(165) Improving Longitudinally in Rare Disease Data Capture in Real-world Evidence Combining Clinical Trials and Observational Data: A Case Study Using EVOLVE

Publication Number: 1160

Background: Interest in real-world evidence (RWE) to expedite and enrich the development of new biopharmaceutical products has proliferated in recent years. Regulators increasingly consider RWE in their decisions to address gaps traditional clinical trials (CT) do not capture and meet growing payer/provider demands for long-term data. Data longevity and continuity are key for patients especially with rare diseases such as Duchenne muscular dystrophy (DMD), a severe, genetic, neurodegenerative disease characterized by progressive muscle deterioration and premature death. Linkage of CT data with real-world data via methods including internal-linkage and tokenization can be used to capture the patient trajectory and disease progression comprehensively.

Objectives: To assess the value of combining CT data with observational studies, EVOLVE, an ongoing, 5-year, Phase 4, multicenter, observational study evaluating eteplirsen, golodirsen, or casimersen in routine clinical practice.

strong>Methods: An interim analysis of EVOLVE was conducted with results describing the use, safety, and clinical outcomes of long-term eteplirsen use in routine clinical practice in the United States. These data were then linked and analyzed using industry standard quality processing to allow for comparison with patients originally participating in CT. Linkage via tokenization, a HIPAA-compliant process by which patient healthcare data are de-identified through generation of an encrypted patient-specific “token” and linked to real-world data, can be used in the future to evaluate the patient journey.

Results: As of December 2021, 123 eteplirsen patients were enrolled: mean (SD) age was 13.7 (5.5) years, mean total duration of treatment was 4.68 (1.9) years. Of the patients who had prior clinical study experience, 39/39 (100%) were able to be linked to the real-world EVOLVE. The mean (SD) follow-up time in these patients from CT treatment initiation through the EVOLVE study data cut-off was 6.3 (1.6) years, whereas the follow-up time from EVOLVE baseline was 5.1 (1.7) years, demonstrating an average 1.2-year longer follow-up duration. Longitudinal data from CT treatment initiation through real-world exposure will continue to be added to assess long-term outcomes as the EVOLVE study progresses.

Conclusions: This study demonstrates an efficient and broadly applicable way to assess the patient journey beyond CT using the observational EVOLVE study. Data tokenization and linkage methods of CT with real-world studies can yield complete and quality data that can inform regulators, payers, healthcare professionals, and families about treatment safety and effectiveness to optimize care for patients with rare diseases.