Fitness-for-Use Assessment across Four Data Sources for Real-World Safety and Effectiveness Studies of CAR-T cell therapies

Study identification

• EU PAS number:
  EUPAS1000000955
• Study ID:
  1000000955
• Official title and acronym:
  Fitness-for-Use Assessment across Four Data Sources for Real-World Safety and Effectiveness Studies of CAR-T cell therapies
• DARWIN EU® study:
  No
• Study countries:
  France

  United Kingdom

  United States
• Study description:
  Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an important cancer treatment, with six treatments approved by the EMA since 2018. Non-interventional studies play an important role for supporting regulatory decisions especially when randomised controlled trials are unfeasible or unethical, which was often the case in the CAR-T cell area whose effectiveness and safety evidence mostly rely on single arm trials.; This assessment evaluates the fitness-for-use of the National Cancer Registration and Analysis Service (NCRAS) & Hospital Episode Statistics (HES), US Flatiron Health Research Database, Système National des Données de Santé (SNDS [French national health system main database]), and Dispositif d'Enregistrement et Suivi des patients traités par CAR-T cells (DESCAR T) for conducting research into CAR-T cell therapy. The study assesses whether each data source contains the necessary data elements, completeness, structure, and quality to support future regulatory relevant non interventional studies on CAR T cell therapies. The assessment involved the simulation of the following 3 theoretical scenarios.; ; 1. To estimate the incidence rates of five safety outcomes (neurotoxicity, CRS, neutropenia, infections, second primary malignancies) among patients treated with CAR-T cell therapy; 2. To develop an external control arm for CARTITUDE-1, a single-arm phase 1b/2 trial (NCT03548207) to assess the effectiveness of cilta-cel among adult patients with RRMM; 3. To emulate the CARTITUDE-4 (NCT04181827) clinical trial to compare the effectiveness of cilta-cel to standard of care among adult patients with lenalidomide-refractory MM who had received 1-3 prior LOT; ; A retrospective, observational cohort design was used as a template for each theoretical scenario, to simulate how such studies would be implemented using the available data. Upon creation of the study cohorts, data quality metrics were assessed and the fitness-for-use assessment was undertaken.
• Study status:
  Ongoing

Research institutions and networks

Institutions

Evidence and Access/Analytica Laser, Certara

France

United Kingdom (Northern Ireland)

1. Dispositif d'Enregistrement et Suivi des patients traités par CAR-T cells (DESCAR-T)
2. Flatiron Health

Study timelines

Date when funding contract was signed

Actual:08/12/2024

Study start date

Actual:27/11/2025

Data analysis start date

Actual:27/11/2025

Date of final study report

Planned:15/07/2026

Sources of funding

EMA

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable