Therapeutic Results and Survival of Patients with Myelofibrosis Treated with Ruxolitinib-A Real-Life Longitudinal Study.

The aim of this study was to analyze the therapeutic results and survival of patients with myelofibrosis treated with ruxolitinib in comparison with a group on standard therapy. It is a cross-sectional, retrospective, non-interventional, real-life study that was performed between January 2000 and February 2023. Patients treated between 2000 and 2016, before the introduction of ruxolitinib, constituted the control group (n = 45), while those treated after May 2016, after ruxolitinib inclusion, constituted the active group (n = 66). Demographic characteristics, clinical indicators, the severity of the disease, and survival were explored using Kaplan-Meier survival analyses. Spearman's correlation, linear regression, and other statistical analyses were performed. According to the Kaplan-Meier analysis, there was a 75.33% reduction in the fatality risk in the sample. On a general-population level, the fatality risk in the group treated with ruxolitinib varied between 7.9% and 77.18% compared to that of the risk in the control group. There was a decrease in blood parameters (leukocytes, hemoglobin, and platelets) and spleen size. During the first six months, the spleen size of the patients on ruxolitinib decreased by 6%, and during the second six months, it decreased by another 9%. This study shows that patients in a real-life clinical setting treated with ruxolitinib exhibited improved clinical signs of the disease, had a lower symptom severity, and survived longer than patients on standard therapy before ruxolitinib's entrance into the national market. The improvements correlate with those reported in randomized clinical trials.

Recommendations for wider adoption of clinical pharmacy in Central and Eastern Europe in order to optimise pharmacotherapy and improve patient outcomes.

Clinical pharmacy as an area of practice, education and research started developing around the 1960s when pharmacists across the globe gradually identified the need to focus more on ensuring the appropriate use of medicines to improve patient outcomes rather than being engaged in manufacturing and supply. Since that time numerous studies have shown the positive impact of clinical pharmacy services (CPS). The need for wider adoption of CPS worldwide becomes urgent, as the global population ages, and the prevalence of polypharmacy as well as shortage of healthcare professionals is rising. At the same time, there is great pressure to provide both high-quality and cost-effective health services. All these challenges urgently require the adoption of a new paradigm of healthcare system architecture. One of the most appropriate answers to these challenges is to increase the utilization of the potential of highly educated and skilled professionals widely available in these countries, i.e., pharmacists, who are well positioned to prevent and manage drug-related problems together with ensuring safe and effective use of medications with further care relating to medication adherence. Unfortunately, CPS are still underdeveloped and underutilized in some parts of Europe, namely, in most of the Central and Eastern European (CEE) countries. This paper reviews current situation of CPS development in CEE countries and the prospects for the future of CPS in that region.

Study of Symptom Severity and Adherence to Therapy of Myelofibrosis Patients Treated with Ruxolitinib.

We aimed to explore symptom severity and adherence to therapy for patients with myelofibrosis treated with ruxolitinib in Bulgaria. It is a prospective, non-interventional study performed at the specialized hospital for active treatment of hematological diseases in Sofia during 2022-2023. Date of diagnosis, demographic characteristics, clinical indicators, ruxolitinib dose, and other data points were collected. Clinical indicators were assessed at baseline, in the middle, and at the end of observation. Severity of symptoms was measured with MPN-SAF TSS and adherence to therapy with the Morisky 4 questionnaire six times during the observation. The mean age of diagnosis was 58.5 years, with the average duration of disease of 3 years. Patients' laboratory results were within physiological ranges, with spleen size experiencing a constant decrease. The average value for the severity of the symptoms per MPN-SAF TSS results decreased significantly, indicating better disease control. The average adherence to therapy did not change and remained high at around 9 points, except for one patient. In conclusion the treatment of myelofibrosis patients with ruxolitinib decreased symptom severity and spleen size. Patients were adherent to the therapy over the observed period, but as treatment duration increases, the risk of adherence decreases.

Budget cap and pay-back model to control spending on medicines: A case study of Bulgaria.

Central and Eastern European countries (CEEC) have among the highest rates of increase in healthcare expenditure. External reference pricing, generics and biologics price capping, regressive scale for price setting, health technology assessment (HTA), and positive drug lists for reimbursed medicines are among the variety of implemented cost-containment measures aimed at reducing and controlling the rising cost for pharmaceuticals. The aim of our study was to analyze the influence of a recently introduced measure in Bulgaria-budget capping in terms of overall budget expenditure. A secondary goal was to analyze current and extrapolate future trends in the healthcare and pharmaceutical budget based on data from 2016 to 2021. The study is a retrospective, observational and prognostic, macroeconomic analysis of the National Health Insurance Fund's (NHIF) budget before (2016-2018) and after (2019-2021) the introduction of the new budget cap model. Subgroups analysis for each of the three new budget groups of medicines (group A: medicines for outpatient treatment, prescribed after approval by a committee of 3 specialists; group B: all other medicines out of group A; and group C: oncology and life-saving medicines out of group A) was also performed, and the data were extrapolated for the next 3 years. The Kruskal-Wallis test was applied to establish statistically significant differences between the groups. During 2016-2021, healthcare services and pharmaceutical spending increased permanently, observing a growth of 82 and 80%, respectively. The overall healthcare budget increased from European €1.8 billion to 3.3 billion. The subgroup analysis showed a similar trend for all three groups, with similar growth between them. The highest spending was observed in group C, which outpaced the others mainly due to the particular antineoplastic (chemotherapy) medicines included in it. The rising overall healthcare cost in Bulgaria (from European €1.8 billion to 3.3 billion) reveals that implementation of a mechanism for budget predictability and sustainability is needed. The introduced budget cap is a relatively effective measure, but the high level of overspending and pay-back amount (from European €34 billion to 59 billion during 2019-2021) reveals that the market environmental risk factors are not well foreseen and practically implemented.

Barriers to Use Artificial Intelligence Methodologies in Health Technology Assessment in Central and East European Countries.

The aim of this paper is to identify the barriers that are specifically relevant to the use of Artificial Intelligence (AI)-based evidence in Central and Eastern European (CEE) Health Technology Assessment (HTA) systems. The study relied on two main parallel sources to identify barriers to use AI methodologies in HTA in CEE, including a scoping literature review and iterative focus group meetings with HTx team members. Most of the other selected articles discussed AI from a clinical perspective (n = 25), and the rest are from regulatory perspective (n = 13), and transfer of knowledge point of view (n = 3). Clinical areas studied are quite diverse-from pediatric, diabetes, diagnostic radiology, gynecology, oncology, surgery, psychiatry, cardiology, infection diseases, and oncology. Out of all 38 articles, 25 (66%) describe the AI method and the rest are more focused on the utilization barriers of different health care services and programs. The potential barriers could be classified as data related, methodological, technological, regulatory and policy related, and human factor related. Some of the barriers are quite similar, especially concerning the technologies. Studies focusing on the AI usage for HTA decision making are scarce. AI and augmented decision making tools are a novel science, and we are in the process of adapting it to existing needs. HTA as a process requires multiple steps, multiple evaluations which rely on heterogenous data. Therefore, the observed range of barriers come as a no surprise, and experts in the field need to give their opinion on the most important barriers in order to develop recommendations to overcome them and to disseminate the practical application of these tools.

Impact of Polypharmacy, Drug-Related Problems, and Potentially Inappropriate Medications in Geriatric Patients and Its Implications for Bulgaria-Narrative Review and Meta-Analysis.

Objective: Polypharmacy and inappropriate prescribing are overlooked issues in Bulgaria. We aimed at collecting and analyzing global literature on the most prevalent risk factors and investigating what they could reveal about current practice. Materials and Methods: A systematic narrative review and meta-analysis was conducted on the topic, investigating the prevalence of polypharmacy, odds of potentially inappropriate medications (PIMs) due to polypharmacy, and the likelihood of developing a drug-related problem (DRP) due to PIMs. The results were then related to current demographic statistics to estimate the potential impact on Bulgarian elderly patients. Results: The prevalence of polypharmacy was estimated at 41% in elderly populations. The odds of a potentially inappropriate medication being prescribed were 2.095, with an expected 30.84% of those leading to a DRP. These numbers indicated that the expected Bulgarian elderly with polypharmacy should be 709,676 with 212,903 cases of DRPs. Conclusion: Global polypharmacy rates seem to be on the rise, with an expected increase in DRPs.

Evaluation of potentially inappropriate medication in older patients with cardiovascular diseases-STOPP/START-based study.

Objective: This study aims to evaluate the use of STOPP/START criteria in the identification of Potentially inappropriate medication and potential prescribing omissions in older patients with cardiovascular diseases in Bulgaria. Excessive morbidity and mortality has been linked to drug-related problems and increased use of healthcare services and is an understudied problem for Bulgaria. Materials and methods: A prospective, questionnaire-based study was conducted among 543 older patients across 25 pharmacies in Bulgaria. Socio-demographic characteristic, disease profile, symptoms, and medication data were collected. The questionnaire was developed for the purposes of the EUROAGEISM project. Out of all 543 patients, only those with documented cardio-vascular diseases were extracted and the medication profile per patient was evaluated for Potentially inappropriate medication (PIMs) and potentially prescribing omissions (PPOs) using STOPP/START criteria version 2. In addition, several risks for potentially inappropriate prescribing (PIPs), PPOs and PIMs were calculated with the focus being on the Odds and Risks to develop a PIP. Results: Four hundred and twenty eight from 531 patients with known therapy for cardiovascular diseases (CVDs) were included in the analysis of PIP (40.52% aged 65-69 years, 61.88% female, 64% had up to 6 comorbidities, and 21.72% presenting with polypharmacy). A total of 71 PIMs in 64 patients with polypharmacy were identified during applying STOPP criteria. 56% of patients taking above five medicines daily had PIMs. The majority of PIMs (31%) were related to CVDs treatment, followed by PIMs in the treatment of endocrine diseases (22.54%), duplication of medicines (8.46%) and prolonged treatment with benzodiazepines (8.46%). Forty four PPOs were identified with START criteria. 22.72% were related to lack of proton pump inhibitors (PPI) in the presence of gastroesophageal disorders, and the same percentage was for lack of Calcium-vitamin D supplementation in osteoporosis. Applying the methodology of risks calculation the sample risk for PPO was 2.1% and for PIM 3.4%. At sample level the relative risk for PPO was 62% out of the risk for PIM and at population level varied between 42.8 and 89.8% and it is statistically significant. The number needed to treat for the event to happen is 77.5, meaning that at every 78 prescriptions there is a chance to appear PIP. Conclusion: Application of methodologies for detection of potentially inappropriate prescribing is not part of routine clinical practice in Bulgaria. Our study demonstrates a high percentage of potentially inappropriate medication among older patients with polypharmacy. Along with the aging population in Bulgaria, economic burden of polypharmacy and the prevalence of cardiovascular diseases, it is especially important to address potentially inappropriate medication use in cardiovascular patients. There is a considerable necessity for implementation of measures for early detection of potentially inappropriate medication and potentially prescribing omission as a part of de-prescribing strategies in older patients.

Pharmacotherapeutic Patterns and Patients' Access to Pharmacotherapy for Some Rare Diseases in Bulgaria - A Pilot Comparative Study.

Provision of the latest innovative and advanced therapies for rare diseases (RDs) patients, following the international therapeutic recommendations, is crucial and necessary for both practitioners and patients. The goal is to assess the access of Bulgarian patients with the most cost-consuming RDs to medicines and to compare the pharmacotherapeutic patterns in Bulgaria and the relevant European professional associations. Pharmaco-therapeutic guidelines for treating the most cost-consuming RDs in Bulgaria were analyzed to assess their compliance with the European ones. Market entrance was evaluated through analysis of the availability of medicines in the Positive Drug List (PDL) and their date of inclusion since marketing authorization. Guidelines' compliance index was calculated and patient access was analyzed through evaluation of the National Health Insurance Fund (NHIF) standards, which provide additional criteria for treatment initiation. The analyzed guidelines follow the adopted recommendations by the relevant European professional associations. NHIF have exclusion and inclusion criteria for initiating treatment with medicines for rare diseases and for continuation. The average time-lag between centralized procedure approval and inclusion in the Bulgarian PDL for orphan medicinal products (MPs) is 6.75 years (SD = 4.96) with the longest time observed for eptacog alfa (20 years) and the shortest for rurioctocog alfa pegol, octocog alfa and simoctocog alfa (1 year). Bulgarian patients with cystic fibrosis with pulmonary manifestation had a wait time of only 1.6 years to get access to innovative, centrally authorized medicines, whereas the period for access to acromegaly treatment was 8.2 years. The main factors influencing market entrance and patient access are the time to inclusion in the PDL and the NHIF criteria.

Economic consequences of the implementation of national screening program for chronic HCV infection.

BACKGROUND: Chronic HCV infection is still one of the leading causes for liver morbidity and mortality worldwide. Increase in testing and diagnosis would result in early identification of people with chronic infection and would enable timely access to care and treatment, as well as prevent or delay progression of liver disease. The aim of the present study is to examine the cost and benefits of introducing ones per life testing for HCV infection among the group of 39-64 years old people who regularly go to prophylactic examinations in Bulgaria. RESEARCH DESIGN AND METHODS: Combined cost-effectiveness and cost-benefit analysis was performed to evaluate the cost-effectiveness and net benefit of three screening approaches. RESULTS: Screening of the birth-cohort type (aged 39-64 and born before the blood testing became available) provides benefits compared to the current practice of symptomatic testing and leads to more LYGs. Testing among this age group is efficient with an ICER below the proposed by WHO threshold of 1-3 times GDP/capita. CONCLUSIONS: Targeted testing among adults between 39 and 64 years with anti-HCV antibody once per their life in Bulgaria could be considered as cost-effective and provides benefits both for the paying institutions and the patients.

Cost-of-illness studies in nine Central and Eastern European countries.

BACKGROUND: To date, a multi-country review evaluating the cost-of-illness (COI) studies from the Central and Eastern European (CEE) region has not yet been published. Our main objective was to provide a general description about published COI studies from CEE. METHODS: A systematic search was performed between 1 January 2006 and 1 June 2017 in Medline, EMBASE, The Cochrane Library, CINAHL, and Web of Science to identify all relevant COI studies from nine CEE countries. COI studies reporting costs without any restrictions by age, co-morbidities, or treatment were included. Methodology, publication standards, and cost results were analysed. RESULTS: We identified 58 studies providing 83 country-specific COI results: Austria (n = 9), Bulgaria (n = 16), Croatia (n = 3), the Czech Republic (n = 10), Hungary (n = 24), Poland (n = 11), Romania (n = 3), Slovakia (n = 3), and Slovenia (n = 4). Endocrine, nutritional, and metabolic diseases (18%), neoplasms (12%), infections (11%), and neurological disorders (11%) were the most frequently studied clinical areas, and multiple sclerosis was the most commonly studied disease. Overall, 57 (98%) of the studies explicitly stated the source of resource use data, 45 (78%) the study perspective, 34 (64%) the costing method, and 24 (58%) reported at least one unit costs. Regardless of methodological differences, a positive relationship was observed between costs of diseases and countries' per capita GDP. CONCLUSIONS: Cost-of-illness studies varied considerably in terms of methodology, publication practice, and clinical areas. Due to these heterogeneities, transferability of the COI results is limited across Central and Eastern European countries.

Humanistic and economic aspects of haemophilia treatment in Bulgaria. Comparison between two therapeutic approaches: prophylactic vs. on-demand treatment.

The aim of the present study was to calculate the cost-effectiveness of on-demand and prophylactic treatments of severe haemophilia A for Bulgarian patients. The point of view is that of all patients suffering from severe haemophilia A. An epidemiological model was created, which includes data regarding the number of patients divided into age groups up to 74 years. In the model, the transition age from prophylactic to on-demand treatment was gradually increased to up to 40 years. Costs of blood clotting factor, hospitalization, major surgery and indirect costs were considered; incremental cost-effectiveness ratio was calculated. The results showed that despite the increase in the costs for factor VIII with 20 million BGN, the saving obtained from other health services and indirect expenses reduce the overall expenses with 5.3 million BGN. If there is a gradual increase in the age when patients are transferred from a prophylactic to an on-demand regimen, the costs for factor VIII would increase from 10.4 million to 19.7 million BGN, but due to a decrease in indirect costs as well as other health service costs, the total costs would decrease. The sensitivity analysis showed that the costs for clotting factor VIII are what influences the cost-effectiveness in both regimes. This indicates that decreases in the factor VIII cost will increase the overall efficiency in both regimes. In conclusion, the application of the prophylactic regime for patients up to 40 years of age will provide better treatment, increase the quality of life and decrease the incremental costs.