Intelligent treatment decision support combining variant interpretation and phenotype analytics can transform healthcare

Abstract

Introduction: Digital precision medicine solutions are fundamentally changing the way therapies are developed and prescribed. Rapid interpretation of clinico-molecular data is poised to transform clinical practice. From amolecular analytics perspective, this multifactorial process involves identifying personalized treatment options, optimizing response likelihood, and avoiding toxicity. We therefore examined the concordance between approved drugs and genomic evidence in patient cohorts.We also examined the feasibility of assessing drug safety by using outcomes data. Methods: SNVs, INDELs, and fusion proteins were identified using a gene NGS panel or exon Seq and an analytical platform that screens aberrations against >5.5K peerreviewed predictive biomarkers. Actionable aberrations were defined to be mutations within genes targeted by approved or investigational drugs. Results: We analyzed >20 different cohorts of cancer patients. Our analysis revealed that biomarker profiling enables informed decision support. In many cases biomarker data suggested non-approved drug use, emphasizing the potential utility of such information in clinical trial recruitment and/or prescription of off-label drugs. We also scanned >6.8M adverse events (AEs) to analyze possible treatment outcomes and report on the breadth of information contained in>671K cancer AEs. Conclusion: While more prospective studies are required to fully characterize the financial impact of potential treatment readjustments based on genomic evidence, the benefits of reliable and efficient clinico-molecular data interpretation are expected to include not only better informed clinical options but also reduced healthcare expenditures. Key to any healthcare system stakeholder is the adoption of integrated safety assessment and variant interpretation strategies, not only to avoid toxicity incidence and costs, but Importantly to accommodate opportunities improving patient-s personal awareness and quality of care.