Methodological Challenges and Preferred Approaches for the Economic Evaluation of CAR T Therapies: Evidence Review and Expert Consensus from NICE Appraisals.

Background

Chimeric antigen receptor T cell (CAR T) therapies pose challenges for economic evaluation because of complex treatment pathways and uncertainty around long-term outcomes. Within health technology assessment (HTA) bodies such as the National Institute for Health and Care Excellence (NICE), these features have led to recurring methodological debates.

Objectives

To identify methodological challenges specific to the HTA of CAR T therapies within NICE technology appraisals and to develop Delphi-informed recommendations to support more consistent modelling practice.

Methods

A three-phase mixed-methods study was conducted. Phase 1 involved qualitative content analysis of published NICE appraisals of CAR T therapies to identify methodological issues and solutions. Phase 2 used a modified Delphi to determine which issues were specific to CAR T therapies and to agree upon preferred methodological approaches. Phase 3 involved clinical sense-checking of the preferred methodological approaches.

Results

Phase 1 reviewed nine NICE appraisals, identifying 16 issues around survival modelling, cure assumptions, costing and long-term outcomes. Ten issues were specified in relation to CAR T. Phase 2 identified one further relevant issue. The preferred approaches included modelling from leukapheresis (85%), applying cure assumptions consistently across treatment arms (95%) and applying modest utility decrements for long-term survivors (94%). For delivery costs, 61% preferred the most recent NHS England CAR T tariff with targeted supplements, while 28% preferred the most transparent tariff choice, indicating less uniform agreement. UK-specific real-world data were preferred to inform assumptions on treatment delivery, resource use and subsequent therapies. Phase 3 provided a clinical sense-check of these preferred approaches and identified important additional considerations for future appraisals.

Conclusions

Methodological challenges in the economic evaluation of CAR T therapies recur across NICE appraisals and materially influence cost-effectiveness results. Drawing on evidence from NICE appraisals combined with Delphi findings and clinical sense-checking, this study provides practical recommendations relating to model start-point, cure modelling and long-term survivor utility decrements supporting more consistent and transparent economic evaluation within the NICE framework.