Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations
NJ Lennon et al, Nature Medicine, February 19, 2024
From the abstract: " From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. "
We need to stand together on the shoulders of giants: consolidating effective approaches for translating genomics into practice with implementation science.
Stephanie Best et al. Public Health Genomics 2023 12
From the article: "Adopting a genomics learning implementation system approach would provide opportunities to bring together clinical and implementation data from observational studies and clinical trials, providing real-world evidence. These findings could be housed in the Digital Implementation Toolshed (DIT), an online bi-directional platform for resources generated from implementation science activity in genomics. The highly curated DIT (Fig. 1) would augment the Centers for Disease Control and Prevention Genomics and Precision Health Weekly Update. " "
Cost Effectiveness of Genomic Population Health Screening in Adults: A Review of Modeling Studies and Future Directions.
Robert S Wildin et al. J Appl Lab Med 2024 1 (1) 92-103
From the abstract: " Eight recent cost-effectiveness modeling studies for high penetrance monogenic dominant diseases that used input parameters from 3 different countries are reviewed. Results and their uses in refining implementations are analyzed and the roles for laboratory medicine in facilitating success are discussed. The reviewed studies generally found evidence for cost-effectiveness of genomic population health screening in at least a subset of their base case screening scenario. Sensitivity analyses identified opportunities for improving the likelihood of cost-effectiveness. On the whole, the modeling results suggest genomic population health screening is likely to be cost-effective for high penetrance disorders in younger adults."
Real-world diagnostic outcomes and cost-effectiveness of genome-wide sequencing for developmental and seizure disorders: evidence from Canada
DA Regier et al, Genetics in Medicine, January 8, 2024
From the abstract: "Based on medical records review, we estimated real-world costs and outcomes for 491 patients who underwent standard of care (SOC) diagnostic testing at BC Children’s Hospital. Results informed a state-transition Markov model examining cost-effectiveness of three competing diagnostic strategies: (1) SOC with last-tier access to ES; (2) streamlined ES access; (3) first-tier GS. We found earlier access to ES may yield more rapid genetic diagnosis of childhood developmental and seizure disorders and cost savings compared to current practice. "