Implementation Science to Improve Case Finding, Cascade Screening, and Treatment for Familial Hypercholesterolemia: A Prototype for Precision Public Health Research

Familial Hypercholesterolemia (FH) is a common genetic disorder, affecting more than 1 million people in the United States. FH causes lifelong high levels of low-density lipoprotein cholesterol, and if untreated, leads to a high risk of premature coronary heart disease. Most patients with FH are undiagnosed or inadequately treated with regular or high-intensity statins, leaving too many people at high risk of preventable morbidity and mortality from heart disease and stroke. Identifying and diagnosing FH and cascade screening directed at family members is a tier 1 genomic application for public health programs.

Successful implementation of cascade screening in the U.S. faces considerable challenges These include issues navigating privacy policies, provider and patient education, and limited access to genetic and medical services. In addition to hereditary cancers, familial hypercholesterolemia has emerged as the leading edge of implementation research in precision medicine.

In an effort to address the implementation challenges mentioned above, the National Heart, Lung, and Blood Institute (NHLBI), in collaboration with the CDC Office of Genomics and Precision Public Health, convened an expert panel workshop in 2018 to discuss an implementation science agenda for FH. This workshop, along with other advances in the field discussed in annual global FH summits sponsored by the FH Foundation, has led to a Funding Opportunity Announcement (FOA) released by the NHLBI. This announcement supports implementation research that addresses barriers that impede population-level implementation of case finding and cascade screening; explores methodologies to assess the uptake, cost-effectiveness, feasibility, and scalability of family-based cascade screening programs; and develop or improve machine learning algorithms and data mining techniques to find high-risk individuals using electronic health records.

Given the scarcity of implementation research in genomic medicine in general, this announcement provides a unique opportunity to showcase precision approaches to human genomics by studying how to enhance finding FH patients and their relatives.

Research examples of implementation science in FH include:

• Develop and test generalizable, cost-effective, and sustainable strategies at the local, state, or national levels for finding FH and connecting patients to clinical sources of care.
• Develop and test strategies that leverage data science approaches using electronic health record (EHR), clinical decision tools, machine learning, and clinical algorithms to test models for finding FH index patients, cascade screening, and optimizing treatment strategies across rural and urban areas.
• Develop and test the feasibility, cost-effectiveness, and scalability of case detection and cascade screening strategies across diverse clinical settings.
• Develop and test optimal and sustainable strategies to promote the adoption and sustainability of diagnosis, cascade screening for FH within under-represented populations, rural communities, and low-resource settings.
• Explore facilitators and barriers to cascade screening across key stakeholder groups (patients, providers, communities, health systems, and healthcare payers, and policy makers) using qualitative and qualitative methods.
• Develop and test innovative and generalizable strategies for increasing provider and patient adherence to guideline-based treatment for FH patients with established heart disease.
• Develop and test sustainable models for successfully transitioning pediatric patients with FH to appropriate care as young adults.
• Identify novel and generalizable methods for engaging health systems, clinics, communities, and patients for more effective implementation of health interventions.
• Evaluate systems-level approaches, tailored to large community health systems such as the Federally Qualified Health Centers, for sustained improvements in the overall management of patients with FH.
• Develop and test multi-level strategies that influence sustainability and high-fidelity delivery of evidence-based care for FH patients.
• Explore novel, systems-level strategies for implementation of local, state, and/or national policies and guidelines to achieve equitable access to and quality cardiovascular disease and risk factor care across vulnerable populations.