Existing guidance on the design and conduct of externally controlled trials places emphasis on early engagement with regulatory and HTA bodies to justify the rationale for using an external control arm (ECA), and to discuss the preliminary study design and statistical analyses. With the increasing use of ECAs in both regulatory and HTA submissions, the acceptable use cases for ECAs (e.g., single arm trials in rare indications, undefined control/standard of care) and important design and analytic considerations are becoming clearer. However, key questions remain for manufacturers:

1) When is the most optimal timing in the development process to plan for an ECA?

2) When and how should a company best prepare for early interactions to address differing regulatory and HTA perspectives?

In this session, we will discuss these questions, as well as differences in how regulatory vs HTA stakeholders appraise ECAs, the most common key issues from each perspective, and proposed solutions. We will also cover early planning strategies that should be considered by clinical development/regulatory and HEOR teams to optimize both regulatory and market access pathways. Finally, we will conclude with recommendations for early ECA feasibility assessments and demonstrate how to successfully navigate early stakeholder interactions through an example case study.