A Sustainable Future In The Implementation Of Clinical Pharmacogenomics

Purpose: The sustainability of clinical pharmacogenomics requires further study of clinical education on the topic, its effects on clinical workflow, and the responsibilities of different providers for its delivery. Tools from the discipline of implementation science were utilized herein to help achieve the purposes of the three studies. The broad purpose of this dissertation is to advance the work of clinical pharmacogenomic implementation through a more rigorous convergence with implementation science. Methods: Three studies constitute the whole of this dissertation. The first is a scoping review that provides a broad characterization of the methods utilized in available peer-revieliterature focusing on provider use of and experience with using pharmacogenomics in practice or the study setting. The second study used semi-structured in-depth interviews to elicit strategies and perspectives from leadership in current implementation programs using the Consolidated Framework for Implementation Science (CFIR) Process Domain. The third used a cross-sectional quantitative survey with experimental vignettes to explore the potential for pharmacist-physician collaboration using newly developed implementation science outcomes. Results: The scoping review included 25 studies, with many focused on the interactions of providers with clinical decision support systems and adherence to therapeutic recommendations represented. Results from the interviews were extensive but several highlights included a focus on understanding pharmacogenomic use prior to implementation, high-touch informal communication with providers, and the power of the patient case. The survey analysis revealed that the primary care physicians believe that it is more appropriate to deliver clinical pharmacogenomics when a pharmacist is physically located in a clinic and is responsible for managing and modifying a drug therapy based on these results. Conclusion: These three studies further the convergence of implementation science and genomic medicine, with particular focus on pharmacogenomics and the foundational concept of implementation science, sustainability. The scoping review should provide future researchers with a landscape of available and previously used methodologies for interventional pharmacogenomic studies. The interview results will help new implementers of pharmacogenomics steer around avoidable hurdles or make them easier to address. The survey results showcase the potential for pharmacist-physician collaboration in clinical pharmacogenomics

Multi-site 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. Key differences between programs included the test result turnaround time and timing of therapy changes which are both related to CYP2C19 testing model and platform used. Sites reported the need for new informatics infrastructure, expert clinicians such as pharmacists to interpret results, physician champions, and ongoing education. Consensus lessons learned are presented to provide a path forward for those seeking to implement similar clinical pharmacogenomics programs within their institutions. This article is protected by copyright

Pharmacogenomic testing in paediatrics: Clinical implementation strategies

Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been variable and limited. As with most paediatric pharmacological studies, there are well-recognised barriers to obtaining high-quality PGx evidence, particularly when patient numbers may be small, and off-label or unlicensed prescribing remains widespread. Furthermore, trials enrolling small numbers of children can rarely, in isolation, provide sufficient PGx evidence to change clinical practice, so extrapolation from larger PGx studies in adult patients, where scientifically sound, is essential. This review paper discusses the relevance of PGx to paediatrics and considers implementation strategies from a child health perspective. Examples are provided from Canada, the Netherlands and the UK, with consideration of the different healthcare systems and their distinct approaches to implementation, followed by future recommendations based on these cumulative experiences. Improving the evidence base demonstrating the clinical utility and cost-effectiveness of paediatric PGx testing will be critical to drive implementation forwards. International, interdisciplinary collaborations will enhance paediatric data collation, interpretation and evidence curation, while also supporting dedicated paediatric PGx educational initiatives. PGx consortia and paediatric clinical research networks will continue to play a central role in the streamlined development of effective PGx implementation strategies to help optimise paediatric pharmacotherapy

Pharmacogenomics J

Clinician attitudes toward multiplexed genomic testing may be vital to the success of translational programs. We surveyed clinicians at an academic medical center about their views on a large pharmacogenomics implementation, the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) program. Participants were asked about test ordering, major factors influencing use of results, expectations of efficacy and responsibility for applying results to patient care. Virtually all respondents (99%) agreed that pharmacogenomics variants influence patients' response to drug therapy. The majority (92%) favored immediate, active notification when a clinically significant drug-genome interaction was present. However, clinicians were divided on which providers were responsible for acting on a result when a prescription change was indicated and whether patients should be directly notified of a significant result. We concluded genotype results were valued for tailoring prescriptions, but clinicians do not agree on how to appropriately assign clinical responsibility for actionable results from a multiplexed panel.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.57.K23 HD000001/HD/NICHD NIH HHS/United StatesKL2 TR000446/TR/NCATS NIH HHS/United StatesU01 HG006378/HG/NHGRI NIH HHS/United StatesU01 HG007253/HG/NHGRI NIH HHS/United StatesU01 HG008672/HG/NHGRI NIH HHS/United StatesU01 HL105198/HL/NHLBI NIH HHS/United StatesU01 HL122904/HL/NHLBI NIH HHS/United StatesU47 CI000824/CI/NCPDCID CDC HHS/United StatesUL1 TR000445/TR/NCATS NIH HHS/United States2016-08-10T00:00:00Z26261062PMC475107

Research Directions in the Clinical Implementation of Pharmacogenomics: An Overview of US Programs and Projects

Response to a drug often differs widely among individual patients. This variability is frequently observed not only with respect to effective responses but also with adverse drug reactions. Matching patients to the drugs that are most likely to be effective and least likely to cause harm is the goal of effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision medicine through elucidating the genetic determinants responsible for pharmacological outcomes and using them to guide drug selection and dosing. Here we survey the US landscape of research programs in PGx implementation, review current advances and clinical applications of PGx, summarize the obstacles that have hindered PGx implementation, and identify the critical knowledge gaps and possible studies needed to help to address them

Implementing Pharmacogenomics in Europe: Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium

Immunopathology of vascular and renal diseases and of organ and celltransplantationIP

Payer Perspectives On Preemptive Pharmacogenetic Testing

Purpose: As preemptive pharmacogenetics expands in the academic healthcare setting, further study is needed to assess the views of additional stakeholders in the marketplace on this technology and the barriers and facilitators to their uptake. The purpose of this study is to investigate the perspectives and opinions about coverage policies for preemptive pharmacogenetic testing of third-party payers. Methods: A qualitative study utilizing a blended inductive and directed approach was conducted. A screener survey determined interview eligibility as well as demographic data. Semi-structured interviews were conducted with payers from organizations of varying structure and beneficiary populations. Meaning units and codes were used for each interview and aggregated to identify the subthemes and major themes. Results: A total of 14 payers were interviewed, covering 122,000,000 million lives, or almost 40% of the U.S. population. Positive and negative opinions were noted. Most positive opinions were prefaced with a position that pharmacogenetics held great potential for the healthcare system, but that full implementation was several years away. The work of the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Pharmacogenomics Research Network (PGRN) was viefavorably. However, this would not drive policy decisions. Negative opinions came from a concern of the lack of data that would make these tests actionable for a payer from a policy development point of view. Concerns about the cost of testing large numbers of people was mentioned frequently, as well as the inability to predict when a patient or physician would use the data from a test or potential cost savings from the technology. Discussion: Preemptive pharmacogenetic testing remains a cautious pursuit for many payers. Lacking clinical outcomes data, the inability to evaluate the economic benefits from testing, and high costs are a few central concerns. Real-world implementations from academic institutions and the work of CPIC were seen as promising endeavors. The research community of pharmacogenetic advocates should review this study and focus their efforts on providing the data needed to guide informed policy decision making with regard to pharmacogenetic testing