Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators.

Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events.

Pharmacogenomic knowledge and awareness among diverse patients treated with angiotensin converting enzyme inhibitors.

We developed novel electronic phenotyping algorithms for the Bio biobank data, which accurately identified angiotensin converting enzyme inhibitor (ACEi)-induced angioedema cases and controls. A survey was mailed to all 1075 patients and 91 were returned. Over a third reported that prescribing physicians had not discussed with them the concepts of interindividual drug response variability or adverse event risk, and 73% of patients were previously unaware of pharmacogenomics; however, most patients were interested in having pharmacogenomic testing.

Prescriber Adoption of SLCO1B1 Genotype-Guided Simvastatin Clinical Decision Support in a Clinical Pharmacogenetics Program.

Pharmacogenetic implementation programs are increasingly feasible due to the availability of clinical guidelines for implementation research. The utilization of these resources has been reported with selected drug-gene pairs; however, little is known about how prescribers respond to pharmacogenetic recommendations for statin therapy. We prospectively assessed prescriber interaction with point-of-care clinical decision support (CDS) to guide simvastatin therapy for a diverse cohort of primary care patients enrolled in a clinical pharmacogenetics program.

Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.

Multisite investigation of strategies for the clinical implementation of pre-emptive pharmacogenetic testing.

Purpose: The increased availability of clinical pharmacogenetic (PGx) guidelines and decreasing costs for genetic testing have slowly led to increased utilization of PGx testing in clinical practice. Pre-emptive PGx testing, where testing is performed in advance of drug prescribing, is one means to ensure results are available at the time of prescribing decisions. However, the most efficient and effective methods to clinically implement this strategy remain unclear.

Rapid response to the alpha-1 adrenergic agent phenylephrine in the perioperative period is impacted by genomics and ancestry.

The emergence of genomic data in biobanks and health systems offers new ways to derive medically important phenotypes, including acute phenotypes occurring during inpatient clinical care. Here we study the genetic underpinnings of the rapid response to phenylephrine, an α1-adrenergic receptor agonist commonly used to treat hypotension during anesthesia and surgery. We quantified this response by extracting blood pressure (BP) measurements 5 min before and after the administration of phenylephrine.

Development and Analytical Validation of a 29 Gene Clinical Pharmacogenetic Genotyping Panel: Multi-Ethnic Allele and Copy Number Variant Detection.

To develop a novel pharmacogenetic genotyping panel, a multidisciplinary team evaluated available evidence and selected 29 genes implicated in interindividual drug response variability, including 130 sequence variants and additional copy number variants (CNVs). Of the 29 genes, 11 had guidelines published by the Clinical Pharmacogenetics Implementation Consortium. Targeted genotyping and CNV interrogation were accomplished by multiplex single-base extension using the MassARRAY platform (Agena Biosciences) and multiplex ligation-dependent probe amplification (MRC Holland), respectively.

Development of Customizable Implementation Guides to Support Clinical Adoption of Pharmacogenomics: Experiences of the Implementing GeNomics In pracTicE (IGNITE) Network.

Introduction: Clinical adoption of genomic medicine has lagged behind the pace of scientific discovery. Practice-based resources can help overcome implementation challenges.

Methods: In 2015, the IGNITE (Implementing GeNomics In pracTicE) Network created an online genomic medicine implementation resource toolbox that was expanded in 2017 to incorporate the ability for users to create targeted implementation guides.

Development of a Genomic Data Flow Framework: Results of a Survey Administered to NIH-NHGRI IGNITE and eMERGE Consortia Participants.

Precision health's more individualized molecular approach will enrich our understanding of disease etiology and patient outcomes. Universal implementation of precision health will not be feasible, however, until there is much greater automation of processes related to genomic data transmission, transformation, and interpretation. In this paper, we describe a framework for genomic data flow developed by the Clinical Informatics Work Group of the NIH National Human Genome Research Institute (NHGRI) IGNITE Network consortium.

Knowledge and attitudes on pharmacogenetics among pediatricians.

Increasing enthusiasm for clinical pharmacogenetic testing and the availability of pharmacogenetic-based guidelines indicate that pediatricians will increasingly be expected to interpret and apply pharmacogenetic test results into medical care. Previous studies have identified a lack of knowledge on pharmacogenetics across many physician specialties; however, this has not been systematically assessed among pediatricians. To evaluate pediatrician knowledge, attitude, and educational interest in pharmacogenetics, we surveyed physician cohorts from both the United States (U.

A stepwise approach to implementing pharmacogenetic testing in the primary care setting.

Pharmacogenetic testing can help identify primary care patients at increased risk for medication toxicity, poor response or treatment failure and inform drug therapy. While testing availability is increasing, providers are unprepared to routinely use pharmacogenetic testing for clinical decision-making. Practice-based resources are needed to overcome implementation barriers for pharmacogenetic testing in primary care.

Pharmacy students' attitudes and perceptions toward pharmacogenomics education.

Purpose: To evaluate final-year pharmacy students' perceptions toward pharmacogenomics education, their attitudes on its clinical relevance, and their readiness to use such knowledge in practice.

Methods: A 19-question survey was developed and modified from prior studies and was pretested on a small group of pharmacogenomics faculty and pharmacy students. The final survey was administered to 978 final-year pharmacy students in 8 school/colleges of pharmacy in New York and New Jersey between January and May 2017.

Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing.

Purpose: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers.

Methods: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption.

Physician-Reported Benefits and Barriers to Clinical Implementation of Genomic Medicine: A Multi-Site IGNITE-Network Survey.

Genetic medicine is one of the key components of personalized medicine, but adoption in clinical practice is still limited. To understand potential barriers and provider attitudes, we surveyed 285 physicians from five Implementing GeNomics In pracTicE (IGNITE) sites about their perceptions as to the clinical utility of genetic data as well as their preparedness to integrate it into practice. These responses were also analyzed in comparison to the type of study occurring at the physicians' institution (pharmacogenetics versus disease genetics).

Views Of Primary Care Providers On Testing Patients For Genetic Risks For Common Chronic Diseases.

We surveyed 488 primary care providers in community and academic practices in New York City in the period 2014-16 about their views on genetic testing for chronic diseases. The majority of the providers, most of whom were current or recent physicians in training, had had formal genetics education and had positive views of the utility of genetic testing. However, they felt unprepared to work with patients at high risk for genetic conditions and were not confident about interpreting test results.

Multisite Investigation of Strategies for the Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy.

CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program.

Institutional profile: translational pharmacogenomics at the Icahn School of Medicine at Mount Sinai.

For almost 50 years, the Icahn School of Medicine at Mount Sinai has continually invested in genetics and genomics, facilitating a healthy ecosystem that provides widespread support for the ongoing programs in translational pharmacogenomics. These programs can be broadly cataloged into discovery, education, clinical implementation and testing, which are collaboratively accomplished by multiple departments, institutes, laboratories, companies and colleagues. Focus areas have included drug response association studies and allele discovery, multiethnic pharmacogenomics, personalized genotyping and survey-based education programs, pre-emptive clinical testing implementation and novel assay development.

Pharmacogenomics Implementation: Considerations for Selecting a Reference Laboratory.

One of the initial steps for implementing pharmacogenomics into routine patient care is selecting an appropriate clinical laboratory to perform the testing. With the rapid advances in genotyping technologies, many clinical laboratories are now performing pharmacogenomic testing. Selection of a reference laboratory depends on whether a particular genotype assay is already performed by an internal health care organization laboratory or only available externally.

Review of Opioid Pharmacogenetics and Considerations for Pain Management.

Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics.

Concordance between Research Sequencing and Clinical Pharmacogenetic Genotyping in the eMERGE-PGx Study.

There has been extensive debate about both the necessity of orthogonal confirmation of next-generation sequencing (NGS) results in Clinical Laboratory Improvement Amendments-approved laboratories and return of research NGS results to participants enrolled in research studies. In eMERGE-PGx, subjects underwent research NGS using PGRNseq and orthogonal targeted genotyping in clinical laboratories, which prompted a comparison of genotyping results between platforms. Concordance (percentage agreement) was reported for 4077 samples tested across nine combinations of research and clinical laboratories.

Genetic Determinants of P2Y Inhibitors and Clinical Implications.

There is significant interpatient variability in clopidogrel effectiveness, which is due in part to cytochrome P450 (CYP) 2C19 genotype. Approximately 30% of individuals carry CYP2C19 loss-of-function alleles, which have been consistently shown to reduce clopidogrel effectiveness after an acute coronary syndrome and percutaneous coronary intervention. Guidelines recommend consideration of prasugrel or ticagrelor in these patients.