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.     

Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network

PurposeWhile there is growing scientific evidence for and significant advances in the use of genomic technologies in medicine, there is a significant lag in the clinical adoption and sustainability of genomic medicine. Here we describe the findings from the National Human Genome Research Institute’s (NHGRI) Implementing GeNomics In pracTicE (IGNITE) Network in identifying key constructs, opportunities, and challenges associated with driving sustainability of genomic medicine in clinical practice.MethodsNetwork members and affiliates were surveyed to identify key drivers associated with implementing and sustaining a genomic medicine program. Tallied results were used to develop and weigh key constructs/drivers required to support sustainability of genomic medicine programs.ResultsThe top three driver–stakeholder dyads were (1) genomic training for providers, (2) genomic clinical decision support (CDS) tools embedded in the electronic health record (EHR), and (3) third party reimbursement for genomic testing.ConclusionPriorities may differ depending on healthcare systems when comparing the current state of key drivers versus projected needs for supporting genomic medicine sustainability. Thus we provide gap-filling guidance based on IGNITE members’ experiences. Although results are limited to findings from the IGNITE network, their implementation, scientific, and clinical experience may be used as a road map by others considering implementing genomic medicine programs.     

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.     

Using the Consolidated Framework for Implementation Research to Identify Barriers and Facilitators for the Implementation of an Internet-Based Patient-Provider Communication Service in Five Settings: A Qualitative Study

Background

Although there is growing evidence of the positive effects of Internet-based patient-provider communication (IPPC) services for both patients and health care providers, their implementation into clinical practice continues to be a challenge.

Objective

The 3 aims of this study were to (1) identify and compare barriers and facilitators influencing the implementation of an IPPC service in 5 hospital units using the Consolidated Framework for Implementation Research (CFIR), (2) assess the ability of the different constructs of CFIR to distinguish between high and low implementation success, and (3) compare our findings with those from other studies that used the CFIR to discriminate between high and low implementation success.

Methods

This study was based on individual interviews with 10 nurses, 6 physicians, and 1 nutritionist who had used the IPPC to answer messages from patients.

Results

Of the 36 CFIR constructs, 28 were addressed in the interviews, of which 12 distinguished between high and low implementation units. Most of the distinguishing constructs were related to the inner setting domain of CFIR, indicating that institutional factors were particularly important for successful implementation. Health care providers’ beliefs in the intervention as useful for themselves and their patients as well as the implementation process itself were also important. A comparison of constructs across ours and 2 other studies that also used the CFIR to discriminate between high and low implementation success showed that 24 CFIR constructs distinguished between high and low implementation units in at least 1 study; 11 constructs distinguished in 2 studies. However, only 2 constructs (patient need and resources and available resources) distinguished consistently between high and low implementation units in all 3 studies.

Conclusions

The CFIR is a helpful framework for illuminating barriers and facilitators influencing IPPC implementation. However, CFIR’s strength of being broad and comprehensive also limits its usefulness as an implementation framework because it does not discriminate between the relative importance of its many constructs for implementation success. This is the first study to identify which CFIR constructs are the most promising to distinguish between high and low implementation success across settings and interventions. Findings from this study can contribute to the refinement of CFIR toward a more succinct and parsimonious framework for planning and evaluation of the implementation of clinical interventions.

ClinicalTrial

Clinicaltrials.gov NCT00971139; http://clinicaltrial.gov/ct2/show/NCT00971139 (Archived by WebCite at http://www.webcitation.org/6cWeqN1uY)     

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.     

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.     

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.     

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     

Complexity and the science of implementation in health IT—Knowledge gaps and future visions

ObjectivesThe intent of this paper is in the examination of health IT implementation processes – the barriers to and facilitators of successful implementation, identification of a beginning set of implementation best practices, the identification of gaps in the health IT implementation body of knowledge, and recommendations for future study and application.MethodsA literature review resulted in the identification of six health IT related implementation best practices which were subsequently debated and clarified by participants attending the NI2012 Research Post Conference held in Montreal in the summer of 2012. Using the framework for implementation research (CFIR) to guide their application, the six best practices were applied to two distinct health IT implementation studies to assess their applicability.ResultsAssessing the implementation processes from two markedly diverse settings illustrated both the challenges and potentials of using standardized implementation processes. In support of what was discovered in the review of the literature, “one size fits all” in health IT implementation is a fallacy, particularly when global diversity is added into the mix. At the same time, several frameworks show promise for use as “scaffolding” to begin to assess best practices, their distinct dimensions, and their applicability for use.ConclusionsHealth IT innovations, regardless of the implementation setting, requires a close assessment of many dimensions. While there is no “one size fits all”, there are commonalities and best practices that can be blended, adapted, and utilized to improve the process of implementation. This paper examines health IT implementation processes and identifies a beginning set of implementation best practices, which could begin to address gaps in the health IT implementation body of knowledge.     

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.     

Mainstreaming genetics and genomics: a systematic review of the barriers and facilitators for nurses and physicians in secondary and tertiary care

PurposeGenetic and genomic health information increasingly informs routine clinical care and treatment. This systematic review aimed to identify the barriers and facilitators to integrating genetics and genomics into nurses’ and physicians’ usual practice (mainstreaming).MethodsA search of MEDLINE, EMBASE, CINAHL, and PsycINFO generated 7873 articles, of which 48 were included. Using narrative synthesis, barriers and facilitators were mapped to the Theoretical Domains Framework (TDF).ResultsBarriers were limitations to genetics knowledge and skill, low confidence initiating genetics discussions, lack of resources and guidelines, and concerns about discrimination and psychological harm. Facilitators were positive attitudes toward genetics, willingness to participate in discussions upon patient initiation, and intention to engage in genetics education.ConclusionNurses and physicians are largely underprepared to integrate genetic and genomic health information into routine clinical care. Ethical, legal, and psychological concerns surrounding genetic information can lead to avoidance of genetics discussions. The knowledge–practice gap could limit patients’ and families’ access to vital genetic information. Building the capacity of the current and next generation of nurses and physicians to integrate genetics and genomics into usual clinical practice is essential if opportunities afforded by precision medicine are to be fully realized.     

Factors influencing organizational adoption and implementation of clinical genetic services

PurposeWe sought to identify characteristics of genetic services that facilitate or hinder adoption.MethodsWe conducted semi-structured key informant interviews in five clinical specialties (primary care, medical oncology, neurology, cardiology, pathology/laboratory medicine) within 13 Veterans Administration facilities.ResultsGenetic services (defined as genetic testing and consultation) were not typically characterized by informants (n = 64) as advantageous for their facilities or their patients; compatible with organizational norms of low cost and high clinical impact; or applicable to patient populations or norms of clinical care. Furthermore, genetic services had not been systematically adopted in most facilities because of their complexity: knowledge of and expertise on genetic testing was limited, and organizational barriers to utilization of genetic services were formidable. The few facilities that had some success with implementation of genetic services had knowledgeable clinicians interested in developing services and organizational-level facilitators such as accessible genetic test–ordering processes.ConclusionAdoption and implementation of genetic services will require a multilevel effort that includes education of providers and administrators, opportunities for observing the benefits of genetic medicine, strategies for reducing the complexity of genomic medicine, expanded strategies for accessing genetics expertise and streamlining utilization, and resources dedicated to assessing the value of genetic information for the outcomes that matter to health-care organizations.Genet Med 2014:16(3):238–245.     

“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.     

2022 Association of Professors of Human and Medical Genetics (APHMG) consensus–based update of the core competencies for undergraduate medical education in genetics and genomics

PurposeThe field of genetics and genomics continues to expand at an unprecedented pace. As scientific knowledge is translated to clinical practice, genomic information is routinely being used in preventive, diagnostic, and therapeutic decision-making across a variety of clinical practice areas. As adoption of genomic medicine further evolves, health professionals will be required to stay abreast of new genetic discoveries and technologies and implementation of these advances within their scope of practice will be indicated.MethodsThe Association of Professors of Human and Medical Genetics previously developed medical school genetics core competencies, last updated in 2013. The competencies were reviewed and updated through a structured approach incorporating a modified Delphi method.ResultsThe updated Association of Professors of Human and Medical Genetics core competencies are presented. Current revisions include competencies that are concise, specific, and assessable. In addition, they incorporate recent advances in clinical practice and promote equity and inclusion in clinical care.ConclusionThe 2022 competencies will serve as a guide for medical school leadership and educators involved in curriculum development, implementation, and assessment. Use of these competencies across the undergraduate medical curricula will foster knowledge, skills, and behaviors required in medical practice across a wide range of specialties.     

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

PurposeThe 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.MethodsIn this report, we compare and contrast implementation strategies for pre-emptive PGx testing by 15 early-adopter institutions. We surveyed these groups, collecting data on testing approaches, team composition, and workflow dynamics, in addition to estimated third-party reimbursement rates.ResultsWe found that while pre-emptive PGx testing models varied across sites, institutions shared several commonalities, including methods to identify patients eligible for testing, involvement of a precision medicine clinical team in program leadership, and the implementation of pharmacogenes with Clinical Pharmacogenetics Implementation Consortium guidelines available. Finally, while reimbursement rate data were difficult to obtain, the data available suggested that reimbursement rates for pre-emptive PGx testing remain low.ConclusionThese findings should inform the establishment of future implementation efforts at institutions considering a pre-emptive PGx testing program.     

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.     

Is faster better? An economic evaluation of rapid and ultra-rapid genomic testing in critically ill infants and children

PurposeTo evaluate whether the additional cost of providing increasingly faster genomic results in pediatric critical care is outweighed by reductions in health care costs and increases in personal utility.MethodsHospital costs and medical files from a cohort of 40 children were analyzed. The health economic impact of rapid and ultra-rapid genomic testing, with and without early initiation, relative to standard genomic testing was evaluated.ResultsShortening the time to results led to substantial economic and personal benefits. Early initiation of ultra-rapid genomic testing was the most cost-beneficial strategy, leading to a cost saving of AU$26,600 per child tested relative to standard genomic testing and a welfare gain of AU$12,000 per child tested. Implementation of early ultra-rapid testing of critically ill children is expected to lead to an annual cost saving of AU$7.3 million for the Australian health system and an aggregate welfare gain of AU$3.3 million, corresponding to a total net benefit of AU$10.6 million.ConclusionEarly initiation of ultra-rapid genomic testing can offer substantial economic and personal benefits. Future implementation of rapid genomic testing programs should focus not only on optimizing the laboratory workflow to achieve a fast turnaround time but also on changing clinical practice to expedite test initiation.     

Clinical phenotyping in selected national networks: demonstrating the need for high-throughput,portable, and computational methods

ObjectiveThe combination of phenomic data from electronic health records (EHR) and clinical data repositories with dense biological data has enabled genomic and pharmacogenomic discovery, a first step toward precision medicine. Computational methods for the identification of clinical phenotypes from EHR data will advance our understanding of disease risk and drug response, and support the practice of precision medicine on a national scale.MethodsBased on our experience within three national research networks, we summarize the broad approaches to clinical phenotyping and highlight the important role of these networks in the progression of high-throughput phenotyping and precision medicine. We provide supporting literature in the form of a non-systematic review.ResultsThe practice of clinical phenotyping is evolving to meet the growing demand for scalable, portable, and data driven methods and tools. The resources required for traditional phenotyping algorithms from expert defined rules are significant. In contrast, machine learning approaches that rely on data patterns will require fewer clinical domain experts and resources.ConclusionsMachine learning approaches that generate phenotype definitions from patient features and clinical profiles will result in truly computational phenotypes, derived from data rather than experts. Research networks and phenotype developers should cooperate to develop methods, collaboration platforms, and data standards that will enable computational phenotyping and truly modernize biomedical research and precision medicine.