This PCORI Funding Announcement (PFA) invites applications for high-quality comparative clinical effectiveness research (CER) projects that will address critical decisions faced by patients, caregivers, clinicians, and stakeholders across the health and healthcare community and for which there is insufficient evidence. Investigators should propose an individual-level or cluster randomized controlled trial of significant scale and scope for this PFA. The proposed trials should address critical decisional dilemmas that require important new evidence about the comparative clinical effectiveness of available interventions. Proposed studies should compare interventions that already have evidence of efficacy or are in widespread use. Clinical interventions (such as medications, diagnostic tests, or procedures) and delivery system interventions are appropriate for these studies.

This funding announcement anticipates that proposed research projects will require two phases of funding. The initial phase (feasibility phase) of funding supports a distinct feasibility phase intended for purposes of study refinement, infrastructure establishment, stakeholder engagement, and feasibility testing of study operations, including the ability to recruit and enroll participants successfully. Using the feasibility phase to establish evidence of an intervention’s efficacy is not permitted. Approval to proceed to the second phase will be contingent on achieving specific milestones and deliverables established for the feasibility phase.

Considering the scale, complexity, and scope of trials being solicited under this PFA, PCORI requires that applications include shared trial leadership by a data coordinating center to provide an independent role in study leadership, advising on the analytical, statistical, and data management aspects of both study phases.

Letter of Intent (LOI) Deadline: May 31, 2023