Since its enactment in 2000, the European Orphan Medicinal Products Regulation has allowed the review and approval of approaching 70 treatments for some 55 different conditions in Europe. Success ...does not come without a price, however. Many of these so-called "orphan drugs" have higher price points than treatments for more common diseases. This has been raising debate as to whether the treatments are worth it, which, in turn risks blocking patient access to treatment. To date, orphan drugs have only accounted for a small percentage of the overall drug budget. It would appear that, with increasing numbers of orphan drugs, governments are concerned about the future budget impact and their cost-effectiveness in comparison with other healthcare interventions. Orphan drugs are under the spotlight, something that is likely to continue as the economic crisis in Europe takes hold and governments respond with austerity measures that include cuts to healthcare expenditures. Formally and informally, governments are looking at how they are going to handle orphan drugs in the future. Collaborative proposals between EU governments to better understand the value of orphan drugs are under consideration. In recent years there has been increasing criticism of behaviours in the orphan drug field, mainly centring on two key perceptions of the system: the high prices of orphan drugs and their inability to meet standard cost-effectiveness thresholds; and the construct of the system itself, which allows companies to gain the benefits that accrue from being badged as an orphan drug. The authors hypothesise that, by examining these criticisms individually, one might be able to turn these different "behaviours" into criteria for the creation of a system to evaluate new orphan drugs coming onto the market. It has been acknowledged that standard methodologies for Health Technology Assessments (HTA) will need to be tailored to take into account the specificities of orphan drugs given that the higher price-points claimed by orphan drugs are unlikely to meet current cost-effectiveness thresholds. The authors propose the development of a new assessment system based on several evaluation criteria, which would serve as a tool for Member State governments to evaluate each new orphan drug at the time of pricing and reimbursement. These should include rarity, disease severity, the availability of other alternatives (level of unmet medical need), the level of impact on the condition that the new treatment offers, whether the product can be used in one or more indications, the level of research undertaken by the developer, together with other factors, such as manufacturing complexity and follow-up measures required by regulatory or other authorities. This will allow governments to value an orphan drug that fulfilled all the criteria very differently from one that only met some of them. An individual country could determine the (monetary) value that it places on each of the different criteria, according to societal preferences, the national healthcare system and the resources at its disposal - each individual government deciding on the weighting attributed to each of the criteria in question, based on what each individual society values most. Such a systematic and transparent system will help frame a more structured dialogue between manufacturers and payers, with the involvement of the treating physicians and the patients; and foster a more certain environment to stimulate continued investment in the field. A new approach could also offer pricing and reimbursement decision-makers a tool to handle the different characteristics amongst new orphan drugs and to redistribute the national budgets in accordance with the outcome of a differentiated assessment. The authors believe that this could, therefore, facilitate the approach for all stakeholders.
The health economic literature has questioned the cost-effectiveness and affordability of advanced therapies, proposed adjustments to value assessment frameworks, and discussed the use of ...outcome-based managed entry agreements and staggered payments in the last few years. The aim of this manuscript is to conduct a critical reflection on assessment criteria and access conditions for reimbursement of advanced therapies.
A narrative review of the peer-reviewed literature and grey literature was conducted in April 2021 by searching PubMed; Google Scholar; policy and legislative documents; websites of health technology assessment agencies, advanced therapy organisations, governmental advanced therapy innovation programmes, consultancy agencies; ISPOR conference abstracts and presentations.
Based on the available evidence, this manuscript argues that: a) advanced therapies can be cost-effective at high prices set by manufacturers; b) the economic evaluation framework adopted by many payers under-values these products; c) advanced therapies can be affordable and may not require spread payments; d) outcome-based managed entry agreements are theoretically attractive, but challenging in practice; e) the cost-effectiveness of advanced therapies depends on the outcome-based managed entry agreement and payment approach; f) there is a role for multinational collaborations to manage reimbursement and access of advanced therapies.
This manuscript shows that there is no single approach to reimbursement and access of advanced therapies. Instead, we support a more tailored assessment of health economic aspects of advanced therapies, which considers the heterogeneity of these products and their target populations.
This study aims to discuss approaches to assessing the value of medicines. Economic evaluation assesses value by means of the incremental cost-effectiveness ratio (ICER). Health is maximized by ...selecting medicines with increasing ICERs until the budget is exhausted. The budget size determines the value of the threshold ICER and vice versa. Alternatively, the threshold value can be inferred from pricing/reimbursement decisions, although such values vary between countries. Threshold values derived from the value-of-life literature depend on the technique used. The World Health Organization has proposed a threshold value tied to the national GDP. As decision makers may wish to consider multiple criteria, variable threshold values and weighted ICERs have been suggested. Other approaches (i.e., replacement approach, program budgeting and marginal analysis) have focused on improving resource allocation, rather than maximizing health subject to a budget constraint. Alternatively, the generalized optimization framework and multi-criteria decision analysis make it possible to consider other criteria in addition to value.
•Use of patient preferences in decision making is limited but gaining attention.•Some situations and decisions are more sensitive to patient preferences than others.•Patient centeredness in design, ...conduct and communication of results is key.•In method selection and instrument design many factors can affect validity.•Capturing preference heterogeneity greatly increases the value of patient preference studies.
Industry, regulators, health technology assessment (HTA) bodies, and payers are exploring the use of patient preferences in their decision-making processes. In general, experience in conducting and assessing patient preference studies is limited. Here, we performed a systematic literature search and review to identify factors and situations influencing the value of patient preference studies, as well as applications throughout the medical product lifecyle. Factors and situations identified in 113 publications related to the organization, design, and conduct of studies, and to communication and use of results. Although current use of patient preferences is limited, we identified possible applications in discovery, clinical development, marketing authorization, HTA, and postmarketing phases.
This study can inform different stakeholders on how to conduct, assess, and use patient preference studies and on when to include patient preference studies in development plans.
This research aims to evaluate the methodological quality of budget impact analyses for orphan drugs and to provide suggestions for future analyses.
Conference abstracts and peer-reviewed literature ...on budget impact analyses were collected through searches of Pubmed and Embase. ISPOR good practice guidelines were used as a methodological standard for budget impact analyses. Examined parameters encompassed: perspective, target population, data sources, intervention and comparator(s), time horizon, scope of costs, discounting, validation, assumptions and sensitivity analysis.
Seventy studies on individual orphan drugs and 21 studies on a combination of orphan drugs analyzing budget impact were identified. Overall, analyses considered a third-party payer perspective, reported periodic budget impacts over a one-to-five-year time horizon, and did not apply discounting. A dynamically fluctuating population and costs beyond drug costs were accounted for in 18.7% and 51.7% of studies, respectively. Input data were retrieved from published literature, clinical trials, registries, claims databases, expert opinions, historical data and market research. Assumptions were mostly made about population size and intervention/comparator(s) market uptake, but these assumptions were rarely justified and their impact was insufficiently explored through sensitivity analyses. Budget impact results were rarely validated.
Existing budget impact analyses for orphan drugs are concise, vary greatly and are of substandard methodological quality. To eliminate possible bias in future budget impact analyses, future studies should adhere to national or ISPOR good practice guidelines on budget impact analysis.
Background: Access to biologic medicines (including biosimilars) across Europe is largely governed by a process of tendering conducted by health authorities. Over-reliance on treatment costs in ...awarding tenders has the potential to hinder competition and undermine the long-term sustainability of biosimilars.
Objective: To assess the extent and impact of consideration of 'value-added services' (VAS) in tendering for biosimilars, we conducted a narrative review of published literature.
Results: Findings from survey-based publications indicated that tendering practices for biosimilars are widely used, with cost being the main determinant of success and little detail being available on other criteria where these apply. Criteria (of therapeutic and technical interest) beyond price were included in one tendering specification for infliximab (originator and biosimilars), while a separate tender for the same product included VAS in the form of therapeutic drug monitoring, measurement of antibodies and calprotectin.
Conclusions: Published evidence concerning inclusion of VAS in tendering for biosimilars is lacking. Development and implementation of standardized criteria and methods of assessment for tenders may avoid manufacturers facing segmented markets, encourage competition and the longer-term sustainability of biosimilars, and realize the healthcare system and patient benefits these treatments can bring.
Successful development of new treatments for rare diseases (RDs) and their sustainable patient access require overcoming a series of challenges related to research and health technology assessment ...(HTA). These impediments, which may be unique to RDs or also apply to common diseases but are particularly pertinent in RDs, are diverse and interrelated.
To develop for the first time a catalog of primary impediments to RD research and HTA, and to describe the cause and effect of individual challenges.
Challenges were identified by an international 22-person expert working group and qualitative outreach to colleagues with relevant expertise. A broad range of stakeholder perspectives is represented. Draft results were presented at annual European and North American International Society for Pharmacoeconomics and Outcomes Research (ISPOR) congresses, and written comments were received by the 385-strong ISPOR Rare Disease Review Group from two rounds of review. Findings were refined and confirmed via targeted literature search.
Research-related challenges linked to the low prevalence of RDs were categorized into those pertaining to disease recognition and diagnosis, evaluation of treatment effect, and patient recruitment for clinical research. HTA-related challenges were classified into issues relating to the lack of a tailored HTA method for RD treatments and uncertainty for HTA agencies and health care payers.
Identifying and highlighting diverse, but interrelated, key challenges in RD research and HTA is an essential first step toward developing implementable and sustainable solutions. A collaborative multistakeholder effort is required to enable faster and less costly development of safe, efficacious, and appropriate new RD therapies that offer value for money.
To compare the market dynamics of biosimilar infliximab among four Organization for Economic Cooperation and Development (OECD) countries (UK, France, Japan, and Korea) where supply-side and ...demand-side policies varied greatly, given high and growing expenditure on biological medicines to treat immunological diseases across countries.
A quarterly dataset covering October 2012 to March 2018 was constructed from the MIDAS-IQVIA International database. The sales value (in USD) and volume (in standard units) of originator infliximab and biosimilar products and their relative price in each country were compared.
With the introduction of biosimilars, the sales value of infliximab increased approximately 2.5 times in Korea, whereas it only slightly increased (1.2 times for France and the UK) or decreased (0.9 for Japan) in other countries. While stable market size dynamics were observed in the other countries, an escalating market size, attributable to the increase in originator infliximab, was observed in Korea. In the UK and France, which have implemented demand-side policies, the sales volume of originator infliximab appreciably decreased after the entry of biosimilar infliximab while that of biosimilars increased; however, in Korea, which has supply-side policies based on price-linking with few demand-side policies, the volume of originator infliximab actually increased by 70% alongside a very limited increase in biosimilar infliximab. The lowest price ratio between biosimilar and originator infliximab was found in Japan, at 68%. In France and Korea, the ex-factory prices of biosimilar infliximab were 99 and 95%, respectively, of the originator infliximab price. In the UK, the ex-factory price of biosimilar infliximab started at 87% of that of originator infliximab and then decreased to 80% as the market matured. However, actual price differences might differ.
The uptake of biosimilar infliximab varied greatly, and in contrast to the UK, France, and Japan, the introduction of biosimilar infliximab resulted in market expansion in Korea, which might be explained by a lack of demand-side policies in Korea. Both supply- and demand-side measures are necessary for health authorities to achieve desired savings from the availability of biosimilars.
Introduction: Biosimilars have the potential to enhance the sustainability of evolving health care systems. A sustainable biosimilars market requires all stakeholders to balance competition and ...supply chain security. However, there is significant variation in the policies for pricing, procurement, and use of biosimilars in the European Union. A modified Delphi process was conducted to achieve expert consensus on biosimilar market sustainability in Europe. Methods: The priorities of 11 stakeholders were explored in three stages: a brainstorming stage supported by a systematic literature review (SLR) and key materials identified by the participants; development and review of statements derived during brainstorming; and a facilitated roundtable discussion. Results: Participants argued that a sustainable biosimilar market must deliver tangible and transparent benefits to the health care system, while meeting the needs of all stakeholders. Key drivers of biosimilar market sustainability included: (i) competition is more effective than regulation; (ii) there should be incentives to ensure industry investment in biosimilar development and innovation; (iii) procurement processes must avoid monopolies and minimize market disruption; and (iv) principles for procurement should be defined by all stakeholders. However, findings from the SLR were limited, with significant gaps on the impact of different tender models on supply risks, savings, and sustainability. Conclusions: A sustainable biosimilar market means that all stakeholders benefit from appropriate and reliable access to biological therapies. Failure to care for biosimilar market sustainability may impoverish biosimilar development and offerings, eventually leading to increased cost for health care systems and patients, with fewer resources for innovation.
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