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

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

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.Personalised Therapeutic

A theory-informed systematic review of barriers and enablers to implementing multi-drug pharmacogenomic testing

PGx testing requires a complex set of activities undertaken by practitioners and patients, resulting in varying implementation success. This systematic review aimed (PROSPERO: CRD42019150940) to identify barriers and enablers to practitioners and patients implementing pharmacogenomic testing. We followed PRISMA guidelines to conduct and report this review. Medline, EMBASE, CINAHL, PsycINFO, and PubMed Central were systematically searched from inception to June 2022. The theoretical domain framework (TDF) guided the organisation and reporting of barriers or enablers relating to pharmacogenomic testing activities. From the twenty-five eligible reports, eleven activities were described relating to four implementation stages: ordering, facilitating, interpreting, and applying pharmacogenomic testing. Four themes were identified across the implementation stages: IT infrastructure, effort, rewards, and unknown territory. Barriers were most consistently mapped to TDF domains: memory, attention and decision-making processes, environmental context and resources, and belief about consequences

Front-Line Physicians' Satisfaction with Information Systems in Hospitals

Day-to-day operations management in hospital units is difficult due to continuously varying situations, several actors involved and a vast number of information systems in use. The aim of this study was to describe front-line physicians' satisfaction with existing information systems needed to support the day-to-day operations management in hospitals. A cross-sectional survey was used and data chosen with stratified random sampling were collected in nine hospitals. Data were analyzed with descriptive and inferential statistical methods. The response rate was 65 % (n = 111). The physicians reported that information systems support their decision making to some extent, but they do not improve access to information nor are they tailored for physicians. The respondents also reported that they need to use several information systems to support decision making and that they would prefer one information system to access important information. Improved information access would better support physicians' decision making and has the potential to improve the quality of decisions and speed up the decision making process.Peer reviewe

Configuring an implementation model for multi-drug pharmacogenomic testing in the NHS

Backgrounds Pharmacogenomic testing can improve patient outcomes through safer and more efficient dose and drug selection. Implementation of multi-drug pharmacogenomic testing in clinical care has been fragmented internationally and is largely absent within the NHS. The aim of this thesis was to develop and refine a programme theory using behaviour science for the implementation of multi-drug pharmacogenomic testing within an NHS context. Methods Underpinned by behavioural science, the research programme comprised three empirical studies. The first study modelled the impact of multi-drug pharmacogenomic testing in UK primary care, by estimating the occurrence of actionable drug gene interactions in daily practice, using first prescription volumes for 56 PGx drugs and phenotype frequency data. The second study involved a systematic review and narrative synthesis of the barriers and enablers to implementing multi-drug pharmacogenomic testing, using the TDF to map factors affecting prescriber, pharmacist, and patient behaviours. Finally, the third study was a qualitative exploration of the real-world implementation of multi-drug pharmacogenomic testing in the NHS, conducted using a case study methodology. Results Over 20% of all new prescriptions annually issued for 56 medicines in UK primary care had an actionable drug-gene interaction according to guidelines from the Dutch Pharmacogenetic Working Group and/or the Clinical Pharmacogenetics Implementation Consortium. A multi-drug pharmacogenomic testing programme which constitutes testing genetic variants in four genes (CYP2C19, CYP2D6, SLCO1B1, HLA-B) would cover more than 95% of the potential drug-gene interactions occurring in UK primary care. The systematic review found barriers to the implementation of multi-drug pharmacogenomic testing can be organised around four themes influencing behaviours of prescribers, pharmacists and patients. These are: IT infrastructure, Effort, Rewards and Unknown Territory. Barriers were most consistently mapped to TDF domains: memory, attention and decision-making processes, environmental context and resources, and belief about consequences. Pharmacists played a vital role in PGx testing implementation model and enabled prescribers to order and deliver PGx testing for patients. Empirical data using a case study methodology of real-world implementation of multi-drug pharmacogenomic testing, found pharmacists were key drivers for PGx testing implementation model within an NHS context. Training to prepare health professionals to deliver and utilise PGx testing in clinical decision making, should focus on skills development and managing expectations of both patients and health professionals of what PGx testing can provide. Conclusions These three studies advance the understanding of implementing multi-drug pharmacogenomic testing by converging implementation science and genomic medicine. The modelling study provides researchers and policy makers with new knowledge to design a minimum drug-gene panel for a PGx testing panel relevant to the UK population. The multi-drug PGx testing implementation configuration informed by the systematic review and case study requires further modelling and feasibility testing to optimise before implementation across NHS settings. Keywords: pharmacogenomics, personalised medicine, implementatio

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

Immunopathology of vascular and renal diseases and of organ and celltransplantationIP