[Cost-effectiveness analysis for HIV pre-exposure prophylaxis in a high-risk population in the Czech Republic].

OBJECTIVES: To assess the cost-effectiveness of pharmacological pre-exposure prophylaxis (PrEP) using a combination of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) with respect to HIV transmission in high-risk patients in the Czech Republic. MATERIAL AND METHODS: A pharmacoeconomic model was constructed to compare costs and outcomes in a cohort with and without PrEP. Initially, a decision tree is used to evaluate short-term benefits of PrEP (proportion of HIV-infected individuals), followed by Markov cycles to simulate the course of the disease based on CD4 lymphocyte counts. The efficacy of PrEP, probability of transition between HIV infection stages, costs per category and quality of life data were derived from the literature. The results are presented as an incremental cost effectiveness ratio of incremental costs and incremental quality adjusted life-years (ICER/QALY) in a lifetime horizon with a 3% annual discount rate of costs and benefits. RESULTS: The FTC/TDF prophylaxis is dominant, that is, it generates lower costs and higher benefits (expressed as QALYs) in comparison with the control group without prophylaxis. A sensitivity analysis modelled all relevant parameters and all scenarios confirmed the PrEP dominance. CONCLUSIONS: A cost-effectiveness analysis in the Czech Republic setting confirmed that pharmacological PrPE intervention is cost-effective, or cost-saving, in a high-risk population of men having sex with men, using a lifetime horizon.

Indacaterol/Glycopyrronium versus Salmeterol/Fluticasone in Patients with COPD-A Cost-Effectiveness Analysis in the Czech Republic.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) represents an illness with significant healthcare and societal impacts. Fixed combinations of long-acting beta-agonists (LABA) and inhaled corticosteroids have been used for COPD treatment as the standard of care for many years. A daily dose of indacaterol and glycopyrronium (IND/GLY) at 110/50 µg has recently been gaining attention due to its improved efficacy and tolerability versus the standard of care.The study aims to evaluate the cost-effectiveness of once daily IND/GLY vs. twice daily salmeterol/fluticasone propionate (SFC) at 50/500 µg in COPD patients. METHODS: A microsimulation model in MS Excel was adapted to the Czech setting. Effectiveness data and disease severity stages were obtained from the FLAME study, which is a head-to head trial comparing IND/GLY vs. SFC. Quality of life data were derived from a literature review. Costs (medication, monitoring and complications) were taken from published Czech sources. The incremental cost-effectiveness ratio (ICER) was expressed as cost per quality-adjusted life year (QALY) gained. Costs and outcomes were discounted at 3 %. A lifetime horizon was used for the analysis. Cost-effectiveness was studied from the perspective of a health care system in the Czech Republic. RESULTS: Mean QALYs were higher in the IND/GLY arm (difference 0.167 QALYs). The ICER of IND/GLY compared with SFC was €13,628 per QALY gained. Deterministic sensitivity analyses and probabilistic sensitivity analyses confirmed the base-case result to be robust. CONCLUSIONS: From the perspective of the Czech health care system, managing COPD using IND/GLY is cost-effective in this analysis because the base-case is clearly below the willingness-to-pay threshold in the Czech Republic, which is automatically set at 3 times GDP/capita (approximately €44,000/ QALY). This is the first available economic analysis utilizing FLAME study results in the Central East European (CEE) countries showing IND/ GLY as a highly cost-effective investment into COPD patients.

Drug Policy in the Czech Republic.

BACKGROUND: The legal background of the current pharmaceutical pricing and reimbursement (P&R) setting in the Czech Republic is based on Act 48/1997. Since 2008, the P&R process has been coordinated by the State Institute for Drug Control, which is the main stakeholder in the decision-making process; marketing authorization holders and insurance funds (IFs) also participate. OBJECTIVES: To present a general overview of the current Czech health care system and its P&R principles. METHODS: The study used publicly available sources concerning health care, mainly acts related to public health care and public health care insurance, public notices related to P&R setting, and statistical data. RESULTS: Regulation covers P&R. The official price represents the highest exfactory price, which cannot be exceeded. It is calculated as the mean of the three lowest prices in the European Union reference basket. Reimbursement is based on the lowest price per daily dose across the whole European Union. For reimbursement, products can be clustered into jumbo groups (mutually interchangeable), stated by law. In each group, reimbursement is set at the lowest price of any substance within the group. For highly innovative drugs a temporary reimbursement can be granted for a period of 3 years. During the administrative proceeding, efficacy, safety, cost-effectiveness, and budget impact are assessed. The cost-effectiveness principles are aligned with the guidelines of the National Institute for Health and Clinical Care Excellence, preferring cost-utility analyses. The willingness-to-pay threshold has been implicitly set at 3 times the gross domestic product per capita. Products exceeding this threshold are subject to further risk-sharing negotiations. Budget impact is becoming increasingly important mainly for IFs. The IFs have recently introduced their own methodology, which allows only products with a budget impact in the range of CZK16 to CZK48 million (CZK = Czech koruna; ∼€600,000 to €1.8 million) to enter the system. Products exceeding this budget impact have to negotiate risk-sharing schemes, mainly further discounts and/or budget caps. CONCLUSIONS: The Czech pricing and reimbursement system is rather complex, taking into account clinical evidence, cost-effectiveness and budget impact. The strict regulations are a result of financial scarcity.

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.

[Centres for Tobacco-Dependent in the Czech Republic in 2012: overview and economy]. / Centra pro závislé na tabáku v Ceské republice v roce 2012: prehled, ekonomika.

BACKGROUND: Since 2005, in the Czech Republic the Centres for Tobacco-Dependent are being established at hospitals. METHODS: Evaluation of the activity of these 37 centres in 2012, economic analysis of treatment costs and assessment of the cost of life year gained (LYG). RESULTS: Most of the centres (26 of 37) are based at pulmonary clinics with opening hours for smokers: on average 7 hours/week. Treatment codes 25501 and 25503 are used at 28 centres. Entry visit usually takes on average 61 minutes, follow-up visits 22 minutes. Nicotine replacement therapy and varenicline are indicated in all centres, but only 14 centres use bupropion. Virtually all centres use links to other clinical disciplines, about 10.5 % of patients are sent to other departments. The most common barriers for wider activity are insufficient salaries and staffing. In 2012, the Centre for Tobacco-Dependent at the 3rd Medical Department, 1st Faculty of Medicine, Charles University in Prague and the General University Hospital treated 430 patients for the price of 3792 CZK per treated patient ( 150 Euro), respectively, with 38 % success rate for the price of 10,003 CZK per abstinent patient ( 400 Euro), or for 1,334 CZK per LYG ( 50 Euro/LYG). CONCLUSION: In the future it would be good to improve working conditions in centres and to take advantage of their potential for the indispensable, effective and highly cost-effective treatment.

Persistence with first line anticholinergic medication in treatment-naïve overactive bladder patients.

OBJECTIVE: The aim of this study was to evaluate the persistence of first line anticholinergic medication use by patients with overactive bladder (OAB). Data from a hospital outpatient database were matched with information obtained by a telephone survey of patients to determine which patients discontinued use of anticholinergic medication and to identify the reasons underlying discontinuation. MATERIAL AND METHODS: The study group included 377 OAB patients (52 men, 325 women) with a mean age of 60.29 ± 13.84 years. In total, 189 patients (50.1%) were treated with trospium (median dose 27.86 ± 12.73 mg), 41 patients (10.9%) with propiverine (28.17 ± 4.97 mg), nine patients (2.4%) with extended-release tolterodine (4.0 ± 0 mg), 48 patients (12.7%) with solifenacin (5.94 ± 1.97 mg) and 90 patients (23.9%) with fesoterodine (6.09 ± 2.01 mg). RESULTS: The median time for persistence with the first line anticholinergic treatment was 6.53 ± 3.84 months. Persistence was significantly higher in patients treated with anticholinergic medication with an extended-release formulation than in patients treated with immediate-release anticholinergics. The most common reasons for termination of treatment were healing/resolution of symptoms (35.9%), low effectiveness (30.9%) and side-effects (23.7%). CONCLUSIONS: More than half of the OAB patients were not satisfied with their first line treatment. Other treatment options should be sought, such as changing the medication or dosage, or possibly combining treatments.

Health Economic Data Requirements and Availability in the European Union: Results of a Survey Among 10 European Countries.

OBJECTIVES: To compare data requirements and their availability for health economic (HE) evaluations in five countries in Central/Eastern Europe (CEE) (Poland, the Czech Republic, Slovakia, Hungary, and Romania) and five countries in Western Europe (WE) (the United Kingdom, France, Germany, The Netherlands, and Sweden). METHODS: A questionnaire was developed and distributed to market access personnel from Pfizer who were asked to complete the questionnaire either from their own knowledge or with support of external experts. The questionnaire focused on the obligation to conduct HE assessment for reimbursement submissions, local HE guidelines, applied discount rates for future costs and effects, willingness-to-pay thresholds, and available data sources. RESULTS: HE is mandatory in all CEE and three WE participating countries for reimbursement applications of innovative drugs. Usually, cost-effectiveness analysis and budget-impact analyses are required. The preferred outcome of cost-effectiveness analysis is quality-adjusted-life years. In Romania, France, and the Czech Republic, guidelines could not be identified at the time of the survey. The applicant usually prepares HE evaluations; in Sweden, the United Kingdom, The Netherlands, and Poland, unlocked models have to be presented for scrutiny. Discount rates vary from 1.5% to 5%, and, usually, is the same for costs and outcomes (except in The Netherlands and Poland). Only the United Kingdom, Poland, and Slovakia have an explicit willingness-to-pay threshold. In Poland, it is based on the gross domestic product per capita, and in Slovakia, it is based on multiples of average monthly salary. Differences were found on data availability. In WE, data can be acquired easier than in CEE. Health insurance funds do not provide their data unless they were published. Patient registries are either not available in CEE or difficult to access, so applicants mostly rely on retrospective medical chart data, hospital information systems, or expert panels. CONCLUSIONS: We found similar requirements for HE analyses in CEE and WE but differences in data availability. This results in less accurate inputs across the CEE, influencing analyses' outcomes.

Economic and clinical comparison of atypical depot antipsychotic drugs for treatment of chronic schizophrenia in the Czech Republic.

PURPOSE: The Czech Republic is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. A pharmacoeconomic analysis was conducted to determine the cost-effectiveness of atypical depots. METHODS: An existing 1-year decision-analytic framework was adapted to model drug use in this healthcare system. The average direct costs to the General Insurance Company of the Czech Republic of using paliperidone palmitate (Xeplion®), risperidone (Risperdal Consta®), and olanzapine pamoate (Zypadhera®) were determined. Literature-derived clinical rates populated the model, with costs adjusted to 2012 Euros using the consumer price index. Outcomes included quality-adjusted life-years (QALYs), days in remission, and proportions hospitalized or visiting emergency rooms. One-way sensitivity analyses were calculated for all important inputs. A multivariate probability analysis was used to examine the stability of results using 10,000 iterations of simulated input over reasonable ranges of all included variables. RESULTS: Expected average costs/per patient treated were €5377 for PP-LAI, €6118 for RIS-LAI, and €6537 for OLZ-LAI. Respective QALYs were 0.817, 0.809, and 0.811; ER visits were 0.127, 0.134, and 0.141; hospitalizations were 0.252, 0.298, and 0.289. Results were generally robust in sensitivity analyses. PP-LAI dominated RIS-LAI and OLZ-LAI in 90.2% and 92.1% of simulations, respectively. Results were insensitive to drug prices but sensitive to adherence and hospitalization rates. CONCLUSIONS: PP-LAI dominated the other two drugs, as it had a lower overall cost and superior clinical outcomes, making it the preferred choice. Using PP-LAI in place of RIS-LAI for chronic relapsing schizophrenia would reduce the overall costs of care for the healthcare system.

Access to biologic treatment for rheumatoid arthritis in Central and Eastern European (CEE) countries.

BACKGROUND: The aim of this study was to assess and compare patients' access to biologic anti-RA drugs in selected Central and Eastern European (CEE) countries and to analyze the determinants of differences between countries. MATERIAL/METHODS: This is a multi-country survey study, based on a combination of desk research and direct contact with national RA stakeholders. Data was collected using a pre-defined questionnaire. Affordability was measured using an affordability index, calculated comparing the index of health care expenditures to the price index, using Poland as an index of 1. RESULTS: The percentage of patients on biologic treatment in 2009 was highest in Hungary (5% RA patients on biologic treatment), followed by Slovenia (4.5%), Slovakia (3.5%), Czech Republic (2.92%), Romania (2.2%), Estonia (1.8%), and Croatia, Serbia, Poland (below 1.5%). Infliximab, etanercept, adalimumab and rituximab were included in the reimbursement system in all countries, but abatacept and tocilizumab were included only in Slovakia. In Slovenia, public payer covered 75% of the price, and 25% is covered by supplementary health insurance; in Bulgaria public payer covered 50% of etanercept and adalimumab costs, and 75% of rituximab cost. In other countries, biologic drugs are reimbursed at 100%. Affordability index for biologic drugs was the lowest in Slovenia (0.4). In each country national guidelines define which patients are eligible for biologic treatment. Disease Activity Score (DAS28) of over 5.1 and failure of 2 or more disease-modifying anti-RA drugs, including methotrexate, are commonly used criteria. CONCLUSIONS: The most important factors limiting access to biologic anti-RA treatment in the CEE region are macroeconomic conditions and restrictive treatment guidelines.

Costs of illness and care in Parkinson's disease: an evaluation in six countries.

We investigated the costs of Parkinson's Disease (PD) in 486 patients based on a survey conducted in six countries. Economic data were collected over a 6-month period and presented from the societal perspective. The total mean costs per patient ranged from EUR 2620 to EUR 9820. Direct costs totalled about 60% to 70% and indirect costs about 30% to 40% of total costs. The proportions of costs components of PD vary notably; variations were due to differences in country-specific health system characteristics, macro economic conditions, as well as frequencies of resource use and price differences. However, inpatient care, long-term care and medication were identified as the major expenditures in the investigated countries.

Costs of Parkinson's disease in eastern Europe: a Czech cohort study.

Life expectancy is increasing worldwide and the burden of Parkinson's disease (PD) is growing. There are several cost-of-illness studies for PD from Western Europe and the USA, however, data about the costs associated with PD in Eastern Europe are still lacking. The objective of this study was to evaluate direct and indirect costs in a cohort of Czech patients with idiopathic PD and to identify cost-driving factors. Study participants (n=100) were recruited from the neurological department of the Charles University in Prague. Health-economic data were collected using a "bottom-up" approach. Costs were calculated from the societal perspective and the human capital approach was used to estimate indirect costs. Czech currency was converted into 2004 Euros (EUR) and inflated to 2008 prices. Independent cost-driving factors were identified in multivariate regression analysis. Total semi-annual costs of PD were EUR 5510 (95% CI: 4470-7090) per patient. Direct costs accounted for 60% of the total costs and indirect costs for 40%. Patients' expenditures accounted for 40% of their income. Independent cost-driving factors included disease severity, motor complications, psychosis and age. In conclusion, our study demonstrates a considerable economic burden of PD in the Czech Republic. Total costs are generally lower than in Western Europe but the proportion of costs that fall on patients is higher because of lower incomes. More intensive government support for patients with chronic diseases such as PD and the development of disease-management programs that incorporate both the clinical and economic effects of PD treatment are needed.

Challenges in economic evaluation of new drugs: experience with rituximab in Hungary.

BACKGROUND: Implementation of a new therapy into clinical practice is a complex process. Various countries have different requirements for information but most often focus on economic evaluation, which often plays a stronger role in healthcare decision making than does clinical evidence. MATERIAL/METHODS: To identify all potential challenges in economic evaluation, the case of a new biological drug, rituximab, used to treat rheumatoid arthritis, has been taken as an example. We present methods and results of economic assessment, highlighting the specific issues that should be considered in countries with economic and health care conditions similar to those of Hungary. RESULTS: In principle, economic evaluation requires data on characteristics of target population, disease progression, treatment impact, preferences, resource utilization and unit prices. Treatment effect/relative risk reduction and clinical practice patterns (resource use) may be more generalizable, whereas prices and baseline risk need to be jurisdiction specific. In order to address issues of transferability, investments need to be made in the collection of epidemiological and demographic data, plus data on clinical practice patterns, resource use, costs and health state valuation. In Hungary this problem has been solved through conducting a well designed 255 patient cross-sectional study. CONCLUSIONS: The Hungarian example shows that there should be more investment in data collection for those parameters that are thought to differ most from place to place. Owing to the similarities between Central and Eastern Europe countries in health care systems, clinical practice patterns and economic indicators, they may be able to develop partnerships to develop relevant regional databases and registries.

Efficacy of isotonic nasal wash (seawater) in the treatment and prevention of rhinitis in children.

OBJECTIVE: To evaluate the potential of nasal isotonic saline application to prevent reappearance of cold and flu in children during the winter. DESIGN: Prospective, multicenter, parallel-group, open, and randomized comparison. SETTING: Eight pediatric outpatient clinics. PATIENTS: A total of 401 children (aged 6-10 years) with uncomplicated cold or flu. INTERVENTIONS: We randomly assigned patients to 2 treatment groups, one with just standard medication, the other with nasal wash with a modified seawater solution (Physiomer) plus standard medication, and observed them for 12 weeks. MAIN OUTCOME MEASURES: The primary efficacy end points were nasal symptoms resolution during acute illness (visits 1 and 2). We also looked for reappearance of cold or flu, consumption of medication, complications, days off school, and reported days of illness during the following weeks when preventive potential was evaluated (visits 3 and 4). RESULTS: At visit 2, patients in the saline group achieved primary end points (measured on a 4-point numeric scale on which 1 indicated no symptoms and 4, severe symptoms) in the parameters nasal secretion and obstruction (mean scores vs nonsaline group, 1.79 vs 2.10 and 1.25 vs 1.58, respectively) (P < .05 for both). During the prevention phase (at visit 3, 8 weeks after study entry) patients in the saline group showed significantly lower scores in sore throat, cough, nasal obstruction, and secretion (P < .05 for all). By visit 3, significantly fewer children in the saline group were using antipyretics (9% vs 33%), nasal decongestants (5% vs 47%), mucolytics (10% vs 37%), and systemic antiinfectives (6% vs 21%) (P < .05 for all). During the same period children in the saline group also reported significantly fewer illness days (31% vs 75%), school absences (17% vs 35%), and complications (8% vs 32%) (P < .05 for all). Similar results were found at the final visit. CONCLUSION: Children in the saline group showed faster resolution of some nasal symptoms during acute illness and less frequent reappearance of rhinitis subsequently.