Blonda Alessandra, Denier Yvonne, Huys Isabelle, Simoens Steven
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium.
Front Pharmacol. 2021 May 12;12:631527. doi: 10.3389/fphar.2021.631527. eCollection 2021.
Decision-makers have implemented a variety of value assessment frameworks (VAFs) for orphan drugs in European jurisdictions, which has contributed to variations in access for rare disease patients. This review provides an overview of the strengths and limitations of VAFs for the reimbursement of orphan drugs in Europe, and may serve as a guide for decision-makers. A narrative literature review was conducted using the databases Pubmed, Scopus and Web of Science. Only publications in English were included. Publications known to the authors were added, as well as conference or research papers, or information published on the website of reimbursement and health technology assessment (HTA) agencies. Additionally, publications were included through snowballing or focused searches. Although a VAF that applies a standard economic evaluation treats both orphan drugs and non-orphan drugs equally, its focus on cost-effectiveness discards the impact of disease rarity on data uncertainty, which influences an accurate estimation of an orphan drug's health benefit in terms of quality-adjusted life-years (QALYs). A VAF that weighs QALYs or applies a variable incremental cost-effectiveness (ICER) threshold, allows the inclusion of value factors beyond the QALY, although their methodologies are flawed. Multi-criteria decision analysis (MCDA) incorporates a flexible set of value factors and involves multiple stakeholders' perspectives. Nevertheless, its successful implementation relies on decision-makers' openness toward transparency and a pragmatic approach, while allowing the flexibility for continuous improvement. The frameworks listed above each have multiple strengths and weaknesses. We advocate that decision-makers apply the concept of accountability for reasonableness (A4R) to justify their choice for a specific VAF for orphan drugs and to strive for maximum transparency concerning the decision-making process. Also, in order to manage uncertainty and feasibility of funding, decision-makers may consider using managed-entry agreements rather than implementing a separate VAF for orphan drugs.
决策者已在欧洲各司法管辖区实施了多种孤儿药价值评估框架（VAFs），这导致罕见病患者获得药物的机会出现差异。本综述概述了欧洲孤儿药报销VAFs的优势和局限性，可为决策者提供指导。使用PubMed、Scopus和Web of Science数据库进行了叙述性文献综述。仅纳入英文出版物。作者已知的出版物也被纳入，还有会议或研究论文，或报销和卫生技术评估（HTA）机构网站上发布的信息。此外，通过滚雪球或重点搜索纳入了出版物。虽然应用标准经济评估的VAF对孤儿药和非孤儿药一视同仁，但其对成本效益的关注忽略了疾病罕见性对数据不确定性的影响，这影响了对孤儿药在质量调整生命年（QALYs）方面健康效益的准确估计。权衡QALYs或应用可变增量成本效益（ICER）阈值的VAF允许纳入QALY之外的价值因素，尽管其方法存在缺陷。多标准决策分析（MCDA）纳入了一组灵活的价值因素，并涉及多个利益相关者的观点。然而，其成功实施依赖于决策者对透明度和务实方法的开放态度，同时允许持续改进的灵活性。上述框架各有优缺点。我们主张决策者应用合理问责制（A4R）的概念来证明其选择特定孤儿药VAF的合理性，并努力使决策过程达到最大透明度。此外，为了管理资金的不确定性和可行性，决策者可考虑使用有管理的进入协议，而不是为孤儿药实施单独的VAF。
