Statistical analysis plan considerations for autologous cell and cell-based gene therapy clinical trials

Area of Science:

• Biomedical Science
• Clinical Trials
• Gene Therapy

Background:

• Over 100 gene, cell, and RNA products approved globally by early 2023.
• Autologous cell and gene therapy administration involves complex, multi-stage treatment protocols.
• These stages include leukapheresis, bridging therapy, conditioning, and product dosing.

Purpose of the Study:

• To review FDA-approved autologous cell and gene therapy products.
• To provide general considerations for statistical analysis plans (SAP) in clinical trials.
• To discuss specific aspects like treatment exposure, safety, and efficacy analyses.

Main Methods:

• Review of all FDA-approved autologous cell and cell-based gene therapy products.
• Application of the estimand framework for key statistical facets.
• In-depth discussion of statistical considerations for clinical trial design.

Main Results:

• Complex treatment administration necessitates robust SAP development.
• The estimand framework is crucial for addressing trial complexities.
• Specific analyses for treatment exposure, safety, and efficacy are highlighted.

Conclusions:

• Statistical analysis plans for autologous cell and gene therapies must account for intricate treatment pathways.
• Utilizing FDA-approved products as examples aids in developing effective SAPs.
• Careful planning ensures rigorous evaluation of safety and efficacy in gene therapy trials.