Pharmacogenomics and Global Precision Medicine in the Context of Adverse Drug Reactions: Top 10 Opportunities and Challenges for the Next Decade

Abstract

In a move indicative of the enthusiastic support of precision medicine, the U.S. President Barack Obama announced the Precision Medicine Initiative in January 2015. The global precision medicine ecosystem is, thus, receiving generous support from the United States ($215 million), and numerous other governments have followed suit. In the context of precision medicine, drug treatment and prediction of its outcomes have been important for nearly six decades in the field of pharmacogenomics. The field offers an elegant solution for minimizing the effects and occurrence of adverse drug reactions (ADRs). The Clinical Pharmacogenetics Implementation Consortium (CPIC) plays an important role in this context, and it aims at specifically guiding the translation of clinically relevant and evidence-based pharmacogenomics research. In this forward-looking analysis, we make particular reference to several of the CPIC guidelines and their role in guiding the treatment of highly relevant diseases, namely cardiovascular disease, major depressive disorder, cancer, and human immunodeficiency virus, with a view to predicting and managing ADRs. In addition, we provide a list of the top 10 crosscutting opportunities and challenges facing the fields of precision medicine and pharmacogenomics, which have broad applicability independent of the drug class involved. Many of these opportunities and challenges pertain to infrastructure, study design, policy, and science culture in the early 21st century. Ultimately, rational pharmacogenomics study design and the acquisition of comprehensive phenotypic data that proportionately match the genomics data should be an imperative as we move forward toward global precision medicine.

Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium–Based Treatment in Brazilian Kidney Transplant Recipients

“…AEs result in considerable morbidity and mortality, exacerbating the problems faced by health care systems . Therefore, it is important to identify genetic biomarkers that can predict individual susceptibility to the risk of AEs for safe treatment with immunosuppressive drugs.…”

A Review of the Challenges of Using Biomedical Big Data for Economic Evaluations of Precision Medicine

“…Demand for storage capacity for genomic and clinical data is constantly rising [21]. The use of BBD requires extensive storage capacity and high computational processing power [15, 22, 23]. Both requirements involve significant costs, which could present an obstacle for some research institutions, limiting their ability to conduct health economic evaluations in this context [13, 15, 23–27].…”

“…Solving some of these challenges will likely require effective collaboration between highly skilled individuals from different disciplines (including bio-informatics, statistics and medicine, as well as health economics). The challenge of keeping up with the dynamic developments in the field of big data analytics will have to be overcome if the full potential of BBD is to be realised from a health economic perspective [22, 23, 27].…”

Host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis C infection

“…Decreasing the occurrence of ADRs, and hence the cost of healthcare services, is one of the most important opportunities and challenges of precision medicine. Developing tools that help in achieving such goals and rationalize pharmacogenomic study designs is extremely important to address this challenge [ 51 ]. A potential strategy to define candidate genes that modulate a phenotype (e.g., developing an ADR) is to predict drug targets, disease-related genes, and genetic pathways that underlie this phenotype [ 52 ]; this is the strategy used in PHARMIP.…”