OBJECTIVES: This study aimed to provide the first evidence of the socioeconomic burden of cystic fibrosis (CF) in Czechia. METHODS: In a cross-sectional questionnaire-based primary data collection conducted from 2020 to 2021 among Czech patients with CF, we collected demographic, clinical, and healthcare resource use data, out-of-pocket and social transfer costs, and questionnaires: Cystic Fibrosis Questionnaire-Revised, Work Productivity and Activity Impairment, EQ-5D, and Zarit Burden Interview. Productivity loss/costs were assessed using the human capital approach with patient patient-assumed life expectancy of 45 years and caregiver retirement age of 64 years and discounted by 3%. RESULTS: A total of 257 patients completed the questionnaires (37% of the Czech CF population). The average age was 17 years; most were females (59%), and the average forced expiratory volume in 1 second was 81.4% (SD 25.4%). A total of 107 patients had caregivers with an average age of 39 years and a significant caregiver time burden (extra 4.6 hours/day). The average Zarit Burden Interview score (25.4) was comparable with advanced cancer, dementia, or Duchenne muscular dystrophy. The proportion of unemployed caregivers was 10× higher than the general population (31% vs 3.2%). Total out-of-pocket family costs related to CF were €278/month, mainly for medicines (€105), foods (€73), and transport (€59); 25% received a disability pension and 18% other social security benefits. The work impairment of employed patients and caregivers was 25% and 15%, respectively, mostly due to presenteeism. Total lifetime productivity costs extrapolated to all Czech patients with CF (n = 687) and their caregivers were €155 181 286 (€225 883/person). CONCLUSIONS: The societal burden imposed on Czech patients with CF and their caregivers is significant. Caregivers seem to be affected by higher disease activity more than patients.

• Klíčová slova
• caregiver burden, cystic fibrosis, productivity costs, quality of life, societal burden,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Out of 185 orphan medicinal products (OMPs) registered in 2015-2021, a mere 110 (59 percent) were available to Czech patients, and only 54 (29 percent) were officially reimbursed. Moreover, this proportion has steadily decreased over time. After years of public debate induced by this unsatisfactory OMP patient access, the national viewpoint shifted toward creating a special pathway for the reimbursement of OMP. Thus, a rigorous pricing and reimbursement procedure with strict timelines and elaborated methodology has been recently adopted in Czechia. METHODOLOGY: The innovative legislation follows the recommendations for value assessment and funding processes for rare diseases and incorporates additional elements of value, such as the societal perspective. First, the application with clinical evidence, cost-effectiveness, and budget impact analyses is submitted to the governmental health technology assessment (HTA) agency by the Marketing Authorization Holder or a Health Insurance Fund. Moreover, professional associations and patients' organizations are rightful participants in the proceeding, providing evidence and comments. Then, the HTA agency performs the assessment/appraisal of the evidence. It subsequently publishes the assessment report summarizing available information. The report is then forwarded to the Ministry of Health and its advisory body consisting of patients, clinical experts, health insurance funds, and the State. They critically evaluate the documents and issue a binding opinion following prespecified decision-making criteria. Based on this binding opinion, the decision is issued by the HTA agency. Thus, the role of the advisory body in this process is crucial. CONCLUSION: We believe that this novel approach may offer satisfactory patient access to orphan drugs. Moreover, it serves as a real-world example of "value-based" decision making.

• Klíčová slova
• health policy, health technology assessment, orphan drugs, rare diseases, reimbursement,
• MeSH
• hodnocení biomedicínských technologií MeSH
• lidé MeSH
• rozhodování MeSH
• úhrada zdravotního pojištění MeSH
• výroba orphan drugs * MeSH
• vzácné nemoci * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVES: The comparative efficacy between riociguat and selexipag in patients with pulmonary arterial hypertension (PAH) has never been described in literature. Our aim was to prepare indirect treatment comparison (ITC) to evaluate the cost-effectiveness of riociguat in Czechia. METHODS: A systematic literature review identified two relevant trials with comparable endpoints to inform a Bucher ITC of relative and absolute effects. Given the comparable efficacy of riociguat and selexipag, a cost-minimization analysis (CMA) was conducted. RESULTS: A Bucher ITC provided evidence for the comparable relative efficacy of riociguat defined as the odds of unimproved functional class III 0.761 (95% CI 0.372 to 1.558; p = 0.455) compared to selexipag and a comparable absolute efficacy defined as a difference in the 6-minute walking distance of 10.560 meters (95% CI -10.692 to 31.812; p = 0.330). The CMA identified riociguat as the cost-saving therapy. CONCLUSIONS: Switching to riociguat represents the cost-saving therapy for PAH patients who were inadequately compensated with the PDE5i+ERA therapy. Consequently, riociguat has been introduced to the list of reimbursed medicines in Czechia from October 2021. Based on two global trials, we prepared the first indirect treatment comparison followed with CMA of these therapies that may improve future decision-making for PAH indications.

• Klíčová slova
• Bucher indirect comparison, cost-minimization analysis, pulmonary arterial hypertension, riociguat, selexipag, systematic review,
• MeSH
• antihypertenziva MeSH
• lidé MeSH
• náklady a analýza nákladů MeSH
• plicní arteriální hypertenze * MeSH
• plicní hypertenze * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH
• Názvy látek
• antihypertenziva MeSH
• riociguat MeSH Prohlížeč
• selexipag MeSH Prohlížeč

OBJECTIVE: Achieving targeted disease activity (DA) is the primary therapeutic strategy in RA. Point measurements of DA are done at out-patient visits, however true DA between visits remains unobserved. This study sought to describe and validate a new outcome measure, i.e. time in remission (TIR). METHODS: Patients were enrolled in the Czech ATTRA-RA registry. TIR was calculated using linear interpolation of the DAS28-ESR determined at outpatient visits. Correlation coefficients were computed between TIR and DAS28-CRP, HAQ, Simple Disease Activity Index (SDAI), patient global assessment (PGA) and physician global assessment (PhGA). Using logistic regression, TIR was used as a predictor of remission (SDAI ≤3.3) and non-disability (HAQ <0.5). The predictive value of TIR was compared with point and sustained remission using the cross-validated area under receiver-operating curves. RESULTS: Since 2010, 2618 RA patients started anti-TNF therapy and were followed until 2020 or until treatment discontinuation. During the first 6 months of therapy, 56% of patients had no remission (TIR = 0), and 22% of patients reached sustained remission (TIR = 1), while 22% of patients had point remissions with 0 < TIR < 1. EULAR good responders and moderate/non-responders spent 64 ± 42% and 6 ± 18% of time in remission, respectively. The mean TIR grew during the follow-up and was correlated with DAS28-CRP, SDAI, HAQ, PGA, and PhGA (P < 0.0001). TIR at 3 and 6 months predicted remission (SDAI ≤3.3) and non-disability (HAQ <0.5) at 13 and 19 months better than point or sustained remission. CONCLUSIONS: TIR is an intuitive way of estimating unobserved DA between scheduled visits; its calculation only requires two consecutive DA values (https://www.medevio.cz/tir-calculator/). TIR is a valid predictor of RA outcomes.

• Klíčová slova
• Czech Republic, RA, anti-TNF, biological therapy, disease activity, interpolation, outcome measure, prediction, registry, remission,
• MeSH
• antirevmatika * terapeutické užití   MeSH
• hodnocení výsledků zdravotní péče MeSH
• indukce remise MeSH
• inhibitory TNF MeSH
• lidé MeSH
• prospektivní studie MeSH
• revmatoidní artritida * farmakoterapie   MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antirevmatika * MeSH
• inhibitory TNF MeSH

BACKGROUND: Despite worldwide use of parenteral methotrexate (pMTX), health economic evidence for its use in Crohn's disease (CD) is limited. The low price of this generic drug has removed any commercial incentive to further invest in research. However, there is an unmet need for treatment of mild-to-moderate CD, since biological/targeted therapies are usually reserved for patients with more severe disease due to the higher costs of these treatments. OBJECTIVE: To evaluate the cost-effectiveness of pMTX compared to the standard of care (SOC, i.e., high doses of oral corticosteroids (hdCS) followed by gradual tapering) for the treatment of mild-to-moderate CD in the Czech Republic. METHODS: We developed a 3-year Markov model with a 1-week cycle length comprising five health states. The model projected quality-adjusted life-years (QALYs) and costs from the healthcare payers' perspective. Efficacy data were obtained from a systematic literature review of clinical trials and extrapolated using survival analysis. RESULTS: Over a 3-year time-horizon, pMTX yields additional 0.111 QALYs (1.798 vs. 1.687) at an additional cost of €513 (€3087 vs. €2574), with an incremental deterministic (probabilistic) cost-effectiveness ratio of €4627 (€4742)/QALY, far below the willingness-to-pay (WTP) threshold (≈ €47,000/QALY). The probabilistic sensitivity analysis showed that the probability of pMTX being cost-effective was 100%. A one-way sensitivity and scenario analysis confirmed the robustness of the base-case result. CONCLUSION: Parenteral MTX proved to be cost-effective in patients with mild-to-moderate CD. This is the first published cost-effectiveness analysis of pMTX for this indication. It also shows an example of a lack of valuation of generic therapy despite its cost-effectiveness and a clear benefit to the healthcare system.

• MeSH
• analýza nákladů a výnosů MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• kvalitativně upravené roky života MeSH
• lidé MeSH
• methotrexát * terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH
• Názvy látek
• methotrexát * MeSH

BACKGROUND: The Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model has been widely used for the prediction of the outcome of metastatic renal cell carcinoma (mRCC) patients treated with systemic therapies, however, data from large studies are limited. This study aimed at the evaluation of the impact of the MSKCC score on the outcomes in mRCC patients treated with first-line sunitinib, with a focus on the intermediate-risk group. METHODS: Clinical data from 2390 mRCC patients were analysed retrospectively. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were analysed according to the MSKCC risk score. RESULTS: ORR, median PFS, and OS for patients with one risk factor were 26.7%, 10.1, and 28.2 months versus 18.7%, 6.2, and 16.2 months, respectively, for those with two risk factors (ORR: p = 0.001, PFS: p < 0.001, OS: p < 0.001). ORR, median PFS, and OS were 33.0%, 17.0, and 44.7 months versus 24.1%, 9.0, and 24.1 months versus 13.4%, 4.5, and 9.5 months in the favourable-, intermediate-, and poor-risk groups, respectively (ORR: p < 0.001, PFS: p < 0.001, OS: p < 0.001). CONCLUSIONS: The results of the present retrospective study demonstrate the suitability of the MSKCC model in mRCC patients treated with first-line sunitinib and suggest different outcomes between patients with one or two risk factors.

• Klíčová slova
• Memorial Sloan–Kettering Cancer Center risk, first line, outcome, renal cell carcinoma, sunitinib,
• Publikační typ
• časopisecké články MeSH

Objectives: To assess the role of short-term response to first anti-TNF in long-term prediction of disability.Methods: In nationwide registry ATTRA, we identified ankylosing spondylitis patients starting anti-TNF between 01/2003 and 12/2016. Full disability and work impairment (WI; WPAI questionnaire) were predicted via the Cox- and lagged-parameter mixed-effect regression.Results: 2,274 biologicals-naïve patients newly indicated to anti-TNF were prospectively followed (6,333 patient-years; median follow-up 1.9 years). Reaching BASDAI < 4 (77.4%) and ASDAS-CRP < 2.1 (61.1%) after 3 months of anti-TNF both decreased the risk of future disability by ≈2.5-fold. ASDAS-CRP < 2.1 predicted non-disability better than BASDAI < 4 & CRP < 5 mg/L (p = 0.032). BASDAI < 4 & CRP < 5 mg/L was comparable to BASDAI < 4 (p = 0.941) and to BASDAI change by >50% or by >2 points (p = 0.902). ASDAS-CRP change >1.1 and >2.0 both failed to predict non-disability. Once on anti-TNF therapy, the strongest predictor of WI was Pain (SF36). Yearly increase in indirect costs remains below €3,000 in those reaching ASDAS-CRP < 2.1.Conclusions: Low disease activity measured by ASDAS-CRP ≤ 2.1 should be used to measure the outcome of new anti-TNF therapy. Continuous WI could be decreased through pain management.

• Klíčová slova
• ASDAS, Ankylosing spondylitis, BASDAI, anti-TNF, disability, multivariate modeling, predictive power, work impairment,
• MeSH
• absentérství MeSH
• ankylózující spondylitida komplikace   diagnóza   farmakoterapie   epidemiologie   MeSH
• biologické přípravky terapeutické užití   MeSH
• časové faktory MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• postižení statistika a číselné údaje   MeSH
• posuzování pracovní neschopnosti MeSH
• prognóza MeSH
• průzkumy a dotazníky MeSH
• registrace statistika a číselné údaje   MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa antagonisté a inhibitory   imunologie   MeSH
• výkonnost * účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• biologické přípravky MeSH
• TNF-alfa MeSH

BACKGROUND: In situations of markedly different population characteristics and weak population overlap, inverse propensity score (PS) weights suffer from extreme values. The new propensity score weighting method using overlap weights (PSOW) overcomes this limitation by estimating the overlap population at the point of highest mutual overlap, thus may be preferred to other balancing methods (trimming, target, or inverse weights) in some situations. OBJECTIVES: To evaluate the performance of PSOW with regorafenib effectiveness data from previously treated patients with metastatic colorectal cancer based on the Czech national registry data (regorafenib) and a global phase 3 randomized clinical trial (RCT) (placebo). The second goal was to assess the cost-effectiveness of regorafenib versus placebo. METHODS: Individual data on progression-free survival (PFS)/overall survival (OS) were balanced via PSOW for age, sex, Eastern Cooperative Oncology Group performance status, number of treatment lines, metastatic colorectal cancer location, KRAS mutation, and time from metastases estimated using logistic regression. The weighted Kaplan-Meier PFS/OS curves were used in a 3-state partitioned survival model. The R code is provided. RESULTS: In comparison with target or inverse PS weights, PSOW showed remarkable performance measured by effective sample size and PS weight distribution or extreme weights despite the weak overlap between the registry and RCT. In the registry or RCT cohort, regorafenib provided better survival compared with the RCT. The new PSOW hazard ratio for OS was 0.53 (RCT: 0.79), which is conservative compared with inverse or target weights with a hazard ratio of 0.44 and 0.27, respectively. CONCLUSION: This is the first use of PSOW for clinical data and cost-effectiveness analysis. It is promising in cases of weak or small population overlap and makes pharmacoeconomic modeling, in such cases, feasible.

• Klíčová slova
• colorectal cancer, cost-effectiveness analysis, overlap weights, propensity score, propensity score weighting via overlap weights, regorafenib,
• MeSH
• analýza nákladů a výnosů MeSH
• doba přežití bez progrese choroby MeSH
• fenylmočovinové sloučeniny ekonomika   terapeutické užití   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• kolorektální nádory farmakoterapie   ekonomika   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• přežití bez známek nemoci MeSH
• pyridiny ekonomika   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• registrace MeSH
• tendenční skóre * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fenylmočovinové sloučeniny MeSH
• pyridiny MeSH
• regorafenib MeSH Prohlížeč

BACKGROUND: Highly innovative drugs (HIDs) can be granted 2 to 3 years of temporary reimbursement (TR) to provide timely patient access and to collect real-world evidence through registries in the Czech Republic. A TR applicant does not need to comply with cost-effectiveness (CE) requirements and the willingness-to-pay threshold. It is only when mandatory transition to permanent reimbursement (PR) status occurs does the drug need to comply with CE and willingness-to-pay requirements. OBJECTIVES: To describe and evaluate the HID program in the Czech Republic by analyzing the pharmacoeconomic results when a drug starts with TR status and transitions to PR status. METHODS: The study was a retrospective analysis of reimbursement decisions of HIDs. All drugs approved for TR (valid from January 2008 to January 2018) were identified. A description of the HIDs and their pharmacoeconomic results were analyzed. RESULTS: Fifty TR drugs were identified. Most (68%) were oncology drugs and 44% were orphan drugs. After the expiration of their TR status, 83% were successfully transitioned to PR status. Cost-utility analysis was used to support CE results in 42% of the TR drugs. The mean incremental cost-effectiveness ratio (cost/quality-adjusted life-year) of drugs that entered TR status was €97,868. When the time came for transition to PR status, the mean incremental cost-effectiveness ratio was €34,086 (lower by 65%). Net budget impact increased by 3% and decreased by 25% in the first and fifth years, respectively, after applying for PR. CONCLUSIONS: This analysis provides better insight into the HID program for costly innovative drugs over a 10-year follow-up. A successful transition to PR status was observed for most of the HIDs (83%).

• Klíčová slova
• Czech Republic, budget impact, cost-effectiveness, highly innovative drug program, orphan, pharmacoeconomics, pricing and reimbursement,
• MeSH
• analýza nákladů a výnosů * MeSH
• dávkové mechanismy ekonomika   MeSH
• ekonomika farmaceutická * MeSH
• kvalitativně upravené roky života MeSH
• léčivé přípravky ekonomika   zásobování a distribuce   MeSH
• lidé MeSH
• náklady na léky statistika a číselné údaje   trendy   MeSH
• retrospektivní studie MeSH
• vládní regulace MeSH
• výroba orphan drugs MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• léčivé přípravky MeSH

BACKGROUND: Clinical trials and observational studies lacking measures of health-related quality of life (QoL) are often inapplicable when conducting cost-effectiveness analyses using quality-adjusted life-years (QALYs). The only solution is to map QoL ex post from additionally collected clinical outcomes and generic QoL instruments. Nonetheless, mapping studies are absent in psoriatic arthritis (PsA). METHODS: In this 2-year, prospective, multicentre, non-interventional study of PsA patients, EQ-5D and key clinical parameters such as Disease Activity in PsA (DAPsA), clinical DAPsA (cDAPsA; DAPsA without C-reactive protein [CRP]), and Health Assessment Questionnaire disability index (HAQ) were collected. We employed a linear mixed-effect regression model (ME) of the longitudinal dataset to explore the best predictors of QoL. RESULTS: A total of 228 patients were followed over 873 appointments/observations. DAPsA, cDAPsA and HAQ were stable and highly significant predictors of EQ-5D utilities in both cross-sectional and longitudinal analyses. The best prediction was provided using a linear ME with HAQ and cDAPsA or DAPsA. A HAQ increase of 1 point represented a decrease in EQ-5D by -0.204 or -0.203 (p < 0.0001); a one-point increase in cDAPsA or DAPsA dropped EQ-5D equally by -0.005 (p < 0.0001). The ME revealed steeper and more accurate association compared with cross-sectional regressions or non-linear models/transformations. CONCLUSIONS: This is the first mapping study conducted in PsA and we hope that our study will encourage further mapping studies in PsA. The results showed that in cases where CRP is absent, cDAPsA provides similar results to DAPsA in predicting QoL.

• MeSH
• dospělí MeSH
• kvalita života psychologie   MeSH
• kvalitativně upravené roky života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• posuzování pracovní neschopnosti MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• psoriatická artritida psychologie   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• zdravotní stav * MeSH
• zdravotnické přehledy statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH