Expert-based collaborative analysis of the situation and prospects of biomarker test implementation in oncology in Spain / Análisis colaborativo de expertos de la situación y perspectivas de la implementación de pruebas de biomarcadores en oncología en España

Purpose: Biomarkers as screening for precision medicine is a fundamental step. The purpose of this article is twofold. First, to highlight the existing barriers in the implementation of Precision Medicine in Spain, with a special emphasis on barriers in access to the determination of biomarkers. Second, to provide a Roadmap that can help implement Precision Medicine equitably at the national level and optimize the use of biomarkers. Methods: A systematic review of literature (SRL) and a focus group (FG) with multidisciplinary experts has been carried out in 2023. Participants were contacted individually, and discourse analysis was processed anonymously. Results: We carried out a quantitative (SRL) and a qualitative approach (FG). The discourse analysis and roadmap were sent individually to each expert for approval. Conclusions: The potential of Precision Medicine has not been fulfilled in Spain. While several regional initiatives are in place, a national plan or strategy around Precision Medicine and use of biomarkers is lacking. In a general context of rapid progress at a global and European level, including the 2021 Europe’s Beating Cancer Plan, it is time to define and implement a National Plan to make the promise come true. While some comparable countries within Europe – such as the UK or France – are mature enough to adopt such strategies, in Spain there is still a long way to go. We consider that the different strands of work outlined in the Roadmap can be used as basis for such purpose.(AU)

Expert-based collaborative analysis of the situation and prospects of biomarker test implementation in oncology in Spain.

PURPOSE: Biomarkers as screening for precision medicine is a fundamental step. The purpose of this article is twofold. First, to highlight the existing barriers in the implementation of Precision Medicine in Spain, with a special emphasis on barriers in access to the determination of biomarkers. Second, to provide a Roadmap that can help implement Precision Medicine equitably at the national level and optimize the use of biomarkers. METHODS: A systematic review of literature (SRL) and a focus group (FG) with multidisciplinary experts has been carried out in 2023. Participants were contacted individually, and discourse analysis was processed anonymously. RESULTS: We carried out a quantitative (SRL) and a qualitative approach (FG). The discourse analysis and roadmap were sent individually to each expert for approval. CONCLUSIONS: The potential of Precision Medicine has not been fulfilled in Spain. While several regional initiatives are in place, a national plan or strategy around Precision Medicine and use of biomarkers is lacking. In a general context of rapid progress at a global and European level, including the 2021 Europe's Beating Cancer Plan, it is time to define and implement a National Plan to make the promise come true. While some comparable countries within Europe - such as the UK or France - are mature enough to adopt such strategies, in Spain there is still a long way to go. We consider that the different strands of work outlined in the Roadmap can be used as basis for such purpose.

A Review of Current Approaches to Evaluating and Reimbursing New Medicines in a Subset of OECD Countries.

OBJECTIVES: The aim of this study was to review the current evaluation and funding processes for new drugs in different developed countries, to provide a comparative framework with detailed, homogeneous, and up-to-date information. METHODS: Scientific publications, reports and websites were reviewed between July and December 2021 using PubMed, Google Scholar, and grey literature sources. The main items searched were actors and processes, including timelines, characteristics of clinical and economic evaluations, participation of stakeholders, elements of price and reimbursement decisions, cost-effectiveness thresholds and specific funds. The analysed 13 countries were Australia, Canada, England, France, Germany, Italy, Japan, the Netherlands, Portugal, Scotland, South Korea, Spain and Sweden. RESULTS: Eight countries perform the assessment process separated from the pricing decision. Countries measure each drug's added therapeutic value through multi-attribute value scales, algorithms, non-prescriptive lists of criteria, or quality-adjusted life years (QALYs). Health technology assessment (HTA) methodologies differ in their outcome measures, elicitation techniques, comparators, and perspectives. The criteria used for pricing and reimbursement include humanistic, clinical, and economic aspects. Only Scotland, England, the Netherlands, Canada and Portugal use explicit efficiency thresholds. Health care professionals participate in all assessment committees, and patients are becoming increasingly involved in most countries. The official time from marketing authorisation to the completion of the evaluation and pricing processes varied from 126 to 540 days. CONCLUSIONS: Most analysed countries show a trend towards value-based approaches that consider value for money to society, but also other economic, clinical, and humanistic criteria. Good practices included robustness, transparency, independence, and participation.

Leveraging the holistic benefits of biosimilars in Europe - part 2: how payers can safeguard the future of a healthy biosimilar market environment.

INTRODUCTION: Biosimilars have improved access to biologic medicines; however, historical thinking may jeopardize the viability of future markets. AREAS COVERED: An expert panel of eight diverse European stakeholders provided insights about rethinking biosimilars and cost-savings, reducing patient access inequalities, increasing inter-market equity, and improving education. The insights reported here (Part 2) follow a study that provides perspectives on leveraging the holistic benefits of biosimilars for market sustainability based on independent survey results and telephone interviews of stakeholders from diverse biosimilar markets (Part 1). Directional recommendations are provided for payers. EXPERT OPINION: The panel's market maturity framework for biosimilars has three stages: 'Invest,' 'Expand' and 'Harvest.' Across market stages, re-thinking the benefits of biosimilars beyond cost-savings, considering earlier or expanded access/new indications, product innovations, and re-investment of biosimilar-generated cost-savings should be communicated to stakeholders to promote further engagement. During 'Expand' and 'Harvest' stages, development of efficient, forward-looking procurement systems and mechanisms that drive uptake and stabilize competition between manufacturers are key. Future biosimilars will target various therapy areas beyond those targeted by existing biosimilars. To ensure a healthy, accessible future market, stakeholders must align their objectives, communicate, collaborate, and coordinate via education, incentivization, and procurement, to maximize the totality of benefits.

Capturing the holistic value of biosimilars in Europe - part 1: a historical perspective.

INTRODUCTION: Approved biosimilars exhibit comparable efficacy, safety, and immunogenicity to reference products. This report provides perspectives on the societal value of biosimilars within Europe and potential factors that have influenced market dynamics. METHODS: An independent, self-administered survey or one-on-one in-depth interview was used to collect viewpoints about the impact of biosimilar medicines within European markets. Key insights were also sought from an expert panel of European stakeholders. RESULTS: Survey respondents were clinicians, pharmacists, and payers from Europe (N = 103). Perceived benefits of biosimilars included increased access to innovative medicines (73% of respondents) or biologic treatments (66%). Biosimilar competition was thought to expand access to biologics (~50% of respondents) or drug combinations (~36%) and reduce biologic access time (34%). Key drivers of biologic access after biosimilar competition included increased biologic awareness (51%) and changes to prescribing guidelines (37%) and/or treatment paradigms (28%). The expert panel developed a market maturity framework of biosimilar adoption/opportunities comprising three stages: 'Invest,' 'Expand,' and 'Harvest.' Findings were supported by published literature. CONCLUSIONS: In Europe, the perceptions of well-informed survey/interview respondents are that biosimilars have improved patient outcomes via increased access to biologics and innovative biologic products, contributing to earlier and longer treatment of a broader population.

Evaluation of antibody-based preventive alternatives for respiratory syncytial virus: a novel multi-criteria decision analysis framework and assessment of nirsevimab in Spain.

BACKGROUND: Respiratory syncytial virus (RSV) is a highly infectious disease that poses a significant clinical and medical burden, as well as social disruption and economic costs, recognized by the World Health Organization as a public health issue. After several failed attempts to find preventive candidates (compounds, products, including vaccines), new alternatives might be available, one being nirsevimab, the first and only option approved for RSV prevention in neonates and infants during their first RSV season. The objective of this study was to develop a novel multi-criteria decision analysis (MCDA) framework for RSV antibody-based preventive alternatives and to use it to assess the value of nirsevimab vs. placebo as a systematic immunization approach to prevent RSV in neonates and infants during their first RSV season in Spain. METHODS: Based on a pre-established model called Vaccinex, an ad-hoc MCDA framework was created to reflect relevant attributes for the assessment of current and future antibody-based preventive measures for RSV. The estimated value of nirsevimab was obtained by means of an additive linear model combining weights and scores assigned by a multidisciplinary committee of 9 experts. A retest and three sensitivity analyses were conducted. RESULTS: Nirsevimab was evaluated through a novel framework with 26 criteria by the committee as a measure that adds value (positive final estimated value: 0.56 ± 0.11) to the current RSV scenario in Spain, by providing a high efficacy for prevention of neonates and infants. In addition, its implementation might generate cost savings in hospitalizations and to the healthcare system and increase the level of public health awareness among the general population, while reducing health inequities. CONCLUSIONS: Under a methodology with increasing use in the health field, nirsevimab has been evaluated as a measure which adds value for RSV prevention in neonates and infants during their first RSV season in Spain.

Not one, but many: developing a multi-indication pricing model for medicines in Belgium.

Back ground: Current pricing and reimbursement models that focus on one indication at a time are not suited to address the market access of multi-indication medicines. Therefore, the aim of this study is to co-create with Belgian stakeholders a multi-indication pricing model and procedural pathway, to identify conditions for implementation, and to illustrate the multi-indication pricing model with a case study. Methods: Different multi-indication pricing models were identified from the literature, case studies and pilots in other countries. Semi-structured interviews were conducted with 21 representatives from the National Institute for Health and Disability Insurance, insurance funds, clinicians, patients, the policy cell of the Minister of Health, pharmaceutical industry and academia. These provided insight in the opinions of stakeholders about possible multi-indication pricing models and their feasibility in the Belgian context. Agreement on the preferred multi-indication pricing model and procedural pathway was reached in a multi-stakeholder round table. Results: The international review generated four main multi-indication pricing models that vary in terms of whether a uniform price or differential prices are applied, whether prices are adjusted for the volume and/or value of the medicine in each indication, and whether a proactive or retroactive dynamic pricing approach is used. However, Belgian stakeholders preferred a fifth model, which sets a single price as the volume- and value-weighted average price across all indications at launch. Over time, the price is adapted based on volume and value of the medicine in real-life practice for each indication. To implement this model, a legal framework, horizon scanning and early dialogue, data infrastructure, an evidence plan for the medicine, technical expertise and governance model need to be developed. Conclusion: Although the multi-indication pricing model preferred by Belgian stakeholders raises the administrative burden, it allows for the price of a medicine to vary during the lifecycle based on its initial and real-life performance in multiple indications.

New pricing models for generic medicines to ensure long-term sustainable competition in Europe.

Background: Price erosion of generic medicines over time as a result of existing pricing policies in combination with increasing operational costs of these products due to high inflation, undermine long-term sustainable competition in European off-patent medicines markets. Therefore, the aim of this study is to identify new potential pricing models for retail generic medicines in Europe, examine their pros and cons, and illustrate them with examples inside or outside the pharmaceutical sector. Methods: A targeted literature review, one-to-one interviews and a joint advisory board meeting with experts from five European countries were carried out to assess potential pricing models for generic medicines. Results: We identified ten pricing models that can be applied to generic medicines. The tiered pricing model is viewed as a sustainable solution ensuring competitiveness, but requires market monitoring using a supportive IT infrastructure. De-linking the price of generic medicines from that of the off-patent originator medicine prevents the originator from forcing generic medicines' prices to unsustainable levels. Higher costs due to inflation can be compensated in the automatic indexation model. Other pricing models that have less implementation potential include the one-in-one/multiple-out model, tax credits, value-based pricing, volume for savings and guaranteed margin/fee models. The hypothecated tax and cost allocation models, which add a patient fee to generic medicines prices, are not likely to be socially acceptable. Conclusion: When considering a new pricing model for generic medicines, the impact on innovative medicines and the characteristics of the healthcare system in a given country need to be taken into account. Also, there is a need to continuously follow up the level of competition in off-patent medicines markets and to identify sustainability risks.

Data Governance for Real-World Data Management: A Proposal for a Checklist to Support Decision Making.

OBJECTIVES: Real-world data (RWD) and real-world evidence (RWE) can provide extensive information on healthcare for use in health technology assessment and decision making. Nevertheless, there is a lack of consensus surrounding the appropriate data governance (DG) practices for RWD/RWE. Data sharing is also a large concern, especially considering evolving data protection regulations. Our objective is to propose recommendations for international standards of evaluating the acceptability of RWD governance practices. METHODS: After reviewing the literature, we created a checklist targeting DG practices for RWD/RWE. We then carried out a 3-round Delphi panel, including European policy makers, health technology assessment experts, and hospital managers. The consensus for each statement was measured and the checklist adjusted accordingly. RESULTS: The literature review identified the main topics regarding RWD/RWE DG practices: data privacy and security, data management and linkage, data access management, and the generation and use of RWE. Members of the Delphi panel (21 experts/25 invited) were presented a total of 24 statements related to each of the topics. Experts demonstrated a progressive level of consensus and importance ratings in all topics and to most statements. We suggest a refined checklist in which the statements rated less important or with less consensus have been removed. CONCLUSIONS: This study suggests how the DG of RWD/RWE could be qualitatively evaluated. We propose checklists that could be used by all RWD/RWE users to help ensure the quality and integrity of RWD/RWE governance and complement data protection law.

Review and Assessment of Policy Options for Improving Access to Combination Therapies in Oncology in Europe.

OBJECTIVES: Combinations of on-patent therapies (CTs) are increasingly common in oncology. They cause challenges for funding and affordability, and hence patient access, especially when constituent therapies are owned by different manufacturers. The aim of our study was to develop policy proposals for the assessment, pricing, and funding of CTs and identify which might be relevant in different European countries. METHODS: Following a review of available literature, seven hypothetical policy proposals were developed and subsequently assessed through 19 semi-structured interviews with health policy, pricing, technology assessment and legal experts in seven European countries to identify those most likely to gain traction. RESULTS: Experts saw a need for agreed approaches within a country to manage affordability and funding challenges for CTs. Changes to health technology assessment (HTA) and funding models were considered unlikely, but other policy proposals were seen as mostly useful, with country-specific adaptations. Bilateral discussions between manufacturers and payers were deemed important, and less challenging and protracted than arbitrated dialogue between manufacturers. Usage-specific pricing, possibly using weighted average prices, was considered a prerequisite for the financial management of CTs. CONCLUSIONS: There is a growing need to ensure that CTs are affordable to health systems. It would appear that there is no one set of policies that is appropriate for all countries in Europe, so countries wishing to ensure that patients have (or continue to have) access to CTs of value to them must explore and implement the policies that are best suited to their general approach to funding health care and to the assessment and reimbursement of medicines.

The Real-World Evidence Workstream in EUreccA 2025: How the Task Was Addressed.

This is one of a series of articles that consider the barriers to optimal use of real-world evidence (RWE) in health technology assessment (HTA) as well as ways to overcome them. The work was carried out as part of EUreccA 2025 (European Initiative for New Reimbursement and Access Approaches 2025), in particular with the RWE workstream embodied within that collaboration. The starting premises of this workstream were as follows: (1) the acceptance of RWE by HTA agencies and payers in the assessment of drugs is suboptimal and variable between jurisdictions, and (2) if that were not the case, the path of new pharmaceuticals to patients could be quicker and less expensive. Elsewhere in this issue we set out the conclusions we had reached in the EUreccA RWE workstream. In this article, we set out the methodology used to conduct the totality of the EureccA 2025 RWE workstream effort, which led us to those conclusions. The main results, strengths, and limitations of the individual parts are discussed further in separate articles in this supplement. Through scoping work, we generated 4 key topics within which to identify and address the barriers to optimal RWE use in HTA. Through pragmatic literature searches, stakeholder engagement, and case studies, we suggest ways in which the problems identified may be addressed as a contribution to progress in this area.

Across-Country Variations of Real-World Data and Evidence for Drugs: A 5-European-Country Study.

OBJECTIVES: This study aimed to describe the role of real-world data (RWD) and real-world evidence (RWE) in health technology assessment (HTA) in 5 European countries and to identify the hurdles to the acceptance of RWE and suggest directions toward its more effective use. METHODS: Authors from France, Germany, Italy, and Sweden used a common template to extract evidence. For England, the Cancer Drugs Fund was described and analyzed as a particular model for the use of RWD to provide evidence for coverage decisions and managed entry agreements. RESULTS: In all countries except Germany, HTA bodies acknowledged the relevance of RWD/RWE to address postlaunch uncertainties. In Germany, evidence from randomized controlled trials remains the gold standard, and evidence based on RWD is generally rejected. Multiple sources of RWD exist, but the quality, the immediate relevance of existing sources, and their interoperability limit their adaptation to the specifics of a given drug. This leads to skepticism about the validity of the evidence. Timing is also a key issue: the production of evidence may not be synchronized with the HTA and pricing bodies' agendas. The Cancer Drugs Fund case emphasizes that a strong partnership among all stakeholders and a pragmatic use of existing data, alongside clinical evidence provided by companies, are key success factors. CONCLUSIONS: A continuous investment in national health information systems is a key issue for providing valid RWE. Processes and aids to guide the acceptability and usage of RWE derived from pairing between sources and questions are essential.

Using Real-World Data in the Health Technology Assessment of Pharmaceuticals: Strengths, Difficulties, and a Pragmatic Way Forward.

In the past decade, there have been increasing calls for greater use of real-world evidence (RWE) and data (RWD), with the explicit goal of enabling faster provision of effective medicines to patients in need. The push for decision makers to accept RWE is especially noticeable in the pursuit of regulatory approval, but RWE, particularly when used to estimate the relative effectiveness of interventions, is not always readily accepted by agencies responsible for reimbursement and pricing of new pharmaceuticals and, to a varying degree, is not accepted across jurisdictions. This lack of trust hampers the use of RWE despite a very large and growing literature base on the principles of how RWE should be used. In this article, we suggest an important part of the explanation of why this situation has arisen and make suggestions for its alleviation. Given that problems commonly arise that are particular to the question being asked and the data sources being used, general guidance on the principles of how to use RWD cannot cover all eventualities. Therefore, we are suggesting the creation of an archive, or repository, to record uses of RWD in support of decisions by funding bodies or their advisors. This article introduces a proposed, structured classification of decision types using RWE, around which evidence can be assembled in a curated source (RWD/RWE taxonomy) and thus facilitate judgments on when evidence is "good enough." This article is part of a series in a special issue of this journal that looks at the barriers to optimal use of RWE in health technology assessment and how to overcome them. We begin significantly to populate our "taxonomy" with examples in an accompanying article. We also propose recommendations for international standards of evaluating the acceptability of RWD governance practices.

Structure and Content of a Taxonomy to Support the Use of Real-World Evidence by Health Technology Assessment Practitioners and Healthcare Decision Makers.

This is one of a series of articles that consider the barriers to optimal use of real-world evidence (RWE) in health technology assessment and how to overcome them. The work was performed as part of EUreccA 2025, in particular with the RWE workstream embodied within that collaboration. Elsewhere in this issue we described the reasoning and process that led us to develop practical tools to support RWE use, including this taxonomy and explained the methods used to do so. The taxonomy classifies questions that are typically addressed using real-world data in health technology assessment and the data sources typically used to address these questions. In this article, we describe the taxonomy itself. For as many of the pairings as possible, we have provided links to advice and methods on how to address the associated question using those data. We have also provided links to examples of RWE use in practical decision making to answer the questions posed. Our work is not complete, but we believe it is sufficient to demonstrate the value of such a taxonomy and information source if it is completed and curated as a "wiki" by the community that would use it.

Инструменты политики (не связанные с ценовыми факторами) в поддержку инноваций в области медицины: Технический доклад Инициативы Осло по лекарственным средствам: основные положения.

Под инструментами инновационной политики имеются в виду вмешательства в сферу политики с особым механизмом действия, который оказывает влияние на процесс нововведений. В техническом докладе Инициативы Осло по лекарственным средствам представлен широкий диапазон таких инструментов для использования национальными органами, отвечающими за формирование политики, в поддержку инноваций в области новых лекарственных препаратов (за исключением тех, которые ориентированы на факторы цены, о чем говорится в других материалах серии докладов). Этот доклад посвящен анализу различных типов инструментов политики, проведенному в результате обзора литературных источников по вопросам инновационной политики в медицинском и других секторах. По каждому из этих типов в отчете дается описание их механизмов действий, характера воздействия и в чем он проявляется, а также уточняется размах внедрения этих инструментов в практику в глобальном масштабе. Здесь также изложены соображения по эффективному осуществлению таких механизмов. Доклад наглядно показывает, что давно сложившуюся пуш/пул-конструкцию (соотношение спроса и предложения), занимающую доминирующее положение в связи с полемикой вокруг нововведений в области медицины, можно расширить, вооружив определяющих политику лиц инструментами в дополнение к пуш/пул-подходам через актуализацию функции коммуникации, сотрудничества и координации в процессе содействия появлению новых лекарственных средств для удовлетворения потребностей населения.

Innovation policy instruments (non-price) for medical innovation

Innovation policy instruments are policy interventions with a specific mechanism of action that influences the innovation process. This Oslo Medicines Initiative technical report presents a broad range of such instruments available to national policy-makers in support of innovation for new medicines (excluding those focused on price, which are covered elsewhere in the report series). This report explores various types of policy instrument, based on reviews of the literature on policies for innovation in the medical and other sectors. For each type identified, the report explores the mechanisms of action, the effects these have and where they occur, and the extent to which these instruments have been implemented globally. It also sets out considerations for their effective implementation. The report demonstrates that the long-established push/pull (supply/demand) framing that dominates discourse around medical innovation can be broadened, providing policy-makers with instruments to supplement push/pull approaches, by emphasizing the role of communication, collaboration and coordination in supporting the emergence of medicines to address societal needs.