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 must 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 robust evidence of efficacy and are in current use. If efficacy is not well-established, then widespread use must be documented. Clinical interventions (such as medications, diagnostic tests, or procedures) and delivery system interventions (such as workforce, technologies, and healthcare service delivery designs) 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 or effect size is not permitted. Approval to proceed to the second phase will be contingent on achieving specific milestones and deliverables established for the feasibility phase.

This funding opportunity seeks applications addressing three of PCORI’s National Priorities for Health. To be considered responsive, applications must propose research meeting the distinctive requirements of this PFA and address at least one of the following National Priorities for Health:

• Increase Evidence for Existing Interventions and Emerging Innovations in Health
  • Goal: Strengthen and expand ongoing comparative clinical effectiveness research focused on both existing interventions and emerging innovations to improve healthcare practice, health outcomes, and health equity.
• Accelerate Progress Toward an Integrated Learning Health System
  • Goal: Foster actionable, timely, place-based, and transformative improvements in patient-centered experiences, care provision, and ultimately improved health outcomes through collaborative, multisectoral research to support a health system that understands and serves the needs and preferences of individuals.
• Achieve Health Equity
  • Goal: Expand stakeholder engagement, research, and dissemination approaches that lead to continued progress toward achieving health equity in the United States.

Applicants will be asked to select one of the three National Priorities above as primary, and if relevant, a secondary and/or tertiary National Priority in their Letter of Intent (LOI) and, if invited, full application.

PCORI’s Topic Themes are also introduced in this funding opportunity. Applicants have the option to choose up to three Topic Themes, based on how their proposed research aligns with the themes. However, aligning with a topic theme is not required.

The National Priorities for Health and Topic Themes will assist PCORI in determining the optimal review pathway for the proposed research.

Meaningful stakeholder engagement is viewed as an essential component of funded PLACER studies, and the feasibility phase provides an opportunity to further develop engagement plans and activities. Applicants’ use of multiple approaches that occur along a continuum of engagement from input to shared leadership are encouraged. Funded studies will be required to submit a full roster of engaged stakeholders and detailed engagement plan after contract execution.

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. PCORI also requires that applications include experienced engagement leadership with demonstrated experience in patient and stakeholder engagement in large research studies or projects. Investigators may request up to $2 million in direct costs for a feasibility phase up to 18 months in duration, with up to $20 million in direct costs for continuation to a full-scale study phase up to five years in duration. Total direct costs for the full proposal should not exceed $22 million.

In addition to Cycle 2 2023, this funding opportunity will be re-posted for Cycle 3 2023.