Challenges for Economic Evaluations of Advanced Therapy Medicinal Products: A Systematic Review

Objectives: Advanced therapy medicinal products (ATMPs) are drugs for human use for the treatment of chronic, degener-ative, or life-threatening diseases that are based on genes, tissues, or cells. This article aimed to identify and critically review published economic analyses of ATMPs.Methods: A systematic review of economic analyses of ATMPs was undertaken. Study characteristics, design, sources of data, resources and unit costs, modeling and extrapolation methods, study results, and sensitivity analyses were assessed.Results: A total of 46 economic analyses of ATMP (from 45 articles) were included; 4 were cell therapy medicinal products, 33 gene therapy medicinal products, and 9 tissue-engineered products. 30 therapies had commercial marketing approval; 39 studies were cost-utility analysis, 5 were cost-effectiveness analysis, and 2 were cost only studies. Four studies predicted that the ATMP offered a step change in the management of the condition and 10 studies estimated that the ATMP would offer a lower mean cost.Conclusions: Comparison with historical controls, pooling of data, and use of techniques such as mixture cure fraction models should be used cautiously. Sensitivity analyses should be used across a plausible range of prices. Clinical studies need to be designed to align with health technology assessment requirements, including generic quality of life, and payers should aim for clarity of criteria. Regulators and national payers should aim for compatibility of registers to allow interchange of data. Given the increasing reliance on industry-funded economic analyses, careful critical review is recommended.