*Purpose: The Transplant Therapeutics Consortium established a real-world evidence workgroup evaluating the potential of supplementing internal control arms with external controls to understand the impact of new therapies on long-term survival. Collaboratively, UNOS conducted a pilot study to retrospectively simulate the use of a contemporaneous external control group analysis as a supplement to the BENEFIT study’s cyclosporine arm.

*Methods: Phase 1 of the pilot study compared the cyclosporine arm from the BENEFIT study and applied the study’s enrollment criteria to the OPTN registry population transplanted during the same time frame (January 2006-June 2007). Two external control groups were formed based on maintenance immunosuppressive regimen: Group 1 (tacrolimus + mycophenolate mofetil) and Group 2 (cyclosporine + mycophenolate mofetil). Only subjects from non-BENEFIT study centers were included in Group 2 to avoid overlap (bolded-Table 1). Overall and death-censored graft survival, as well as recipient survival were estimated via Kaplan-Meier (KM) methods at 3 years post-transplant.

*Results: Recipient age, race, history of diabetes, and living donor transplants are four covariates with significant imbalances between the BENEFIT study and the historical control groups (bolded-Table 2). Despite baseline differences, KM estimates for patient and graft survival rates were similar to the BENEFIT study cyclosporine arm.

*Conclusions: Applying BENEFIT study enrollment criteria to OPTN registry data resulted in a small, non-overlapping historical cyclosporine arm (n=153) but a substantial alternative historical tacrolimus arm (n=1064). Similar survival rates were found despite an imbalance in four covariates demonstrating the potential of supplementing internal controls with external registry controls for long-term survival. Phase 2 analyses will utilize propensity methods for covariate-balanced survival rate estimates.

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