Endpoints in trials for clinical liver transplantation

The past decade has seen significant improvements in patient and graft survival following liver transplantation. Likewise, acute rejection rates have been dramatically reduced with newer immunologic agents. To this end, past and present conventional endpoints, such as short-term graft survival and acute rejection rates, are no longer adequate themselves.

Alternative endpoints, such as long-term patient or graft survival are ideal endpoints as these would capture a number of secondary endpoints over this time. This approach requires, however, a large cohort of patients with longer follow-up. Using other endpoints such as renal function or histologic parameters, which may predict long-term outcomes, may be beneficial. The use of multiple endpoints in composite fashion may also be beneficial in predicting outcomes. Renal function following liver transplantation, or histological indices may be used potentially as a composite endpoint, in combination with conventional endpoints, such as graft loss, death and acute rejection. The evolution of immunosuppressive therapeutics has resulted in a change in the standard agents used and thus the need for contemporary control groups.

One balanced approach for assessing newer immunosuppressive therapies might be to use composite endpoints, combining conventional endpoints (graft loss, death, acute rejection) with contemporary endpoints (renal function, histological indices). A re-assessment of contemporary control groups is warranted.