Establishing the value of genomics in medicine: the IGNITE Pragmatic Trials Network

Abstract

Purpose: A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions. Methods: The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions; to assess approaches for real-world application of genomic medicine in diverse clinical settings; and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation. Results: Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression. Conclusions: IGNITE PTN is the first network to carry out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers.

A shared genetic signature for common chronic pain conditions and its impact on biopsychosocial traits

“…Further work is required such as: (i) genetic epidemiology studies collecting data on more specific chronic pain diagnoses and clinical traits (e.g., pro- and anti-nociceptive phenotypes, medication/treatment responses 22 ); (ii) replication with other large genotyped datasets 4,7 including population samples with non-European ancestry; (iii) employing genomic structural equation modelling to identify other underlying latent factors 35 with a focus on the traits delineated in the current study (e.g., musculoskeletal & visceral pathologies, psychiatric disorders, occupation, cardiovascular disease & analgesic use); (iv) incorporating genetic risk stratification of placebo/control groups in randomised clinical trials of chronic pain interventions, 2,3,22 and (v) investigating gene-environment interactions and epigenetic mechanisms in chronic pain (e.g., early life stress, physical activity). 36…”

“…21 Further, the proposition of a shared genetic signature underlying different types of regional chronic pain invites further investigation of genetic risk for chronic pain, 22,23 which may have potential applications for genetic stratification of patients in clinical trials, 24 to allow targeting of patients most at risk of developing chronic pain. Based on the precedent for genetically supported therapeutic targets, 2,3 traits with genetic causal effects identified in our study may represent potential treatment targets in management of chronic pain, providing convergent support for established approaches for treatment (e.g., weight-loss in knee osteoarthritis 25 ) or prevention of chronic pain (e.g., targeting post-traumatic stress after injury 26,27 ), as well as insight for development of emerging strategies (e.g., dietary 28 ).…”

Multi-Institutional Implementation of Clinical Decision Support for APOL1, NAT2, and YEATS4 Genotyping in Antihypertensive Management

“…PGx CDS implemented at a single institution utilizing multiple genes have been previously described [19]. However, this study looks at a large multi-institutional attempt to develop PGx CDS for a small number of genes [20]. General frameworks for CDS have previously been applied to genomic medicine with success [1].…”

Multiomics subtyping for clinically prognostic cancer subtypes and personalized therapy: A systematic review and meta-analysis

“…13 Recent work highlights the need for equitable access to precision medicine in diverse populations 14 in addition to the growing need to validate the clinical utility and processes behind advances in genetic medicine. [15][16][17] Molecular pathology has become ingrained in cancer diagnostics and therapeutic decision-making. However, molecular subtyping is complicated by the many aberrations contributing to cancer (variants, amplifications, deletions, translocations, fusions, structural variations, etc.…”