Advanced therapy medicinal products: value judgement and ethical evaluation in health technology assessment

Abstract

Advanced therapy medicinal products (ATMPs) are a heterogeneous class of medicinal products that by offering the potential of cure represent a paradigm shift in the approach of many life-threatening diseases. Although a common regulatory framework for ATMPs has been established in the EU, the health technology assessment (HTA) and financing decisions remain local. The aim of this article is to present an integrated analysis of the current status of the value judgment of ATMPs and the integration of ethical evaluation in the HTA process. It has been identified that approaching the specificities of ATMPs in terms of market access will require a broadening of the definition of value to be able to systematically capture elements of value not traditionally considered. Outcomes modelling will play an important role in the pricing and reimbursement of ATMPs, providing a way to bridge the gap caused by the absence of data from clinical studies or real-world data. Given the nature and disruptive consequences of ATMPs the assessment and adoption of these medicinal products raises important ethical questions, both at a policy and at society level that should be properly addressed. HTA can be made more transparent and reliable, and simultaneously promote robust and accountable decision making, by turning explicit the value judgments implicit in HTA. Ultimately, there should be no core conflict between ethical requirements and HTA in a scenario where the goal is to promote equity and access of patients to truly innovative therapies such as ATMPs, while assuring the sustainability of healthcare systems.

Methodological Challenges in the Economic Evaluation of a Gene Therapy for RPE65-Mediated Inherited Retinal Disease: The Value of Vision

“…Due to the short timeframe of the clinical trial, an important part of the value hypothesis of VN (i.e. long-term benefit) is not substantiated by trial data [ 27 ]. However, the current data and biological knowledge on the (patho)physiology of the targeted cells supported the suggestion of maintained improvement of visual function after injection with VN beyond what has been observed in the RCT.…”

“…Payers are faced with the challenge to determine whether to reimburse the high one-time costs of VN that potentially, but not certainly, result in lifelong benefits. Managed entry agreements (MEA) between manufacturers and payers are a way to reduce the uncertainty related to the lack of long-term data at launch [ 27 ]. MEAs can take the form of discounts or be outcome-based (e.g.…”

“…In the case of VN, uncertainty was mostly related to the extrapolation of the treatment effect. According to Gonçalves, the willingness to consider economic models that include extrapolating longer-term benefit from limited existing data varies between HTA agencies [ 27 ]. In the case of VN, both NICE and ZIN did not have objections about the extrapolation of treatment effect proposed by the manufacturer for the base-case analysis, but in the UK, this was set to 40 years, while in the Netherlands a more conservative assumption of 20 years was applied.…”

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“…According to this view in catastrophic health situation such as lethal hereditary diseases the value-creating elements should essentially justify much higher cost-effectiveness thresholds than used generally for orphan drugs ( 75 ). However, others argue that considering ethical, political, sociological principles society should enforce as much distributive equivalence as possible when allocating resources for advanced therapies ( 76 ).…”

Short Time to Market and Forward Planning Will Enable Cell Therapies to Deliver R&D Pipeline Value

“…[12][13][14][15] CGT candidates have struggled to meet the requirements for successful Health Technology Assessments and demonstrate short-term cost effectiveness versus noncurative comparators. [16][17][18] Patients face barriers to access as these therapies may only be offered at a small number of specialized medical centers. The unclear reimbursement landscape had led developers to pursue various approaches like outcome-based payments impacting pricing and market access.…”