Hemophilia Gene Therapy Value Assessment: Methodological Challenges and Recommendations

Gene therapy for hemophilia is designed to produce health gains for patients over many years. Rewarding that value creation on the basis of a one-time treatment implies a large upfront cost. This cost can only be justified by long-term health benefits and being cost-effective compared with conventional treatments. Yet, uncertainties about the long-term benefits make it challenging to assess clinical and economic value of gene therapies at launch. We identify and discuss key methodological challenges in assessing the value of gene therapy for hemophilia, including the immaturity of evidence on the durability of benefits, lack of definition and valuation of cure for chronic diseases, absence of randomized controlled trials, limitations of traditional quality of life measures in hemophilia, approach for qualifying cost-savings compared with current treatments, and choice of perspective. The Institute for Clinical and Economic Review has developed a framework for assessing single or short-term therapies (ICER-SST) and has applied it in hemophilia. After reviewing this framework and its application, we recommend the following when assessing the value of hemophilia gene therapies: (1) leveraging expert clinical opinion to justify assumptions on the durability of benefits; (2) using external synthetic controls and lead-in, self-controlled trials to assess comparative effectiveness; (3) addressing limitations of traditional quality of life measures through the use of modified utility collection approaches; (4) adjusting cost offsets from gene therapies with caution; (5) considering outcome-based contracting to address uncertainties about prices and long-term outcomes; and (6) presenting societal and healthcare system perspectives in parallel. •Hemophilia gene therapy—as a one-time or short-term treatment—is designed to produce long-term health gains. Rewarding expected value at launch implies a large upfront cost, which may be offset by greater long-term benefits relative to current standard-of-care treatments. Nevertheless, the uncertain durability and magnitude of these benefits make it challenging to accurately assess the added value of gene therapies in hemophilia.•Key methodological challenges need to be considered when conducting economic evaluations of hemophilia gene therapies, including (1) the immaturity of evidence and lack of definition of cure, (2) the absence of randomized controlled trials, (3) limitations of traditional quality of life measures in