FDA Listening Session: Approaches for Capturing Post-approval Data for Cell and Gene Therapy Products

This blog was authored by the Medidata Patient Insights Board.

The best way to stay up to date with key issues facing patient populations in a given disease state is to attend a Food and Drug Administration (FDA) listening session. The Patient Insights team at Medidata regularly attends these sessions to make sure the patient perspective is amplified when designing and developing new solutions for the industry.

In April, the Food and Drug Administration (FDA) Center for Biologics, Evaluation, and Research (CBER) Office of Therapeutic Products held a public listening session seeking input on methods and approaches for capturing post-approval safety and efficacy data on cell and gene therapy products.

There’s an increasing number of these products in development and the potential for more treatments expected in the future. The FDA has an obligation to understand the full spectrum of long-term effects and to collect accurate, timely, and comprehensive data to ensure the safety, efficacy, and quality of these products. It’s important to consider alternative study designs, including the incorporation of decentralized trials, the use of registries, and the capture of clinical data and real world evidence in the collection of long term post-approval data. 

Decentralized Trials for Cell & Gene Therapy Products

Decentralized clinical trials allow for robust data collection from a variety of sources, including patient-reported outcomes (PRO), wearables, and more. The primary focus lies in an effort to move to the lowest burden method for patients, sites, and healthcare providers. In this context, focusing on the collection of post-approval data presents another opportunity to use decentralized solutions for trials involving cell and gene therapy products.

Decentralized solutions, including the incorporation of technology, are essential when devising strategies for long-term monitoring. While hybrid approaches are likely necessary, required periodic assessments should be designed to maximize patient participation while minimizing burden and cost. The industry might consider methods to incentivize patients to encourage their ongoing engagement throughout the post-approval process.

All treatment information must be readily shared with trial participants, including signals regarding any potential limitation of the therapy (such as its durability and all observed but unforeseen side effects). The choice of technology for post-approval data collection would be guided by the specific therapeutic area being studied and the types of data required.

Patient Registries and EMR Data Collection

Data collected in clinical settings using electronic health records, insurance claims, and other administrative databases, along with population-based sources including registries and natural history studies, provides a more comprehensive understanding of the disease landscape. The expanded use of validated outcome measures affords the capture of more robust and meaningful data for trials involving cell and gene therapy products.

A coordinated effort is essential to leverage the full potential of these data sources. Some concerns that may be considered are the technological support necessary to accommodate differing systems, the requirements of the overseeing institutional review board, and the need for updated consent forms from patient participants.

A registry that combines real-world data with patient-derived data gathered from multiple sources encourages the long-term engagement of both patients and sponsors. There’s a critical need for the coordination and combination of global disease registries, including those sponsored by patient advocacy groups, industry, and government.

There’s an ongoing development of a global registry to collect long-term data on all people treated with new hemophilia gene therapy products. This registry aims to successfully integrate data from national registries and treatment centers and appears to have industry support. This initiative, a product of the World Federation of Hemophilia, is currently being reviewed by the EMA for validation. There was broad agreement that “enforced collaboration” will be necessary if registries are to be successfully implemented for long-term gene and cell therapy monitoring.

The natural history relevant to specific diseases should be considered when designing registries. This allows for the comparison and evaluation of cell and gene therapy products in treated and untreated patients in the post approval setting with the ability to capture many other points in time. It’s encouraged to incorporate features within registries that enable easy patient input, including survey completion, still and video image capture, and required PROs. Innovation with enhancements under development, including “automated blurring” of facial or other identifying features, lets stakeholders assess treatment effects while also adding a measure of privacy for patients.

Takeaways for the Industry

Flexibility in study design allows for the gathering of data from a variety of sources, including medical charts, PROs, claims data, and wearables. There’s value in the continuous collection of this data at the trial’s conclusion. When used in combination with registry data, a robust collection of detailed information is assembled for both post-approval evidence generation and ongoing safety monitoring. Confirmatory evidence of clinical benefit for all FDA approvals is essential and serves additional purposes, including the potential benefits of combination therapy, strategies to enhance durability, and a foundation for additional clinical research.

The industry must maintain an innovative focus on rapid advancements in cell and gene therapy products to keep pace with technological advances, any new therapeutic uses, and changes to regulatory guidance for all therapies to address patient expectations.