A Review of Methodological Considerations for Economic Evaluations of Gene Therapies and Their Application in Literature

Abstract

Objectives: To identify methodological considerations discussed in literature addressing economic evaluations (EEs) of gene therapies (GTs). Additionally, we assessed if these considerations are applied in published GT EEs to increase understanding and explore impact.Methods: First a peer-reviewed literature review was performed to identify research addressing methodological considerations of GT EEs until August 2019. Identified considerations were grouped in themes using thematic content analysis. A second literature search was conducted in which we identified published evaluations. The EE quality of reporting was assessed using Consolidated Health Economic Evaluation Reporting Standards.Results: The first literature search yielded 13 articles discussing methodological considerations. The second search provided 12 EEs. Considerations identified were payment models, definition of perspectives, addressing uncertainty, data extrapolation, discount rates, novel value elements, and use of indirect and surrogate endpoints. All EEs scored satisfactory to good according to Consolidated Health Economic Evaluation Reporting Standards. Regarding methodological application, we found 1 methodological element (payment models) was applied in 2 base cases. Scenarios explored alternative perspectives, survival assumptions, and extrapolation methods in 10 EEs.Conclusions: Although EE quality of reporting was considered good, their informativeness for health technology assessment and decision makers seemed limited owing to many uncertainties. We suggest accepted EE methods can broadly be applied to GTs, but few elements may need adjustment. Further research and multi-stakeholder consensus is needed to determine appropriateness and application of individual methodological considerations. For now, we recommend including scenario analyses to explore impact of methodological choices and (clinical) uncertainties. This study contributes to better understanding of perceived appropriate evaluation of GTs and informs best modeling practices.

Modeling Benefits, Costs, and Affordability of a Novel Gene Therapy in Hemophilia A

“…If a therapy turns out to be less effective than initially claimed this treatment cannot be discontinued due to the one-off nature of provision, nor can the cost be recouped. 67 Second, the initial budget impact and/or the proposed timing of payments may pose affordability challenges among payers. 68 This raises the question whether affordability may not only be associated with high prices but also with timing of payment.…”

Gene Therapy Evidence Generation and Economic Analysis: Pragmatic Considerations to Facilitate Fit-for-Purpose Health Technology Assessment

“…First, the inclusion of other types of non-randomized study designs could provide complementary evidence to single-arm trial data. For example, these designs could include natural history studies, observational studies, patient registry databases, or medical chart extractions to serve as historical controls ( 20 , 22 – 25 ).…”

“…However, by having to extrapolate based on biomarker-based treatment benefits, payers are left with the uncertainty of the treatment's true clinical benefits ( 32 ). Hence, determining the appropriate approaches for the measurement and validation of surrogate endpoints for GTs concerning final clinical endpoints [e.g., mortality, survival, or health-related quality-of-life (HRQoL)] is a key consideration in HTA ( 22 – 24 ).…”

“…The type of treatment benefits associated with GTs ranges broadly and include clinical benefits, including quality-adjusted life-year (QALY) gains, and indirect benefits, such as the continuation of normal education, improvement of productivity, and reduction in the caring burdens of family members. In addition, GTs can bring other broader forms of value, such as scientific spillover, adherence improving factors, health equity issues, and value of cure ( 17 , 19 , 22 – 25 , 31 , 37 , 42 ).…”

“…However, these broader values are not or insufficiently captured in the QALY and incremental cost-effectiveness ratio (ICER) calculation in current HTA reference cases. Hence, it has been argued that cost-effectiveness should provide references cases analyses from both healthcare payer and societal perspectives ( 17 , 22 , 23 , 25 , 26 ). Cost-benefit analysis has also been proposed as an option to allow capturing of all types of benefits as measured in monetary terms ( 17 ).…”