OBJECTIVES: Identify and critically review published economic analyses of Advanced therapy medicinal products (ATMP).

METHODS: A systematic review was carried out (prospero:CRD42021233727). The searches were validated by a specialized librarian in public health and adapted for PubMed, Embase, WoS, Google Scholar and The Cochrane. Search strategy includes commercial names and International Nonproprietary Names of ATMPs with marketing authorization in US, Europe, Japan or South Korea, and “tissue-engineered”, “somatic-cell therapy”, “gene therapy” as general terms. Study characteristics, design, sources of data, resources and unit costs, modelling and extrapolation methods, study results and sensitivity analyses were assessed. The risk of bias was evaluated using a checklist.

RESULTS: A total of 46 economic analyses of ATMP (from 45 papers) 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 Cost-Effectiveness Analysis and two were cost only studies. 23 predicted that the ATMP offered a step-change in the management of the condition and six studies estimated that the ATMP would offer a lower mean cost. In cost-utility studies, most of them (34/39) used mathematical models to extrapolate clinical effectiveness from trial data in the intervention and control group to longer term outcomes, using time horizons of 40 years or more.

CONCLUSIONS: Comparison with historical controls, pooling of data and use of techniques such as mixture cure fraction models should be employed cautiously. Sensitivity analyses should be used across a plausible range of prices. Clinical studies need to be designed to align with HTA 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.