P40 HTA Agencies Perspective on Survival Modelling in Cell or Gene Therapy Appraisals


      The first cell- and gene therapies, so called advanced therapy medicinal products (ATMPs), have recently become available, making it possible to treat, and even potentially cure, very severe and sometimes previously untreatable conditions. These characteristics have led to a discussion among health economists about whether a specific methodological reference case is required for economic evaluation of gene therapies and the conclusion has been that a new methodological reference case is not required but that “the confluence of various characteristics can lead to specific methodological challenges...”. Traditional survival modeling may underestimate outcomes by assuming the same mortality rate for all patients, in situations where the treatment could lead to the cure of a patients. Mixture cure models have been suggested as a supplementary analysis, alongside standard parametric models. The aim of this study was to review reimbursement appraisal reports of the 12 EMA approved ATMPs, to identify the differences in methods and assumptions in survival modelling of long-term treatment effects across different HTA agencies.


      Publicly available assessment reports were retrieved from each reimbursement agency’s website in the Nordics, the Netherlands, England and Wales, Canada and Australia for the relevant drugs.


      Across the HTA agencies different level of acceptance to non-standard survival modelling is seen. E.g. in appraisals of cell-therapies, mixture cure models have been accepted in the Nordic countries and in England and Wales but assumptions around the percentage of cured patients and the preferred source for the survival extrapolation post clinical trial follow-up differs. In appraisals of gene-therapies, the exploration of the impact of the main assumptions that drive model results have been recommended across the HTA agencies.


      There is yet not an established golden standard on how to apply survival modelling to ATPMs and the preferences on the methodology varies across HTA agencies.