphasizes the urgent need to collect more country-specific data on the incidence of macrosomic births and health outcomes. In addition, it would be of interest to further explore the long-term health economic consequences of macrosomia and related risk factors.

Cost-effectiveness of prucalopride in the treatment of chronic constipation in the Netherlands.

OBJECTIVE: To assess the cost-effectiveness of prucalopride vs. continued laxative treatment for chronic constipation in patients in the Netherlands in whom laxatives have failed to provide adequate relief. METHODS: A Markov model was developed to estimate the cost-effectiveness of prucalopride in patients with chronic constipation receiving standard laxative treatment from the perspective of Dutch payers in 2011. Data sources included published prucalopride clinical trials, published Dutch price/tariff lists, and national population statistics. The model simulated the clinical and economic outcomes associated with prucalopride vs. standard treatment and had a cycle length of 1 month and a follow-up time of 1 year. Response to treatment was defined as the proportion of patients who achieved "normal bowel function". One-way and probabilistic sensitivity analyses were conducted to test the robustness of the base case. RESULTS: In the base case analysis, the cost of prucalopride relative to continued laxative treatment was € 9015 per quality-adjusted life-year (QALY). Extensive sensitivity analyses and scenario analyses confirmed that the base case cost-effectiveness estimate was robust. One-way sensitivity analyses showed that the model was most sensitive in response to prucalopride; incremental cost-effectiveness ratios ranged from € 6475 to 15,380 per QALY. Probabilistic sensitivity analyses indicated that there is a greater than 80% probability that prucalopride would be cost-effective compared with continued standard treatment, assuming a willingness-to-pay threshold of € 20,000 per QALY from a Dutch societal perspective. A scenario analysis was performed for women only, which resulted in a cost-effectiveness ratio of € 7773 per QALY. CONCLUSION: Prucalopride was cost-effective in a Dutch patient population, as well as in a women-only subgroup, who had chronic constipation and who obtained inadequate relief from laxatives.

Nutrition economic evaluation of a probiotic in the prevention of antibiotic-associated diarrhea.

INTRODUCTION: Antibiotic-associated diarrhea (AAD) is common and frequently more severe in hospitalized elderly adults. It can lead to increased use of healthcare resources. We estimated the cost-effectiveness of a fermented milk (FM) with probiotic in preventing AAD and in particular Clostridium difficile-associated diarrhea (CDAD). METHODS: Clinical effectiveness data and cost information were incorporated in a model to estimate the cost impact of administering a FM containing the probiotic Lactobacillus paracasei ssp paracasei CNCM I-1518 in a hospital setting. Preventing AAD by the consumption of the probiotic was compared to no preventive strategy. RESULTS: The probiotic intervention to prevent AAD generated estimated mean cost savings of £339 per hospitalized patient over the age of 65 years and treated with antibiotics, compared to no preventive probiotic. Estimated cost savings were sensitive to variation in the incidence of AAD, and to the proportion of patients who develop non-severe/severe AAD. However, probiotics remained cost saving in all sensitivity analyses. CONCLUSION: Use of the fermented dairy drink containing the probiotic L. paracasei CNCM I-1518 to prevent AAD in older hospitalized patients treated with antibiotics could lead to substantial cost savings.

The economic value of enteral medical nutrition in the management of disease-related malnutrition: a systematic review.

Economic evaluations for medical nutrition, such as oral nutritional supplements (ONS), are relatively uncommon compared with other health technologies, and represent an area that has not been reviewed so far. In this systematic review, economic evaluations of enteral medical nutrition in the management of disease-related malnutrition (DRM) were reviewed and qualified to estimate the economic value. Initially, 481 studies were found, of which 37 full-text articles were assessed for eligibility and were rated on their quality using the Quality of Health Economic Studies (QHES) instrument. The final review focused on the high QHES quality economic evaluation studies. As both the studied medical nutrition intervention and the form of the economic evaluation varied, a quantitative synthesis (meta-analysis) was not attempted but a critical analysis and comparison of the individual study results were performed. ONS was the most studied intervention, covering several patient populations and different health care settings. Outcomes included cost savings (n = 3), no significant extra costs per unit of clinical and/or functional improvement (n = 1), or significantly higher costs per unit of clinical and/or functional improvement but still cost-effective for the used threshold (n = 4). This review shows that the use of enteral medical nutrition in the management of DRM can be efficient from a health economic perspective.

The economic costs of disease related malnutrition.

BACKGROUND & AIMS: Disease related malnutrition (under-nutrition caused by illness) is a worldwide problem in all health care settings with potentially serious consequences on a physical as well as a psycho-social level. In the European Union countries about 20 million patients are affected by disease related malnutrition, costing EU governments up to € 120 billion annually. The aim of this study is to calculate the total additional costs of disease related malnutrition in The Netherlands. METHODS: A cost-of-illness analysis was used to calculate the additional total costs of disease related malnutrition in adults (>18 years of age) for The Netherlands in 2011 in the hospital, nursing- and residential home and home care setting, expressed as an absolute monetary value as well as a percentage of the total Dutch national health expenditure and as a percentage of the total costs of the studied health care sectors in The Netherlands. RESULTS: The total additional costs of managing adult patients with disease related malnutrition were estimated to be € 1.9 billion in 2011 which equals 2.1% of the total Dutch national health expenditure and 4.9% of the total costs of the health care sectors analyzed in this study. CONCLUSIONS: The results of this study show that the additional costs of disease related malnutrition in adults in The Netherlands are considerable.

Primary prevention of nephrolithiasis is cost-effective for a national healthcare system.

UNLABELLED: Study Type--Therapy (cost-effectiveness meeting) Level of Evidence 2b. What's known on the subject? and What does the study add? One of the major problems with nephrolithiasis is the high rate of recurrence, which can effect up to 50% of patients over a 5-year period. Patients with recurrent stones are recommended to increase fluid intake based on prospective studies that show a reduction in recurrence rates in patients who intake a high volume of water. Strategies to reduce stones in recurrent stone formers are quite effective with a >50% risk reduction with increased fluid intake alone. Unfortunately, despite a high societal cost and morbidity, there are no prospective studies evaluating the benefit of fluid intake to prevent stone disease in subjects without a prior history of stone but at risk for stones. The budget impact analyses show that prevention of nephrolithiasis can have a significant cost savings for a payer in a healthcare system and reduce the stone burden significantly. Future studies will need to assess the feasibility and effectiveness of such an approach in a population. OBJECTIVE: • To evaluate the impact of primary prevention of stones using a strategy of increased fluid intake. SUBJECTS AND METHODS: • A Markov model was constructed and analysed using Excel to calculate and compare the costs and outcomes for a virtual cohort of subjects with low vs high water intake. • A literature search was used to formulate assumptions for the model including an annual incidence of urolithiasis of 0.032%, annual risk of stone recurrence of 14.4% and 40% risk reduction in subjects with high water intake. • Costs were based on resource utilisation from the Delphi panel and official price lists in France. • Outcomes were based on payer perspective and included direct and indirect costs and loss of work. RESULTS: • The base-case analysis found total cost of urolithiasis is €4267 with direct costs of €2767, including cost of treatment and complications. The annual budget impact for stone disease based on 65 million inhabitants is €590 million for the payer. • The use of high water intake by 100% of the population results in annual cost savings of €273 million and 9265 fewer stones. Even if only 25% of the population is compliant, there is still a cost saving of €68 million and 2316 stones. • The model was evaluated to determine the impact of varying the assumptions by ±10%. For example, when the incidence of stone disease is increased or decreased by 10% then the mean (range) baseline cost will change by €59(531-649) million for the payer and savings will either increase or decrease by €27 (246-300) million. • The largest impact on cost savings occurs when varying risk reduction of water by 10% resulting in either a mean (range) increase or decrease by €35 (238-308) million. • Varying cost of stone management by 10% has an impact of ±€17 million. Varying other factors such as stone recurrence by 10% has only an impact of ±€9 million and varying risk of chronic kidney disease ±€1 million, as they affect only a portion of the population. CONCLUSIONS: • The budget impact analyses show that prevention of nephrolithiasis can have a significant cost savings for a payer in a healthcare system and reduce the stone burden significantly. • Future studies will need to assess the feasibility and effectiveness of such an approach in a population.

Cost-effectiveness of escitalopram in major depressive disorder in the Dutch health care setting.

OBJECTIVE: This study assessed the cost-effectiveness of escitalopram for the treatment of depression in the Netherlands from a societal perspective. METHODS: A decision tree model was constructed using decision analytical techniques. Data sources included published literature, clinical trials, official price/tariff lists, national population statistics, and Delphi panel data. The comparators were venlafaxine XR and citalopram. The primary perspective of this health economic evaluation was that of the society in the Netherlands in 2010. The time horizon was 26 weeks. The effectiveness outcomes of the study were quality-adjusted life-years (QALYs). RESULTS: Escitalopram was associated with a cost savings per patient of €263 versus venlafaxine XR and €1992 versus citalopram over a period of 26 weeks from a societal perspective. Escitalopram was also associated with a gains QALYs: 0.0062 versus venlafaxine XR and 0.0166 versus citalopram. Escitalopram was dominant over both venlafaxine XR and citalopram. CONCLUSION: Based on the findings from this cost-effectiveness analysis, the favorable clinical benefit of escitalopram resulted in a positive health economic benefit in the Netherlands.

The budget impact of oral nutritional supplements for disease related malnutrition in elderly in the community setting.

A health economic analysis was performed to assess the economic impact on the national health care budget of using oral nutritional supplements (ONS), being a food for special medical purposes also known as medical nutrition, for the treatment of disease related malnutrition (DRM) in the community in the Netherlands. An economic model was developed to calculate the budget impact of using ONS in community dwelling elderly (>5 years) with DRM in the Netherlands. The model reflects the costs of DRM and the cost reductions resulting from improvement in DRM due to treatment with ONS. Using ONS for the treatment of DRM in community dwelling elderly, leads to a total annual cost savings of € 13 million (18.9% savings), when all eligible patients are treated. The additional costs of ONS (€ 57 million) are more than balanced by a reduction of other health care costs, e.g., re-/hospitalization (€ 70 million). Sensitivity analyses were performed on all parameters, including duration of treatment with ONS and the prevalence of DRM. This budget impact analysis shows that the use of ONS for treatment of DRM in elderly patients in the community may lead to cost savings in the Netherlands.

Cost-effectiveness of palivizumab for respiratory syncytial virus infection in high-risk children, based on long-term epidemiologic data from Austria.

OBJECTIVE: To assess the cost-effectiveness of palivizumab, a monoclonal antibody against respiratory syncytial virus (RSV), in infants at high risk for severe RSV lower respiratory tract infection, such as premature infants, infants with bronchopulmonary dysplasia, and those with congenital heart disease, based on long-term epidemiologic data from Austria. METHODS: A decision-tree model was used, and the analysis was based on a lifetime follow-up investigating cost-effectiveness of palivizumab versus no RSV infection prevention. The primary perspective of the study was that of the healthcare system, the second that of society. Cost and effects were discounted by 5%. The base case analysis included only direct medical costs, and a scenario analysis included various indirect costs. RESULTS: Analyses were based on epidemiologic data on a total of 1579 children hospitalized because of RSV lower respiratory tract infection during 16 seasons. The incremental cost-effectiveness ratio for the first outcome measure (life years gained) amounted to discounted costs of €34,956 (for all preterm infants), €35,056 (for < 33 weeks' gestational age [wGA] infants), €35,233 (for 33-35 wGA infants), €35,611 (for infants with bronchopulmonary dysplasia), and €8956 (for infants with congenital heart disease). Use of palivizumab compared with no prophylaxis had an incremental cost-utility ratio of €26,212, €26,292, €24,392, €24,654, and €8484, respectively, per quality-adjusted life years. Results from the society perspective were more cost-effective in all study populations. An additional scenario analysis with 7 injections for the 33 to 35 wGA group revealed cost-effectiveness as well. CONCLUSIONS: Our results based on nationwide long-term epidemiologic data suggest that palivizumab is cost-effective in prevention of RSV disease in high-risk infants.

A cross-market cost comparison of erlotinib versus pemetrexed for first-line maintenance treatment of patients with locally advanced or metastatic non-small-cell lung cancer.

Erlotinib and pemetrexed were approved by the European Medicines Agency for first-line maintenance treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) to prolong overall survival after first-line therapy. An adjusted, matched, indirect comparison of erlotinib and pemetrexed suggested that survival benefits were not statistically significantly different between treatments. We conducted a cost-comparison analysis of erlotinib versus pemetrexed in first-line maintenance treatment of locally advanced or metastatic, non-squamous NSCLC in France, Germany, Italy and Spain, performed from the perspective of national health-care decision-makers or purchasers. The analysis was limited to direct costs and comprised drug-acquisition costs, administration costs and costs of treating adverse events (AEs). A one-way sensitivity analysis on administration, acquisition and AE costs was also performed. Total monthly per-patient treatment costs for erlotinib in France, Germany, Italy and Spain were €2140, €2732, €1518 and €2048, respectively, and for pemetrexed €3453, €5534, €2921 and €3164, respectively. AE cost was greater for pemetrexed in all countries, as was administration cost. As an oral treatment, erlotinib is not associated with any administration costs, except in Germany, where the cost is lower than for pemetrexed. The sensitivity analysis showed acquisition costs to be the main driver of total monthly per-patient costs. Erlotinib appears to be a cost-saving treatment alternative to pemetrexed, producing comparable survival benefits, based on an indirect comparison, at a lower cost.

An indirect comparison of the efficacy of bevacizumab plus carboplatin and paclitaxel versus pemetrexed with cisplatin in patients with advanced or recurrent non-squamous adenocarcinoma non-small cell lung cancer.

OBJECTIVE: There are two new treatment options available for the treatment of adenocarcinoma histology non-small cell lung cancer (NSCLC) which offer improved benefit in terms of progression-free (PFS) and overall survival (OS) over chemotherapy. Both bevacizumab and pemetrexed when combined with chemotherapy significantly increase PFS and OS in patients with advanced NSCLC versus chemotherapy alone. The aim of this analysis was to compare the efficacy for patients with non-squamous adenocarcinoma NSCLC treated with bevacizumab, carboplatin and paclitaxel (BCP) to pemetrexed and cisplatin (PC) by using indirect comparison (ITC) methodology. EXPERIMENTAL DESIGN: In the absence of head-to-head trials, ITC was performed on patients with adenocarcinoma histology non-squamous NSCLC to compare the relative benefit of first-line therapies BCP vs. PC by hazard ratios (HR). Subsequently, these HRs were used in a decision-analytic Markov model with a lifelong time horizon to extrapolate the long-term effectiveness of the two treatments. RESULTS: ITC estimated HRs for the primary endpoints in the bevacizumab study E4599 showed that BCP treatment in non-squamous adenocarcinoma NSCLC patients resulted in a BCP HR of 0.82 versus PC. The long-term predictions from the Markov model yielded a mean survival of 1.48 years (95% CI 1.34, 1.62 years) (or 17.7 months) for BCP compared with 1.29 years (95% CI 1.16, 1.42 years) (or 15.4 months) for PC. CONCLUSIONS: Based on our decision analysis, triplet BCP targeted therapy in patients with advanced non-squamous adenocarcinoma NSCLC compared with doublet PC chemotherapy results in improved expected values for overall long-term survival. Therefore, from the efficacy perspective, bevacizumab in combination with platinum-based chemotherapy can be considered as the targeted therapy of choice for patients with advanced non-squamous adenocarcinoma NSCLC.

Cost-utility analysis: current methodological issues and future perspectives.

The use of cost-effectiveness as final criterion in the reimbursement process for listing of new pharmaceuticals can be questioned from a scientific and policy point of view. There is a lack of consensus on main methodological issues and consequently we may question the appropriateness of the use of cost-effectiveness data in health care decision-making. Another concern is the appropriateness of the selection and use of an incremental cost-effectiveness threshold (Cost/QALY). In this review, we focus mainly on only some key methodological concerns relating to discounting, the utility concept, cost assessment, and modeling methodologies. Finally we will consider the relevance of some other important decision criteria, like social values and equity.

A concise equation that captures the essential elements of one-way sensitivity analyses in health economic models.

OBJECTIVE: Sensitivity analyses are often performed on only a limited number of variables without justification of the choice of variables and range of each variable. External parties such as health authorities are increasingly requiring submission of the actual model, often in order to test the robustness of the outcomes of the model by performing additional sensitivity analyses. The objective of this work was to develop an alternative method to capture the critical issues of a sensitivity analysis in a health economic model, especially regarding the selection of variables and determining the range for each variable. Apart from external parties such as health authorities, journal readers who want to perform their own sensitivity analysis but do not have access to the model may find this useful. METHODS AND RESULTS: Statistical methods based on Markov chain modeling and regression analysis, using the framework of the Taylor series expansion around a point, are used to derive an equation for 1-way sensitivity analyses. In particular, equations for costs and effects are being developed, from which the cost-effectiveness ratio is built. The article shows the feasibility of such equations for the execution of 1-way sensitivity analyses. CONCLUSION: An equation that can be derived in the manner described in this article provides a substantial amount of information. The inclusion of such an equation in a report may increase transparency of the reporting of outcomes of health economic models.

Cost-effectiveness of palivizumab against respiratory syncytial viral infection in high-risk children in Austria.

OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of palivizumab, a monoclonal antibody against severe respiratory syncytial virus infection, in high-risk infants in Austria. METHODS: A decision tree model was developed to determine cost-effectiveness in infants born prematurely (

Pricing matrix model: dealing with uncertainty.

A previous publication in this journal showed that the pricing matrix model (PMM) allows an assessment of the pricing potential of a new innovative product. When the PMM is going to be used for the determination of a drug price for a new drug in the strategic product planning process, it is important that this methodology is reliable. In the initial paper the PMM only yielded an expected price for the new antidepressant without generating an estimate of the probability that the new drug would indeed be listed at this expected price. In this manuscript we present various methodologies to deal with uncertainty in the PMM. We introduce the concept of price acceptability curves. The conclusion of this paper is that the incorporation of uncertainty into the PMM will lead to a more accurate assessment of the pricing potential of a new drug.

Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis.

OBJECTIVE: To assess the cost effectiveness of palivizumab (a preventative treatment against severe respiratory syncytial virus [RSV] infection) in children at high risk of hospitalisation, i.e. preterm infants < or = 35 weeks gestation, children with bronchopulmonary dysplasia (BPD) and children with congenital heart disease (CHD). METHODS: A decision tree model was developed employing data sources from the published literature, palivizumab clinical trials, official UK price/tariff lists and national population statistics. The comparator was no prophylaxis. The primary perspective of the study was that of the UK NHS. In a societal perspective scenario analysis, the future lost productivity of a child resulting from RSV-related mortality (indirect costs) was also included. The cost of administration of palivizumab, hospital care for RSV infections and the cost of asthma treatment were included. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. The primary efficacy outcome in the palivizumab clinical trials was the number of RSV hospitalisations avoided, which was extrapolated to effectiveness outcomes, i.e. number of life-years gained and number of QALYs. Costs and effects were discounted by 3.5%. RESULTS: In preterm infants and children with BPD, prophylaxis with palivizumab compared with no prophylaxis had an incremental cost-effectiveness ratio (ICER) of 7042 pounds/QALY without discounting outcomes, increasing to 16,720 pounds/QALY after discounting. In babies with CHD, the use of palivizumab resulted in an ICER of 2427 pounds/QALY without discounting outcomes and 6664 pounds/QALY after discounting. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. A scenario analysis showed that the inclusion of indirect costs leads to further improvement in the cost-effectiveness outcomes for palivizumab. CONCLUSION: This study suggests that palivizumab prophylaxis against severe RSV infection in children at high risk may be cost effective from the NHS perspective (vs no prophylaxis), and that the positive clinical and economic benefits may persist beyond one RSV season.

Economic evaluation of tramadol/paracetamol combination tablets for osteoarthritis pain in the Netherlands.

OBJECTIVE: To compare the costs of treating osteoarthritis (OA) pain using combination tramadol/paracetamol tablets, NSAIDs alone, NSAIDs plus proton pump inhibitors (PPIs), or NSAIDs plus histamine H(2)-receptor antagonists (H(2)RAs) from the perspective of the Dutch healthcare system. DESIGN AND METHODS: A decision-analytical model was constructed to model the cost outcomes of the four treatment strategies over 6 months. A cost-minimisation approach was used, which considered data related to resource utilisation, medication costs and costs for the treatment of adverse events. Data, derived mainly from the clinical literature, were supplemented by inputs from a Delphi panel as well as official price and tariff lists. The base-case analysis considered direct medical costs, including those for treating all adverse events with tramadol/paracetamol and gastrointestinal (GI) adverse events with NSAIDs. Separate scenario analyses explored costs of NSAID-based regimens: (i) according to 21 levels of risk for GI adverse events, and (ii) when renal events attributable to NSAIDs were considered. Robustness of the model was tested using univariate sensitivity analysis. RESULTS: In the base-case analysis, costs for 6 months' treatment of OA pain using tramadol/paracetamol were euro244.45, compared with euro317.32 for NSAIDs + PPIs, euro200.67 for NSAIDs + H(2)RAs, and euro125.86 for NSAIDs alone. This provided a cost saving of euro72.87 per patient over 6 months for tramadol/paracetamol compared with NSAIDs + PPIs. Tramadol/paracetamol became cost saving compared with NSAIDs alone and NSAIDs + H(2)RAs for GI risk levels >13 and >10, respectively. When renal adverse events of NSAIDs were con- sidered, tramadol/paracetamol was cost saving compared with all NSAID-based regimens (saving euro228.40 vs NSAIDs, euro418.42 vs NSAIDs + PPIs, and euro302.69 vs NSAIDs + H(2)RAs [year of costing 2005]). Sensitivity analysis confirmed the model was robust to wide-ranging changes in the value of input parameters. CONCLUSION: Tramadol/paracetamol is cost saving compared with NSAIDs + PPIs for the treatment of OA pain over a period of 6 months regardless of the risk of GI or renal complications. Tramadol/paracetamol is also cost saving compared with treatment with NSAIDs alone and NSAIDs + H(2)RAs for patients at medium and high risk of GI adverse events and in all cases if considering renal adverse events. Despite not being quantified in monetary terms, the lower incidence of adverse events with tramadol/paracetamol is a clinical benefit.

Pricing of pharmaceuticals. Assessing the pricing potential by a pricing matrix model.

Pricing and reimbursement of new pharmaceuticals have been based until recently on the traditional clinical trial outcomes (efficacy, safety, and quality parameters) used for registration. Now we can distinguish various additional data requirements which relate to the use of the drug in real daily practice. The most important new data requirements are effectiveness, cost-effectiveness, and budgetary impact. A main question is how much the impact is of the various types of data in the pricing and reimbursement process. The objective of this contribution is to present a method for quantifying this type of uncertainty in order to develop a more solid pricing and reimbursement strategy for a new innovative drug. The concepts are illustrated for a new hypothetical antidepressant drug in The Netherlands. This method is based on the analytic hierarchy process (AHP) concept which measures decision makers' preferences for the critical success factors. This study shows that the AHP concept may be applied to the pricing and reimbursement environment. The method may be used to assess the pricing potential of a new drug, considering the various data requirements in the reimbursement process.

Incorporation of statistical uncertainty in health economic modelling studies using second-order Monte Carlo simulations.

Health economic modelling studies are of interest to many parties with different responsibilities and diverging interests. Therefore, it is obvious that recognising the relevance of statistical uncertainty and dealing with it appropriately are required to obtain unbiased results from health economic modelling studies, especially when those data are being used for reimbursement decisions. In this manuscript we explore the relevance of the incorporation of statistical uncertainty in a health economic model and identify various types of statistical uncertainty. The concepts were applied to a hypothetical Markov model for a hypothetical antiparkinsonian (AP) product. The method was based on the incorporation of probability distributions in the input variables using a second-order Monte Carlo simulation and the definition of minimum relevant differences for clinical and economic input variables and outcomes. Our paper shows that the outcomes of a health economic model might be severely biased when statistical uncertainty is not taken into account, which justifies the need for the incorporation of statistical uncertainty in a health economic model.