Derisking Phase II Clinical Trials in Heart Failure

Phase II clinical trials play an important role in drug development, providing key data that guide decision-making for promising therapeutic candidates. An important objective of phase II is to establish proof of concept by demonstrating that the drug produces its intended biological effects in the target population. Phase II trials also evaluate pharmacokinetics, pharmacodynamics, safety, and dose-response relationships. Ultimately, the goal is to generate the evidence needed to inform go/no-go decisions for further development. However, as we will discuss, phase II studies have inherent limitations and cannot fully predict phase III outcomes. In this JACC: Basic to Translational Science and Heart Failure Collaboratory position paper, we examine the value and constraints of phase II programs, using prior examples of heart failure trials, with the goal of providing insights that will help investigators and sponsors to derisk go/no-go decisions.