Implementation of coverage with evidence development schemes for medical devices: A decision tool for late technology adopter countries.

Experiences with coverage with evidence development (CED) schemes are fairly limited in Central and Eastern European (CEE) countries, which are usually late adopters of new health technologies. Our aim was to put forward recommendations on how CEE health technology assessment bodies and payer organizations can apply CED to reduce decision uncertainty on reimbursement of medical devices, with a particular focus on transferring the structure and data from CED schemes in early technology adopter countries in Western Europe. Structured interviews on the practices and feasibility of transferring CED schemes were conducted and subsequently, a draft tool for the systematic classification of decision alternatives and recommendations was developed. The decision tool was reviewed in a focus group discussion and validated within a wider group of CEE experts in a virtual workshop. Transferability assessment is needed in case of (1) joint implementation of a CED scheme; (2) transferring the structure of an existing CED scheme to a CEE country; (3) reimbursement decisions that are linked to outcomes of an ongoing CED scheme in another country and (4) real-world evidence transferred from completed CED schemes. Efficient use of available resources may be improved by adequately transferring evidence and policy tools from early technology adopter countries.

Development of a core evaluation framework of value-added medicines: report 2 on pharmaceutical policy perspectives.

BACKGROUND: A core evaluation framework that captures the health care and societal benefits of value added medicines (VAMs, also often called repurposed medicines) was proposed in Report 1, aiming to reduce the heterogeneity in value assessment processes across countries and to create incentives for manufacturers to invest into incremental innovation. However, this can be impactful only if the framework can be adapted to heterogeneous health care financing systems in different jurisdictions, and the cost of evidence generation necessitated by the framework takes into account the anticipated benefits for the health care system and rewards for the developers. AREAS COVERED: The framework could potentially improve the pricing and reimbursement decisions of VAMs by adapting it to different country specific decision-contexts such as deliberative processes, augmented cost-effectiveness frameworks or formal multi-criteria decision analysis (MCDA); alternatively, some of its domains may be added to current general evaluation frameworks of medicines. The proposed evaluation framework may provide a starting point for practices based on which VAMs can be exempted from generic pricing mechanisms or can be integrated into the reimbursement and procurement system, allowing for price differentiation according to their added value. Besides evidence from RCTs, pricing and reimbursement decision processes of VAMs should allow for ex-ante non-RCT evidence for certain domains. Alternatively, relying on ex-post evidence agreements-such as outcome guarantee or coverage with evidence development-can also reduce decision uncertainty. CONCLUSIONS: The core evaluation framework for VAMs could trigger changes in the existing pricing, reimbursement and procurement practices by improving the appraisal of the added value created by incremental innovation.

Development of a core evaluation framework of value-added medicines: report 1 on methodology and findings.

BACKGROUND: Medicines that are based on known molecules and are further developed to address healthcare needs and deliver relevant improvement for patients, healthcare professionals and/or payers are called value-added medicines (VAMs). The evaluation process of VAMs is heterogeneous across countries, and it has been primarily designed for originator pharmaceuticals with confirmatory evidence collected alongside pivotal clinical trials. There is a mismatch between evidence requirements by public decision-makers and evidence generated by manufacturers of VAMs. Our objective was to develop a core evaluation framework for VAMs. METHODS: Potential benefits offered by VAMs were collected through a systematic literature review and allocated to separate domains in an iterative process. The draft list of domains and their applicability were validated during two consecutive virtual workshops by health policy experts representing countries with different economic statuses, geographical and decision-making contexts. RESULTS: Based on 158 extracted studies, the final consensus on the evaluation framework resulted in 11 value domains in 5 main clusters, including unmet medical needs, health gain (measured by health care professionals), patient-reported outcomes, burden on households, and burden on the health care system. CONCLUSIONS: The proposed framework could reduce the heterogeneity in value assessment processes across countries and create incentives for manufacturers to invest in incremental innovation. However, some domains may not be equally relevant or accepted in all countries, therefore the core framework needs thorough adaptation in specific jurisdictions.

High-Temperature Cycling of Plasma Sprayed Multilayered NiCrAlY/YSZ/GZO/YAG Thermal Barrier Coatings Prepared from Liquid Feedstocks.

High-enthalpy hybrid water/argon-stabilized plasma (WSP-H) torch may be used for efficient deposition of coatings from dry powders, suspensions, and solutions. WSP-H torch was used to deposit two complete thermal barrier coatings (TBCs) with multilayered top-coat. NiCrAlY was used as bond-coat and deposited on nickel-based superalloy substrates. Top-coat consisted of up to three sublayers: (i) yttria-stabilized zirconia (ZrO2-8 wt.%Y2O3-YSZ) deposited from solution, (ii) gadolinium zirconate (Gd2Zr2O7-GZO) deposited from suspension, and (iii) optional yttrium aluminum garnet (Y3Al5O12-YAG) overlayer deposited from suspension. Each of the sublayers was intended to provide different functionalities, namely improved fracture toughness, low thermal conductivity, and high erosion resistance, respectively. High-temperature performance and thermal shock resistance of the deposited coatings were tested by thermal cycling fatigue "TCF" test (maximum temperature 1100 °C, 1 h dwell per cycle) and "laser-rig" test (maximum temperature ~ 1530 °C, 5 min dwell per cycle) exposing samples to isothermal and gradient thermal conditions, respectively. In both tests, coatings endured around 800 test cycles which shows great potential for further development of these layers and their application in demanding thermal conditions. Analysis of the samples after the test showed microstructural changes and identified reason of ultimate coating failure.

Antibiotics and the quality indicators for outpatient antibiotic use in Slovakia.

The aims of this study was to compare the data on the consumption of antibiotics in the outpatient care sector for Slovakia from 2019 to 2020 and to calculate quality indicators for outpatient antibiotic use. The data source on the consumption of antibiotics (ATC group J01), is the sales data from the NCZI. The main indicator describing the consumption of antibacterials for systemic use is the number of DDDs per 1000 inhabitants per day (DID). The data released by the European Centre for Disease Protection were used as the source for antibiotic consumption for 2019. The most frequently consumed antibacterials for systemic use in the outpatient care sector in 2020 were other beta-lactam antibacterials (J01D); macrolides, lincosamides and streptogramins (J01); and betalactam antibacterials, penicillins (J01C), with the levels of 3.30 DID, 3.30 DID and 3.27 DID, respectively. Consumption levels of 1.66 DID for tetracyclines (J01A), 1.14 DID for quinolone antibacterials (J01M), 0.41 DID for sulfonamides and trimethoprim (J01E), 0.07 DID for other antibacterials (J01X), and 0.01 DID for other antibiotics (J01B, J01G and J01R combined) can be seen. Overall, antibiotic consumption in the outpatient care sector did significantly change in Slovakia from 2019 to 2020 as a result of the COVID-19 pandemic.

Development of transferability guidance for integrated care models with special focus on Central and Eastern European countries.

AIM: To develop pragmatic recommendations for Central and Eastern European (CEE) policymakers about transferability assessment of integrated care models established in higher income European Union (EU) countries. METHODS: Draft recommendations were developed based on Horizon 2020-funded SELFIE project deliverables related to 17 promising integrated care models for multimorbid patients throughout Europe, as well as on an online survey among CEE stakeholders on the relevance of implementation barriers. Draft recommendations were discussed at the SELFIE transferability workshop and finalized together with 22 experts from 12 CEE countries. RESULTS: Thirteen transferability recommendations are provided in three areas. Feasibility of local implementation covers the identification and prioritization of implementation barriers and proposals for potential solutions. Performance measurement of potentially transferable models focuses on the selection of models with proven benefits and assurance of performance monitoring. Transferability of financing methods for integrated care explores the relevance of financing methodologies and planning of adequate initial and long-term financing. CONCLUSIONS: Implementation of international integrated care models cannot be recommended without evidence on its local feasibility or scientifically sound and locally relevant performance assessment in the country of origin. However, if the original financing method is not transferable to the target region, development of a locally relevant alternative financing method can be considered.

Evaluation of adherence to treatment in patients suffering from diabetes mellitus.

BACKGROUND: Diabetes mellitus type 2 (DM) is a disease which is becoming pandemic these days. A successful treatment of chronic diabetes mellitus depends on early diagnosis and proper treatment. Just as the role of the doctor in treating the disease is important, so the community pharmacist plays an important role in taking the initiative in motivating patients to adhere to individual treatment regimes. OBJECTIVE: The main aim of the study was to analyze and assess patient adherence to pharmacological or non-pharmacological treatment, including the influence of the community pharmacist on that. METHOD: All necessary data for the assessment were collected by anonymous questionnaire survey methods conducted within 7 months, as well as by personal consulting among pharmacists and patients. The results were assessed according to patients gender and age. RESULTS: 117 respondents got involved in the survey, with 67 (57%) females and 50 (43%) males. The majority were aged 60-74 (48%), 84% suffered from diabetes mellitus type 2. Adherence to non-pharmacological treatment (regime and dietary measures) was 96% in females and 76% in males according to gender, and over 80% in each age category. Adherence to pharmacological treatment was up to 83% in females and 79% in males. According to age, over 70% adhered to pharmacological treatment all the time in each age category (except for 75+), with up to 88% aged 60-74. CONCLUSION: According to the outcomes, we can observe that in our selected sample of patients the majority followed pharmacological or non-pharmacological treatment. The pharmacist also plays an important role in improving adherence to treatment. By providing patients with their expertise and professional knowledge while drug dispensing or individual conselling, the pharmacist can motivate the patient to follow not only pharmacological but also non-pharmacological treatment and thereby increase patient adherence itself to treatment.

Patient-related characteristics associated with non-persistence with statin therapy in elderly patients following an ischemic stroke.

PURPOSE: This study was aimed at evaluating the extent of non-persistence with statin therapy in elderly patients after an ischemic stroke and identifying patient-related characteristics that are risk factors for non-persistence. METHODS: The evaluable study cohort (n = 2748) was derived from the database of the largest health insurance provider in the Slovak Republic. Patients aged ≥65 years who were initiated on statin therapy following the diagnosis of an ischemic stroke during one full year (1 January 2010 to 31 December 2010) constituted this cohort. Each patient was followed for a period of 3 years from the date of the first statin prescription. Patients with a continuous treatment gap of 6 months without statin prescription were designated as non-persistent. The Cox proportional hazard model was applied to determine patient-associated characteristics that influenced the likelihood of non-persistence. RESULTS: During the 3-year follow-up period, 39.7% of patients in the study cohort became non-persistent. Factors associated with decreased probability of a patient becoming non-persistent were age ≥75 years (hazard ratio (HR) 0.75), polypharmacy (concurrent use of ≥6 drugs) (HR 0.79), diabetes mellitus (HR 0.80), dementia (HR 0.81) and hypercholesterolemia (HR 0.50). On the other hand, the presence of anxiety disorders (HR 1.33) predicted an increased likelihood of a patient being non-persistent. CONCLUSIONS: Our findings suggest that patients aged ≥75 years or those with the presence of diabetes mellitus, dementia, hypercholesterolemia or polypharmacy were likely to be persistent with statin therapy, whereas those with anxiety disorders may need greater assistance with persistence of statin therapy. Copyright © 2016 John Wiley & Sons, Ltd.

INTRODUCTION OF HEALTH TECHNOLOGY ASSESSMENT FOR MEDICINES IN SLOVAKIA.

OBJECTIVES: The aim of our study was to describe approaches to health technology assessment (HTA) for medicines in the Slovak healthcare system and the related decision-making processes concerning reimbursement for medicines. METHODS: Analysis of the Slovak legislative framework related to HTA and the reimbursement process for medicines was performed. Additionally, current practices of the Working Group for Pharmacoeconomics, Clinical Outcomes and Health Technology Assessment of the Slovak Ministry of Health were evaluated. RESULTS: In Slovakia, there is always at least one treatment available in each determined therapeutic class with no co-payment. HTA is becoming an established method for the evaluation of cost-effectiveness of medicines in Slovak healthcare policy. The majority of decision makers within Slovakia support the idea of increased use of and the quality and efficiency of HTA methods. However, it is crucial to overcome several practical barriers to facilitate progress in the field of HTA in the Slovak Republic. CONCLUSIONS: It can be seen that participation within the European Network for Health Technology Assessment (EUnetHTA JA 2 and EUnetHTA JA 3 projects) has significantly improved the quality of the process of HTA in Slovakia. Further legislative activities in this field are required due to the approved strategy for European Union cooperation on HTA.

Non-persistence with antiplatelet therapy in elderly patients after a transient ischemic attack.

BACKGROUND: Antiplatelet therapy following a transient ischemic attack (TIA) constitutes an important secondary prevention measure. AIMS: The study was aimed at evaluating the development of non-persistence with antiplatelet therapy in elderly patients after a TIA and identifying patient-related characteristics associated with the probability of non-persistence during the follow-up period. METHODS: The study cohort (n = 854) was selected from the database of the largest health insurance provider of the Slovak Republic. It included patients aged ≥65 years, in whom antiplatelet medication was initiated following a TIA diagnosis during the period between 1 January 2010 and 31 December 2010. Each patient was followed for a period of 3 years from the date of the first antiplatelet medication prescription associated with TIA diagnosis. Patients in whom there was a treatment gap of at least 6 months without antiplatelet medication prescription were defined as "non-persistent". The factors predicting non-persistence were identified in the Cox proportional hazards model. RESULTS: At the end of the follow-up period, 345 (40.4%) patients were non-persistent with antiplatelet medication. Protective factors decreasing a patient´s likelihood of becoming non-persistent were age ≥75 years [hazard ratio (HR) = 0.75], polypharmacy (concurrent use of ≥6 drugs) (HR = 0.79), arterial hypertension (HR = 0.68), diabetes mellitus (HR = 0.74), hypercholesterolemia (HR = 0.75), and antiplatelet medication switching during the follow-up period (HR = 0.73). CONCLUSIONS: It is concluded that following a TIA, elderly patients aged <75 years or those with normal serum cholesterol levels, without certain comorbid conditions and polypharmacy may benefit from special counselling to encourage persistence with secondary preventive medication.

Clinical aspects of reimbursement policies for orphan drugs in Central and Eastern European countries.

Objectives: The aim of this study was to characterize the reimbursement policy for orphan drugs (ODs) in Central and Eastern European (CEE) countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedure, selected economic indicators, and the drug type according to indications. Materials and methods: A list of authorized medicines with orphan designation and information about active substance, Anatomical Therapeutic Chemical (ATC) classification, and therapeutic area was extracted from the web-based register of the European Medicines Agency (EMA). A country-based questionnaire survey was performed between September 2021 and January 2022 in a group of selected experts from nine CEE countries (an invitation was sent to 11 countries). A descriptive and statistical analysis was conducted to determine statistical significance, correlations, between the drug or country characteristic and the positive recommendation or reimbursement of ODs. Results: The proportion of reimbursed orphan drugs differed between countries, ranging from 17.7% in Estonia to 49.6% in Hungary (p < 0.001). The odds that ODs were reimbursed were reduced in countries with a "strong" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), the presence of other additional specific clinical aspects (e.g., genomic data) considered in the reimbursement decision (p < 0.001) and mandatory (without exception) safety assessments (p=0.004). The probability that ODs were reimbursed was increased in countries with a "moderate" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), when reimbursement decisions are dependent on the EMA registration status and orphan drug designation (p < 0.001), the presence of the "positive HTA recommendation guarantees reimbursement" policy (p < 0.001), higher GDP per inhabitant (p=0.003), and higher healthcare expenditure (p < 0.001). Conclusion: We found that there are differences among CEE countries in the reimbursement of orphan drugs, and we identified aspects that may influence these differences. Safety, efficacy, and specific clinical aspect issues significantly influenced reimbursement decisions. Antineoplastic and immunomodulating agents drugs were the largest group of ODs and increased the chance of getting a positive recommendation. The higher GDP per inhabitant and healthcare expenditures per inhabitant were positively linked to the chance that an OD receives reimbursement.

Pharmacological approaches to pulmonary fibrosis following COVID-19.

Background: In the past few years, COVID-19 became the leading cause of morbidity and mortality worldwide. Although the World Health Organization has declared an end to COVID-19 as a public health emergency, it can be expected, that the emerging new cases at the top of previous ones will result in an increasing number of patients with post-COVID-19 sequelae. Despite the fact that the majority of patients recover, severe acute lung tissue injury can in susceptible individuals progress to interstitial pulmonary involvement. Our goal is to provide an overview of various aspects associated with the Post-COVID-19 pulmonary fibrosis with a focus on its potential pharmacological treatment options. Areas covered: We discuss epidemiology, underlying pathobiological mechanisms, and possible risk and predictive factors that were found to be associated with the development of fibrotic lung tissue remodelling. Several pharmacotherapeutic approaches are currently being applied and include anti-fibrotic drugs, prolonged use or pulses of systemic corticosteroids and non-steroidal anti-inflammatory and immunosuppressive drugs. In addition, several repurposed or novel compounds are being investigated. Fortunately, clinical trials focused on pharmacological treatment regimens for post-COVID-19 pulmonary fibrosis have been either designed, completed or are already in progress. However, the results are contrasting so far. High quality randomised clinical trials are urgently needed with respect to the heterogeneity of disease behaviour, patient characteristics and treatable traits. Conclusion: The Post-COVID-19 pulmonary fibrosis contributes to the burden of chronic respiratory consequences among survivors. Currently available pharmacotherapeutic approaches mostly comprise repurposed drugs with a proven efficacy and safety profile, namely, corticosteroids, immunosuppressants and antifibrotics. The role of nintedanib and pirfenidone is promising in this area. However, we still need to verify conditions under which the potential to prevent, slow or stop progression of lung damage will be fulfilled.

Analysis of spontaneous reports of suspected adverse reactions after vaccination against COVID-19 in Slovakia.

Introduction: The COVID-19 pandemic has resulted in more than 6.5 million deaths worldwide yet. Vaccination against the SARS-CoV-2 virus is a reliable way out of the pandemic, however, vaccination rate reaches only 58% in the Slovak Republic. Concerns about the adverse reactions of vaccines are one of the reasons for the low vaccination rate. Objective: The aim of our analysis was to review reported suspicions of adverse reactions (ARs) of registered COVID-19 vaccines (Comirnaty, Vaxzevria, Spikevax), which State Institute for Drug Control received from healthcare professionals and patients in the period from 1 January 2021 to 31 May 2021. Methods: Data were collected from the State Institute for Drug Control database, a retrospective analysis was carried out focusing on trends in the number of all reports of suspicions of adverse reactions sent to the State Institute for Drug Control during the previously mentioned period. We analysed the Retrieved data were analysed with the usage of descriptive statistics and comparison to historical data on drug adverse reactions in Slovakia was performed. Results: During the evaluation period, 5,763 reported suspicions of adverse reactions were analysed, overall, there was a significant (p < 0.0001) increase in the number of reported adverse reactions fivefold. 93% of ARs (n = 5,346) were reported for COVID-19 vaccines. In comparison of the extentof all adverse reactions, there is clearly a statistically significant difference between all types of vaccines administered at that time (p ≤ 0.0001). No statistically significant difference (p ≤ 0.238) was identified between Spikevax and Comirnaty in the proportion of serious adverse reactions. However, a significantly higher (p ≤ 0.00001) proportion of reported suspicions of serious adverse reactions was observed after the administration of Vaxzevria. Conclusion: This is the first analysis conducted in Slovakia aimed to reported adverse reactions in relation to the administration of COVID-19 vaccines. The rate of spontaneously reported suspected adverse reactions has been insufficient in the past for a long time; during the period from January to May 2021 the reporting rate increased due active calls for adverse reactions reporting. In concordance with European data, Vaxzevria had a significantly higher ratio of reported suspicions of serious adverse reactions.

Reinitiation and Subsequent Discontinuation of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers among New and Prevalent Users Aged 65 Years or More with Peripheral Arterial Disease.

Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) are recommended in the treatment of arterial hypertension in patients with peripheral arterial disease (PAD). The aims of our study were: (a) to analyse the extent of reinitiation and subsequent discontinuation in older hypertensive PAD patients non-persistent with ACEIs/ARBs; (b) to determine patient and medication factors associated with reinitiation and subsequent discontinuation; and (c) to compare these factors between prevalent and new users. The analysis of reinitiation was performed on a sample of 1642 non-persistent patients aged ≥65 years with PAD newly diagnosed in 2012. Patients reinitiating ACEIs/ARBs were used for the analysis of subsequent discontinuation identified according to the treatment gap period of at least 6 months without any prescription of ACEI/ARB. In the group of non-persistent patients, 875 (53.3%) patients reinitiated ACEIs/ARBs during a follow-up (24.8 months on average). Within this group, subsequent discontinuation was identified in 414 (47.3%) patients. Being a new user was associated with subsequent discontinuation, but not with reinitiation. Myocardial infarction during non-persistence and after reinitiation was associated with reinitiation and lower likelihood of subsequent discontinuation, respectively. Being a prevalent or a new user is associated with the use of medication also after initial discontinuation.

Factors associated with non-adherence to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in older patients with peripheral arterial disease.

Introduction: As in other chronic conditions, medication adherence is important in the treatment of peripheral arterial disease (PAD). Our study aimed at a) analysing non-adherence to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in groups of older ACEI and ARB users with PAD, and b) identifying characteristics associated with non-adherence. Methods: We focused on the implementation phase of adherence (i.e., after treatment initiation and before possible discontinuation of treatment). The study cohort included ACEI/ARB users aged ≥65 years in whom PAD was newly diagnosed during 2012. Non-adherence was defined as Proportion of Days Covered (PDC) < 80%. Results: Among 7,080 ACEI/ARB users (6,578 ACEI and 502 ARB users), there was no significant difference in the overall proportion of non-adherent patients between ACEI and ARB users (13.9% and 15.3%, respectively). There were differences in factors associated with non-adherence between the groups of persistent and non-persistent (i.e., discontinued treatment at some point during follow-up) ACEI and ARB users. Increasing age, dementia and bronchial asthma were associated with non-adherence in persistent ACEI users. General practitioner as index prescriber was associated with adherence in the groups of non-persistent ACEI users and persistent ARB users. Conclusion: Identified factors associated with non-adherence may help in determining the groups of patients who require increased attention.

Recommendations to overcome barriers to the use of artificial intelligence-driven evidence in health technology assessment.

Background: Artificial intelligence (AI) has attracted much attention because of its enormous potential in healthcare, but uptake has been slow. There are substantial barriers that challenge health technology assessment (HTA) professionals to use AI-generated evidence for decision-making from large real-world databases (e.g., based on claims data). As part of the European Commission-funded HTx H2020 (Next Generation Health Technology Assessment) project, we aimed to put forward recommendations to support healthcare decision-makers in integrating AI into the HTA processes. The barriers, addressed by the paper, are particularly focusing on Central and Eastern European (CEE) countries, where the implementation of HTA and access to health databases lag behind Western European countries. Methods: We constructed a survey to rank the barriers to using AI for HTA purposes, completed by respondents from CEE jurisdictions with expertise in HTA. Using the results, two members of the HTx consortium from CEE developed recommendations on the most critical barriers. Then these recommendations were discussed in a workshop by a wider group of experts, including HTA and reimbursement decision-makers from both CEE countries and Western European countries, and summarized in a consensus report. Results: Recommendations have been developed to address the top 15 barriers in areas of (1) human factor-related barriers, focusing on educating HTA doers and users, establishing collaborations and best practice sharing; (2) regulatory and policy-related barriers, proposing increasing awareness and political commitment and improving the management of sensitive information for AI use; (3) data-related barriers, suggesting enhancing standardization and collaboration with data networks, managing missing and unstructured data, using analytical and statistical approaches to address bias, using quality assessment tools and quality standards, improving reporting, and developing better conditions for the use of data; and (4) technological barriers, suggesting sustainable development of AI infrastructure. Conclusion: In the field of HTA, the great potential of AI to support evidence generation and evaluation has not yet been sufficiently explored and realized. Raising awareness of the intended and unintended consequences of AI-based methods and encouraging political commitment from policymakers is necessary to upgrade the regulatory and infrastructural environment and knowledge base required to integrate AI into HTA-based decision-making processes better.

Recommendations for patient involvement in health technology assessment in Central and Eastern European countries.

Introduction: Meaningful patient involvement in health technology assessment (HTA) is essential in ensuring that the interests of the affected patient population, their families, and the general public are accurately reflected in coverage and reimbursement decisions. Central and Eastern European (CEE) countries are generally at less advanced stages of implementing HTA, which is particularly true for patient involvement activities. As part of the Horizon2020 HTx project, this research aimed to form recommendations for critical barriers to patient involvement in HTA in CEE countries. Methods: Built on previous research findings on potential barriers, a prioritisation survey was conducted online with CEE stakeholders. Recommendations for prioritised barriers were formed through a face-to-face workshop by CEE stakeholders and HTx experts. Results: A total of 105 stakeholders from 13 CEE countries completed the prioritisation survey and identified 12 of the 22 potential barriers as highly important. The workshop had 36 participants representing 9 CEE countries, and 5 Western European countries coming together to discuss solutions in order to form recommendations based on best practices, real-life experience, and transferability aspects. Stakeholder groups involved in both phases included HTA organisation representatives, payers, patients, caregivers, patient organisation representatives, patient experts, health care providers, academic and non-academic researchers, health care consultants and health technology manufacturers/providers. As a result, 12 recommendations were formed specified to the CEE region's context, but potentially useful for a broader geographic audience. Conclusion: In this paper, we present 12 recommendations for meaningful, systematic, and sustainable patient involvement in HTA in CEE countries. Our hope is that engaging more than a hundred CEE stakeholders in the study helped to spread awareness of the importance and potential of patient involvement and that the resulting recommendations provide tangible steps for the way forward. Future studies shall focus on country-specific case studies of the implemented recommendations.

Gender Differences in Non-Persistence with Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers among Older Hypertensive Patients with Peripheral Arterial Disease.

The beneficial effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in hypertensive patients with peripheral arterial disease (PAD) depends on long-term persistence. The aims of our study were to analyse gender differences in non-persistence with ACEIs/ARBs, and to identify the characteristics associated with the likelihood of non-persistence. Our study cohort included 7080 hypertensive patients (4005 women and 3075 men) aged ≥65 years, treated with ACEIs/ARBs, in whom PAD was diagnosed between 1 January and 31 December 2012. Non-persistence was identified according to a treatment gap of 6 months without ACEI/ARB prescriptions. The characteristics associated with non-persistence were identified using the Cox regression model. At the end of the 5-year follow-up, 23.2% of the whole study cohort, 22.3% of men, and 23.9% of women were non-persistent with ACEIs/ARBs, with no significant gender differences in persistence. While a number of characteristics were associated with non-persistence, only three characteristics had consistent, statistically significant associations in both genders: being a new ACEI/ARB user increased the likelihood of non-persistence, and general practitioner as index prescriber and increasing the overall number of medications decreased the likelihood of non-persistence. Information on the differences in characteristics that are associated with non-persistence between genders may help to better identify patients for whom special attention should be paid to improve their persistence.

The Impact of Reimbursement Practices on the Pharmaceutical Market for Off-Patent Medicines in Slovakia.

Background: The aim of this study was to investigate the impact of selected legislative initiatives and their implementation for off-patent medicinal products in Slovakia compared with the rest of the Visegrád Group (V4 countries). Methods: We analyzed the development of applications for the reimbursement of generic and biosimilar drugs. Particular emphasis was placed on a) the availability and penetration of biosimilars from 2006 to 2020 in Slovakia, b) a comparative analysis of biosimilars in V4 countries based on the national reimbursement lists of medicinal products for August 2021. Data relating to the sales of generic and biosimilar medicines in Czechia, Hungary, Poland, and Slovakia were based on the IQVIA MIDAS MAT July 2021. Results: The number of applications for the reimbursement of generic drugs decreased from 296 in 2016 to 165 in 2020. In financial terms, the sales of generic medicines in Slovakia increased from 21.7% in 2015 to 22.3% in 2020. Over the same period, the sales of generic drugs in Poland fell from 40.4% in 2015 to 35.0% in 2020, from 26.2 to 22.1% in Hungary, and from 29.6 to 20.4% in Czechia. When considering the 66 biosimilars registered by the European Medicines Agency 38 drugs (58%) were available on the Slovak market as of August 1, 2021; this compared to 32 drugs (48%) in Poland, 38 drugs (58%) in Hungary, and 40 drugs (61%) in Czechia. In financial terms, the sales of biosimilars in Slovakia increased from 0.94% in 2015 to 2.00% in 2020. Over the same period, the sales of biosimilars in Poland increased from 0.59% in 2015 to 1.29% in 2020, from 0.72 to 2.23% in Hungary, and from 0.76 to 2.15% in Czechia. Conclusion: To intensify the use of generic and biosimilar medicines, we suggest the comprehensive re-evaluation of combinations of the three-threshold entry, the amount of mandatory price reductions, and external reference pricing requirements (as the average of the three lowest prices among the official prices of a medicinal product in other Member States) for generic and biosimilar drugs. We also suggest cancellation of the exception from the fixed co-payment of the insured.

Consumption of Antibacterials for Systemic Use in Slovakia: A National Study and the Quality Indicators for Outpatient Antibiotic Use.

This paper aims to analyse the consumption of antibiotics in the Slovak health care system from 2011 to 2020. The data source on the consumption of antibiotics is sales data from SUKL and NCZI. The study employed the ATC/DDD Index and focused on the consumption of antibiotics in the primary care sector. Total antibiotic consumption decreased from 19.21 DID in 2011 to 13.16 DID in 2020. Consumption of beta-lactamase-sensitive penicillins, expressed as a percentage of the total consumption of antibiotics, decreased from 8.4% in 2011 to 4.2% in 2020. Consumption of the combination of penicillins, including beta-lactamase inhibitor, expressed as a percentage of the total consumption of antibiotics, increased from 16.2% in 2011 to 17.9% in 2020. Consumption of third- and fourth-generation cephalosporins, expressed as the percentage of the total consumption of antibiotics, increased from 2.0% in 2011 to 4.6% in 2020. Consumption of fluoroquinolones, expressed as the percentage of the total consumption of antibiotics, decreased from 10.7% in 2011 to 8.6% in 2020. Overall, antibiotic consumption significantly changed in Slovakia from 2011 to 2020. The ratio of the consumption of broad-spectrum to the consumption of narrow-spectrum penicillins, cephalosporins and macrolides decreased from 14.98 in 2011 to 13.38 in 2020.