Health economic evaluation of gene replacement therapies: methodological issues and recommendations

Abstract

Objective : To provide recommendations for addressing previously identified key challenges in health economic evaluations of Gene Replacement Therapies (GRTs), including: 1) the assessment of clinical effectiveness; 2) the valuation of health outcomes; 3) the time horizon and extrapolation of effects beyond trial duration; 4) the estimation of costs; 5) the selection of appropriate discount rates; 6) the incorporation of broader elements of value; and 7) affordability. Methods : A literature review on economic evaluations of GRT was performed. Interviews were conducted with 8 European and US health economic experts with experience in evaluations of GRT. Targeted literature reviews were conducted to investigate further potential solutions to specific challenges. Recommendations : Experts agreed on factors to be considered to ensure the acceptability of historical cohorts by HTA bodies. Existing prospective registries or, if not available, retrospective registries, may be used to analyse different disease trajectories and inform extrapolations. The importance of expert opinion due to limited data was acknowledged. Expert opinion should be obtained using structured elicitation techniques. Broader elements of value, beyond health gains directly related to treatment, can be considered through the application of a factor to inflate the quality-adjusted life years (QALYs) or a higher cost-effectiveness threshold. Additionally, the use of cost-benefit analysis and saved young life equivalents (SAVE) were proposed as alternatives to QALYs for the valuations of outcomes of GRT as they can incorporate broader elements of value and avoid problems of eliciting utilities for paediatric diseases. Conclusions : While some of the limitations of economic evaluations of GRT are inherent to limited clinical data and lack of experience with these treatments, others may be addressed by methodological research to be conducted by health economists.

Do Advanced Therapies Have a Future in the Low- and Middle-Income Countries - The Case of Bulgaria, Romania, and Poland

“…All of them identified as main and significant obstacles the extremely high prices of the advanced therapies and the uncertainty about their clinical effect in a long-term period. Additional barriers highlighted by the authors are related to inadequate existing methodology for economic and pharmacoeconomic evaluations—QALY concept, extrapolation of the benefits, application of biased models based on too many assumptions with limit capability to deal with uncertainty and comparison with the conventional threshold are pointed out as not suitable ways for assessment of the new advanced therapies ( 6 , 16 , 17 ).…”

“…Many studies about advanced therapies have been published in the recent years. The barriers for health technology assessment of ATMPs and a number of measures how to overcome them are widely discussed especially for Western European countries and USA (2,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). All of them identified as main and significant obstacles the extremely high prices of the advanced therapies and the uncertainty about their clinical effect in a long-term period.…”

“…The authors proposed various, in most articles overlapping suggestions how to deal with the obstacles: adopting of new methodology for HTA of ATMPs, implementation of innovative outcomes-based performance payments, change in the discounting rates, collecting of real-world evidence and not applying cost-utility but cost-benefit analysis from the broader societal perspective due to the expected long-term benefits of the advanced curative therapies (17,21,22). Each country should specify its own methodology on the basis of its health system financing, current practice and available best practices worldwide.…”

“…So, SAVE (saved young life equivalents) is suggested as a preferred method to value lifetime health profiles of curative treatments such as gene therapies. Cost-benefit analysis could be also used as beneficial alternative for assessment of ATMPs ( 17 ). Type of health system should be also considered—whether it is a private or public, multi-, or single payer.…”

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

“…Randomized controlled parallel trials (RCTs) are inarguably accepted as the gold standard approach for establishing the safety and efficacy of a new intervention (12,13). However, RCTs for evaluating some therapies are not always feasible, especially in life-threatening or rare diseases for which therapeutic options have been exhausted (14,15), Hence, evidence standards for regulatory approval have been made flexible to allow rapid approval of potentially effective therapies such as GTs, allowing small sample sizes or single-arm studies (16)(17)(18) being accepted to enable licensing of the treatments (19,20).…”