Evaluation of Advanced Therapy Medicinal Products by the National Institute for Health and Care Excellence (NICE): An Updated Review

This review discusses the methodological challenges to the evaluation of advanced therapy medicinal products (ATMPs) by the UK National Institute for Health and Care Excellence (NICE). We analysed the health technology appraisals (both published and in development) of ATMPs conducted by NICE in England until July 2021. A total of 14 health technology appraisals of ATMPs were included, of which two were in development and 12 had been published. There were ten gene therapy products (talimogene laherparepvec TA410, strimvelis HST7, tisagenlecleucel TA554 and TA567, axicabtagene ciloleucel TA559, voretigene neparvovec HST11, autologous anti-CD19-transduced CD3+ cells TA677, betibeglogene autotemcel ID968, onasemnogene abeparvovec HST15 and OTL-200 ID1666), one tissue engineered product (holoclar TA467) and three somatic cell therapy products (darvadstrocel TA556 and autologous chondrocyte implantation ACI TA477 and TA508). Only three of these technologies were not recommended by NICE, although four were only recommended within the Cancer Drugs Fund. There was large uncertainty in the assessment of clinical effectiveness, as evidence relied mostly on small, single-arm, open-label studies. There were also several concerns in the cost-effectiveness evaluations, such as limited information on health-related quality of life, immature survival data due to short follow-up, and unclear curative potential. Substantial risk may be incurred with ATMPs, which have high upfront and possibly irrecoverable costs but uncertain long-term benefits. In conclusion, the challenges raised by the economic appraisal of ATMPs, albeit not unique, may be exacerbated by the uncertainty related to the often scant evidence base. Adaptations of the conventional decision-making process rather than completely new methods may improve appraisals of ATMPs.