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Introduction1
Genomic applications are being integrated into a broad range of clinical and research activities at health care systems across the United States. This trend can be attributed to a variety of factors, including the declining cost of genome sequencing and the potential for improving health outcomes and cutting the costs of care. The implementation and sustainability of such genomics-based programs are often dependent upon securing funding and finding a genomic medicine champion to get the program started. The goals of these genomics-based programs may be to identify individuals with clinically actionable variants as a way of preventing disease, providing diagnoses for patients with rare diseases, and advancing research on genetic contributions to health and disease. Of particular interest are genomics-based screening programs, which will, in this publication, be clinical screening programs that examine genes or variants in unselected populations in order to identify individuals who are at an increased risk for a particular health concern (e.g., diseases, adverse drug outcomes) and who might benefit from clinical interventions (see Box 1-1).
Although the adoption of genomics-based screening programs has increased in recent years, there is still much to be determined about the
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1 This workshop was organized by an independent planning committee whose role was limited to identification of topics and speakers. This Proceedings of a Workshop was prepared by the rapporteurs as a factual summary of the presentations and discussion that took place at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants, and are not endorsed or verified by the National Academies of Sciences, Engineering, and Medicine, and they should not be construed as reflecting any group consensus.
potential health benefits and possible harms of these programs and their effectiveness, safety, and clinical utility (i.e., the ability of a genetic test to improve clinical outcomes and add value to patient-management decision making). Many current genomics-based screening programs examine germline variability in specific genes that have been evaluated and recommended by groups such as the American College of Medical Genetics and Genomics (ACMG),2 the U.S. Preventive Services Task Force (USPSTF),3 and the Evaluation of Genomics Applications in Practice and Prevention (EGAPP) initiative.4 These include variants that are associated with adverse drug reactions, hereditary cancers, and rare diseases. However, some health care systems are screening for additional variants that lack strong evidence of clinical validity (i.e., the accuracy and reliability of a test in identifying or predicting the biological and medical significance of the test result) and clinical utility. Another concern related to the early implementation of genomic screening programs is that while meaningful data are being generated, those data frequently remain siloed at each individual organization or laboratory that is carrying out screening. There is an opportunity to develop incentives to share clinical and economic data from genomics-based
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2 To view the ACMG’s recommendations for reporting of incidental findings in clinical exome and genome sequencing, see https://www.ncbi.nlm.nih.gov/clinvar/docs/acmg (accessed January 10, 2018).
3 A list of current U.S. Preventive Task Force Services Grade A and B recommendations is available at https://www.uspreventiveservicestaskforce.org/Page/Name/uspstf-a-and-b-recommendations (accessed January 10, 2018).
4 Summaries of the recommendations from the EGAPP initiative are available at https://www.cdc.gov/genomics/gtesting/egapp/recommend/index.htm (accessed January 10, 2018).
screening programs as a way to advance the field, support more consistent reimbursement policies for genomics-based services and downstream care, and encourage additional health care systems to begin implementing similar programs if the evidence demonstrates that genomics-based screening programs are valuable to patients, providers, and health care systems.
On November 1, 2017, the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine hosted a public workshop to explore the challenges and opportunities associated with integrating genomics-based screening programs into health care systems.5 The workshop planning committee provided definitions to help lay the groundwork for the workshop (see Box 1-1). One goal of the workshop was to further develop the ideas presented at previous Roundtable workshops that covered the economics of genomic medicine,6 genomics-enabled learning health care systems,7 implementation science–based approaches to genomic medicine,8 and data sharing.9 This workshop was developed as a way to explore the challenges and opportunities associated with integrating genomics-based programs in health care systems in the areas of evidence collection, sustainability, data sharing, infrastructure, and equity of access. Box 1-2 lists the specific workshop objectives that were developed by the planning committee.
When the Roundtable was established in 2007, conversations about using genomics in health care settings were very speculative and far from
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5 The workshop agenda, speaker biographical sketches, statement of task, and list of registered attendees can be found in Appendixes A, B, C, and D, respectively.
6 Resources from the Roundtable’s 2012 workshop The Economics of Genomic Medicine are available at http://nationalacademies.org/hmd/Activities/Research/GenomicBasedResearch/2012-JUL-17.aspx (accessed January 8, 2018).
7 A learning health care system, as defined by the Institute of Medicine in 2013, is a “system in which science, informatics, incentives, and culture are aligned for continuous improvement and innovation, with best practices seamlessly embedded in the care process, patients, and families active participants in all elements, and new knowledge captured as an integral by-product of the care experience” (IOM, 2013, p. ix). Resources from the Roundtable’s 2014 workshop Genomics-Enabled Learning Health Care Systems: Gathering and Using Genomic Information to Improve Patient Care and Research are available at http://www.nationalacademies.org/hmd/Activities/Research/GenomicBasedResearch/2014-DEC-08.aspx (accessed January 8, 2018).
8 Resources from the Roundtable’s 2015 workshop Applying an Implementation Science Approach to Genomic Medicine are available at http://www.nationalacademies.org/hmd/Activities/Research/GenomicBasedResearch/2015-NOV-19.aspx (accessed January 8, 2018).
9 Resources from the 2012 workshop Sharing Clinical Research Data are available at http://www.nationalacademies.org/hmd/Activities/Research/SharingClinicalResearchData.aspx (accessed January 24, 2018). This project was a coordinated effort of the Forum on Drug Discovery, Development, and Translation; the Forum on Neuroscience and Nervous System Disorders; the National Cancer Policy Forum; and the Roundtable on Genomics and Precision Health.
reality, said workshop co-chair W. Gregory Feero of the Maine Dartmouth Family Medicine Residency Program. Now, he said, multiple health care systems both nationally and internationally have made the commitment to generate large amounts of genomic information in the context of clinical care and are beginning to use that information for population health management. Although the origin of each program is unique, best practices are emerging that can help organizations in the early stages of launching genomics initiatives. Developing evidence of clinical validity and clinical utility remains a challenge that might be met by collaboration across large health care systems, Feero said. Workshop participants were asked to look to the future, and to think about how to leverage existing programs to develop more robust data on how genomics may or may not improve the health of populations.
OVERVIEW OF CROSS-CUTTING TOPICS HIGHLIGHTED DURING PRESENTATIONS AND DISCUSSIONS10
A number of topics were discussed during the various workshop sessions and discussions as participants considered the different aspects of integrating genomics-based programs into health care systems. The issues
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10 This is the rapporteurs’ summary of the workshop’s main topics and recurring themes, drawn from the presentations, panel sessions, open discussions, and summary remarks by the moderators. Items on this list should not be construed as reflecting any consensus of the workshop participants or any endorsement by the National Academies of Sciences, Engineering, and Medicine.
highlighted below were drawn from individual speakers’ remarks and the open discussions and are described further in the succeeding chapters.
Data Needs and Data Sharing
Additional data on clinical utility and cost effectiveness would support the implementation and sustainability of genomics-based screening programs. However, it is unlikely that the data collected by individual organizations carrying out these types of programs would alone provide the statistical power necessary to draw meaningful conclusions. Furthermore, said Debra Leonard, the chair of pathology and laboratory medicine at the University of Vermont Medical Center, the field has not yet determined exactly what data and metrics should be collected and shared. Throughout the workshop, participants discussed the types of infrastructure needed for effective data sharing, including the usefulness of common data models and data standards. Many existing data networks do not contain structured data on whether a clinical genomic test took place and what the test results indicated. Many of the workshop participants also discussed incentives for collaboration and data sharing, including funding, statistical power, economies of scale, risk mitigation, and shared solutions.
Measuring the Value of Genomics-Based Screening Programs
The value of genomic testing from a traditional economic perspective was discussed at length during the workshop, and individual speakers emphasized the need to develop quantitative measures and data to demonstrate to health care system leadership and decision makers the clinical utility and return on investment of genomic screening. Dean Regier, an assistant professor at the University of British Columbia, stressed the importance of also considering personal utility in value assessments. Personal utility is the value that individuals receive from genomic information apart from their health outcomes (“the value of knowing”). Regier presented a survey at the workshop that indicated that patients place a high value on the return of actionable findings but that many also want to receive incidental findings (unintentional discoveries of potential medical significance), regardless of whether the identified condition is treatable (Regier et al., 2015).
Community Engagement, Diversity, and Equity
Understanding patient and public perspectives could strengthen the development of genomic screening programs and help determine the utility of these programs for the intended population. Sara Knight, a professor in the division of preventive medicine at the University of Alabama at Birming-
ham, said that policies developed with public participation are more likely to be perceived as legitimate and trusted and are more likely to be implemented. Throughout the workshop individual speakers emphasized that typically underrepresented populations should be meaningfully engaged in developing genomic programs (see Chapter 5). Diversity, including of race, ethnicity, education, socioeconomic status, and material hardship, should be considered when designing genomic programs in health care systems.
Implementation of Screening Programs
The important role of health care system leadership in driving genomic screening programs was emphasized by several workshop speakers, including Leonard. The long-term sustainability of genomics-based screening programs was identified as a challenge, and approaches to leveraging existing systems and resources were discussed. The size of the current genetic counseling workforce may not be large enough to meet the needs associated with a broad implementation of genomic screening programs in health care systems, and workshop participants discussed the perceived shortage of genetic counselors, which could be due in part to resource-intensive service delivery models. Potential solutions to this challenge include exploring new care delivery models, and training other health care system and community members to deliver screening results.
Returning Results to Screening Participants
Returning the results of screening programs to participants presents several practical and ethical challenges, including special issues associated with returning results for children. In one example discussed, return of results was found to be the key motivator for participation in genomic screening, even though the number of participants who would directly benefit was generally modest. Participants want to have actionable findings returned; however, as was discussed, there is no clear, agreed-upon definition of what is actionable. Concerns regarding false negative and false positive results (leading to, respectively, false reassurance and unnecessary treatment) were also discussed, as well as issues related to understanding prevalence and penetrance. Several speakers emphasized that individuals undergoing genomic screening need to understand that a negative result does not exclude the possibility that they have a pathogenic variant, even among the genes being analyzed. Across the discussions, panelists highlighted the need for transparency and clarity for participants when implementing genomic screening programs for research purposes, as opposed to using the programs for clinical testing.
ORGANIZATION OF THE WORKSHOP AND PROCEEDINGS
This Proceedings of a Workshop summarizes the presentations and discussion that took place at the workshop. The workshop began with a presentation from Michael Murray, the director of clinical genomics at Geisinger Health Systems, who shared his insights on how genomic programs have been implemented to advance population health management, using the Geisinger MyCode program as an example. This was followed by additional presentations from representatives from two health care systems, a state-based program, and a panel discussion about the evidence considerations for integrating genomics-based programs into health care systems (Chapter 2). The second panel session focused on the financial and sustainability aspects of genomics-based screening programs (Chapter 3). A third panel discussed approaches to optimizing data sharing among early implementers of genomics-based programs in order to work toward demonstrating clinical utility (Chapter 4). The fourth panel session addressed issues of equity and ensuring the participation of all segments of the population that are cared for in health care systems as well as issues of data security and participant privacy (Chapter 5). In the final session of the workshop, a model for accelerating evidence generation for genomic technologies was presented, and members of a panel shared their final insights on the policies and infrastructure needed to enable data sharing across institutions. The workshop co-chairs then summarized potential action steps drawn from the workshop discussions for supporting the implementation of genomics-based programs in health care systems (Chapter 6).
This workshop is critically important as the field moves forward toward a vision of having genomics as part of everyday health care, said Geoffrey Ginsburg, the director of the Duke Center for Applied Genomics & Precision Medicine and a co-chair of the Roundtable on Genomics and Precision Health. However, there are still barriers associated with implementing genomics programs into health care delivery systems, Ginsburg said, and additional evidence will be needed to convince physicians to adopt, payers to reimburse, and patients to accept this new paradigm of health care. He called upon workshop participants to identify the action items needed to develop a learning health care system focused on genomic medicine and evidence development.
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