Multistakeholder Perceptions of Additional Value Elements for United States Value Assessment of Health Interventions.

OBJECTIVES: Limitations in conventional cost-effectiveness methods have led to calls for incorporation of additional value elements in assessments of health technologies. However, gaps remain in how additional value elements may inform decision making. This study aimed to prioritize additional value elements from the perspective of healthy individuals without a specific condition or indicated for a specific treatment in the United States among a multistakeholder panel and compare the importance of perspective-specific value elements. METHODS: Additional value elements were prioritized in 2 phases: (1) we identified and categorized additional value elements in a targeted literature review, and (2) we convened a multistakeholder group-based preference elicitation study (N = 28) to evaluate the description of each value element and rank and generate normalized weights of each value element for its significance in value assessment. The importance of additional value elements was also weighted relative to patient-centric value elements. RESULTS: The rank and weight of contextual value elements among 28 stakeholders were "severity of the disease" (26.2%), "disadvantaged and vulnerable target populations highly represented" (21.8%), "broader economic impact" (17.3%), "risk protection" (13.8%), "rarity of the disease" (11.3%), and "novel mechanism of action" (9.7%). Relative weight of the additional value elements versus patient-centric value elements was 52% and 48%, respectively. CONCLUSIONS: Study findings may inform priority setting for value frameworks and emerging US government assessments. The group-based elicitation method is repeatable and useful for structured deliberative processes in value assessment and may help improve the consistency and predictability of what is important to stakeholders.

Mapping Health Technology Assessment Agency Approaches for Biosimilar Value Assessment: An ISPOR Special Interest Group Report.

OBJECTIVES: A systematic literature review undertaken by the ISPOR Biosimilar Special Interest Group highlighted that limited guidance exists on how to assess biosimilars value and on appropriate economic evaluation techniques. This study described current health technology assessment (HTA) agency approaches for biosimilar value assessment. METHODS: Semi-structured interviews (n = 16) were carried out with HTA experts in Africa, America, Asia, Australia, and Europe to investigate current HTA practices for biosimilars. Data categorization was based on a thematic analysis approach. Findings from the qualitative data analysis were interpreted in view of relevant published literature. RESULTS: Our research suggests that in systems in which frameworks for biosimilar regulatory approval are well established, HTA agencies can accept the regulators' comparability exercise, and reimbursement decisions can generally be based on price comparisons. This approach is accepted in practice and allows streamlining of biosimilars value assessment. Nevertheless, conducting HTAs for biosimilars can be relevant when (1) the originator is not reimbursed, (2) the biosimilar marketing authorization holder seeks reimbursement for indications/populations, pharmaceutical forms, methods and routes of administration that differ with respect to the originator, and (3) a price premium is sought for a biosimilar based on an added-value claim. Further, HTA agencies' role conducting class-review updates following biosimilar availability can support greater patients' access to biologics. CONCLUSIONS: Internationally, there are differences in how national competent authorities on pricing and reimbursement of pharmaceuticals perceive HTA's role for biosimilars. Therefore, HTA agencies are encouraged to issue clear guidance on when and how to conduct HTAs for biosimilars, and on which economic techniques to apply.

Population-level norm values by EQ-5D-3L in Hungary - a comparison of survey results from 2022 with those from 2000.

PURPOSE: Although population norms of the EQ-5D-3L instrument had been available in Hungary since 2000, their evaluation was based on a United Kingdom (UK) value set. Our objective was to estimate the population norms for EQ-5D-3L by using the new Hungarian value set available since 2020, to extend the scope to adolescents, and to compare with norms from 2000. METHODS: A cross sectional EQ-5D-3L survey representative of the Hungarian population was conducted in 2022. The EQ-5D-3L dimensional responses were analyzed by age and sex and compared with the survey from 2000, by estimating population frequencies with their 95% confidence intervals; index values were evaluated by both value sets. RESULTS: Altogether, 11,910 respondents, aged 12 or more (578 between 12 and 17), completed the EQ-5D-3L. There was a notable improvement in reporting problems for both sexes (age 35-64) regarding the pain/discomfort and anxiety/depression compared to 2000. Below the age 44, both sexes had an EQ-5D-3L index plateau of 0.98, while above the age 55, men tended to have numerically higher index values compared to women, with the difference increasing with older age. Improvement in dimensional responses were also translated to numerically higher index values for both sexes between ages 18 and 74 compared to 2000. Multivariate regression analysis showed that higher educational attainment, lower age, larger household size, and active occupational status were associated with higher index values. CONCLUSION: Over the past 22 years, there was a large improvement in HRQoL of the middle-aged to elderly men and women in Hungary.

Health states can be described by a combination of statements of health-related quality of life measures. 'Value sets' are numerical expressions of how preferred a health state is. The provision of population-level health-related quality of life estimates (also known as 'population norms') are expected to improve the precision of patient-level clinical decision making, and health economic and public health studies. However, preference towards these health states is influenced by culture, resulting in differences across populations. While responses for the EQ-5D-3L instrument for adults have been available in Hungary since 2000, the evaluation of these responses was based on a 'value set' from the United Kingdom, rather than a Hungarian one.This research, utilizing the newly introduced Hungarian 'value set' (available since 2020) for the EQ-5D-3L instrument, offers a larger sample size, inclusion of adolescents and potentially improved sampling compared to the prior research conducted in 2000. Comparison of the two surveys allows us to estimate changes in both dimensional responses and overall health-related quality of life of the population over a 20-year time horizon, while we also compare the impact of different 'value sets' on health-related quality of life assessment. A large EQ-5D-3L improvement was observed in middle-aged-to-elderly people.

A Systematic Literature Review of Gaps and Challenges in Value Assessment of Biosimilars: An ISPOR Special Interest Group Report.

OBJECTIVES: This study aims to provide an overview of the gaps and challenges in the value assessment of biosimilars and to identify potential approaches to address them. METHODS: A multidisciplinary, international team of biosimilar experts identified gaps and challenges. A systematic review was conducted of the peer-reviewed literature in PubMed, EMBASE, Web of Science Core Collection, EBSCOhost Business Source Complete; and of the gray literature. Preliminary results were presented at ISPOR conferences and this article benefited from 2 review rounds among ISPOR Biosimilar Special Interest Group members. RESULTS: Given that a biosimilar is highly similar to its reference biologic, health technology assessment agencies should accept the comparability exercise approved by regulatory authorities and, thus, conduct a price comparison when biosimilar reimbursement is requested for the same indication as the reference biologic. If the reference biologic is not reimbursed or is not the standard of care, a full economic evaluation of the biosimilar versus a relevant comparator needs to be conducted. To date, little consideration has been given to specific challenges, such as how biosimilar value assessment can account for the nocebo effect, potential differences between biologic-naive and biologic-experienced patients, the availability of intravenous and subcutaneous administration forms or different administration devices for the same active compound, value-added services, and the contribution of biosimilars for generating health gain at the population level. CONCLUSIONS: There is a need to gather further insights in the methodology of value assessment for biosimilars, and health technology assessment agencies need to develop more elaborate guidance on biosimilar value assessment in specific circumstances.

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.

Health Technology Assessment Implementation in Ukraine: Current Status and Future Perspectives.

OBJECTIVES: The need for improving healthcare decision making by implementing health technology assessment (HTA) has been a top priority in Ukraine since 2016. This study sought to provide a tailor-made HTA implementation roadmap, drawing on insights from national stakeholders. METHODS: We conducted a survey using a questionnaire already applied in previous HTA research. We assessed the status of HTA when reforms were initiated in 2016 and examined perspectives on possible future developments among policy makers and representatives of pharmaceutical companies and patient organizations. RESULTS: Thirty-two respondents answered the survey. Forty-eight percent of respondents were not aware of HTA training in Ukraine, but 91 percent preferred having either a graduate or postgraduate training. Experts stated that funding for HTA research and for critical appraisal of HTA submissions was limited, but in the future, they would increase funding mainly from public sources. A public HTA agency with academic support was the most preferred organizational structure. Eighty-eight percent of respondents opted for full transparency, making the HTA agency's recommendations and the related appraisal reports publicly available. A great majority of participants preferred mandating the use of local data in certain categories and indicated the importance of evaluating the transferability of international evidence. Healthcare priority and cost-effectiveness were the most important criteria for decisions, applied with a soft explicit threshold. CONCLUSIONS: Ukraine is in the early phase of implementing HTA and our study provides a clear vision of national stakeholders about the future directions. In addition, learning from the experiences of other countries may help the implementation process.

Development of multi-criteria decision analysis (MCDA) framework for off-patent pharmaceuticals - an application on improving tender decision making in Indonesia.

BACKGROUND: Off-patent pharmaceuticals (OPPs) hold vital importance in meeting public health objectives, especially in developing countries where resources are limited. OPPs are comprised of off-patent originals, branded generics and unbranded generics; nonetheless, these products are not identical and often there are differences in their equivalence, manufacturing quality standards and reliability of supply. This necessitates reconsideration of the lowest price policy objective in pharmaceutical decision making. The aim of this study was to develop a Multi-Criteria Decision Analysis (MCDA) framework through a pilot workshop to inform the national procurement of OPPs in Indonesia. METHODS: An initial list of potentially relevant criteria was identified based on previous work and a literature review. In a 2-day pilot policy workshop, twenty local experts representing different stakeholder groups and decision-making bodies selected the final criteria, approved the scoring function for each criterion, and assigned weights to each criterion. RESULTS: An MCDA framework was proposed for OPP drug decision making in developing countries, which included price and 8 non-price criteria. Based on the pilot policy workshop 6 + 1 criteria were considered relevant for Indonesia: pharmaceutical price (40% weight), manufacturing quality (18.8%), equivalence with the reference product (12.2%), product stability and drug formulation (12.2%), reliability of drug supply (8.4%), real world clinical or economic outcomes, such as adherence or non-drug costs (4.2%) and pharmacovigilance (3.6%). CONCLUSIONS: According to the pilot policy workshop, other criteria apart from price need to be strengthened in the tendering process. The introduction of additional criteria for OPP procurement in an MCDA framework creates incentives for manufacturers to invest into improved manufacturing standards, equivalence proof, product quality, reliability of supply or even additional real-world data collection, which ultimately may result in more health gain for the society.

Need for multicriteria evaluation of generic drug policies.

Policymakers tend to focus on improving patented drug policies because they are under pressure from patients, physicians, and manufacturers to increase access to novel therapies. The success of pharmaceutical innovation over the last few decades has led to the availability of many off-patent drugs to treat disease areas with the greatest public health need. Therefore, the success of public health programs in improving the health status of the total population is highly dependent on the efficiency of generic drug policies. The objective of this article was to explore factors influencing the true efficiency of generic prescription drug policies in supporting public health initiatives in the developed world. Health care decision makers often assess the efficiency of generic drug policies by the level of price erosion and market share of generics. Drug quality, bioequivalence, in some cases drug formulations, supply reliability, medical adherence and persistence, health outcomes, and nondrug costs, however, are also attributes of success for generic drug policies. Further methodological research is needed to measure and improve the efficiency of generic drug policies. This also requires extension of the evidence base of the impact of generic drugs, partly based on real-world evidence. Multicriteria decision analysis may assist policymakers and researchers to evaluate the true value of generic drugs.

Epidemiology, health-related quality of life and economic burden of binge eating disorder: a systematic literature review.

PURPOSE: To perform a systematic review on the epidemiology, the health-related quality of life (HRQoL) and economic burden of binge eating disorder (BED). METHODS: A systematic literature search of English-language articles was conducted using Medline, Embase, PsycINFO, PsycARTICLES, Academic Search Complete, CINAHL Plus, Business Source Premier and Cochrane Library. Literature search on epidemiology was limited to studies published between 2009 and 2013. Cost data were inflated and converted to 2012 US$ purchasing power parities. All of the included studies were assessed for quality. RESULTS: Forty-nine articles were included. Data on epidemiology were reported in 31, HRQoL burden in 16, and economic burden in 7 studies. Diagnosis of BED was made using 4th Edition of The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria in 46 studies. Lifetime prevalence of BED was 1.1-1.9% in the general population (DSM-IV). BED was associated with significant impairment in aspects of HRQoL relating to both physical and mental health; the Short Form 36 Physical and Mental Component Summary mean scores varied between 31.1 to 47.3 and 32.0 to 49.8, respectively. Compared to individuals without eating disorder, BED was related to increased healthcare utilization and costs. Annual direct healthcare costs per BED patient ranged between $2,372 and $3,731. CONCLUSIONS: BED is a serious eating disorder that impairs HRQoL and is related to increased healthcare utilization and healthcare costs. The limited literature warrants further research, especially to better understand the long-term HRQoL and economic burden of BED.

Framework for Patient Experience Value Elements in Rare Disease: A Case Study Demonstrating the Applicability of Combined Qualitative and Quantitative Methods.

BACKGROUND AND OBJECTIVE: Several novel methods have been suggested to extend a conventional value assessment to capture a more comprehensive perspective of value from a patient perspective. The objective of this research was to demonstrate a framework for implementing a combined qualitative and quantitative method to elicit and prioritize patient experience value elements in rare diseases. Neuromyelitis optica spectrum disorder was used as a case study. METHODS: The method for eliciting and prioritizing patient experience value elements involved a three-step process: (1) collecting potential patient experience value elements from existing literature sources followed by deliberation by a multi-stakeholder research team; (2) a pre-workshop webinar and survey to identify additional patient-reported value elements; and (3) a workshop to discuss, prioritize the value elements using a swing weighting method. Outcomes were prioritized value elements with normalized weights for patients considering a treatment for neuromyelitis optica spectrum disorder. RESULTS: A literature review and deliberation resulted in the following initial value elements: ability to reach important personal milestones, patient's financial burden, value of hope/balance or timing of risks and benefits, Uncertainty about long-term benefits and safety of the treatment, Patient empowerment through therapeutic advancement and technology, Caregiver/family's financial burden, patient experience related to treatment regimen, Therapeutic options, and Caregiver/family's quality of life. Eight patients with neuromyelitis optica spectrum disorder participated in the case study. In the online survey, participants found the nine proposed patient experience value elements both understandable and important with no additions. During the workshop, 'Uncertainty about long-term benefits and safety,' 'Patient experience related to treatment regimen,' and 'Patient's financial burden' were found to be the most important patient experience value elements, with a respective weight of 25%, 19.2%, and 14.4% (out of total 100%). CONCLUSIONS: This case study provides a framework for eliciting and prioritizing patient experience value elements using direct patient input. Although elements/weights may differ by disease, and even in neuromyelitis optica spectrum disorder, additional research is needed, value frameworks, researchers, and manufacturers can use this practical method to generate patient experience value elements and evaluate their impact on treatment selection.

Corrigendum to "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications".

[This corrects the article DOI: 10.1155/2021/9996193.].

Health-related quality of life and utility in patients receiving biological and non-biological treatments in rheumatoid arthritis.

Biological treatments earn increasing significance in the treatment of rheumatoid arthritis (RA) but are associated with high incremental cost-effectiveness ratio compared to conventional antirheumatic treatments such as disease-modifying antirheumatic drugs. As the most important objective of medical technologies should be to increase life years and/or patients' health-related quality of life (HRQoL), measuring QoL and utility in RA patients treated with biological therapies is crucial. The objective of this study is to compare the utility and QoL of patients treated with biological (n = 85) and non-biological (n = 168) antirheumatic drugs in Hungary in a cross-sectional non-interventional study. A measure of impairment (Disease Activity Score (DAS)-28), QoL measure (EuroQol five Dimension (EQ-5D) Visual Analogue Scale (VAS), Rheumatoid Arthritis Quality of Life (RAQoL)) and utility measures (indirect: EQ-5D index, direct: time trade-off (TTO)) were applied using an interview method. The Pearson correlation was used to assess the strength of the relationship of different measures in the total study group (n = 253). The EQ-5D index (biological treatment: 0.608, non-biological treatment: 0.483; P = 0.012) and DAS-28 (biological treatment: 3.8, non-biological treatment: 4.5; P = 0.003) showed statistically significant difference between the two subcohorts after adjusting data by age, gender and disease duration. Our results indicate that patients on biological treatment have lower disease activity and higher utility; however, it was not statistically significant in all cases. According to our knowledge, TTO was not used previously in Hungarian RA patients. Utility data concerning biological treatments are essential for cost-utility models in health technology assessment reports for public reimbursement.

Attempt to increase the transparency of fourth hurdle implementation in Central-Eastern European middle income countries: publication of the critical appraisal methodology.

BACKGROUND: In middle income countries the number of trained health technology assessment specialists is limited and the public budget for health technology assessment is considerably lower compared to developed countries. These countries therefore must develop their own solutions to improve the quality and efficiency of health technology assessment implementation in reimbursement decisions. Our study aimed to develop a scientifically rigorous and detailed appraisal checklist for economic evaluations of pharmaceuticals in the single health technology assessment process. METHODS: The research design entailed a review of economic evaluations, submitted for reimbursement of pharmaceuticals, by two independent academic reviewers to identify the most common methodological problems. Fifty economic evaluations submitted in 2007-2008, randomly selected by the Health Technology Assessment Office served as data sources. The new checklist was developed by an iterative working process: first by assessing ten economic evaluations, then improving the checklist by generating new question items, then employing the improved checklist to assess the next ten economic evaluations. After appraising 25 documents, the reviewers reconciled their opinions and improved the checklist with the researchers of the Health Technology Assessment Office during an expert panel discussion. The reviewers scrutinized the second 25 economic evaluations, after which the expert panel finalized the checklist with consensus. RESULTS: The final checklist consists of 91 yes or no questions in 11 main topics concerning comparator selection, efficacy, effectiveness, costs, sensitivity analysis, methodological approach, transparency, and interpretation of results. The new checklist is based on current Hungarian evaluation practice. As the published checklist will be part of the official single health technology assessment process of pharmaceuticals, submitters will be able to assure the quality of their economic evaluation. CONCLUSIONS: The transparent critical appraisal method should improve the consistency of pharmaceutical reimbursement decisions and facilitate the utilization of economic evaluations in other fields of health care decision-making in other Central-Eastern European countries.

Determinants of NSAID choice in rheumatoid arthritis--a drug utilization study.

Long term nonsteroidal anti-inflammatory drug (NSAID) medication is associated with gastrointestinal (GI) adverse events. This paper aimed to depict main determinants of NSAID drug choice (GI safe/traditional NSAIDs) in a rheumatoid arthritis (RA) patient sample (n=143). According to our logistic regression model, current/prior GI adverse events in the anamnesis was the only significant determinant of GI safer NSAID use (OR 3.1, p = 0.01). There was significant difference regarding most NSAIDs between the RA study sample and the total Hungarian population, suggesting that chronic administration could also influence the NSAID choice. GI safe NSAIDs were much preferred in the RA study sample than in the total population. In conclusion, the NSAID medication of the observed 143 patients was considered to be reasonable regarding both cardiovascular and GI safety.

[Risk sharing methods in middle income countries]. / Kockázat-megosztási technikák alkalmazása a közepes jövedelmu országokban.

The pricing strategy of innovative medicines is based on the therapeutic value in the largest pharmaceutical markets. The cost-effectiveness of new medicines with value based ex-factory price is justifiable. Due to the international price referencing and parallel trade the ex-factory price corridor of new medicines has been narrowed in recent years. Middle income countries have less negotiation power to change the narrow drug pricing corridor, although their fair intention is to buy pharmaceuticals at lower price from their scarce public resources compared to higher income countries. Therefore the reimbursement of new medicines at prices of Western-European countries may not be justifiable in Central-Eastern European countries. Confidential pricing agreements (i.e. confidential price discounts, claw-back or rebate) in lower income countries of the European Union can alleviate this problem, as prices of new medicines can be adjusted to local purchasing power without influencing the published ex-factory price and so the accessibility of patients to these drugs in other countries. In order to control the drug budget payers tend to apply financial risk sharing agreements for new medicines in more and more countries to shift the consequences of potential overspending to pharmaceutical manufacturers. The major paradox of financial risk-sharing schemes is that increased mortality, poor persistence of patients, reduced access to healthcare providers, and no treatment reduce pharmaceutical spending. Consequently, payers have started to apply outcome based risk sharing agreements for new medicines recently to improve the quality of health care provision. Our paper aims to review and assess the published financial and outcome based risk sharing methods. Introduction of outcome based risk-sharing schemes can be a major advancement in the drug reimbursement strategy of payers in middle income countries. These schemes can help to reduce the medical uncertainty in coverage decisions for valuable innovative healthcare technologies. However risk-sharing schemes can also reduce the transparency of pharmaceutical pricing and reimbursement, as the payback, and consequently the actual price per patient can be calculated only retrospectively. Therefore risk-sharing agreements can be interpreted as special forms of confidential pricing agreements to facilitate the implementation of differential pricing in middle income countries.

Factors associated with medication adherence in patients with chronic obstructive pulmonary disease.

BACKGROUND: Predictors of medication adherence are not well known in chronic obstructive pulmonary disease (COPD). It is therefore necessary to identify factors associated with adherence to improve the effectiveness of COPD management within real-world situations. OBJECTIVES: The goals of this study were to estimate adherence to respiratory medication and to identify factors related to adherence in COPD patients. METHODS: This was an observational, cross-sectional study conducted on a sample of COPD outpatients. The following information was obtained: adherence to respiratory therapy (Morisky Medication Adherence Scale), age, gender, smoking status, COPD severity [Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage], lung function [post-bronchodilator forced expiratory volume in 1 s (FEV(1))], treatment regimen for COPD, COPD medication costs per month paid by the patient and health-related quality of life (EuroQol 5-dimension questionnaire). A multivariate logistic regression analysis was performed to identify the independent predictors of adherence. RESULTS: Of the 170 participants (mean age 63.8 years, 41.8% male), 58.2% reported optimal adherence. Adherence to respiratory therapy was associated with age, current smoking status, number of respiratory drugs, number of daily respiratory drug doses and quality of life (p < 0.005). Adherence to respiratory therapy was not related to gender, GOLD stage, FEV(1) or COPD medication costs. CONCLUSIONS: Adherence to COPD medication regimens is poor. Less frequent dosing regimens could be an effective method to enhance adherence to respiratory therapy. Quality-of-life monitoring within clinical practice settings could facilitate improved medication adherence.

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.

Systematic review of real-world studies evaluating the impact of medication non-adherence to endocrine therapies on hard clinical endpoints in patients with non-metastatic breast cancer.

Breast cancer, one of the most common malignancies, is associated with significant economic and health burden both at the patient and societal level. Although medication non-adherence to endocrine breast cancer therapies is common, so far only limited systematic evidence has been available on its quantitative consequences, as previous systematic reviews focused mainly on factors contributing to medication non-adherence. The objective of this review was to explore the implications of medication non-adherence to endocrine therapies on hard clinical outcomes in breast cancer based on real-world studies. A systematic literature review was conducted on PubMed; empirical evidence on hard clinical endpoints (i.e., survival, disease-free survival, metastasis and recurrence) were extracted from uni- or multivariate statistical analyses from retrospective or prospective cohort studies. Of the 2,360 identified records, 12 studies met the inclusion criteria. Two studies identified significant positive association between medication non-adherence and the risk of distant metastasis, three articles between medication non-adherence and the recurrence of breast cancer, two studies between medication non-adherence- and non-persistence and of worse disease-free survival and eight articles between medication non-adherence and mortality. There was only one study where the positive association between medication adherence and survival did not apply to all subgroups. The strong evidence on the negative health consequences of non-adherence to breast cancer treatments indicates the need for the regular monitoring of medication adherence. Furthermore, explicit inclusion of adherence enhancing interventions into health policy agenda would be warranted to improve medication adherence also at a system level.

Proposal for capturing patient experience through extended value frameworks of health technologies.

BACKGROUND: Inclusion of patient experience (PEx) in health technology assessment (HTA) has become increasingly important; however, no harmonized approach exists to help manufacturers or decision makers ensure PEx considerations are fair, consistent, and thorough within global HTA frameworks. OBJECTIVE: To develop a proposal for including PEx in the HTA frameworks of health technologies. METHODS: A systematic literature review (SLR) on existing value frameworks (VFs) was conducted to capture how PEx-related value judgment is currently considered. Guided by the results of the SLR, a research group including HTA experts and patient representatives used an iterative process to develop potential value domains to capture PEx, in accordance with international guidelines. Subsequently, a panel of international payer experts was used to challenge the proposed PEx domains and provide recommendations for implementation. RESULTS: The SLR found 61 VFs and multi-criteria decision analyses (MCDAs) that considered PEx; however, PEx-related value elements were often referred to superficially, without clear definitions. Five potential PEx domains, with proposed measures for each, were developed and refined using expert feedback: (1) responsiveness to patient's individual needs, (2) improved health literacy and empowerment, (3) patient and caregiver reported outcomes, (4) household's financial burden, and (5) improved access for vulnerable patient populations. A flexible approach for framework implementation was proposed. CONCLUSIONS: Proposed PEx domains could be implemented at multiple levels of healthcare decision making to formalize consideration of PEx in the assessment of value, either through the extension of existing VFs or to create new PEx-focused VFs and more holistic decision making tools. DISCLOSURES: This study was funded and sponsored by UCB Pharma. The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. Charokopou, Mountain, and Szegvari are employed by UCB Pharma. Inotai, Jakab, and Kalo are employed by Syreon Research Institute, which received funding from UCB Pharma for this research. Brixner has received fees from AbbVie, Elevar, Millcreek Outcomes Group, Novartis, Sanofi, UCB Pharma, and Xcenda. Campbell has received grants and contracts from the PhRMA Foundation and the Institute for Clinical and Economic Review. During a sabbatical leave, Campbell collaborated with Syreon Research Institute on research projects that included funding from UCB Pharma. Hawkins has received consultancy fees from UCB Pharma. Kristensen has received speakers bureau fees from Pfizer, AbbVie, Amgen, UCB Pharma, Celgene, Bristol-Myers Squibb, MSD, Novartis, Eli Lilly, and Janssen Pharmaceuticals and consultancy fees from UCB Pharma.