Portal de Periódicos da CAPES

The undiscovered country: the future of integrating genomic information into the EHR

2013; Elsevier BV; Volume: 15; Issue: 10 Linguagem: Inglês

10.1038/gim.2013.130

1530-0366

Joseph Kannry, Marc S. Williams,

Genomics and Rare Diseases

The articles in this special issue take advantage of the research and experience of the Electronic Medical Records and Genomics (eMERGE) Network and are designed to provide operational and academic leaders with a “getting started” guide for integrating genomic information into the electronic health record (EHR). As noted in the article by Gottesman et al.,1.Gottesman O. Kuivaniemi H. Tromp G. The Electronic Medical Records and Genomics (eMERGE) Network: past, present and future..10.1038/gim.2013.72Genet Med. 2013; 15: 761-771Google Scholar the eMERGE network has been actively researching issues that shed light on the integration of genomic information into the EHR. However, as the authors in this special issue have indicated, many questions and challenges remain. We have completed mapping of terra incognita and have now arrived at the shores of the undiscovered country. Additional discussion, education, and research need to occur in order to determine the placement and role of genomic results in the EHR. One challenge is that guidelines for the interpretation and use of genomic results in clinical care need to be established. In addition, provider education on the interpretation and value of genomic results in clinical care is sorely needed. Previously, germline genetic results were the province of geneticists and involved extensive counseling, whereas genomic results, which have the potential to impact care in multiple specialties, involve providers who are not geneticists. How much education is then required? Enough to interpret results and, if necessary, facilitate referral to experts for further evaluation of the test and treatment such as an echocardiogram and cardiology, or more like lab test results for which providers know what the result is and are given reference ranges that guide action on it? There is the added wrinkle of direct-to-consumer (DTC) testing, which will require additional provider understanding and education.2.Powell K.P. Christianson C.A. Cogswell W.A. Educational needs of primary care physicians regarding direct-to-consumer genetic testing..10.1007/s10897-011-9471-9J Genet Couns. 2012; 21: 469-478Google Scholar As Hartzler et al.3.Hartzler A. McCarty C.A. Rasmussen L.V. Stakeholder engagement: a key component of integrating genomic information into electronic health records..10.1038/gim.2013.127Genet Med. 2013; 15: 792-801Google Scholar noted in their article, there are many discussions that need to take place among the various stakeholders. The complex ethical issues among the stakeholders were well covered by Hazin et al.4.Hazin R. Brothers K.B. Malin B.A. Ethical, legal and social implications of incorporating genomic information into electronic health records..10.1038/gim.2013.117Genet Med. 2013; 15: 810-816Google Scholar Hartzler et al.3.Hartzler A. McCarty C.A. Rasmussen L.V. Stakeholder engagement: a key component of integrating genomic information into electronic health records..10.1038/gim.2013.127Genet Med. 2013; 15: 792-801Google Scholar also touched upon genomic results being available in personal health records (PHRs) or patient portals. Will genomic information obtained at medical centers be available in the PHR? Test results in PHRs can either be manually released, in which case the provider must release the result to the patient, or autoreleased, in which case the result is automatically sent to the patient after a fixed interval of time. Most sites have found that autorelease of lab test results is well accepted by patients and does not generate excessive phone calls or PHR messages.5.Kannry J. Beuria P. Wang E. Nissim J. Personal health records: meaningful use, but for whom?.10.1002/msj.21334Mt Sinai J Med. 2012; 79: 593-602Google Scholar The underlying assumption is that the patient will ask questions and/or the provider will contact the patient to discuss any abnormal results. Can the same approach for release of lab results in the PHR be used for genomic results? Are genomic results more equivalent to sensitive tests such as that for HIV? In New York State, HIV test results require counseling, which precludes autorelease. Current standards for the reporting of single-gene test results recommend genetic counseling,6.Japan Society of Human genetics, Council Committee of Ethics Guidelines for genetic testing. The Japan Society of Human Genetics, Council Committee of Ethics..1:STN:280:DC%2BD3M3hslChtQ%3D%3D10.1007/s100380170107J Hum Genet. 2001; 46: 163-165Google Scholar and certain extremely sensitive test results such as presymptomatic testing for Alzheimer or Huntington diseases require extensive pre- and posttest counseling.7.American College of Medical Genetics and the National Society of Genetic Counselors Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors..10.1097/GIM.0b013e31821d69b8Genet Med. 2011; 13: 597-605Google Scholar,8.Craufurd D. Tyler A. Predictive testing for Huntington’s disease: protocol of the UK Huntington’s Prediction Consortium..1:STN:280:DyaK3s7isVCrug%3D%3D10.1136/jmg.29.12.915J Med Genet. 1992; 29: 915-918Google Scholar Alternatively, are genomic results more akin to radiology results, which many centers are wrestling with given that the reports are written for providers and are not easily interpretable by the lay public? These reports also include incidental findings that may or may not have been discussed with the patient by the ordering clinician. Radiology results and pathology results are not routinely autoreleased at many sites,5.Kannry J. Beuria P. Wang E. Nissim J. Personal health records: meaningful use, but for whom?.10.1002/msj.21334Mt Sinai J Med. 2012; 79: 593-602Google Scholar although one of the authors (M.S.W.) notes that radiology reports as well as patient-controlled image downloads are now available at Geisinger Health System. It is difficult to prognosticate how much direct access to genomic test results patients will have because of two developments. Unlike the diagnostic testing discussed above, (i.e., laboratory, imaging, and pathology) patients can order and view their own results through DTC genomic testing. How DTC testing will interact with provider-ordered testing, viewable in the PHR, is unclear. It also remains an open question of whether or not there will be widespread uptake of DTC genomic testing. Nevertheless, companies involved in the DTC space have developed innovative ways to represent genomic test results that have been shown to be comprehensible and accessible to consumers.9.Kaufman D.J. Bollinger J.M. Dvoskin R.L. Scott J.A. Risky business: risk perception and the use of medical services among customers of DTC personal genetic testing..10.1007/s10897-012-9483-0J Genet Couns. 2012; 21: 413-422Google Scholar,10.Vayena E. Gourna E. Streuli J. Hafen E. Prainsack B. Experiences of early users of direct-to-consumer genomics in Switzerland: an exploratory study..1:STN:280:DC%2BC3s7js1aktA%3D%3D10.1159/000343792Public Health Genomics. 2012; 15: 352-362Google Scholar These methods may be instructional to PHR designers. The appropriately named Open Notes research project, is releasing all progress notes to the patient, and the initial results are encouraging.11.Delbanco T. Walker J. Bell S.K. Inviting patients to read their doctors’ notes: a quasi-experimental study and a look ahead..10.7326/0003-4819-157-7-201210020-00002Ann Intern Med. 2012; 157: 461-470Google Scholar This would make any discussion of which test results to autorelease in the PHR potentially moot as progress notes may contain test interpretations by providers. It remains unclear which diagnostic tests genomic results are most analogous to in terms of provider reporting and interpretation.12.McGuire A.L. Cho M.K. McGuire S.E. Caulfield T. Medicine. The future of personal genomics..1:CAS:528:DC%2BD2sXhtV2ksrjL10.1126/science.1147475Science. 2007; 317: 1687Google Scholar,13.Starren J. Williams M.S. Bottinger E.P. Crossing the omic chasm: a time for omic ancillary systems..1:CAS:528:DC%2BC3sXlvFSgs70%3D10.1001/jama.2013.1579JAMA. 2013; 309: 1237-1238Google Scholar Articles in this issue have discussed delivering the raw data, the result, and the interpretation. Genomic education of both providers and patients remains a pressing need because results and interpretation of results may be confusing or meaningless to many providers14.Nickola T.J. Green J.S. Harralson A.F. O’Brien T.J. The current and future state of pharmacogenomics medical education in the USA..1:CAS:528:DC%2BC38Xhtlanu7zK10.2217/pgs.12.113Pharmacogenomics. 2012; 13: 1419-1425Google Scholar,15.Bonter K. Desjardins C. Currier N. Pun J. Ashbury F.D. Personalised medicine in Canada: a survey of adoption and practice in oncology, cardiology and family medicine..10.1136/bmjopen-2011-000110BMJ Open. 2011; 1: e000110Google Scholar,16.Babyatsky M. Giovanni M. Murray M. Clinical Genomics: Practical Applications in Adult Patient Care. McGraw Hill, 2013Google Scholar,17.Liaw S.T. Genetics and genomics in general practice..20877778Aust Fam Physician. 2010; 39: 689-691Google Scholar,18.Gullapalli R.R. Desai K.V. Santana-Santos L. Kant J.A. Becich M.J. Next generation sequencing in clinical medicine: Challenges and lessons for pathology and biomedical informatics..10.4103/2153-3539.103013J Pathol Inform. 2012; 3: 40Google Scholar as well as to most patients.19.Brewer N.T. Tzeng J.P. Lillie S.E. Edwards A.S. Peppercorn J.M. Rimer B.K. Health literacy and cancer risk perception: implications for genomic risk communication..10.1177/0272989X08327111Med Decis Making. 2009; 29: 157-166Google Scholar To date, other than the specialty of genetics and the need for counseling, few providers seem to want to see the raw genomic data, let alone have the means to understand it.20.Manolio T.A. Chisholm R.L. Ozenberger B. Implementing genomic medicine in the clinic: the future is here..10.1038/gim.2012.157Genet Med. 2013; 15: 258-267Google Scholar As in the setting of other complex tests, most providers want interpreted reports, although, as noted earlier, challenges remain with education. Laboratory tests are generally stored in EHRs as discrete, interpreted results. The raw data are not presented, as health-care providers do not want to read spectrograms to determine the patient’s electrolyte levels. By contrast, imaging presents the raw data, images, and interpretation to EHR users. Imaging uses links to a picture archival communication system and the interpretation is stored as a text blob. In the case of imaging, specialists prefer reading their own imaging with assistance available as needed from, for example, radiologists. Pathology is somewhere in between in that the interpreted free text reports are always stored in an EHR, but viewing pathology specimens requires going to the pathology department to view them. Like pathology results, genomic test results are returned as unstructured text. The near future evolution of pathology reporting may be a guide to what could happen to genomic test reports. To improve the utility of the reports, the College of American Pathologists has recommended the use of synoptic reporting for certain cancers.21.Hassell L. Aldinger W. Moody C. Electronic capture and communication of synoptic cancer data elements from pathology reports: results of the Reporting Pathology Protocols 2 (RPP2) project..J Registry Manag Winter. 2009; 36: 117-124PubMed Google Scholar,22.Baskovich B.W. Allan R.W. Web-based synoptic reporting for cancer checklists..215725043073063J Pathol Inform. 2011; 2: 16Google Scholar Synoptic reporting incorporates free text into a structured format that allows for the data to be represented also as discrete elements. This concept has been expanded to create documents that are both human and machine readable through the use of clinical document architecture (CDA). In their 2006 article, Dolin et al.23.Dolin R.H. Alschuler L. Boyer S. HL7 Clinical Document Architecture, Release 2..10.1197/jamia.M1888J Am Med Inform Assoc. 2006; 13: 30-39Google Scholar state, “CDA is a … standard that specifies the structure and semantics of a clinical document … for the purpose of exchange. A CDA document is a defined and complete information object that can include text, images, sounds, and other multimedia content. It can be transferred within a message and can exist independently, outside the transferring message.”23.Dolin R.H. Alschuler L. Boyer S. HL7 Clinical Document Architecture, Release 2..10.1197/jamia.M1888J Am Med Inform Assoc. 2006; 13: 30-39Google Scholar Some have suggested that CDA documents could be used for genetic and genomic test reporting, and the Health Level Seven clinical genomics workgroup has created a CDA implementation guide for genetic testing reports.24.Groups HCGaSDW. CDA Implementation Guide: Genetic Testing Report (GTR), 2013. http://www.hl7.org/documentcenter/public_temp_20DA1AE7-1C23-BA17-0CCEBE0F4D95D6A8/wg/clingenomics/presentations/CDA%20IG%20for%20Genetic%20Testing%20Report%20-%20May%202013%20-%20Shabo.pdfAccessed 16 July 2013.Google Scholar This prototype is now available for testing, and the model is being extended to support genomic data. Chute et al.25.Chute C.G. Ullman-Cullere M. Wood G. Lin S.M. He M. Pathak J. Some experiences and opportunities for big data in translational research..10.1038/gim.2013.121Genet Med. 2013; 15: 802-809Google Scholar discuss this in more detail. Is this the solution to the reporting conundrum? Overby’s26.Overby C.L. Kohane I. Kannry J.L. Opportunities for genomic clinical decision support interventions..10.1038/gim.2013.128Genet Med. 2013; 15: 817-823Google Scholar and Marsolo’s27.Marsolo K. Spooner S.A. Clinical genomics in the world of the electronic health record..10.1038/gim.2013.88Genet Med. 2013; 15: 786-791Google Scholar articles address the use of clinical decision support (CDS) to facilitate the use of genomic information in health care as well as the current state of CDS in eMERGE sites. Many sites have focused their CDS work on pharmacogenomics, which provides prescribing recommendations based on genomics and for which there are published guidelines.28.PharmaGKb CPICC. CPIC Gene-Drug Pairs. http://www.pharmgkb.org/page/cpicGeneDrugPairs. Accessed 2 July 2013.Google Scholar Use of this information has become increasingly routine. For clopidogrel, the Food and Drug Administration has a black box warning that recommends genomic testing be considered as “an aid for determining therapeutic strategy.”29.US Food and Drug Administration. Black Box Warning for Plavix, 2010. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020839s042lbl.pdf. Accessed 11 July 2013.Google Scholar,30.Goswami S. Cheng-Lai A. Nawarskas J. Clopidogrel and genetic testing: is it necessary for everyone?.22293861Cardiol Rev. 2012; 20: 96-100Google Scholar,31.Kim K.M. Murray M.D. Tu W. Pharmacogenetics and healthcare outcomes in patients with chronic heart failure..1:CAS:528:DC%2BC38XhsVyiu7fN10.1007/s00228-012-1280-zEur J Clin Pharmacol. 2012; 68: 1483-1491Google Scholar,32.Mette L. Mitropoulos K. Vozikis A. Patrinos G.P. Pharmacogenomics and public health: implementing ‘populationalized’ medicine..1:CAS:528:DC%2BC38XntFynsr0%3D10.2217/pgs.12.52Pharmacogenomics. 2012; 13: 803-813Google Scholar,33.Bartlett M.J. Green D.W. Shephard E.A. Pharmacogenetic testing in the UK clinical setting..10.1016/S0140-6736(13)61160-5Lancet. 2013; 381: 1903Google Scholar,34.Turner R.M. From the lab to the prescription pad: genetics, CYP450 analysis, and medication response..10.1111/jcap.12028J Child Adolesc Psychiatr Nurs. 2013; 26: 119-123Google Scholar For abacavir, the Food and Drug Administration has a black box warning requiring HLAB*5701 testing.35.US Food and Drug Administration. Ziagen (abacavir) Safety Warning, 2008. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm079913.htm. Accessed 11 July 2013.Google Scholar Denny’s36.Peterson J.F. Bowton E. Field J.R. Electronic health record design and implementation for pharmacogenomics: a local perspective..10.1038/gim.2013.109Genet Med. 2013; 15: 833-841Google Scholar article in this special issue describes pharmacogenomics in an internally developed EHR. Besides clinical utility and focused use, CDS for pharmacogenomics has one other advantage, which is the use of structured data: drug information such as name and dose. Use of structured data also lends itself to capture of outcomes data, which is critical to the development of robust evidence of utility. CDS will require actionable discrete data that can be stored and represented in the EHR.13.Starren J. Williams M.S. Bottinger E.P. Crossing the omic chasm: a time for omic ancillary systems..1:CAS:528:DC%2BC3sXlvFSgs70%3D10.1001/jama.2013.1579JAMA. 2013; 309: 1237-1238Google Scholar Articles in this issue and others have noted that representation and storage of genomic information in the EHR has remained challenging because most commercial EHRs are not up to the task. Although the data need to be stored in a structured form, the article by Kho et al.37.Kho A.N. Rasmussen L.V. Connolly J.J. Practical challenges integrating genomic data into the electronic health record..10.1038/gim.2013.131Genet Med. 2013; 15: 772-778Google Scholar summarizes where we are today with the storage of discrete phenotypic data that can be linked to genomic data, which is equally important to CDS. The article by Tarczy-Hornoch et al.38.Tarczy-Hornoch P. Amendola L. Aronson S.J. A survey of informatics approaches to whole-exome and whole-genome clinical reporting in the electronic health record..10.1038/gim.2013.120Genet Med. 2013; 15: 824-832Google Scholar highlights the needs for standard representation in test results in addition to CDS. Even when sites used the same sequencing technology and commercial EHR, customized solutions were required at each site. As Chute et al.25.Chute C.G. Ullman-Cullere M. Wood G. Lin S.M. He M. Pathak J. Some experiences and opportunities for big data in translational research..10.1038/gim.2013.121Genet Med. 2013; 15: 802-809Google Scholar note, the standards to make this happen are still evolving, and as a result commercial EHR vendors have been slow to incorporate genomic results. By its very nature, CDS depends on a knowledge base and rules engine.39.Wright A. Sittig D.F. A framework and model for evaluating clinical decision support architectures..10.1016/j.jbi.2008.03.009J Biomed Inform. 2008; 41: 982-990Google Scholar,40.Kannry J. Ong K.R. Computerized physician order entry and patient safety: Panacea or Pandora’s Box?.Medical Informatics: An Executive Primer. HIMSS, 2007: xviii, 316Google Scholar This makes CDS challenging for genomic test results in that both the knowledge and the rules around this knowledge are rapidly changing.41.Evans J.P. Khoury M.J. The arrival of genomic medicine to the clinic is only the beginning of the journey..10.1038/gim.2012.133Genet Med. 2013; 15: 268-269Google Scholar As a result, both the knowledge base and the rules engine require frequent and rapid revisions. Ury,42.Ury A. Storing and interpreting genomic information in widely deployed electronic health record systems..10.1038/gim.2013.111Genet Med. 2013; 15: 779-785Google Scholar in his article, explores this problem. It is the long-held belief of the authors that interpreted results residing in the EHR, the CDS rules, and the knowledge itself will need to be “versioned.” This article defines the term “versioning” as the creation of a standardized and systematic methodology for dating and numbering the rules and knowledge in a consistent way, as well as systematically recording changes in content. Older versions of the CDS rules and knowledge would be archived indefinitely in a yet to be developed knowledge maintenance schema. Without versioning, it will be impossible to tell why possibly contradictory actions were taken on what seems to be the same genomic results at different times. Versioning would tie the decision to the knowledge available to the clinician at that specific point in time, which is critical for liability and quality improvement purposes. Because challenges remain for storing genomic results in an EHR as discrete data, as well as the need to rapidly update the knowledge base and the decision rules, several sites have begun developing external CDS. In external CDS, the knowledge base and rules engine reside outside of the EHR. This methodology has begun to be used to help standardize knowledge and implementation of rules across multiple sites39.Wright A. Sittig D.F. A framework and model for evaluating clinical decision support architectures..10.1016/j.jbi.2008.03.009J Biomed Inform. 2008; 41: 982-990Google Scholar,43.Wright A. Sittig D.F. A four-phase model of the evolution of clinical decision support architectures..10.1016/j.ijmedinf.2008.01.004Int J Med Inform. 2008; 77: 641-649Google Scholar and has the potential to accelerate implementation. Efforts to facilitate the adaptation of external CDS have focused on producing agnostic extensible CDS that could be shared by multiple sites.44.Kawamoto K. Del Fiol G. Orton C. Lobach D.F. System-agnostic clinical decision support services: benefits and challenges for scalable decision support..10.2174/1874431101004010245Open Med Inform J. 2010; 4: 245-254Google Scholar,45.Hongsermeier T. Maviglia S. Tsurikova L. A legal framework to enable sharing of Clinical Decision Support knowledge and services across institutional boundaries..221951513243291AMIA Annu Symp Proc. 2011; 2011: 925-933Google Scholar The challenge with external CDS for genomic results is to make the genomic CDS actionable. Without standards, many sites are challenged with presenting little more than recommendations at the point of care that ask the user to consider the information and take action if the user feels appropriate. The approach of presenting CDS as FYI (For Your Information) is not desirable, as David Bates and others have noted.46.Bates D.W. Kuperman G.J. Wang S. Ten commandments for effective clinical decision support: making the practice of evidence-based medicine a reality..10.1197/jamia.M1370J Am Med Inform Assoc. 2003; 10: 523-530Google Scholar Chute et al.’s25.Chute C.G. Ullman-Cullere M. Wood G. Lin S.M. He M. Pathak J. Some experiences and opportunities for big data in translational research..10.1038/gim.2013.121Genet Med. 2013; 15: 802-809Google Scholar article calls attention to the need for standard representation and notes that taxonomy and development of these standards as well as others might solve this conundrum. It is the belief of the authors that within the next few years we will see researchers develop external CDS capable of generating messages that trigger specific actionable items in a commercial EHR. Until standard representation of genomic results occurs, widespread adaptation of CDS by commercial EHRs will continue to be challenging regardless of value propositions by providers and patients. CDS for genomic testing will also have to address issues of confidentiality and privacy. In contrast to other forms of diagnostic testing (i.e., laboratory, imaging, pathology), genomic testing is somewhat unique regarding its privacy and confidentiality issues.17.Liaw S.T. Genetics and genomics in general practice..20877778Aust Fam Physician. 2010; 39: 689-691Google Scholar,47.McGuire A.L. Fisher R. Cusenza P. Confidentiality, privacy, and security of genetic and genomic test information in electronic health records: points to consider..10.1097/GIM.0b013e31817a8aaaGenet Med. 2008; 10: 495-499Google Scholar There remains significant concern about the impact of genomic test results on a patient’s health insurance and perhaps even employment,48.Allain D.C. Friedman S. Senter L. Consumer awareness and attitudes about insurance discrimination post enactment of the Genetic Information Nondiscrimination Act..10.1007/s10689-012-9564-0Fam Cancer. 2012; 11: 637-644Google Scholar despite the passage of the Genetic Information and Nondiscrimination Act.49.Clifton J.M. VanBeuge S.S. Mladenka C. Wosnik K.K. The Genetic Information Nondiscrimination Act 2008: What clinicians should understand..10.1111/j.1745-7599.2010.00504.xJ Am Acad Nurse Pract. 2010; 22: 246-249Google Scholar,50.Feldman E.A. The Genetic Information Nondiscrimination Act (GINA): public policy and medical practice in the age of personalized medicine..10.1007/s11606-012-1988-6J Gen Intern Med. 2012; 27: 743-746Google Scholar Although both Hartzler3.Hartzler A. McCarty C.A. Rasmussen L.V. Stakeholder engagement: a key component of integrating genomic information into electronic health records..10.1038/gim.2013.127Genet Med. 2013; 15: 792-801Google Scholar and Hazin4.Hazin R. Brothers K.B. Malin B.A. Ethical, legal and social implications of incorporating genomic information into electronic health records..10.1038/gim.2013.117Genet Med. 2013; 15: 810-816Google Scholar address this, much still needs to be discussed and done. The age of whole-genome sequencing is rapidly approaching, and patients will be presented with results that they neither want nor understand and which providers struggle to interpret.20.Manolio T.A. Chisholm R.L. Ozenberger B. Implementing genomic medicine in the clinic: the future is here..10.1038/gim.2012.157Genet Med. 2013; 15: 258-267Google Scholar,51.Ginsburg G.S. Willard H.F. Genomic and personalized medicine: foundations and applications..10.1016/j.trsl.2009.09.005Transl Res. 2009; 154: 277-287Google Scholar Unless we provide a secure and trustworthy environment for the storage of genomic information and combine this with public policies that protect against the misuse of this information, there will be concern about the routine use of this information for health care, even when it has been shown to improve outcomes. In conclusion, we have completed an initial mapping of terra incognita with this special issue summarizing the knowledge, experience, and wisdom of eMERGE consortium members. Although much has been learned, many questions remain. A concerted and collaborative effort involving all groups working on these daunting problems will help to generate solutions that will allow genomics to move into clinical care. We have arrived on the shores of the future, the undiscovered country, and although much remains to be resolved, the future looks so bright we ought to be wearing shades. The authors declare no conflict of interest.