Retrospective analysis of NICE CAR-T therapy single technology appraisals and identification of strategies to minimise time to patient access


Cell and gene therapies with a potentially curative or disease modifying effect can face challenges demonstrating long term clinical and economic benefits due to limited data available at launch. Within the NICE assessment process, this can increase the uncertainty associated with the cost-effectiveness of treatment, presenting challenges for appraisal committees when determining whether new treatments should receive reimbursement within the NHS. Effective mitigation of this uncertainty is a critical factor for ensuring reimbursed patient access for high value, transformative healthcare technologies. ​

Analysis of published NICE appraisals for CAR-T cell therapies to date, provides an indication of the extent of the uncertainty in the evidence submitted by the manufacturers, reflected in the variance between manufacturer and ERG ICER estimates. Consistent reasons for divergence in ICER estimates, as identified by the appraisal committees, are limited follow-up data, differences in data extrapolation and variances in the assumption of cure points used by the manufacturer and the ERG. ​

Table 1. Minimising time to CAR-T patient access through proactive application to the CDF to provide coverage with on-going data generation

*Results were considered to highlight precedent from previous appraisals of CAR-T cell therapies however there is uncertainty as to whether this is generalizable to MCL​


Abbreviations: CAR-T: Chimeric Antigen Receptor T cells; CDF: Cancer Drugs Fund; CE: Cost-Effectiveness; EMA: European Medicines Agency; HRQoL: Health Related Quality of Life; IVIG: Intravenous Immunoglobulin; MA: Marketing Authorisation; NHS: National Health Insurance; NICE: National Institute for Care and Excellence; OS: Overall Survival; PFS: Progression Free Survival; PPS: Post-Progression Survival; SoC: Standard of Care​

Uncertainty regarding the cure point was noted for Yescarta and in both Kymriah indications (ALL and DLBCL), with the ERG generally requiring up to 5 years of data before a patient can be assumed ‘cured’ (as seen in Figure.1). Importantly, the cure point was not cited as an area of uncertainty in the most recent NICE appraisal of a CAR-T therapy, Tecartus, which may be due to a greater maturity of evidence within the submission (phase III study vs. phase II studies).​​

The high levels of uncertainty identified for all four CAR-T therapy indications resulted in NICE decisions for conditional reimbursement through the CDF, whilst additional data is collected to address the areas of uncertainty identified by the appraisal committee. For Kymriah this decision was reached by NICE following the manufacturer’s request for routine commissioning, that could not be granted due to uncertainty within the available evidence at launch. For Tecartus and Yescarta, the manufacturer made a direct request for conditional reimbursement through the CDF whilst additional data is generated to support the cost-effectiveness of treatment. All manufacturers are now required to collect comparative long-term survival data (vs. standard of care), with 5 years of follow up required for Kymriah and Yescarta, and 3 years for Tecartus. ​

Figure 1: Divergence between manufacturer and ERG ICER estimates due to uncertainty within the data submitted for NICE Single Technology Appraisal

Sources: NICE, Tecartus FAD (2021). Available at: [Accessed January 2021]; NICE, Kymriah TA554 (2018). Available at: [Accessed January 2021]; NICE, Kymriah TA567 (2019). Available at: [Accessed January 2021]; NICE, Yescarta (2018). Available at: [Accessed January 2021]​ Abbreviations: CDF: Cancer Drugs Fund; CE: Cost-Effectiveness; DLBCL: Diffuse Large B-cell Lymphoma; ERG: Evidence Review Group; ICER: Incremental Cost Effectiveness Ratio; MCL: Mantle Cell Lymphoma; NHS: National Health Service; OS: Overall Survival; R/R: Relapsed or Refractory; RWD: Real World Data​

The findings of this analysis resonate with recent discussions during the Advanced Therapy Congress in 2020, where members of European HTA bodies advised manufacturers with disease modifying ATMPs to anticipate the risks of submitting for reimbursement with immature data, with unacceptable clinical and financial uncertainty for payers. The emphasis is placed on manufacturers to demonstrate that best efforts have been made to generate clinical data (considering potential constraints with the population size and duration of follow up), whilst also pre-empting payer concerns and addressing these through early engagement. 

This approach was well demonstrated for Tecartus, with early planning by Kite Pharma to mitigate likely challenges associated with uncertainty, including a direct application to the CDF with a protocol for RWE generation and a commercial arrangement to reduce payer uncertainty. This approach may also be a causal factor for the significantly shorter time between marketing authorisation and reimbursement in England for Tecartus compared to previously launched CAR-T therapies. ​

Article published 8 March 2021.