Fitness for purpose of data sources relevant for real-world data (RWD) studies on CAR-T cell therapy

The Data will be used for the purpose of a research project: Fitness for purpose of data sources relevant for real-world data (RWD) studies on CAR-T cell therapy

CAR-T cell therapy is a treatment for specific types of blood cancers, such as multiple myeloma. Four types of CAR-T cell therapies are currently available in the UK: axicabtagene ciloleucel, tisangenlecleucel, brexucabtagene autoleucel and lisocabtagene maraleucel. These therapies were approved based upon clinical trials reporting improved outcomes among patients with specific blood cancers. However, since clinical trials often include very carefully selected patients, it’s unclear how well these results apply to the broader population in routine clinical practice. Real-world data plays an important role in determining the safety and effectiveness of these therapies in a wider range of patients. However, to support regulatory and clinical decision-making, evidence generated using real-world data needs to be reliable. A key determinant of the reliability of evidence derived from RWD studies is the quality of the data used and their suitability for the research question of interest.

The purpose of this project is to support a feasibility study assessing the fitness-for-purpose of National Cancer Registration and Analysis Service (NCRAS) data for research into CAR-T cell therapy. Specifically, the study aims to evaluate the quality, completeness, and reliability of the data in relation to two theoretical research scenarios. This includes determining the dataset’s ability to accurately capture safety outcomes, such as the number of safety events per CAR-T treatment, in alignment with the European Medicines Agency (EMA) quality framework for consistent and transparent reporting.

The study does not aim to conduct direct comparative effectiveness or safety analyses between CAR-T treatments.

The project will assess whether NCRAS data

- Captures all the required information (e.g., patient treatments and outcomes) for a representative sample of the population

- Captures precise and accurate data

- Captures complete data for a sufficient number of patients

- Captures and enables access to data that covers relevant time periods

- Captures coherent data (i.e., with standardized approaches to recording)

No data will flow to NHS England for the purposes of this Data Sharing Agreement (DSA).

NHS England will provide access to the relevant records from the Data to authorised users from Certara France S.A.R.L.  The Data will contain no direct identifying data items.  The Data will be pseudonymised and individuals cannot be reidentified through linkage with other data in the possession of the recipient.

NHS England will grant access to the Data via the Secure Data Environment (SDE).  The SDE is a secure data and research analysis platform.  It allows approved researchers with approved projects access to pseudonymised data and industry leading analytics tools.

The Data will not be transferred to any other location.

SDE users can request exportation of aggregated analysis results (suppressed and summarised according to the NHSE SDE Disclosure Control rules) subject to review and approval by the NHS England SDE Output Checking team. The SDE Output Checking team will ensure that no output contains information which could be used either on its own or in conjunction with other data to breach an individual's privacy.

Users must identify themselves via a multi-factor authentication mechanism and are only able to access the datasets detailed within this DSA.  The access and use of the system is fully auditable and all users must comply with the use of the Data as specified in this DSA.

Users will be authorised to access the data specified in this DSA and can utilise a variety of analytical tools available within the SDE platform. Users are not permitted to export record-level data from the SDE.

Remote processing will be from secure locations within the EEA.

The Data will not leave the EEA at any time.

Data will be accessed from France by statisticians at Certara France S.A.R.L

The EMA are not permitted to access the data.

Only substantive staff (statisticians) with training in data protection at Certara France S.A.R.L have access to the data for the purpose of conducting the study. All such individuals are substantive employees of Certara France S.A.R.L.

The data will not be linked with any other data.

No efforts to re-identify individuals will be undertaken.

To optimise the potential public benefits from the use of the data, study findings will be disseminated in the form of conference abstracts, peer-reviewed publications and published reports on the European Medicine’s Agency website. The conferences to which abstracts will be considered for submission will include International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE) annual meetings among others.

The expected outputs of the processing will be:

• Presentations at appropriate conferences (to be decided)

• Abstracts and posters

• Submissions to peer reviewed journals by Q2 2026

• A report of findings to the study sponsor, the European Medicines Agency, expected in March-June 2026. This report might be published online by the Agency.

The outputs, including the report and peer-reviewed publications will primarily be used to increase awareness of the scientific community regarding the fitness-for-use of NCRAS to conduct vital regulatory-level research in CAR-T cell therapy.

The European Medicines Agency will only receive aggregated data as per the protocol and SAP the study develops, similar to aggregated data that will be presented in tabular format for scientific communications.

Only data relating to the study objectives will be presented in both the study report and published abstracts and manuscripts. All outputs will contain aggregated data only, with small numbers suppressed as per HES Analysis guide. Therefore, no individual level data will be presented in any publication and any findings for less than 10 patients will be suppressed to safeguard any possibility of identifying the subjects who contributed to this data.

The generation of real-world data relating to the safety and effectiveness of CAR-T cell therapies is essential for monitoring the safety of new therapies and to inform doctors and patients of their real-world effectiveness. Evidence from real-world data studies will only be useful if the data is of sufficient quality and is fit-for-purpose. Detailed fitness-for-purpose assessments are therefore essential to ensure that data being used for CAR-T cell therapy research is of sufficient quality. This project aims to evaluate the fitness-of-purpose of NCRAS for conducting regulatory-level research into CAR-T cell therapy.

The outputs of this study will provide insight into the feasibility and timely set up of non-interventional studies in CAR-T cell therapies among adult and paediatric populations. Ultimately, this will lead to the efficient conduct of robust CAR-T cell therapy research and the generation of robust evidence to support regulatory decision-making and inform clinicians and patients of the safety and effectiveness of these therapies.

This fitness-for-purpose assessment is anticipated to provide the following important benefits:

- Advance the understanding of data quality and fitness-for-use of NCRAS for CAR-T cell therapy research, enhancing the efficiency and robustness of CAR-T cell therapy research

- Inform decision-making regarding the appropriateness of NCRAS and linked data sources for CAR-T cell therapy research

- By increasing the efficiency and timeliness of CAR-T cell therapy research, clinicians and patients may be informed of any safety concerns and treatment effectiveness sooner, therefore reducing patient harm and improving patient outcomes

Certara UK will conduct an assessment on the fitness-for-purpose of the data source. Certara UK will not undertake advanced statistical approaches to understand clinical benefits / safety of CAR-T cell therapies., but instead, wish to answer, would it be possible to conduct these analyses, and if so, what would some of the strengths and limitations of undertaking this research in NCRAS. The outputs are expected to be helpful for researchers who wish to undertake research into CAR-T cell therapy and will provide researchers with a clear understanding of the fitness-for-purpose of NCRAS, ensuring studies are both feasible and efficient. Ultimately, this will lead to the efficient design and conduct of robust CAR-T cell therapy research, generating robust evidence to support regulatory decision-making and to inform clinicians and patients about the safety and effectiveness of these therapies.

This research project is expected to deliver meaningful benefits to patients in England and Wales through the anticipated utility of the research.

Yielded Benefits is not a requirement for new applications.