Moving towards a novel paradigm in drug development for worsening heart failure: The t1 model (mechanistic translational phase)

Hospitalization for worsening heart failure (WHF) represents a clinical entity with high burden of global disease, unacceptable postdischarge mortality and rehospitalization rates reaching 45% within 60-90 days, and enormous economic expenditures worldwide. Despite the use of evidence-based therapies and implementation of policy measures on the governmental level, there has been minimal impact on the event rate following hospitalization for worsening heart failure over the past decade. In addition, the aging population and improved survival post-myocardial infarction will continue to fuel the growing population of patients with heart failure. There exists a substantial unmet need for novel therapeutic strategies that will improve outcomes in patients hospitalized with WHF. The current paradigm of sequentially conducting trials from phase I to III has not resulted in successful identification of therapies that improve outcomes and a different approach is needed. Herein we describe potential reasons for the failure of current phase III clinical trails, lessons learned, and outline the T1 or translational phase model as a novel paradigm to move forward to successfully develop drug development in patients hospitalized with WHF.