The current state of implementation science in genomic medicine: opportunities for improvement

PurposeThe objective of this study was to identify trends and gaps in the field of implementation science in genomic medicine.MethodsWe conducted a literature review using the Centers for Disease Control and Prevention’s Public Health Genomics Knowledge Base to examine the current literature in the field of implementation science in genomic medicine. We selected original research articles based on specific inclusion criteria and then abstracted information about study design, genomic medicine, and implementation outcomes. Data were aggregated, and trends and gaps in the literature were discussed.ResultsOur final review encompassed 283 articles published in 2014, the majority of which described uptake (35.7%, n = 101) and preferences (36.4%, n = 103) regarding genomic technologies, particularly oncology (35%, n = 99). Key study design elements, such as racial/ethnic composition of study populations, were underreported in studies. Few studies incorporated implementation science theoretical frameworks, sustainability measures, or capacity building.ConclusionAlthough genomic discovery provides the potential for population health benefit, the current knowledge base around implementation to turn this promise into a reality is severely limited. Current gaps in the literature demonstrate a need to apply implementation science principles to genomic medicine in order to deliver on the promise of precision medicine.Genet Med advance online publication 12 January 2017     

Integration of stakeholder engagement from development to dissemination in genomic medicine research: Approaches and outcomes from the CSER Consortium

PurposeThere is a critical need for genomic medicine research that reflects and benefits socioeconomically and ancestrally diverse populations. However, disparities in research populations persist, highlighting that traditional study designs and materials may be insufficient or inaccessible to all groups. New approaches can be gained through collaborations with patient/community stakeholders. Although some benefits of stakeholder engagement are recognized, routine incorporation into the design and implementation of genomics research has yet to be realized.MethodsThe National Institutes of Health–funded Clinical Sequencing Evidence-Generating Research (CSER) consortium required stakeholder engagement as a dedicated project component. Each CSER project planned and carried out stakeholder engagement activities with differing goals and expected outcomes. Examples were curated from each project to highlight engagement strategies and outcomes throughout the research lifecycle from development through dissemination.ResultsProjects tailored strategies to individual study needs, logistical constraints, and other challenges. Lessons learned include starting early with engagement efforts across project stakeholder groups and planned flexibility to enable adaptations throughout the project lifecycle.ConclusionEach CSER project used more than 1 approach to engage with relevant stakeholders, resulting in numerous adaptations and tremendous value added throughout the full research lifecycle. Incorporation of community stakeholder insight improves the outcomes and relevance of genomic medicine research.     

Genomic medicine implementation protocols in the PhenX Toolkit: tools for standardized data collection

PurposeThe PhenX Toolkit (www.phenxtoolkit.org), an online catalog of recommended measurement protocols, facilitates cross-study analyses for research with human participants. The PhenX Steering Committee recommended genomic medicine implementation as a new research domain, with the following scope: genomic knowledge and education (both patients and providers); implementation science; changes in management and treatment; return of results; patient outcomes; and ethical, legal, and social issues (ELSI) associated with genomic research.MethodsA seven-member expert Working Group convened in October 2019 to identify well-established measurement protocols for a new genomic medicine implementation domain and used the established PhenX consensus process to select measurement protocols for inclusion in the PhenX Toolkit.ResultsThe Working Group recommended 15 measurement protocols for inclusion in the PhenX Toolkit, with priority given to those with empirical evidence supporting validity. Consortia funded by the National Institutes of Health, and particularly the National Human Genome Research Institute, proved critical in identifying protocols with established utility in this research domain, and identified protocols that were developed through a rigorous process for scope elements that lacked formally validated protocols.ConclusionUse of these protocols, which were released in September 2020, can facilitate standard data collection for genomic medicine implementation research.     

Qualitative study of system-level factors related to genomic implementation

PurposeResearch on genomic medicine integration has focused on applications at the individual level, with less attention paid to implementation within clinical settings. Therefore, we conducted a qualitative study using the Consolidated Framework for Implementation Research (CFIR) to identify system-level factors that played a role in implementation of genomic medicine within Implementing GeNomics In PracTicE (IGNITE) Network projects.MethodsUp to four study personnel, including principal investigators and study coordinators from each of six IGNITE projects, were interviewed using a semistructured interview guide that asked interviewees to describe study site(s), progress at each site, and factors facilitating or impeding project implementation. Interviews were coded following CFIR inner-setting constructs.ResultsKey barriers included (1) limitations in integrating genomic data and clinical decision support tools into electronic health records, (2) physician reluctance toward genomic research participation and clinical implementation due to a limited evidence base, (3) inadequate reimbursement for genomic medicine, (4) communication among and between investigators and clinicians, and (5) lack of clinical and leadership engagement.ConclusionImplementation of genomic medicine is hindered by several system-level barriers to both research and practice. Addressing these barriers may serve as important facilitators for studying and implementing genomics in practice.     

The Electronic Medical Records and Genomics (eMERGE) Network: past,present, and future

The Electronic Medical Records and Genomics Network is a National Human Genome Research Institute–funded consortium engaged in the development of methods and best practices for using the electronic medical record as a tool for genomic research. Now in its sixth year and second funding cycle, and comprising nine research groups and a coordinating center, the network has played a major role in validating the concept that clinical data derived from electronic medical records can be used successfully for genomic research. Current work is advancing knowledge in multiple disciplines at the intersection of genomics and health-care informatics, particularly for electronic phenotyping, genome-wide association studies, genomic medicine implementation, and the ethical and regulatory issues associated with genomics research and returning results to study participants. Here, we describe the evolution, accomplishments, opportunities, and challenges of the network from its inception as a five-group consortium focused on genotype–phenotype associations for genomic discovery to its current form as a nine-group consortium pivoting toward the implementation of genomic medicine.Genet Med15 10, 761–771.     

Structured approaches to implementation of clinical genomics: A scoping review

PurposeThis study aimed to assess the extent to which structured approaches to implementation of clinical genomics, proposed or adapted, are informed by evidence.MethodsA systematic approach was used to identify peer-reviewed articles and gray literature to report on 4 research questions:1. What structured approaches have been proposed to support implementation?2. To what extent are the structured approaches informed by evidence?3. How have structured approaches been deployed in the genomic setting?4. What are the intended outcomes of the structured approaches?ResultsA total of 30 unique structured approaches to implementation were reported across 23 peer-reviewed publications and 11 gray literature articles. Most approaches were process models, applied in the preadoption implementation phase, focusing on a “service” outcome. Key findings included a lack of implementation science theory informing the development/implementation of newly designed structured approaches in the genomic setting and a lack of measures to assess implementation effectiveness.ConclusionThis scoping review identified a significant number of structured approaches developed to inform the implementation of genomic medicine into clinical practice, with limited use of implementation science to support the process. We recommend the use of existing implementation science theory and the expertise of implementation scientists to inform the design of genomic programs being implemented into clinical care.     

Horizon scanning for translational genomic research beyond bench to bedside

PurposeThe dizzying pace of genomic discoveries is leading to an increasing number of clinical applications. In this report, we provide a method for horizon scanning and 1 year data on translational research beyond bench to bedside to assess the validity, utility, implementation, and outcomes of such applications.MethodsWe compiled cross-sectional results of ongoing horizon scanning of translational genomic research, conducted between 16 May 2012 and 15 May 2013, based on a weekly, systematic query of PubMed. A set of 505 beyond bench to bedside articles were collected and classified, including 312 original research articles; 123 systematic and other reviews; 38 clinical guidelines, policies, and recommendations; and 32 articles describing tools, decision support, and educational materials.ResultsMost articles (62%) addressed a specific genomic test or other health application; almost half of these (n = 180) were related to cancer. We estimate that these publications account for 0.5% of reported human genomics and genetics research during the same time.ConclusionThese data provide baseline information to track the evolving knowledge base and gaps in genomic medicine. Continuous horizon scanning of the translational genomics literature is crucial for an evidence-based translation of genomics discoveries into improved health care and disease prevention.Genet Med16 7, 535–538.     

Stakeholder engagement: a key component of integrating genomic information into electronic health records

Integrating genomic information into clinical care and the electronic health record can facilitate personalized medicine through genetically guided clinical decision support. Stakeholder involvement is critical to the success of these implementation efforts. Prior work on implementation of clinical information systems provides broad guidance to inform effective engagement strategies. We add to this evidence-based recommendations that are specific to issues at the intersection of genomics and the electronic health record. We describe stakeholder engagement strategies employed by the Electronic Medical Records and Genomics Network, a national consortium of US research institutions funded by the National Human Genome Research Institute to develop, disseminate, and apply approaches that combine genomic and electronic health record data. Through select examples drawn from sites of the Electronic Medical Records and Genomics Network, we illustrate a continuum of engagement strategies to inform genomic integration into commercial and homegrown electronic health records across a range of health-care settings. We frame engagement as activities to consult, involve, and partner with key stakeholder groups throughout specific phases of health information technology implementation. Our aim is to provide insights into engagement strategies to guide genomic integration based on our unique network experiences and lessons learned within the broader context of implementation research in biomedical informatics. On the basis of our collective experience, we describe key stakeholder practices, challenges, and considerations for successful genomic integration to support personalized medicine.Genet Med15 10, 792–801.     

“It’s something I’ve committed to longer term”: The impact of an immersion program for physicians on adoption of genomic medicine

ObjectiveTo foster implementation of genomic testing in medical care by providing a cadre of physicians with ‘hands on’ experience in genomics, positioning them as opinion leaders in their medical speciality. This paper presents qualitative evaluation of immediate outcomes, in particular its impact on peer interactions.MethodsProgram design and delivery was informed by implementation science, behavior change and experiential learning theories.Inductive content analysis of transcribed audio-recordings from semi-structured post-project interviews with all participants (n = 12) was conducted.ResultsParticipants reported the immersion experience improved their genomic capability, established them as credible genomic experts within their speciality and altered their practice in genomic medicine. Participants reported strengthening and widening of peer-to-peer and interdisciplinary communication, with both passive diffusion and active dissemination of information to peers. Some also became a resource for genetic professionals.ConclusionsGenomic immersion participants described elements which support sustained integration of an innovation, including immediate changes (e.g. use of genomic tests) and wider impacts (e.g. professional networks).Practice implicationsThis study supports a role for immersion as a successful strategy for enhancing engagement of non-geneticist physicians in genomics. Additional study is needed to understand how immersion experiences change the delivery of genomic services at the provider, practice and health system level.     

Evidence synthesis and guideline development in genomic medicine: current status and future prospects

PurposeWith the accelerated implementation of genomic medicine, health-care providers will depend heavily on professional guidelines and recommendations. Because genomics affects many diseases across the life span, no single professional group covers the entirety of this rapidly developing field.MethodsTo pursue a discussion of the minimal elements needed to develop evidence-based guidelines in genomics, the Centers for Disease Control and Prevention and the National Cancer Institute jointly held a workshop to engage representatives from 35 organizations with interest in genomics (13 of which make recommendations). The workshop explored methods used in evidence synthesis and guideline development and initiated a dialogue to compare these methods and to assess whether they are consistent with the Institute of Medicine report “Clinical Practice Guidelines We Can Trust.”ResultsThe participating organizations that develop guidelines or recommendations all had policies to manage guideline development and group membership, and processes to address conflicts of interests. However, there was wide variation in the reliance on external reviews, regular updating of recommendations, and use of systematic reviews to assess the strength of scientific evidence.ConclusionOngoing efforts are required to establish criteria for guideline development in genomic medicine as proposed by the Institute of Medicine.Genet Med advance online publication 19 June 2014     

The business of genomic testing: a survey of early adopters

PurposeThe practice of “genomic” (or “personalized”) medicine requires the availability of appropriate diagnostic testing. Our study objective was to identify the reasons for health systems to bring next-generation sequencing into their clinical laboratories and to understand the process by which such decisions were made. Such information may be of value to other health systems seeking to provide next-generation sequencing testing to their patient populations.MethodsA standardized open-ended interview was conducted with the laboratory medical directors and/or department of pathology chairs of 13 different academic institutions in 10 different states.ResultsGenomic testing for cancer dominated the institutional decision making, with three primary reasons: more effective delivery of cancer care, the perceived need for institutional leadership in the field of genomics, and the premise that genomics will eventually be cost-effective. Barriers to implementation included implementation cost; the time and effort needed to maintain this newer testing; challenges in interpreting genetic variants; establishing the bioinformatics infrastructure; and curating data from medical, ethical, and legal standpoints. Ultimate success depended on alignment with institutional strengths and priorities and working closely with institutional clinical programs.ConclusionThese early adopters uniformly viewed genomic analysis as an imperative for developing their expertise in the implementation and practice of genomic medicine.Genet Med16 12, 954–961.     

Delivering genomic medicine in the United Kingdom National Health Service: a systematic review and narrative synthesis

PurposeWe sought to assess the readiness of the United Kingdom(UK) National Health Service to implement a Genomic Medicine Service. We conducted a systematic literature review to identify what is known about factors related to the implementation of genomic medicine in routine health care and to draw out the implications for the UK and other settings.MethodsRelevant studies were identified in Web of Science and PubMed from their date of inception to April 2018. The review included primary research studies using quantitative, qualitative, or mixed methods, and systematic reviews. A narrative synthesis was conducted.ResultsFifty-five studies met our inclusion criteria. The majority of studies reviewed were conducted in the United States. We identified four domains: (1) systems, (2) training and workforce needs, (3) professional attitudes and values, and (4) the role of patients and the public.ConclusionMainstreaming genomic medicine into routine clinical practice requires actions at each level of the health-care system. Our synthesis emphasized the organizational, social, and cultural implications of reforming practice, highlighting that demonstration of clinical utility and cost-effectiveness, attending to the compatibility of genomic medicine with clinical principles, and involving and engaging patients are key to successful implementation.     

Proposed outcomes measures for state public health genomic programs

PurposeTo assess the implementation of evidence-based genomic medicine and its population-level impact on health outcomes and to promote public health genetics interventions, in 2015 the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine formed an action collaborative, the Genomics and Public Health Action Collaborative (GPHAC). This group engaged key stakeholders from public/population health agencies, along with experts in the fields of health disparities, health literacy, implementation science, medical genetics, and patient advocacy.MethodsIn this paper, we present the efforts to identify performance objectives and outcome metrics. Specific attention is placed on measures related to hereditary breast ovarian cancer (HBOC) syndrome and Lynch syndrome (LS), two conditions with existing evidence-based genomic applications that can have immediate impact on morbidity and mortality.ResultsOur assessment revealed few existing outcome measures. Therefore, using an implementation research framework, 38 outcome measures were crafted.ConclusionEvidence-based public health requires outcome metrics, yet few exist for genomics. Therefore, we have proposed performance objectives that states might use and provided examples of a few state-level activities already under way, which are designed to collect outcome measures for HBOC and LS.     

Clinical sites of the Undiagnosed Diseases Network: unique contributions to genomic medicine and science

PurposeThe NIH Undiagnosed Diseases Network (UDN) evaluates participants with disorders that have defied diagnosis, applying personalized clinical and genomic evaluations and innovative research. The clinical sites of the UDN are essential to advancing the UDN mission; this study assesses their contributions relative to standard clinical practices.MethodsWe analyzed retrospective data from four UDN clinical sites, from July 2015 to September 2019, for diagnoses, new disease gene discoveries and the underlying investigative methods.ResultsOf 791 evaluated individuals, 231 received 240 diagnoses and 17 new disease–gene associations were recognized. Straightforward diagnoses on UDN exome and genome sequencing occurred in 35% (84/240). We considered these tractable in standard clinical practice, although genome sequencing is not yet widely available clinically. The majority (156/240, 65%) required additional UDN-driven investigations, including 90 diagnoses that occurred after prior nondiagnostic exome sequencing and 45 diagnoses (19%) that were nongenetic. The UDN-driven investigations included complementary/supplementary phenotyping, innovative analyses of genomic variants, and collaborative science for functional assays and animal modeling.ConclusionInvestigations driven by the clinical sites identified diagnostic and research paradigms that surpass standard diagnostic processes. The new diagnoses, disease gene discoveries, and delineation of novel disorders represent a model for genomic medicine and science.     

A logic model for precision medicine implementation informed by stakeholder views and implementation science

PurposePrecision medicine promises to improve patient outcomes, but much is unknown about its adoption within health-care systems. A comprehensive implementation plan is needed to realize its benefits.MethodsWe convened 80 stakeholders for agenda setting to inform precision medicine policy, delivery, and research. Conference proceedings were audio-recorded, transcribed, and thematically analyzed. We mapped themes representing opportunities, challenges, and implementation strategies to a logic model, and two implementation science frameworks provided context.ResultsThe logic model components included inputs: precision medicine infrastructure (clinical, research, and information technology), big data (from data sources to analytics), and resources (e.g., workforce and funding); activities: precision medicine research, practice, and education; outputs: precision medicine diagnosis; outcomes: personal utility, clinical utility, and health-care utilization; and impacts: precision medicine value, equity and access, and economic indicators. Precision medicine implementation challenges include evidence gaps demonstrating precision medicine utility, an unprepared workforce, the need to improve precision medicine access and reduce variation, and uncertain impacts on health-care utilization. Opportunities include integrated health-care systems, partnerships, and data analytics to support clinical decisions. Examples of implementation strategies to promote precision medicine are: changing record systems, data warehousing techniques, centralized technical assistance, and engaging consumers.ConclusionWe developed a theory-based, context-specific logic model that can be used by health-care organizations to facilitate precision medicine implementation.     

Establishing the value of genomics in medicine: the IGNITE Pragmatic Trials Network

PurposeA critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions.MethodsThe Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation.ResultsTwo pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression.ConclusionIGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers.     

The difficulties of broad data sharing in genomic medicine: Empirical evidence from diverse participants in prenatal and pediatric clinical genomics research

PurposeThis study aimed to understand broad data sharing decisions among predominantly underserved families participating in genomic research.MethodsDrawing on clinic observations, semistructured interviews, and survey data from prenatal and pediatric families enrolled in a genomic medicine study focused on historically underserved and underrepresented populations, this paper expands empirical evidence regarding genomic data sharing communication and decision-making.ResultsOne-third of parents declined to share family data, and pediatric participants were significantly more likely to decline than prenatal participants. The pediatric population was significantly more socioeconomically disadvantaged and more likely to require interpreters. Opt-in was tied to altruism and participants’ perception that data sharing was inherent to research participation. Opt-out was associated with privacy concerns and influenced by clinical staff’s presentation of data handling procedures. The ability of participants to make informed choices during enrollment about data sharing was weakened by suboptimal circumstances, which was revealed by poor understanding of data sharing in follow-up interviews as well as discrepancies between expressed participant desires and official recorded choices.ConclusionThese empirical data suggest that the context within which informed consent process is conducted in clinical genomics may be inadequate for respecting participants’ values and preferences and does not support informed decision-making processes.     

Lessons learned from the introduction of personalized genotyping into a medical school curriculum

PurposeThere is an expanding gap between the availability of direct-to-consumer whole genome testing and physician knowledge regarding interpretation of test results. Advances in the genomic literacy of health care providers will be necessary for genomics to exert its potential to affect clinical practice. However, implementation of a major shift in medical education to include genomics is not easily done. The purpose of this educational report is to describe efforts to incorporate knowledge of personalized medicine into a medical school curriculum.MethodsIn this report, we describe the experiences, both good and bad, of a multidisciplinary faculty group that examined ways to improve genomic education at Tufts University School of Medicine during a 16-month period.ResultsThe results of the faculty's deliberation process resulted in the use of anonymous, rather than student genomes, to teach material on genomic medicine.ConclusionIncreased medical school education regarding genomic analysis and personalized medicine is a necessity, both to be able to translate the advances made by the Human Genome Project into improvements in human health and to begin to think of diseases as disruptions in specific pathways. Our experiences illustrate that adding this material to a medical school curriculum is a complex process that deserves careful thought and broad discussion within the academic community.     

The NHGRI Short Course in Genomics: energizing genetics and genomics education in classrooms through direct engagement between educators and scientists

PurposeThe National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) recognizes an urgent need for educator resources on cutting edge scientific topics due to increased public interest in genetics and genomics. We developed a Short Course in Genomics (“Short Course”) to inspire new teaching materials through collaborative course development sessions and lectures, to expand access to cutting edge scientific information, and to provide a framework to consider when crafting new coursework related to scientific education.MethodsWe compared publicly available participant data from 2015 to 2019 with data from the National Center for Education Statistics to assess our progress in serving diverse educator and student populations. We also evaluated course agendas and interviewed participants and instructors.ResultsMiddle school, high school, community college, and tribal college course attendees from the last five years were more likely to teach students from diverse communities underrepresented in science, technology, engineering, and mathematics (STEM). Both attendees and Short Course instructors emphasized the importance of bidirectional learning through interactive curriculum development.ConclusionThis course has the potential to facilitate the engagement of educators and students at all levels, recruit and maintain a diverse STEM workforce, and improve genomic literacy and future health decision-making.     

Developing a common framework for evaluating the implementation of genomic medicine interventions in clinical care: the IGNITE Network’s Common Measures Working Group

PurposeImplementation research provides a structure for evaluating the clinical integration of genomic medicine interventions. This paper describes the Implementing Genomics in Practice (IGNITE) Network’s efforts to promote (i) a broader understanding of genomic medicine implementation research and (ii) the sharing of knowledge generated in the network.MethodsTo facilitate this goal, the IGNITE Network Common Measures Working Group (CMG) members adopted the Consolidated Framework for Implementation Research (CFIR) to guide its approach to identifying constructs and measures relevant to evaluating genomic medicine as a whole, standardizing data collection across projects, and combining data in a centralized resource for cross-network analyses.ResultsCMG identified 10 high-priority CFIR constructs as important for genomic medicine. Of those, eight did not have standardized measurement instruments. Therefore, we developed four survey tools to address this gap. In addition, we identified seven high-priority constructs related to patients, families, and communities that did not map to CFIR constructs. Both sets of constructs were combined to create a draft genomic medicine implementation model.ConclusionWe developed processes to identify constructs deemed valuable for genomic medicine implementation and codified them in a model. These resources are freely available to facilitate knowledge generation and sharing across the field.