ED2 Elements of Value for Gene Therapy: A Systematic Review


      ISPOR recommends that value assessments include elements beyond traditional quality-adjusted life years (QALYs) and costs. We aimed to identify non-traditional value elements relevant to gene therapies as it is unclear to what extent they have been included in gene therapy value assessments.


      We searched PubMed and Embase for full-text articles discussing non-traditional value elements defined by the 2018 ISPOR framework in the context of gene therapy that were published in English between 2015-2020. Health technology assessment (HTA) reports published by the Institute of Clinical and Economic Review and National Institute for Health and Care Excellence were collected. Articles and reports were included if they proposed methods for incorporation or accounted for specified value elements in economic evaluations or real-world decision making.


      Twenty-four of 644 articles identified met inclusion criteria; 17 were peer-reviewed journal articles and 8 HTA reports. Disease areas for which specific gene therapies were discussed included cancer, beta thalassemia, inherited eye disease, hemophilia, spinal muscular atrophy, and severe immunodeficiency. The most common non-traditional value elements were productivity (n=12), severity of disease (n=10), equity (n=4), and scientific spillover (n=4). Productivity was captured as an indirect cost in cost-effectiveness analyses (CEAs). Although severity of disease, equity, and scientific spillover were not explicitly quantified, they were incorporated into HTA body decisions: severity through conditional market access, QALY weighting, higher CEA thresholds, and lower discount rates; equity through higher CEA thresholds and QALY weighting; and scientific spillover through accelerated market access. Multi-criteria decision analysis was also proposed.


      Use of novel value elements for gene therapies appears to be sparse in health economic studies to date. Methods of QALY weighting, varying CEA thresholds, discount rates, and specialized access pathways accounted for novel elements in value assessments. Future research on the feasibility, quantification, and incorporation of novel value elements for gene therapies is warranted.