Precision medicine is making an impact on patients, health care delivery systems, and research participants in ways that were only imagined fifteen years ago when the human genome was first ...sequenced. Discovery of disease-causing and drug-response genetic variants has accelerated, while adoption into clinical medicine has lagged. We define precision medicine and the stakeholder community required to enable its integration into research and health care. We explore the intersection of data science, analytics, and precision medicine in the formation of health systems that carry out research in the context of clinical care and that optimize the tools and information used to deliver improved patient outcomes. We provide examples of real-world impact and conclude with a policy and economic agenda necessary for the adoption of this new paradigm of health care both in the United States and globally.
The last decade has witnessed a steady embrace of genomic and personalized medicine by senior government officials, industry leadership, health care providers, and the public. Genomic medicine, which ...is the use of information from genomes and their derivatives (RNA, proteins, and metabolites) to guide medical decision making—is a key component of personalized medicine, which is a rapidly advancing field of health care that is informed by each person's unique clinical, genetic, genomic, and environmental information. As medicine begins to embrace genomic tools that enable more precise prediction and treatment disease, which include “whole genome” interrogation of sequence variation, transcription, proteins, and metabolites, the fundamentals of genomic and personalized medicine will require the development, standardization, and integration of several important tools into health systems and clinical workflows. These tools include health risk assessment, family health history, and clinical decision support for complex risk and predictive information. Together with genomic information, these tools will enable a paradigm shift to a comprehensive approach that will identify individual risks and guide clinical management and decision making, all of which form the basis for a more informed and effective approach to patient care. DNA-based risk assessment for common complex disease, molecular signatures for cancer diagnosis and prognosis, and genome-guided therapy and dose selection are just among the few important examples for which genome information has already enabled personalized health care along the continuum from health to disease. In addition, information from individual genomes, which is a fast-moving area of technological development, is spawning a social and information revolution among consumers that will undoubtedly affect health care decision making. Although these and other scientific findings are making their way from the genome to the clinic, the full application of genomic and personalized medicine in health care will require dramatic changes in regulatory and reimbursement policies as well as legislative protections for privacy for system-wide adoption. Thus, there are challenges from both a scientific and a policy perspective to personalized health care; however, they will be confronted and solved with the certainty that the science behind genomic medicine is sound and the practice of medicine that it informs is evidence based.
Genomic medicine--an aspirational term 10 years ago--is gaining momentum across the entire clinical continuum from risk assessment in healthy individuals to genome-guided treatment in patients with ...complex diseases. We review the latest achievements in genome research and their impact on medicine, primarily in the past decade. In most cases, genomic medicine tools remain in the realm of research, but some tools are crossing over into clinical application, where they have the potential to markedly alter the clinical care of patients. In this State of the Art Review, we highlight notable examples including the use of next-generation sequencing in cancer pharmacogenomics, in the diagnosis of rare disorders, and in the tracking of infectious disease outbreaks. We also discuss progress in dissecting the molecular basis of common diseases, the role of the host microbiome, the identification of drug response biomarkers, and the repurposing of drugs. The significant challenges of implementing genomic medicine are examined, along with the innovative solutions being sought. These challenges include the difficulty in establishing clinical validity and utility of tests, how to increase awareness and promote their uptake by clinicians, a changing regulatory and coverage landscape, the need for education, and addressing the ethical aspects of genomics for patients and society. Finally, we consider the future of genomics in medicine and offer a glimpse of the forces shaping genomic medicine, such as fundamental shifts in how we define disease, how medicine is delivered to patients, and how consumers are managing their own health and affecting change.
Personalized Medicine: Progress and Promise Chan, Isaac S; Ginsburg, Geoffrey S
Annual review of genomics and human genetics,
01/2011, Letnik:
12, Številka:
1
Journal Article
Recenzirano
Personalized medicine is a broad and rapidly advancing field of health care that is informed by each person's unique clinical, genetic, genomic, and environmental information. Personalized medicine ...depends on multidisciplinary health care teams and integrated technologies (e.g., clinical decision support) to utilize our molecular understanding of disease in order to optimize preventive health care strategies. Human genome information now allows providers to create optimized care plans at every stage of a disease, shifting the focus from reactive to preventive health care. The further integration of personalized medicine into the clinical workflow requires overcoming several barriers in education, accessibility, regulation, and reimbursement. This review focuses on providing a comprehensive understanding of personalized medicine, from scientific discovery at the laboratory bench to integration of these novel ways of understanding human biology at the bedside.
The article discusses the potential that precision medicine has to offer to the health sector as well as health care in general by tailoring treatments to individual needs. Some of the key aspects ...that need to be kept in mind in relation to precision medicine are highlighted.
Family health history (FHH) is the most useful means of assessing risk for common chronic diseases. The odds ratio for risk of developing disease with a positive FHH is frequently greater than 2, and ...actions can be taken to mitigate risk by adhering to screening guidelines, genetic counselling, genetic risk testing, and other screening methods. Challenges to the routine acquisition of FHH include constraints on provider time to collect data and the difficulty in accessing risk calculators. Disease-specific and broader risk assessment software platforms have been developed, many with clinical decision support and informatics interoperability, but few access patient information directly. Software that allows integration of FHH with the electronic medical record and clinical decision support capabilities has provided solutions to many of these challenges. Patient facing, electronic medical record, and web-enabled FHH platforms have been developed, and can provide greater identification of risk compared with conventional FHH ascertainment in primary care. FHH, along with cascade screening, can be an important component of population health management approaches to overall reduction of risk.
Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order ...to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin) and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza.
Objectives We sought to identify single nucleotide polymorphisms associated with mild statin-induced side effects. Background Statin-induced side effects can interfere with therapy. Single nucleotide ...polymorphisms in cytochrome P450 enzymes impair statin metabolism; the reduced function SLCO1B1*5 allele impairs statin clearance and is associated with simvastatin-induced myopathy with creatine kinase (CK) elevation. Methods The STRENGTH (Statin Response Examined by Genetic Haplotype Markers) study was a pharmacogenetics study of statin efficacy and safety. Subjects (n = 509) were randomized to atorvastatin 10 mg, simvastatin 20 mg, or pravastatin 10 mg followed by 80 mg, 80 mg, and 40 mg, respectively. We defined a composite adverse event (CAE) as discontinuation for any side effect, myalgia, or CK >3× upper limit of normal during follow-up. We sequenced CYP2D6 , CYP2C8 , CYP2C9 , CYP3A4 , and SLCO1B1 and tested 7 reduced function alleles for association with the CAE. Results The CAE occurred in 99 subjects (54 discontinuations, 49 myalgias, and 9 CK elevations). Sex was associated with CAE (percent female in CAE vs. no CAE groups, 66% vs. 50%, p < 0.01). SLCO1B1*5 was associated with CAE (percent with ≥1 allele in CAE vs. no CAE groups, 37% vs. 25%, p = 0.03) and those with CAE with no significant CK elevation (p ≤ 0.03). Furthermore, there was evidence for a gene-dose effect (percent with CAE in those with 0, 1, or 2 alleles: 19%, 27%, and 50%, trend p = 0.01). Finally, the CAE risk appeared to be greatest in those carriers assigned to simvastatin. Conclusions SLCO1B1*5 genotype and female sex were associated mild statin-induced side effects. These findings expand the results of a recent genome-wide association study of statin myopathy with CK >3× normal to milder, statin-induced, muscle side effects.
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