How to Value Orphan Drugs? A Review of European Value Assessment Frameworks

Abstract

Background: 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.Methods: 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.Results: 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.Conclusion: 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.

Assessing the Value of Nusinersen for Spinal Muscular Atrophy: A Comparative Analysis of Reimbursement Submission and Appraisal in European Countries

“…Yet, the reports described similar methodological barriers that may have complicated a proper evaluation and reassessment of the cost-effectiveness of nusinersen from the submitted models. We believe that these barriers are in alignment with those encountered for orphan drugs in general, which are extensively described in the peer-reviewed literature (Lagakos, 2003;McCabe et al, 2006;Drummond et al, 2007;Hughes-Wilson et al, 2012;Augustine et al, 2013;Schlander et al, 2016;Pearson et al, 2018;Nestler-Parr et al, 2018;Nicod et al, 2019;Blonda et al, 2021). First of all, the HTA and reimbursement agencies reported uncertainties in utility values and questioned the added value of nusinersen in SMA subtypes, in type 0, type IV, and even type III SMA.…”

“…Indeed, the fact that decision-makers are increasingly balancing efficiency criteria (such as cost-effectiveness and budget impact) with ethical criteria (such as severity or unmet need), when assessing the value of orphan drugs, is not new (Pinxten et al, 2012;Nicod et al, 2017;Burgart et al, 2018;Nicod et al, 2019;Blonda et al, 2021). However, there is a need for more transparency on the factors that influence decision-making after an HTA guidance is issued, as this is becoming increasingly important in order to substantiate decisions on budget allocation, especially in those cases where there is substantial uncertainty on the cost and/or effectiveness of treatment.…”

“…However, there is a need for more transparency on the factors that influence decision-making after an HTA guidance is issued, as this is becoming increasingly important in order to substantiate decisions on budget allocation, especially in those cases where there is substantial uncertainty on the cost and/or effectiveness of treatment. Additionally, by disclosing the grey zone determinants, decision-makers facilitate a broader acceptance of the reimbursement decision among the different stakeholders (Youngkong et al, 2012;Iskrov et al, 2017;Schey et al, 2017;Baltussen et al, 2018;Bond et al, 2020;Blonda et al, 2021). In order to increase transparency on the appraisal process, we therefore advise decision-makers to define and formally include these determinants in the reimbursement process and the final reimbursement report.…”

Availability and Accessibility of Orphan Medicinal Products to Patients in Slovakia in the Years 2010–2019

“…In 10 years, the number of rare disease patients treated with OMPs increased by 52%; however, the expenditure increased by 140%. No clearly formulated criteria for OMPs, including managed entry agreements, result in preferably negative decisions or no interest of the marketing authorization holder to launch the product in Slovakia compared to other countries, which look for innovative reimbursement approaches to provide the treatments for their population (Ferrario and Kanavos, 2013;Morel et al, 2013; EXPH (EXpert Panel on effective ways of investing in Health), 2018; Michelsen et al, 2020;Blonda et al, 2021).…”

Exploring Alternative Financing Models and Early Access Schemes for Orphan Drugs: a Belgian Case Study

“…Depending on the accounted elements in respective countries, orphan drugs are usually deemed not cost-effective and overtaxing for healthcare budgets (12). For that reason, some have implemented exceptional attention to foster access to these orphan drugs (13). For instance, England implemented a higher cost-effectiveness threshold whereas, in France and Germany, no economic evaluation is required for orphan drugs (13).…”