OBJECTIVES: Several gene therapies are getting close to marketing authorization and cost-effectiveness analysis (CEA) we will be needed for HTA. Unlike most current pharmaceuticals, gene therapies offer the potential for a one-time treatment that produces long-term benefits. Our objective was to evaluate whether new methodological frameworks would be required for the economic evaluation of gene therapies.

METHODS: We ran a search on Clinicaltrials.gov focussing on the gene therapies assessed or currently being assessed in a Phase III Clinical trial. We extracted the sample size, the primary and secondary outcomes, planned duration of follow-up. We developed categories of product profiles, presented them to modelling experts, and asked them how they would conceptualise cost-effectiveness model for such products if they had to prepare HTA submissions.

RESULTS: Of 248 clinical studies identified, 96 (39%) were related cancer and 65 (26%) were related to orphan diseases. The average planned follow-up was 4.6 years with a median at 3.4 years whereas the expected impact of gene therapy could be lifetime. For 20% of trials, the number of patients included was lower than 50. The median sample size was 213 patients per trial. Populations could be highly heterogeneous, e.g. with 20% of studies mixing adults and children. The main challenge associated with modelling gene therapy was uncertainty around long-term efficacy and safety, due to utilisation of surrogate outcomes, small patient numbers and relatively short observation period. Other challenges included model complexity related to variability in treatment effects across heterogeneous patient profiles and valuation of health benefits of children.

CONCLUSIONS: Although standard economic evaluation approaches based on CEA are theoretically applicable to gene therapies, they may in reality be of little use to decision-makers, due to substantial uncertainty around results.