Everything To Know About Long-Term Data Collection For Cell And Gene Therapy Trials In The EU

By Jessica Cordes, Clinical Excellence GmbH

Cell and gene therapy (CGT) trials have opened transformative pathways for treating hematologic malignancies and other severe conditions. CAR-T, in particular, has rapidly progressed from early-phase trials to regulatory approvals and commercial use. Yet, while their short-term efficacy is often dramatic, their long-term safety and durability of response must be systematically monitored. The operational implications of this are significant.

Clinical operations professionals now face the challenge of designing and executing CGT trials that not only meet immediate clinical endpoints but also align with long-term data collection requirements.

If your organization is engaged in CAR-T therapies, understanding how to secure uninterrupted access to your data within the European Society for Blood and Marrow Transplantation (EBMT) CAR-T Data Collection Initiative is vital for your success. This pan-European project, spearheaded by the European Society for Blood and Marrow Transplantation (EBMT), was developed to meet EMA-mandated post-authorization safety (PAS) study requirements.

Effective planning for data capture begins with integrating long-term follow-up as a core component of trial design. This requires a multidimensional approach where protocols explicitly outline mechanisms for tracking both clinical and patient-reported outcomes over extended periods. A critical step involves the identification of relevant data sets, which not only address regulatory compliance but also provide insights into real-world therapeutic value. Stakeholder collaboration — encompassing clinicians, the sponsor, patients, and regulatory bodies — is essential to ensure that protocols define standardized variables that align with post-treatment needs.

Technology plays a key role in operationalizing such data capture plans. The deployment of centralized platforms to streamline data entry, validation, and aggregation is fundamental to maintaining the integrity of long-term evidence. Equally important is the incorporation of patient engagement strategies, such as digital tools and telemedicine, to facilitate consistent follow-up. These measures ensure that the operational framework remains adaptable to evolving clinical and regulatory landscapes while preserving alignment with reimbursement models and policy-driven health technology assessments.

The EBMT has recognized this need through its CAR-T Data Collection Initiative, a centralized framework to support post-treatment monitoring. Understanding and integrating this initiative into trial operations is essential for building CGT trials that are both compliant and strategically future-proofed.

Why Long-Term Data Collection Is Non-Negotiable In CGT Trials

Regulatory expectations and clinical realities demand robust long-term follow-up for CGT therapies. Depending on the risk profile, the EMA mandates up to 15 years of follow-up data for CGT products. These extended timelines stem from safety concerns such as cytokine release syndrome (CRS), long-term cytopenias, and the theoretical risk of insertional oncogenesis.

Moreover, long-term data serves a dual purpose. In addition to meeting regulatory requirements, it feeds health technology assessments (HTAs) and informs reimbursement decisions. Without structured, credible real-world evidence (RWE), sponsors may struggle to justify pricing or secure market access, particularly in Europe’s highly cost-conscious healthcare systems.

Operationally, this means that data collection can no longer end with the last dose or primary endpoint. Protocols must incorporate mechanisms for extended patient tracking, which includes not just clinical parameters but also quality-of-life metrics and long-term outcomes. Planning for this data flow must begin at the trial design stage.

Understanding The EBMT CAR-T Registry Initiative

The EBMT CAR-T Data Collection Initiative was launched to standardize post-treatment follow-up across Europe for patients receiving commercial CGT therapies. As of 2024, the initiative includes approved products such as Kymriah, Yescarta, Tecartus, and Breyanzi.

Key aspects of the initiative include:

• Standardized Data Sets: The EBMT registry defines core variables to be captured over a minimum of 15 years.
• Site-Driven Entry: Data is entered by sites, usually those already participating in the EBMT registry for transplant tracking.
• Sponsor Collaboration: Although data collection is performed by the sites, sponsors are expected to support and facilitate this process.
• Compliance & Interoperability: The initiative aligns with GDPR and other regional data protection regulations, ensuring ethical and legal data handling.

For clinical operations teams, this initiative introduces an additional layer of accountability. It is not simply a post-marketing obligation; rather, registry alignment must be integrated into the trial life cycle from the outset.

Operational Challenges In Aligning Trial With Registry Requirements

Aligning a CGT trial with the EBMT registry isn’t as simple as exporting data at the end. Without planning, sponsors risk redundant data entry, inconsistent terminology, and protocol amendments late in the trial.

Common operational pitfalls include:

• Data Fragmentation: Without harmonization, trial and registry data sets may diverge, making integration and analysis difficult.
• Resource Mismatch: Sites may not be staffed to maintain 15-year follow-up records or enter registry data unless adequately supported.
• Patient Dropout: Long-term tracking increases the risk of lost-to-follow-up, especially when patients transition out of academic centers.
• Budget Shortfalls: Extended follow-up and registry alignment require financial planning beyond the typical trial closeout.

Clinical operations professionals must identify these gaps early. Collaborating with data management teams to align the data acquisition tools (e.g., case report forms) with registry fields can reduce duplication. Contracts should define post-study obligations and funding for data entry, even years after trial closure.

Building Operational Infrastructure For Registry-Aligned Trial

To manage these challenges effectively, sponsors must invest in infrastructure that enables registry-ready trial. This begins with SOPs that clearly outline roles and responsibilities for long-term data collection, including coordination with the EBMT registry.

Site-facing documents should explicitly include:

• instructions on dual data entry (electronic case report form [eCRF] + registry)
• registry-specific timelines and required variables
• contact points for operational support and issue escalation.

Training is another critical component. Site staff must be educated on registry expectations, particularly in centers unfamiliar with EBMT workflows. Sponsor teams, including CROs and vendors, should also be briefed on how registry compliance impacts overall data strategy.

Ensuring Continuous Data Access In The EBMT CAR-T Data Collection Initiative

While the initiative offers a robust framework for data collection, sponsors frequently encounter challenges in maintaining consistent access to their data.

One of the most significant hurdles lies in the management of data by local coordinators, typically physicians, who determine its use. This can lead to uncertainties regarding data access and utilization, as well as delays that may not align with your timelines or requirements. Addressing these challenges proactively can make a substantial difference in operational efficiency and regulatory compliance.

To ensure continuous data access, several key strategies should be implemented.

First, establishing direct contracts with EBMT can clarify data access rights and responsibilities. Negotiating a Data Collection Master Agreement and Product-Specific Agreements allows the sponsor to outline the frequency and format of data transfers, as well as the obligations of both parties. These agreements are instrumental in ensuring data accuracy and compliance.

Next, updating informed consent forms (ICFs) used at participating sites is essential. These forms should explicitly mention data sharing with sponsors to streamline the process and avoid potential legal or ethical concerns. Collaborating with sites to validate the use of approved and up-to-date ICF versions ensures that patients are informed about how their data will be utilized.

Maintaining regular communication with local coordinators is another crucial step. Establishing periodic check-ins to discuss data access can build trust and ensure that these coordinators understand your data needs and timelines. This collaborative approach can reduce uncertainties and foster smoother operations.

Implementing internal monitoring systems, such as dashboards to track site reporting timelines and data submissions, helps the sponsor stay on top of the requirements. These tools enable the sponsor to promptly address any discrepancies and ensure timely compliance.

Furthermore, liaising with internal regulatory affairs teams is vital to confirm PAS data requirements and ensure alignment with regulatory expectations. These teams can guide the sponsor through the complexities of data access and utilization, ensuring that collected data meets the necessary standards.

Developing SOPs for engagement with EBMT PAS activities and conducting internal training sessions for your ClinOps teams are also critical. These measures ensure that all team members understand the data access protocols, streamlining the process and minimizing confusion.

The benefits of securing continuous data access are numerous. It enables regulatory compliance, ensuring you can meet PAS study requirements and maintain market authorization. It also enhances operational efficiency by reducing complexity in data collection and analysis. By ensuring data accuracy and reliability, the sponsor can make informed decisions that improve patient outcomes. Additionally, continuous access fosters collaboration with treatment sites and regulatory authorities, building trust and alignment among stakeholders.

By taking these proactive steps, a sponsor can navigate the challenges of data collection and utilization effectively. Continuous data access empowers sponsors to monitor real-world outcomes, enhance patient safety, and ensure the long-term success of CAR-T programs.

Best Practices To Future-Proof CGT Trial

Operational alignment with registries like EBMT’s can be a differentiator for sponsors, especially those preparing for HTA submissions. The following best practices can help clinical operations teams lead the way:

1. Engage Early with Registry Bodies: Initiate discussions with EBMT or relevant national registries during protocol development.
2. Align eCRF Design with Registry Requirements: Minimize rework and data inconsistency by harmonizing data fields up front.
3. Budget for the Long Haul: Include registry-related activities in your trial budget and agreements.
4. Incorporate Long-Term Consent Provisions: Ensure consent language supports 15-year data use and sharing.
5. Track Follow-Up Metrics Proactively: Monitor retention, dropout risk, and site compliance with registry timelines.

These efforts signal a sponsor’s commitment to transparency, patient welfare, and regulatory excellence. They also reduce friction during reimbursement discussions by ensuring that real-world outcomes can be clearly demonstrated.

About The Author:

Jessica Cordes started her clinical operations career in 2009, working at various companies, including Big Pharma and several small to midsize biotech companies. She gained extensive experience on different levels from country study management to global study management and, since 2018, leadership in clinical operations. During her time at Medigene and Immatics, she structured the clinical operations department, built cohesive global teams, and implemented GCP and ATMP-compliant processes. For more than 12 years, she has been working in oncology clinical trials (including hemato-oncology as well as solid tumors) and with ATMPs since 2018. Since 2023, she has been working as an independent consultant and trainer, supporting small companies in building their clinical operations group and setting up their clinical trials for success. She provides a GCP refresher course via her Clinical Excellence Training Academy.