A Global Collaborative to Advance Genomic Medicine
2019; Elsevier BV; Volume: 104; Issue: 3 Linguagem: Inglês
10.1016/j.ajhg.2019.02.010
ISSN1537-6605
Autores Tópico(s)Biotechnology and Related Fields
ResumoCurrently, the genome-wide association studies catalog boasts 3,730 publications and 89,897 unique SNP-trait associations (see Web Resources), yet 16 years after the completion of the first human genome sequence, clinical application focuses largely on detection of rare pathogenic variants, mainly in subspecialty clinics. The disconnect between the rapid pace of discovery and the implementation of those discoveries into practice highlights the need for more robust methods and pathways to bring novel genome-based technologies to the clinic. In addition, many genomic findings today are limited to select populations, with a bias toward those of European descent, although there are trends toward more inclusion as policies are implemented to promote diversity in genomics research.1Hindorff L.A. Bonham V.L. Brody L.C. Ginoza M.E.C. Hutter C.M. Manolio T.A. Green E.D. Prioritizing diversity in human genomics research.Nat. Rev. Genet. 2018; 19: 175-185Crossref PubMed Scopus (193) Google Scholar The international community is poised to provide a platform that will not only accelerate genomic discovery in diverse populations but also provide the means to accelerate clinical validation and demonstration of clinical utility, paving the way toward clinical implementation. The Global Genomic Medicine Collaborative (G2MC) was established as a not-for-profit organization based in the United States in 2016 with the goal of enabling the implementation of genomic medicine worldwide in order to improve individual and population health. The impetus for the G2MC grew from a gathering of 90 leaders in genomic medicine from the US and 25 other countries in January, 2014.2Manolio T.A. Abramowicz M. Al-Mulla F. Anderson W. Balling R. Berger A.C. Bleyl S. Chakravarti A. Chantratita W. Chisholm R.L. et al.Global implementation of genomic medicine: We are not alone.Sci. Transl. Med. 2015; 7: 290ps13Crossref PubMed Scopus (132) Google Scholar A meeting in November 2015, demonstrated growing opportunities for pilot partnerships in the areas of education, policy, pharmacogenomics, and evidence generation. Similar to what was seen in a 2011 gathering of national leaders in genomic medicine from this country,3Manolio T.A. Chisholm R.L. Ozenberger B. Roden D.M. Williams M.S. Wilson R. Bick D. Bottinger E.P. Brilliant M.H. Eng C. et al.Implementing genomic medicine in the clinic: the future is here.Genet. Med. 2013; 15: 258-267Abstract Full Text Full Text PDF PubMed Scopus (391) Google Scholar it was clear that many nations and organizations around the globe were mounting independent and siloed efforts to bring genome-based technologies into healthcare delivery systems across diverse populations, demographics, and economies. The G2MC was formed to lead and coordinate efforts with international organizations to advance the implementation of genomic medicine by leveraging expertise and reducing duplication. To more fully realize the prospects of genomic medicine to benefit patients and populations, we must engage key stakeholders—scientists, bioinformaticians, clinicians, healthcare providers, policy analysts, industry, academia, and government—across the globe. The implementation of genomic medicine is a complex and multi-faceted process; no one sector is capable of providing a complete set of solutions in isolation. The UK’s 100,000 genome project, for example, set up Genomics England as a private company owned by the Department of Health to enable more flexible and rapid procurement of capabilities for sequencing and evaluation. In doing so, it facilitated collaborations between public and private sectors. Genomics England has awarded contracts to private-sector companies across the globe to develop the annotation and evaluation algorithms needed for interpreting the clinical relevance of variants identified in genomic data.4Marx V. The DNA of a nation.Nature. 2015; 524: 503-505Crossref PubMed Scopus (52) Google Scholar It has collaborated with the National Health Service to mobilize clinical genomic expertise from within the academic and health systems to quality check the evaluation of genomic data and provide feedback to physicians and patients. It has also worked with Health Education England to develop the wider genomics skill base within the health-system workforce to support widespread adoption of genomic medicine. Worldwide, many efforts and initiatives to create national implementation strategies for genomic medicine are underway; however, many of these efforts are being carried out in the absence of external collaboration, risking duplication of efforts and slowing the pace of discovery and translation.2Manolio T.A. Abramowicz M. Al-Mulla F. Anderson W. Balling R. Berger A.C. Bleyl S. Chakravarti A. Chantratita W. Chisholm R.L. et al.Global implementation of genomic medicine: We are not alone.Sci. Transl. Med. 2015; 7: 290ps13Crossref PubMed Scopus (132) Google Scholar The G2MC was established in recognition of the fact that achieving a coordinated, global collaborative effort will require an international network consisting of representatives from diverse geographies. The G2MC builds upon the work of the global organizations such as the Global Alliance for Genomics and Health (GA4GH) to promote and facilitate the coordination and development of the genomic agenda across the globe, as well as to offer guidance and resources to nations and organizations in need. As such, the G2MC strategically coordinates global genomic medicine by (1) offering an authoritative portal that governments and other organizations can use to find the expertise needed to implement genomic medicine; (2) providing a platform by which participants can share experience to contribute to the success of new programs around the world; and (3) providing an opportunity to assist less resourced nations in filling gaps in how genomic medicine is implemented. In a recent international meeting in Cape Town South Africa, G2MC members articulated a strong desire to develop and drive programs in less resourced regions of the globe to better understand their implementation challenges and to develop evidence that will drive further development. This will require that governments and healthcare providers agree on the evidentiary standards required for implementation of genomic medicine. These standards will most likely vary depending on whether genomic information would be used clinically for risk prediction, diagnosis, or treatment. A body of evidence will facilitate professional practice guidelines suitable to a specific setting or country. A framework and principles facilitating the translation of genomic tests from discovery to healthcare could be modeled on that developed by Australia’s National Health and Medical Research Council in 2015 (see Web Resources). Despite differences in healthcare delivery systems, multinational consortia have already demonstrated an ability to answer questions that few countries can tackle on their own,5Murray C.J. Ezzati M. Flaxman A.D. Lim S. Lozano R. Michaud C. Naghavi M. Salomon J.A. Shibuya K. Vos T. Lopez A.D. GBD 2010: a multi-investigator collaboration for global comparative descriptive epidemiology.Lancet. 2012; 380: 2055-2058Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar, 6Avila D. Althoff K.N. Mugglin C. Wools-Kaloustian K. Koller M. Dabis F. Nash D. Gsponer T. Sungkanuparph S. McGowan C. et al.IeDEA and ART Cohort CollaborationsImmunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries.J. Acquir. Immune Defic. Syndr. 2014; 65: e8-e16PubMed Google Scholar suggesting that the same might be true for genomic medicine. G2MC has established a Flagship Project Working Group that will focus on developing global implementation programs in pharmacogenomics and disease risk assessment. The goal of the pharmacogenomics programs is to use implementation and pragmatic clinical trial design. HIV treatment using pharmacogenomic approaches has been identified as a high priority, along with the development of data repositories of pharmacogenomic variants across ethnicities not represented in current global genomic data repositories. It was also recognized that structures are needed to encourage and enable African investigators to engage in pharmacogenomics research and clinical implementation, possibly in collaboration with the Human Heredity and Health in Africa program (H3 Africa). A second focus area identified for the G2MC is disease risk assessment. Pilot programs that would collaborate with the World Economic Forum in Rwanda on breast cancer (see Web Resources); family-based studies on colon cancer screening coupled with whole-genome sequencing in subjects with different ethnic backgrounds in South Africa and the Middle East; and the implementation of family health history software for identification of individuals, families and populations at risk for common chronic diseases are under consideration. An educated clinical workforce will be critical to effective implementation. Competencies for healthcare professionals at multiple levels within a given system will need to be defined, and appropriate educational programs will need to be developed.7Korf B.R. Berry A.B. Limson M. Marian A.J. Murray M.F. O’Rourke P.P. Passamani E.R. Relling M.V. Tooker J. Tsongalis G.J. Rodriguez L.L. Framework for development of physician competencies in genomic medicine: report of the Competencies Working Group of the Inter-Society Coordinating Committee for Physician Education in Genomics.Genet. Med. 2014; 16: 804-809Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar Integration of genomics into health professional curricula will become increasingly necessary. As materials developed in one part of the world are shared globally, translation for language and cultural appropriateness will be needed, but these efforts will be worthwhile if effective training paradigms and practices can be identified and shared rather than invented (or re-invented) de novo. Use of distance learning and other online tools will facilitate rapid implementation and global spread. G2MC has ongoing efforts through its Education Working Group to foster the education of genomics professionals. This includes collecting data on genomic professional workforce and training programs in different countries; sharing competencies, curricula, and training programs (with the Inter-Society Coordinating Committee for Practitioner Education in Genomics); exploring the use of telemedicine; and deploying new educational tools for distance learning. Given that this is an international effort, regional differences, language differences, and time-zone differences are a challenge. Recommendations to facilitate data sharing in genomic research are the subject of multiple international initiatives, particularly the Canadian-led Public Population Project in Genomics (P3G)8Knoppers B.M. Fortier I. Legault D. Burton P. The Public Population Project in Genomics (P3G): a proof of concept?.Eur. J. Hum. Genet. 2008; 16: 664-665Crossref PubMed Scopus (66) Google Scholar and the GA4GH.9Stark Z. Dolman L. Manolio T.A. Ozenberger B. Hill S.L. Caulfied M.J. Levy Y. Glazer D. Wilson J. Lawler M. et al.Integrating Genomics into Healthcare: A Global Responsibility.Am. J. Hum. Genet. 2019; 104: 13-20Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar Such efforts are relevant to the implementation of genomic medicine and, as with the evidence realm, an assessment of current activities along with a gap analysis are important initial steps. The G2MC Policy Working Group is focused on developing policy that promotes effective implementation of genomic technologies into clinical care. This includes developing approaches to harmonizing national ethical guidelines and regulatory frameworks to facilitate international collaborations, as well as developing a more complete understanding of regional genomics-relevant laws governing research, privacy, and confidentiality. This group is also examining approaches to evaluating costs, risks, and benefits of genomic interventions and to identifying conditions for which genomic tools could have the greatest effect on patient and population outcomes. Integrating economic assessments into translational research could allow determination of the utility of genomic interventions, and the relative value of such interventions can be assessed so that health care decision-makers can be informed. Expanding single-country studies of cost-effectiveness to multiple healthcare systems might help to identify key structural components that promote favorable cost-benefit ratios. Multinational collaborations could be particularly valuable for examining different systems and models, such as those with one or a few centralized payers, and can thus provide a more unified and systematic examination of the decision-making process. A G2MC resource developed to assist with these activities can be found online (see Web Resources). The G2MC, despite its highly collaborative platform, cannot advance the field on its own. Cooperation and partnership with international organizations, governments, and ministries of health are required. In Cape Town, South Africa this past November more than 125 scientists from 26 countries resolved to call upon governments, intergovernmental agencies, and international development partners (1) to recognize the importance of implementation of evidence-based genomic medicine as an integral part of healthcare, while addressing cross-cutting and country context ethical, legal, and social issues; (2) to establish workforce norms and the development of human-resources capacity to enable the implementation of genomic medicine; (3) to promote genomic-medicine education at all levels (undergraduate, postgraduate, and continuing professional development of medical, other healthcare, scientific, and biomedical informatics professionals) to prepare the workforce of the future; (4) to raise awareness of and trust in genomic medicine among the general public; (5) to promote research and development for low-cost, highly effective genomic-medicine technologies to accelerate its adoption in low- and middle-income countries; and (6) to obtain deeper knowledge of underlying genetic variation in diverse populations worldwide to enhance the use of genomic data for population-specific genomic health programs. An Advocacy Working Group is being established to bring these principles to governments, policy makers, and ministries of health worldwide. The G2MC and its international partners are at the beginning of an era of data sharing, policy development, standardization, and education about the use of genome-based technology to maintain health and treat disease. Efforts to coalesce the global community to collaborate on generating and assessing evidence about the impact of genomic medicine, and on disseminating best practices for effective implementation, will enhance the use of genomics to improve clinical care worldwide. The invitation is open for anyone to join these endeavors, allowing them to expand their reach and impact. G.G. is the founder and president of the G2MC and a member of its Board of Directors. The development, growth, and early successes of the G2MC are attributed to the many extraordinary contributions from the members its Executive Committee (Catalina Lopez-Correa [Canada], Vajira H.W. Dissanayake [Sri Lanka], Geoffrey Ginsburg [USA], Teri Manolio [USA], George Patrinos [Greece], Alan Shuldiner [USA], and Robyn Ward [Australia]) and its associated Steering Committee (Marc Abramowicz [Belgium], Fahd Al-Mulla [Kuwait], Wasun Chantratita [Thailand], Peter Goodhand [Canada], Bruce Korf [USA], Hideyasu Kiyomoto [Japan], Michael Kubo [Japan], Teji Rakhra-Burris [USA], Gadi Rennert [Israel], Gabriela Repetto [Chile], John Wong [Singapore], Ambroise Wonkam [South Africa], and Grant Wood [USA]). The sponsors who have contributed to the G2MC’s mission are also gratefully acknowledged (https://g2mc.org/about-us/our-sponsors-and-funders/). GWAS catalog, https://www.ebi.ac.uk/gwas/G2MC, https://g2mc.org/GA4GH, https://www.ga4gh.org/H3 Africa, https://h3africa.org/National Health and Medical Research Council of Australia Principles for the translation of ‘omics ’-based tests from discovery to health care, https://nhmrc.gov.au/about-us/publications/principles-translation-omics-based-testsWorld Economic Forum in Rwanda on breast cancer, https://www.weforum.org/projects/leapfrogging-with-precision-medicineInter-Society Coordinating Committee for Practitioner Education in Genomics, https://www.genome.gov/27554614/intersociety-coordinating-committee-for-practitioner-education-in-genomics-iscc/G2MC Policy Resource, https://www.genomicspolicy.org/
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