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

Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response

EQUITABLE PHARMACOGENETIC TESTING IMPLEMENTATION FOR RURAL AND UNDERSERVED POPULATIONS

Pharmacogenetic testing has potential to transform healthcare, yet implementation strategies have been limited to major academic medical centers serving metropolitan communities and large health systems. In contrast, rural, community-based health systems are slow to implement these advances, threatening to exacerbate existing healthcare disparities for rural populations. A majority of Montanans live in rural areas, with unique challenges in providing access to pharmacogenetics. We have established partnerships with three clinical sites who serve rural, underserved populations including American Indian, pediatric, and low socioeconomic status patients. We conducted a needs assessment for pharmacogenetic testing implementation by interviewing 48 key stakeholders. Interview questions were centered around participants opinions regarding pharmacogenetics and their perceived barriers and facilitators for implementation of testing. A codebook was created by analysis and organization of common themes. Positive opinions on using pharmacogenetics to guide therapy were common. Perceived benefits included reduced time to symptom management, fewer adverse events, and improved adherence. Concerns expressed in similar studies based in larger medical centers were also present, including conflicts with reimbursement and test turnaround time. Unique concerns for vulnerable, underserved populations included equitable access based on socioeconomic status and sensitivity to culture and historical injustices, particularly for tribal people. Participants were enthusiastic about using telehealth to implement pharmacogenetics in these communities. This will provide an innovative strategy for pharmacogenetic testing and consultations. Participants were eager to implement testing in their facilities. Many concerns can be mitigated with a strategic implementation plan targeted for underserved patients. Our model will implement pharmacogenetics using a telehealth delivery model centered at the University of Montana with outreach to rural health systems and providers. This has the potential to expand as new health innovations are translated into practice. Future work in this area will involve assisting partner sites with implementation efforts and measuring clinical outcomes related to testing services. Our study will help overcome the unique challenges in delivering pharmacogenetics to rural and underserved communities and we aim to provide a model for states with similar patient populations. Our goal is to pave the way for equitable access to pharmacogenetics for all

FARMAPRICE: A Pharmacogenetic Clinical decision support system for precise and Cost-Effective Therapy

Pharmacogenetic (PGx) guidelines for the precise dosing and selection of drugs remain poorly implemented in current clinical practice. Among the barriers to the implementation process is the lack of clinical decision support system (CDSS) tools to aid health providers in managing PGx information in the clinical context. The present study aimed to describe the first Italian endeavor to develop a PGx CDSS, called FARMAPRICE. FARMAPRICE prototype was conceived for integration of patient molecular data into the clinical prescription process in the Italian Centro di Riferimento Oncologico (CRO)-Aviano Hospital. It was developed through a coordinated partnership between two high-tech companies active in the computerization of the Italian healthcare system. Introducing FARMAPRICE into the clinical setting can aid physicians in prescribing the most efficacious and cost-effective pharmacological therapy available

Engineering requirements of a Herpes simplex virus patient registry: discovery phase of a real-world evidence platform to advance pharmacogenomics and personalized medicine

Comprehensive pharmacogenomic understanding requires both robust genomic and demographic data. Patient registries present an opportunity to collect large amounts of robust, patient-level data. Pharmacogenomic advancement in the treatment of infectious diseases is yet to be fully realised. Herpes simplex virus (HSV) is one disease for which pharmacogenomic understanding is wanting. This paper aims to understand the key factors that impact data collection quality for medical registries and suggest potential design features of an HSV medical registry to overcome current constraints and allow for this data to be used as a complement to genomic and clinical data to further the treatment of HSV. This paper outlines the discovery phase for the development of an HSV registry with the aim of learning about the users and their contexts, the technological constraints and the potential improvements that can be made. The design requirements and user stories for the HSV registry have been identified for further alpha phase development. The current landscape of HSV research and patient registry development were discussed. Through the analysis of the current state of the art and thematic user analysis, potential design features were elucidated to facilitate the collection of high-quality, robust patient-level data which could contribute to advances in pharmacogenomic understanding and personalised medicine in HSV. The user requirements specification for the development of an HSV registry has been summarised and implementation strategies for the alpha phase discussed

Pharmacogenomic-based personalized medicine: Multistakeholder perspectives on implementational drivers and barriers in the Canadian healthcare system

Pharmacogenomics (PGx)-based personalized medicine (PM) is increasingly utilized to guide treatment decisions for many drug-disease combinations. Notably, London Health Sciences Centre (LHSC) has pioneered a PGx program that has become a staple for London-based specialists. Although implementational studies have been conducted in other jurisdictions, the Canadian healthcare system is understudied. Herein, the multistakeholder perspectives on implementational drivers and barriers are elucidated. Using a mixed-method qualitative model, key stakeholders, and patients from LHSC’s PGx-based PM clinic were interviewed and surveyed, respectively. Interview transcripts were thematically analyzed in a stepwise process of customer profiling, value mapping, and business model canvasing. Value for LHSC located specialist users of PGx was driven by the quick turnaround time, independence of the PGx clinic, and the quality of information. Engagement of external specialists was only limited by access and awareness, whereas other healthcare nonusers were limited by education and applicability. The major determinant of successful adoption at novel sites were institutional champions. Patients valued and approved of the service, expressed a general willingness to pay, but often traveled far to receive genotyping. This paper discusses the critical pillars of education, awareness, advocacy, and efficiency required to address implementation barriers to healthcare service innovation in Canada. Further adoption of PGx practices into Canadian hospitals is an important factor for advancing system-level changes in care delivery, patient experiences, and outcomes. The findings in this paper can help inform efforts to advance clinical PGx practices, but also the potential adoption and implementation of other innovative healthcare service solutions

A national clinical decision support infrastructure to enable the widespread and consistent practice of genomic and personalized medicine

<p>Abstract</p> <p>Background</p> <p>In recent years, the completion of the Human Genome Project and other rapid advances in genomics have led to increasing anticipation of an era of genomic and personalized medicine, in which an individual's health is optimized through the use of all available patient data, including data on the individual's genome and its downstream products. Genomic and personalized medicine could transform healthcare systems and catalyze significant reductions in morbidity, mortality, and overall healthcare costs.</p> <p>Discussion</p> <p>Critical to the achievement of more efficient and effective healthcare enabled by genomics is the establishment of a robust, nationwide clinical decision support infrastructure that assists clinicians in their use of genomic assays to guide disease prevention, diagnosis, and therapy. Requisite components of this infrastructure include the standardized representation of genomic and non-genomic patient data across health information systems; centrally managed repositories of computer-processable medical knowledge; and standardized approaches for applying these knowledge resources against patient data to generate and deliver patient-specific care recommendations. Here, we provide recommendations for establishing a national decision support infrastructure for genomic and personalized medicine that fulfills these needs, leverages existing resources, and is aligned with the <it>Roadmap for National Action on Clinical Decision Support </it>commissioned by the U.S. Office of the National Coordinator for Health Information Technology. Critical to the establishment of this infrastructure will be strong leadership and substantial funding from the federal government.</p> <p>Summary</p> <p>A national clinical decision support infrastructure will be required for reaping the full benefits of genomic and personalized medicine. Essential components of this infrastructure include standards for data representation; centrally managed knowledge repositories; and standardized approaches for leveraging these knowledge repositories to generate patient-specific care recommendations at the point of care.</p

Pharmacogenomics in Primary Care: Barriers to Implementation

As technology and research evolve it is essential that practitioners in healthcare remain aware and cognizant of the changes that are going on around them and how these advancements may aid them in providing the best care to the patients that seek care from them. The largest breakthrough in the field of genetics has been the complete sequencing of the human genome. This landmark has paved the way for innumerable insights into every part of how care is delivered and stands to change the landscape of medicine entirely. Pharmacogenomics testing exists as a subset of genetic testing, and pertains to the evaluation of individual genetic variants that may interfere with the normal metabolism of many medications. There are specialty care settings where this modality of testing is more prevalent, but it is not well represented in primary care settings, where it stands to provide a wealth of information to primary care providers as they manage their patients. Literature review was conducted on this subject of interest and it was found that there was precedent for the implementation of pharmacogenomics testing in the primary care setting. Through survey of primary care providers, it was determined that there were deficits in knowledge and perspective barriers that were adequately addressed with an educational intervention. This intervention was shown to promote both the potential implementation of pharmacogenomics testing, generate interest in further education on the subject of pharmacogenomics, and address the identified perspective barriers