Facilitating the Implementation of Population-wide Genomic Screening across Diverse Populations and Settings (FOCUS)

PROJECT SUMMARY Population-wide genomic screening (PGS) for Hereditary Breast and Ovarian Cancer Syndrome, Lynch Syndrome, and Familial Hypercholesterolemia offers great promise in identifying the 1-2% of the population that unknowingly carries a pathogenic variant that puts them at elevated risk for serious, yet preventable disease.

Rapidly decreasing sequencing costs, endorsement of PGS by national bodies, and attention to precision medicine applications have rapidly accelerated the spread of PGS programs. To date, no clear guidelines or implementation strategies exist to support the rapid growth of PGS. Contextual factors, including program-level

procedures, organizational structure, and characteristics of the patient population, influence implementation of these large-scale PGS initiatives. To help facilitate growth of PGS programs and enhance recruitment and retention of representative populations into genomic initiatives, we propose to identify best practices for PGS

implementation and develop and test a freely available, online multicomponent implementation guide (FOCUS toolkit). This project will establish a gold standard approach for equitably integrating PGS and offer the field generalizable methods and knowledge about PGS implementation. Specifically, using a stakeholder-engaged

Implementation Mapping approach we will: 1) conduct a qualitative needs assessment among ten PGS programs (FOCUS design sites) at various implementation stages (emerging, implementing, sustaining) guided by the Consolidated Framework for Implementation Research integrated with constructs from the Health Equity

Implementation Framework, 2) develop and produce the FOCUS toolkit consisting of equity-focused implementation strategies, materials, and protocols, and 3) evaluate the impact of the FOCUS toolkit on Reach, Effectiveness, Implementation, Adoption, Maintenance and health equity outcomes for PGS in 12 PGS sites

(FOCUS test sites) with diverse populations and settings using a stepped wedge cluster randomized trial design. All aspects of this project will be conducted by an exceptional investigative team comprised of individuals from diverse backgrounds and across career stages and supported by a ten-person Implementation Mapping Advisory

Panel consisting of representatives from public health and regulatory agencies, communities and patient groups, and clinical stakeholders. Efforts are further bolstered by our Plan for Enhancing Diverse Perspectives, which advances the scientific and technical merit of our project through inclusivity and diverse perspectives among our

team, the sites where research is conducted, and those who participate in the research. These findings will: 1) provide a standardized approach and evaluation framework for programs seeking to strategically implement and expand population-based approaches for identifying individuals and families at high risk of serious, yet

preventable disease, 2) provide generalizable methods and knowledge about PGS, and 3) support efforts to bring the promise of precision health to all.