Hyperkalemia in chronic kidney disease patients with and without heart failure: an Italian economic modelling study.

BACKGROUND: Hyperkalemia (HK) is frequently present in chronic kidney disease (CKD). Risk factors for HK among CKD patients include comorbidities and renin-angiotensin-aldosterone system inhibitor (RAASi) treatment. Current standard of care (SoC) often necessitates RAASi down-titration or discontinuation, resulting in poorer cardiorenal outcomes, hospitalization and mortality. This study evaluates the cost-effectiveness of patiromer for HK in CKD patients with and without heart failure (HF) in an Italian setting. METHODS: A lifetime Markov cohort model was developed based on OPAL-HK to assess the health economic impact of patiromer therapy in comparison to SoC after accounting for the effects of HK and RAASi use on clinical events. Outcomes included accumulated clinical events, number needed to treat (NNT) and the incremental cost-effectiveness ratio (ICER). Subgroup analysis was conducted in CKD patients with and without HF. RESULTS: Patiromer was associated with an incremental discounted cost of €4,660 and 0.194 quality adjusted life years (QALYs), yielding an ICER of €24,004. Per 1000 patients, patiromer treatment prevented 275 moderate/severe HK events, 54 major adverse cardiovascular event, 246 RAASi discontinuation and 213 RAASi up-titration/restart. Subgroup analysis showed patiromer was more effective in preventing clinical events in CKD patients with HF compared to those without; QALY gains were greater in CKD patients without HF versus those with HF (0.267 versus 0.092, respectively). Scenario analysis and sensitivity analysis results support base-case conclusions. CONCLUSION: Patiromer is associated with QALY gains in CKD patients with and without HF compared to SoC in Italy. Patiromer prevented HK events, enabled RAASi therapy maintenance and reduced cardiovascular event risk.

Productivity Loss Among Parents of Children With Inflammatory Bowel Diseases in Relation to Disease Activity and Patient's Quality of Life.

OBJECTIVES: To assess the productivity losses among the parents of children with inflammatory bowel diseases (IBDs) in Poland and their relationship with disease activity and the patient's quality of life. METHODS: A questionnaire-based self-reported Internet survey was conducted among the parents of patients (0--17 years old) with a diagnosis of ulcerative colitis (UC) or Crohn disease (CD). Data on indirect and direct costs, general patient characteristics, disease activity, pharmacological treatment, and children's quality of life measured with the Pediatric Quality of Life Inventory (PedsQL) were collected. RESULTS: A total of 113 completed questionnaires were obtained. Remission was reported in 58.6% of cases. Severe disease was more common in patients with UC (7.3% vs 2.9%). The mean reduction in parents' daily activities was 40% (range: 0%-100%). The mean (SD) reduction of parents' work productivity because of absenteeism was 21% (0.27), and the mean cost was &OV0556;902.77 (1136.90) per year per parent. The mean (SD) productivity loss at paid work of a working parent (presenteeism) was 35% (0.31) and the mean (SD) cost was &OV0556;1125.13 (1121.16) per year per parent. The PedsQL score was significantly higher among patients with inactive than with active disease. CONCLUSIONS: A significant difference between patients with inactive and active disease was observed for the total reduction of parent's work productivity and the PedsQL score. A negative correlation was observed for indirect costs and the PedsQL score for the whole study population; better health-related quality of life among patients in remission was revealed.

Reimbursement Status and Recommendations Related to Orphan Drugs in European Countries.

Objective: To review the reimbursement recommendations issued by selected European health technology assessment agencies for orphan drugs and the reimbursement status of these drugs; to assess the relationship between the type of recommendation and reimbursement status. Methods: The list of orphan drugs to be included in the analysis was obtained from the European Medicines Agency and Orphanet. Seven European states were included in the analysis: Belgium, England, France, Germany, Poland, Scotland, and Spain. For all identified orphan drugs, relevant data on the reimbursement status and type of recommendation were collected for each country. The relationship between the type of recommendation and reimbursement status was evaluated separately for each considered country, using Cohen's kappa coefficient for the measurement of agreement; sub-analyses for oncology and metabolic drugs were performed. Results: Most reimbursement recommendations for orphan drugs were positive (71%), while approximately 17% were negative and almost 13% were conditional. The highest percentage of positive reimbursement recommendations was observed in Spain (97%) and France (95%) and the highest percentage of negative reimbursement recommendations was revealed for Poland (49%). On average, 65% of the 163 analyzed orphan drugs were reimbursed from public funds. The highest number of reimbursed orphan drugs was observed in Germany (n = 148), while the lowest, in Poland (n = 41). Considering all analyzed drugs, the highest agreement between recommendations and reimbursement status was observed for Spain (value of 1), and the lowest, for Germany (κ = -0.03). Conclusions: On average, more than 60% of identified orphan drugs were reimbursed from public funds in the included countries, and the majority of reimbursement recommendations were found to be positive. The agreement between reimbursement recommendations and reimbursement status differed between the countries, but overall, it did not show any patterns, as it ranged from -0.03 to 1 (κ coefficient).

The European challenges of funding orphan medicinal products.

BACKGROUND: Funding of orphan medicinal products (OMPs) is an increasing challenge in the European Union (EU). OBJECTIVES: To identify the different methods for public funding of OMPs in order to map the availability for rare disease patients, as well as to compare the public expenditures on OMPs in 8 EU member states. METHODS: Information on the reimbursement status of 83 OMPs was collected in 8 countries by distinguishing standard and special reimbursements. In two consecutive years, the total public expenditures on OMPs were calculated by using annual EUR exchange rates. Annual total public expenditures were calculated per capita, and as a proportion of GDP, total public pharmaceutical and healthcare budgets. Differences between countries were compared by calculating the deviations from the average spending of countries. RESULTS: In 2015 29.4-92.8% of the 83 OMPs were available with any kind of public reimbursement in participant countries including special reimbursement on an individual basis. In Austria, Belgium and France more OMPs were accessible for patients with public reimbursement than in Bulgaria, Czech Republic, Hungary and Poland. Standard reimbursement through retail pharmacies and/or hospitals was applied from 0 to 41% of OMPs. The average annual total public expenditure ranged between 1.4-23.5 €/capita in 2013 and 2014. Higher income countries spent more OMPs in absolute terms. Participant countries spent 0.018-0.066% of their GDPs on funding OMPs. Average expenditures on OMPs were ranged between 2.25-6.51% of the public pharmaceutical budget, and 0.44-0.96% of public healthcare expenditures. CONCLUSIONS: Standard and special reimbursement techniques play different roles in participant countries. The number of accessible OMPs indicated an equity gap between Eastern and Western Europe. The spending on OMPs as a proportion of GDP, public pharmaceutical and healthcare expenditure was not higher in lower income countries, which indicates substantial differences in patient access to OMPs in favour of higher-income countries. Equity in access for patients with rare diseases is an important policy objective in each member state of the EU; however, equity in access should be harmonized at the European level.

Relationship between physician-based assessment of disease activity, quality of life, and costs of ulcerative colitis in Poland.

INTRODUCTION: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disorder, which requires lifelong treatment. It generates substantial direct and indirect costs, and significantly affects the quality of life, especially in the active state of the disease. AIM: To evaluate the direct and indirect costs of UC as well as to assess disease activity and quality of life reported by patients with UC in Polish settings. MATERIAL AND METHODS: A questionnaire, cross-sectional study among UC patients as well as physicians involved in the therapy of the patients was conducted. The Clinical Activity Index (CAI) was used to assess disease activity, and the WPAI questionnaire to assess productivity loss. The quality of life was presented as utility calculated using the EQ-5D-3L questionnaire. Indirect costs included absenteeism, presenteeism, and informal care were assessed with the Human Capital Approach and expressed in euros (€). The productivity loss among informal caregivers was valuated with the average wage in Poland. Correlations were presented using the Spearman's coefficient, and the between-group difference was assessed with Mann-Whitney U-test. RESULTS: One hundred and forty-seven patients participated in the study, including 95 working persons. Mean cost of absenteeism and presenteeism was €1615.2 (95% CI: 669.5-2561.0) and €3684.4 (95% CI: 2367.8-5001.1), respectively, per year per patient with a disease in remission. The mean yearly cost of productivity loss due to informal care was estimated to be €256.6 (range: 0.0-532.6). The corresponding values for patients with active disease were: €8,913.3 (95% CI: 6223.3-11,603.3), €4325.1 (95% CI: 2282.4-6367.8), and €2396.1 (95% CI: 402.0-4390.3). The between-group difference in total indirect costs, cost of absenteeism, and cost of informal care was statistically significant (p < 0.05). The average weighted monthly costs of therapy with particular drugs categories (e.g. mesalazine or biologic drugs) differed significantly between active disease or remission patients. The difference in utility values between patients with a disease in remission (0.898 ±0.126) and patients with an active disease (0.646 ±0.302) was statistically significant. CONCLUSIONS: Our study revealed the social burden of UC and high dependency of direct and indirect costs as well as quality of life on the severity of UC in Poland. The statistically significant differences were identified in total direct and indirect cost, cost of absenteeism, cost of informal care, and health-related quality of life among patients with an active disease compared to patients with a disease in remission.

A Systematic Review of the Cost-Effectiveness of Biologics for Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic autoimmune inflammation of the colon. The condition significantly decreases quality of life and generates a substantial economic burden for healthcare payers, patients and the society in which they live. Some patients require chronic pharmacotherapy, and access to novel biologic drugs might be crucial for long-term remission. The analyses of cost-effectiveness for biologic drugs are necessary to assess their efficiency and provide the best available drugs to patients. OBJECTIVE: Our aim was to collect and assess the quality of economic analyses carried out for biologic agents used in the treatment of UC, as well as to summarize evidence on the drivers of cost-effectiveness and evaluate the transferability and generalizability of conclusions. METHODS: A systematic database review was conducted using MEDLINE (via PubMed), EMBASE, Cost-Effectiveness Analysis Registry and CRD0. Both authors independently reviewed the identified articles to determine their eligibility for final review. Hand searching of references in collected papers was also performed to find any relevant articles. The reporting quality of economic analyses included was evaluated by two reviewers using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement checklist. We reviewed the sensitivity analyses in cost-effectiveness analyses to identify the variables that may have changed the conclusions of the study. Key drivers of cost-effectiveness were selected by identifying uncertain parameters that caused the highest change of the results of the analyses compared with base-case results. RESULTS: Of the 576 identified records, 87 were excluded as duplicates and 16 studies were included in the final review; evaluations for Canada, the UK and Poland were mostly performed. The majority of the evaluations revealed were performed for infliximab (approximately 75% of total volume); however, some assessments were also performed for adalimumab (50%) and golimumab (31%). Only three analyses were conducted for vedolizumab, whereas no relevant studies were found for etrolizumab and tofacitinib. The reporting quality of the included economic analyses was assessed as high, with an average score of 21 points per 24 maximum possible (range 14-23 points according to the ISPOR CHEERS statement checklist). In the case of most analyses, quality-adjusted life-years were used as a clinical outcome, and endpoints such as remission, response and mucosal healing were less common. The higher clinical effectiveness (based on response rates) of biological treatment over non-biological treatments was presented in revealed analyses. The incremental cost-utility ratios for biologics, compared with standard care, varied significantly between the studies and ranged from US$36,309 to US$456,979. The lowest value was obtained for infliximab and the highest for the treatment scheme including infliximab 5 mg/kg and infliximab 10 mg/kg + adalimumab. The change of utility weights and clinical parameters had the most significant influence on the results of the analysis; the variable related to surgery was the least sensitive. CONCLUSIONS: Limited data on the cost-effectiveness of UC therapy were identified. In the majority of studies, the lack of cost-effectiveness was revealed for biologics, which was associated with their high costs. Clinical outcomes are transferable to other countries and could be generalized; however, cost inputs are country-specific and therefore limit the transferability and generalizability of conclusions. The key drivers and variables that showed the greatest effect on the analysis results were utility weights and clinical parameters.

Prevalence and drug treatment practices of inflammatory bowel diseases in Poland in the years 2012-2014: an analysis of nationwide databases.

BACKGROUND: Inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn's disease (CD) are chronic autoimmune disorders that constitute a major societal and economic burden for individual patients, their families and the society. The aim of this study was to assess the current prevalence and treatment patterns of IBD in Poland. PATIENTS AND METHODS: We carried out a retrospective analysis of the nationwide databases of the National Health Fund for the years from 2012 to 2014 to obtain data on the prevalence and treatment patterns of IBD. Patients with IBD were identified according to the ICD-10 codes indicated in medical records and the type of medical resource utilized during the study. Pharmacotherapy for IBD by age group, sex and IBD types was presented. RESULTS: The prevalence of IBDs was 157/100 000 individuals, including 35 patients with CD per 100 000 individuals. The use of drugs differed by age and diagnosis (P<0.001). Biologics, steroids and immunosuppressants were used more often by patients with CD than those with UC (13.2 vs. 0.3%, 54.5 vs. 37.5%, and 44.8 vs. 15.1%, respectively). Aminosalicylates were used more often by patients with UC than those with CD. Biologics were used most often by the youngest patients (≤18 years) and seldom by patients aged 65 years or older (7.7 and 0.1%, respectively). CONCLUSION: Our study showed a moderate prevalence of IBD in Poland. Treatment patterns depended on the patient's age and IBD type. The use of biologics was higher among young patients with CD than among older patients with other IBDs. Although not recommended, aminosalicylates were still commonly used in patients with CD, even during biologic and/or immunosuppressive treatment.

Cost-effectiveness of biological treatment of ulcerative colitis - a systematic review.

The aim of this systematic review was to collect and summarise all current data on the cost-effectiveness of biological treatment in ulcerative colitis. A literature search was conducted using the Medline, Embase, Centre for Reviews and Dissemination databases and included all cost-effectiveness analyses comparing biological treatment with any comparator. We identified 277 records of which 10 were included in this review. Eighty percent of identified analyses used quality-adjusted life years (QALY) as a measure of outcome. The most commonly assessed biological agent was infliximab. Half of the eight economic analyses, with QALY as an outcome, showed the cost-effectiveness of biological treatment against the comparator. Incremental cost-effectiveness ratios (ICER) ranged from 15,748 euro to 450,791 euro. The highest ICER values were observed when biologicals were compared with standard care alone. This systematic review revealed that in some cases the biological treatment, despite its clinical effectiveness, is too expensive and exceeds the national threshold value.

Pricing and Reimbursement of Biosimilars in Central and Eastern European Countries.

Objectives: The aim of this study was to review the requirements for the reimbursement of biosimilars and to compare the reimbursement status, market share, and reimbursement costs of biosimilars in selected Central and Eastern European (CEE) countries. Methods: A questionnaire-based survey was conducted between November 2016 and January 2017 among experts from the following CEE countries: Bulgaria, Czech Republic, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia, and Romania. The requirements for the pricing and reimbursement of biosimilars were reviewed for each country. Data on the extent of reimbursement of biologic drugs (separately for original products and biosimilars) in the years 2014 and 2015 were also collected for each country, along with data on the total pharmaceutical and total public health care budgets. Results: Our survey revealed that no specific criteria were applied for the pricing and reimbursement of biosimilars in the selected CEE countries; the price of biosimilars was usually reduced compared with original drugs and specific price discounts were common. Substitution and interchangeability were generally allowed, although in most countries they were at the discretion of the physician after a clinical assessment. Original biologic drugs and the corresponding biosimilars were usually in the same homogeneous group, and internal reference pricing was usually employed. The reimbursement rate of biosimilars in the majority of the countries was the same and amounted to 100%. Generally, the higher shares of expenditures were shown for the reimbursement of original drugs than for biosimilars, except for filgrastim, somatropin, and epoetin (alfa and zeta). The shares of expenditures on the reimbursement of biosimilar products ranged from 8.0% in Estonia in 2014 to 32.4% in Lithuania in 2015, and generally increased in 2015. The share of expenditures on reimbursement of biosimilars in the total pharmaceutical budget differed between the countries, with the highest observed value for Slovakia and Hungary and the lowest-for Croatia. Conclusions: The requirements for the pricing and reimbursement of biosimilar products as well as the access of patients to biologic treatment do not differ significantly between the considered CEE countries. Biosimilar drugs significantly influence the reimbursement systems of these countries, and the expenditure on the reimbursement of biosimilars is increasing as they are becoming more accessible to patients.

Disease activity, quality of life, and indirect costs of ulcerative colitis in Poland.

INTRODUCTION: Ulcerative colitis (UC) require expensive, lifelong treatment, which generates huge direct costs and has a significant impact on the quality of life, especially in the active state of the disease. AIM: To assess the indirect costs, health-related quality of life, and clinical characteristics of patients with UC in Poland. Additionally, we investigated the association between activity of UC and productivity loss of patients in a Polish setting. MATERIAL AND METHODS: A questionnaire survey was conducted using the Patient Simple Clinical Colitis Activity Index (P-SCCAI) to assess disease activity, as well as the modified Work Productivity and Activity Impairment Questionnaire to assess productivity loss. The quality of life was presented as utility calculated with the EQ-5D-3L questionnaire. Indirect costs were assessed with the Human Capital Approach and were expressed in Polish zlotys (PLN) as well as in euros (€). Correlations were presented using the Spearman coefficient. RESULTS: We performed our analysis based on 202 full questionnaires collected. Mean patient age and age at disease onset were 33.14 years (standard deviation (SD): 9.90) and 26.35 years (SD: 8.89), respectively. The mean P-SCCAI score in the analysed group of patients was 8.26, and the mean utility was 0.8651. Average and median annual indirect costs per working person were €2043 and €1389 (8543 PLN and 5808 PLN), respectively, calculated using the gross domestic product, as well as €4791 and €3257 (20,026 PLN and 13,615 PLN), respectively, calculated using the gross value added. Total productivity loss was significantly correlated with the disease activity. CONCLUSIONS: Ulcerative colitis causes a decrease in the quality of life as well as patients' productivity loss associated with both absenteeism and with presenteeism.

Pharmaceutical Regulation in Central and Eastern European Countries: A Current Review.

Objectives: The aim of this study was to review reimbursement environment as well as pricing and reimbursement requirements for drugs in selected Central and Eastern Europe (CEE) countries. Methods: A questionnaire-based survey was performed in the period from November 2016 to March 2017 among experts involved in reimbursement matters from CEE countries: Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia, and Romania. A review of requirements for reimbursement and implications of Health Technology Assessment (HTA) was performed to compare the issues in above-mentioned countries. For each specified country, data for reimbursement costs, total pharmaceutical budget, and total public health care budget in the years 2014 and 2015 were also collected. Questionnaires were distributed via emails and feedback data were obtained in the same way. Additional questions, if any, were also submitted to respondents by email. Pricing and reimbursement data were valid for March 2017. Results: The survey revealed that the relation of drug reimbursement costs to total public healthcare spending ranged from 0.12 to 0.21 in the year 2014 and 2015 (median value). It also revealed that pricing criteria for drugs, employed in the CEE countries, were quite similar. External reference pricing as well as internal reference pricing were common in mentioned countries. Positive reimbursement lists were valid in all countries of the CEE region, negative ones were rarely used; reimbursement decisions were regularly revised and updated in the majority of countries. Copayment was common and available levels of reimbursement differed within and between the countries and ranged from 20 to 100%. Risk-sharing schemes were often in use, especially in the case of innovative, expensive drugs. Generic substitution was also possible in all analyzed CEE countries, while some made it mandatory. HTA was carried out in almost all of the considered CEE countries and HTA dossier was obligatory for submitting a pricing and reimbursement application. Conclusions: Pricing and reimbursement requirements are quite similar in the CEE region although some differences were identified. HTA evaluations are commonly used in considered countries.

Cost-Effectiveness Analysis of 1-Year Treatment with Golimumab/Standard Care and Standard Care Alone for Ulcerative Colitis in Poland.

OBJECTIVE: The objective of this study was to assess the cost-effectiveness of induction and maintenance treatment up to 1 year of ulcerative colitis with golimumab/standard care and standard care alone in Poland. METHODS: A Markov model was used to estimate the expected costs and effects of golimumab/standard care and a standard care alone. For each treatment option the costs and quality adjusted life years were calculated to estimate the incremental cost-utility ratio. The analysis was performed from the perspective of the Polish public payer and society over a 30-years time horizon. The clinical parameters were derived mainly from the PURSUIT-SC and PURSUIT-M clinical trials. Different direct and indirect costs and utility values were assigned to the various model health states. RESULTS: The treatment of ulcerative colitis patients with golimumab/standard care instead of a standard care alone resulted in 0.122 additional years of life with full health. The treatment with golimumab/standard care was found to be more expensive than treatment with the standard care alone from the public payer perspective and from social perspective. The incremental cost-utility ratio of golimumab/standard care compared to the standard care alone is estimated to be 391,252 PLN/QALY gained (93,155 €/QALYG) from public payer perspective and 374,377 PLN/QALY gained (89,137 €/QALYG) from social perspective. CONCLUSIONS: The biologic treatment of ulcerative colitis patients with golimumab/standard care is more effective but also more costly compared with standard care alone.

Cost-utility analysis of 1-year treatment with adalimumab/standard care and standard care alone for ulcerative colitis in Poland.

PURPOSE: Until recently, surgery was the only remaining choice for moderate to severe chronic ulcerative colitis patients who failed standard treatment or when it was not tolerated. Anti-TNFα treatment is a new, non-invasive option for the management of ulcerative colitis. The objective of this study was to assess the cost-effectiveness of induction and maintenance treatment up to 1 year of ulcerative colitis with adalimumab/standard care and standard care alone in Poland. METHODS: A Markov model was used to estimate the expected costs and effects of adalimumab/standard care and a standard care alone. For each treatment option, the costs and quality adjusted life years were calculated to estimate the incremental cost-utility ratio. The analysis was performed from the perspective of the Polish public payer and society over a 30-year time horizon. Different direct and indirect costs and utility values were assigned to the various model health states. RESULTS: The treatment of ulcerative colitis patients with adalimumab/standard care up to 1 year instead of a standard care alone resulted in 0.14 additional years of life with full health (QALYs). The incremental cost-utility ratio of adalimumab/standard care compared to the standard care alone is estimated to be 76,120 €/QALY gained from NHF perspective and 71,457 €/QALY gained from social perspective. CONCLUSIONS: The biologic treatment of ulcerative colitis patients with adalimumab/standard care is more effective but also more costly compared with standard care alone.

Cost-Utility Analysis of Infliximab with Standard Care versus Standard Care Alone for Induction and Maintenance Treatment of Patients with Ulcerative Colitis in Poland.

STUDY OBJECTIVE: To assess the cost-effectiveness of infliximab with standard care (e.g., azathioprine, prednisolone, mesalazine, and 6-mercaptopurine) versus standard care alone for induction and maintenance treatment of patients with ulcerative colitis (UC) in Poland. DESIGN: Cost-utility decision analytic model. MEASUREMENTS AND MAIN RESULTS: A Markov model was used to estimate the expected costs and effects of infliximab/standard care and standard care alone. For each treatment option, costs and quality-adjusted life-years (QALYs) were calculated to estimate the incremental cost-utility ratio. The target population consisted of a hypothetical cohort of adult patients with moderately to severely active UC who had an inadequate response to standard treatment, including corticosteroids and 6-mercaptopurine or azathioprine, or who were intolerant to or had medical contraindications to such therapies. The analysis was performed from the perspective of the Polish public payer over a 30-year time horizon. The clinical parameters were derived mainly from the Active Ulcerative Colitis Trial (ACT) 1 and ACT 2 and from the Ulcerative Colitis Long-term Remission and Maintenance with Adalimumab (ULTRA) 2 clinical trial. Different costs and utility values were assigned to the various health states in the model; utility values were derived from a previously published study. Treatment of patients who received infliximab/standard care instead of standard care alone resulted in 0.174 additional QALYs. Treatment with infliximab/standard care was found to be more expensive than treatment with standard care alone from the Polish National Health Fund perspective. The incremental cost-utility ratio of infliximab/standard care compared with standard care alone was estimated to be 402,420 Polish zlotys (PLN)/QALY gained (95% confidence interval [CI] 253,936-531,450 PLN/QALY gained), which is equivalent to $106,743 (U.S. dollars)/QALY gained (95% CI $67,357-140,968 [U.S. dollars]/QALY gained). CONCLUSION: Treatment with infliximab/standard care instead of standard care alone resulted in additional QALYs but also additional costs. The incremental cost per QALY gained of infliximab/standard care compared with standard care alone exceeded the willingness-to-pay threshold in Poland (equivalent to ~$33,400).

Implementation of the 2011 Reimbursement Act in Poland: Desired and undesired effects of the changes in reimbursement policy.

The Act of 12 May 2011 on the Reimbursement of Medicines, Foodstuffs Intended for Particular Nutritional Uses and Medical Devices constitutes a major change of the reimbursement policy in Poland. The main aims of this Act were to rationalize the reimbursement policy and to reduce spending on reimbursed drugs. The Act seems to have met these goals: reimbursement policy (including pricing of reimbursed drugs) was overhauled and the expenditure of the National Health Fund on reimbursed drugs saw a significant decrease in the year following the Act's introduction. The annual savings achieved since then (mainly due to the introduction of risk sharing schemes), have made it possible to include new drugs into the reimbursement list and improve access to innovative drugs. However, at the same time, the decrease in prices of reimbursed drugs, that the Act brought about, led to an uncontrolled outflow of some of these drugs abroad and shortages in Poland. This paper analyses the main changes introduced by the Reimbursement Act and their implications. Since the Act came into force relatively recently, its full impact on the reimbursement policy is not yet possible to assess.

The indirect costs of multiple sclerosis: systematic review and meta-analysis.

The aim of this systematic review is to collect and summarize all current data on the indirect costs related to absenteeism and presenteeism associated with multiple sclerosis. Searches were conducted using Medline, Embase and Centre for Reviews and Dissemination databases. All collected costs were recalculated to average annual cost per patient, expressed in 2014 prices US$ using the consumer price index and purchasing power parity (scenario 1) and expressed as proportion of specific gross domestic product in current local currency unit to adjust for country's development (scenario 2). Identified studies were then analyzed in order to assess their possible inclusion in the meta-analysis. The authors identified 63 records, of which 23 were eligible for meta-analysis. Overall indirect cost per patient calculated in scenario 1 was as high as US$20,167 with US$22,197 in Europe, US$17,382 in North America and US$153 in Asia. Overall indirect cost per patient calculated in scenario 2 was equal to US$16,939, with US$19,612 in Europe, US$11,592 in North America and US$899 in Asia. Overall indirect costs varied from US$3726 for patients with EDSS score less than 3 to US$19,264 for patients with Expanded Disability Status Scale score grater that 7. This review revealed the great economic burden of multiple sclerosis on society. The authors observed a great variety of the considered components of indirect costs and their definitions. Costs were higher for Europe than for other continents and were also higher for patients with a higher Expanded Disability Status Scale score.

Economic evaluation of single-pill combination of indapamide and amlodipine in the treatment of arterial hypertension in the Polish setting.

BACKGROUND: Arterial hypertension is a common disorder that affects around 9 million adults in Poland. Single-pill combinations (SPCs) for the treatment of arterial hypertension have significant advantages over the free combinations, resulting in lower risk of cardiovascular events and lower consumption of medical resources. The current ESC/ESH 2013 guidelines for the first time recommend treatment with a combination of thiazide-like diuretic with calcium channel blocker. Currently, no such combination is reimbursed from public funds in Poland. AIM: To assess the economic value of treatment with SPC of indapamide and amlodipine (Tertens-AM®) for hypertensive patients compared with free combination therapy (FC), in the Polish setting. METHODS: As there are currently no published data directly estimating the additional effect of using indapamide + amlo-dipine SPC vs. FC, two extreme approaches are presented: with difference in effectiveness due to improved adherence to the treatment estimated from published studies on other molecules used in hypertension such as SPCs and FCs - the base-case approach (1); and assuming no difference of effectiveness or adherence between SPC and FC of indapamide and amlodipine - the conservative approach (2). Modelling was carried out based on the Markov process in lifetime horizon. In the base-case approach, with the difference in effectiveness between SPC and FC, it was assumed that the differences in compliance translate into the differences in systolic blood pressure. Patients' characteristics were correlated with the risk of events associated with cardiovascular disease, based on the prediction algorithms from the Framingham Heart Study. Costs were considered from a National Health Fund (NHF) perspective and NHF and patient's perspective, and therefore direct medical costs were only included. RESULTS: The treatment with SPC of indapamide and amlodipine in place of FC resulted in 7.6 additional days of life in full health and longer overall patient survival by 2.9 days. The replacement of FC with SPC would result in national savings from both NHF perspective and NHF and patient's perspective, irrespective of the assumption of the difference in adherence between SPC and FC. The savings would amount to 1.602-3.954 million PLN and 16.498-19.186 million PLN from NHF perspective and NHF and patient's perspective, respectively. CONCLUSIONS: The treatment with SPC of indapamide and amlodipine for hypertensive patients was found to be dominant over FC or at least less expensive than treatment with FC when the difference in effectiveness was neglected. The replacement of FC with SPC would result in savings from both NHF perspective and NHF and patient's perspective.

Prediction of functional sites based on the fuzzy oil drop model.

A description of many biological processes requires knowledge of the 3-D structure of proteins and, in particular, the defined active site responsible for biological function. Many proteins, the genes of which have been identified as the result of human genome sequencing, and which were synthesized experimentally, await identification of their biological activity. Currently used methods do not always yield satisfactory results, and new algorithms need to be developed to recognize the localization of active sites in proteins. This paper describes a computational model that can be used to identify potential areas that are able to interact with other molecules (ligands, substrates, inhibitors, etc.). The model for active site recognition is based on the analysis of hydrophobicity distribution in protein molecules. It is shown, based on the analyses of proteins with known biological activity and of proteins of unknown function, that the region of significantly irregular hydrophobicity distribution in proteins appears to be function related.