OBJECTIVE: Managed entry agreements and especially financial-based agreements are commonly used in European countries for innovative cancer pharmaceuticals. These agreements facilitate access to innovative treatments while mitigating financial risks for payers. This study focuses on the confidential price agreement made by the Dutch government for the reimbursement of pembrolizumab, the implications of broadening indications on cost-effectiveness, and the viability or desirability of said agreement.
METHODS: We selected 5 indications in which pembrolizumab was deemed effective and developed portioned survival models for each indication. Survival and progression-free survival data from the published trials were utilized to recreate individual patient data, and we extrapolated-using parametric models-to a time horizon of 30 years. Inputs for both quality of life and costs were derived from the available literature and were indexed.
RESULTS: The incremental cost-effectiveness ratios ranged between €35 313 and €322 349 per quality-adjusted life-year, depending on the indication. Only 1 indication fell under the €80 000 (or €100 000) cost-effectiveness threshold. When applying the average reported discount on intramural pharmaceuticals in The Netherlands, incremental cost-effectiveness ratios ranged between €20 881 and €252 934 per quality-adjusted life-year gained, and the €80 000 (or €100 000) threshold was met in 3 indications out of 5.
CONCLUSIONS: Our results show that pembrolizumab could be cost-effective in some indications, depending on the confidential price agreement established. However, the possibility of reimbursing not cost-effective care when the price is anchored in 1 indication remains possible. Indication-based pricing could help align value and price for innovative pharmaceuticals that are subject to indication broadening.

Gene therapies (GTs) have recently emerged as revolutionary personalized therapeutic options. Despite their promising potential, challenges such as uncertainty regarding long-term health benefits and safety, along with extreme price tags, pose significant obstacles to patient access. Within the EU, the European Medicines Agency plays a pivotal role with regards to GT market authorization. However, national authorities are responsible for pricing and reimbursement, which results in fragment patient access within the EU. This study aimed to provide an overview of the complex landscape of post-market authorization accessibility for GT products in Bulgaria, comparing it with neighboring EU countries. We applied a mixed-methods approach, including desk research, public data requests, and list price comparisons. As of 1 April 2023, 14 GTs had a valid market authorization at the EU level. In Bulgaria, Kymriah® was the only GT included in the Positive Drug List (PDL), with an official list price of EUR 335,636.94. Similar results were found in Romania, whereas five GTs were included in Greece\'s PDL. Additionally, Zolgensma® was found accessible in Bulgaria through an alternative individual access scheme at an estimated price of EUR 1,945,000.00. In conclusion, this study emphasized targeted policy interventions to address health inequalities and to ensure timely access to GTs within the EU.

In this paper, we explore dynamic market share and public healthcare costs of trastuzumab\'s evergreening (subcutaneous) variant during introduction of trastuzumab\'s competitive biosimilar variants in the Netherlands. We used a time series design to assess dynamic market share of trastuzumab\'s evergreening variant after introducing trastuzumab\'s biosimilar variants, focusing on the number of treatments and patients. The public healthcare costs of this evergreening strategy were estimated using administrative claims data. Our results show that the original trastuzumab was completely replaced by the subcutaneous and biosimilar variants. The uptake of the subcutaneous form peaked at 50% market share but after the introduction of biosimilars progressively reduced to a market share of 20%, resulting in a more competitive market structure. The public healthcare costs for trastuzumab significantly decreased after the introduction of the biosimilars. After the introduction of the biosimilars, a substantial price drop is visible, with the subcutaneous version, still under patent, also falling sharply in price but less strongly than the iv/biosimilar version. As the costs are publicly funded, we recommend a more explicit societal debate to consider if the potential benefits of subcutaneous Herceptin® (and other similar medicines) are worth the additional costs, and at which price it should be reimbursed as the part of the benefit package.

OBJECTIVE: Spain incorporated in 2020 changes in its health technology assessment (HTA), pricing, and reimbursement system for medicines including publishing reports, development of networks of experts, or consultation with stakeholders. Despite these changes, it is unclear how deliberative frameworks are applied and the process has been criticized for not being sufficiently transparent. This study analyses the level of implementation of deliberative processes in HTA for medicines in Spain.
METHODS: We review the grey literature and summarize the Spanish HTA, pricing, and reimbursement process of medicines. We apply the deliberative processes for HTA checklist, developed to assess the overall context of the deliberative process, and identify the stakeholders involved and type of involvement following the framework for evidence-informed deliberative processes, a framework for benefit package design that aims to optimize the legitimacy of decision making.
RESULTS: In the Spanish HTA, pricing, and reimbursement process deliberation takes place in order to exchange viewpoints and reach common ground, mainly during the prioritization, assessment, and appraisal steps. It is closed to the public, not clearly summarized in published documents and limited to the Ministry of Health, the regulatory agency, other Ministries, and experts with mostly clinical and/or pharmaceutical background. The views of stakeholders are only represented through consultation. Communication is the most commonly used form of stakeholder engagement.
CONCLUSIONS: Despite improvements in transparency of the Spanish HTA process for evaluating medicines, aspects related to stakeholder involvement and implementation of deliberative frameworks need further attention in order to achieve further legitimacy of the process.

The increasing rate of manufacturers and consequently the production of the products gave rise to an increase in used products. The growth in old goods, as well as their negative environmental and social consequences, prompted supply chain operators to focus more on reverse logistics for collecting and reusing these items. However, there are a few key issues that should be handled in this manner, covering how to implement an effective collecting plan. What categories of used items should be collected? And how should they be handled for the aim of reusing them? To address these questions, the pricing issues are investigated in a CLSC with a manufacturer and two retailers. As an effective collection strategy, the first retailer, along with selling new products, benefits from the product exchange program (PEP). In this program, the retailer, by offering two types of discounts on a new product\'s price, is able to collect two types of products, including those without and with useful lifetime left as the first- and second-category products, respectively. In terms of used products management, the first-category products are sent to the manufacturer for recycling, and the second-category ones are sold as second-hand products by the first retailer. Besides, the first retailer exercises a full refund return policy, where the returned defective products, after being remanufactured by the manufacturer, are sold to customers by the second retailer in the secondary market. With respect to buy back price of first-category products from the first retailer, two scenarios are considered: 1) the manufacturer pays as much as the difference between the original retail price and discounted retail price in order to encourage the retailer to offer exercise the PEP for returned used items, or 2) by considering the discount on wholesale price, the manufacturer pays as much as the difference between the original wholesale price and discounted wholesale price. In this study, a real-world case study is considered based on an Iranian automotive industry to understand the issue better and obtain practical results. The findings show that the second scenario is more profitable due to lower selling prices and greater demand rates. It is proved that the PEP along with providing environmental benefits can improve supply chain financial profit even for the first or the second-category products.

Neovascular age-related macular degeneration (AMD) is a progressive eye disease and is a leading cause of vision loss in the Western world. Vascular endothelial growth factor inhibitors have become a mainstay of treatment for this disease. Currently, treatment options include three originator biologics with approvals for neovascular AMD (aflibercept, ranibizumab, and brolucizumab-dbll) and one biologic that is commonly used off-label for the condition (bevacizumab). In the USA, Medicare spending on these drugs consistently surpassed $4 billion per year between 2015 and 2019, driven by high prices and varying off-label use of bevacizumab, which is substantially cheaper than the other biologics used to treat neovascular AMD. In this article, we discuss how legal reform can improve market competition for biologic drugs, using AMD therapies as a case study. We chose this group of drugs for their significant contribution to Medicare spending, the price difference between approved therapies and intravitreal bevacizumab, and because there currently exists a large biosimilar pipeline with many drug candidates in the final stage of development. We propose mechanisms for anticipating and facilitating the market introduction of biosimilars, as well as changes to the pricing model in Medicare that can promote use of cost-effective therapies. Reforms such as empowering Medicare to negotiate drug prices may help ensure that introduction of new biologics and biosimilars for AMD will lower spending and increase patient access.

Evidence on determinants of prices for orphan medicines is scarce and not available for Italy. The aim of this paper is to provide an evidence on variables affecting the annual treatment cost of orphan drugs in Italy, testing the hypothesis of a negative correlation with the dimension of the target population and a positive correlation with the added therapeutic value of the drug and the quality of the evidence of pivotal studies.
Drugs with a European orphan designation reimbursed in Italy in the last 6 years (2014-2019) were considered. Univariate, cluster analysis and multiple regression models were used to investigate the correlation between the annual treatment cost and, as explanatory variables, the dimension of the target population, the existence of Randomized Clinical Trials as a proxy of the quality of the pivotal studies, the added therapeutic value.
In the univariate analysis prevalence and added therapeutic value, as expected, have a negative and positive correlation with cost respectively. The correlation with RCT is not significant. In the multivariate model, coefficients for prevalence and added value are confirmed but for the latter are not significant anymore. We also found, through an interaction analysis, that the existence of an RCT has a positive impact on annual treatment cost when the target population is very small.
Our results suggest that value arguments and sustainability (dimension of the target population and its impact on budget impact) issues are considered for orphan drugs pricing: the role played by sustainability is systematically supported by our results. A more transparent and reproducible price negotiation process for orphan drugs is needed in Italy. This paper has contributed to highlight the implicit drivers of this process.

OBJECTIVE: Health technology assessment (HTA) can increase the appropriateness and transparency of pricing and reimbursement decisions. Jordan is still in the early phase of its HTA implementation, although the country has very limited public resources for the coverage of healthcare technologies. The study objective was to explore and validate priorities in the HTA road map for Jordan and propose to facilitate the preferred HTA status.
METHODS: Health policy experts from the public and private sectors were asked to participate in a survey to explore the current and future status of HTA implementation in Jordan. Semistructured interviews with senior policy makers supported by literature review were conducted to validate survey results and make recommendations for specific actions.
RESULTS: Survey and interview results indicated a need for increased HTA training, including both short courses and academic programs and gradually increasing public funding for technology assessment and appraisal. Multiple HTA bodies with central coordination can be the most feasible format of HTA institutionalization. The weight of cost-effectiveness criterion based on local data with published reports and explicit decision thresholds should be increased in policy decisions of pharmaceutical and nonpharmaceutical technologies.
CONCLUSIONS: Currently, HTA has limited impact on health policy decisions in Jordan, and when it is used to support pharmaceutical reimbursement decisions, it is mainly based on results from other countries without considering transferability of international evidence. Policy makers should facilitate HTA institutionalization and use in policy decisions by increasing the weight of local evidence in HTA recommendations.

The aim of this study is to evaluate the effect of the introduction of biosimilars in Bulgaria on the prices and utilization of biologic disease modifying antirheumatic drugs (bDMARD). It is a combined qualitative and quantitative analysis of time of entry of biosimilars on the national market and the respective changes in the prices and utilization during 2015-2020. We found 58 biosimilars for 16 reference products authorized for sale on the European market by the end of 2019, but for 2 of the reference products biosimilars were not found on the national market. Only inflammatory joint disease had more than one biosimilar molecule indicated for therapy. Prices of the observed bDMARD decreased by 17% down to 48%. We noted significant price decreases upon biosimilar entrance onto the market. In total, the reimbursed expenditures for the whole therapeutic group steadily increased from 72 to 99 million BGN. Utilization changed from to 0.5868 to 2.7215 defined daily dose (DDD)/1000inh/day. Our study shows that the entrance of biosimilars in the country is relatively slow because only half of the biosimilars authorized in Europe are reimbursed nationally. Introduction of biosimilars decreases the prices and changes the utilization significantly but other factors might also contribute to this.

To inform allocation decisions in any healthcare system, robust cost data are indispensable. Nevertheless, recommendations on the most appropriate valuation approaches vary or are nonexistent, and no internationally accepted gold standard exists. This costing analysis exercise aims to assess the impact and implications of different calculation methods and sources based on the unit cost of general practitioner (GP) consultations in Austria.
Six costing methods for unit cost calculation were explored, following 3 Austrian methodological approaches (AT-1, AT-2, AT-3) and 3 approaches applied in 3 other European countries (Germany, The Netherlands, United Kingdom). Drawing on Austrian data, mean unit costs per GP consultation were calculated in euros for 2015.
Mean unit costs ranged from €15.6 to €42.6 based on the German top-down costing approach (DE) and the Austrian Physicians\' Chamber\'s price recommendations (AT-3), respectively. The mean unit cost was estimated at €18.9 based on Austrian economic evaluations (AT-1) and €17.9 based on health insurance payment tariffs (AT-2). The Dutch top-down (NL) and the UK bottom-up approaches (UK) yielded higher estimates (NL: €25.3, UK: €29.8). Overall variation reached 173%.
Our study is the first to systematically investigate the impact of differing calculation methods on unit cost estimates. It shows large variations with potential impact on the conclusions in an economic evaluation. Although different methodological choices may be justified by the adopted study perspective, different costing approaches introduce variation in cross-study/cross-country cost estimates, leading to decreased confidence in data quality in economic evaluations.