RESUMEN
Structured representation of clinical genetic results is necessary for advancing precision medicine. The Electronic Medical Records and Genomics (eMERGE) Network's Phase III program initially used a commercially developed XML message format for standardized and structured representation of genetic results for electronic health record (EHR) integration. In a desire to move towards a standard representation, the network created a new standardized format based upon Health Level Seven Fast Healthcare Interoperability Resources (HL7® FHIR®), to represent clinical genomics results. These new standards improve the utility of HL7® FHIR® as an international healthcare interoperability standard for management of genetic data from patients. This work advances the establishment of standards that are being designed for broad adoption in the current health information technology landscape.
Asunto(s)
Registros Electrónicos de Salud , Informática Médica , Genómica , Estándar HL7 , Humanos , Medicina de PrecisiónRESUMEN
BACKGROUND: Implementing clinical phenotypes across a network is labor intensive and potentially error prone. Use of a common data model may facilitate the process. METHODS: Electronic Medical Records and Genomics (eMERGE) sites implemented the Observational Health Data Sciences and Informatics (OHDSI) Observational Medical Outcomes Partnership (OMOP) Common Data Model across their electronic health record (EHR)-linked DNA biobanks. Two previously implemented eMERGE phenotypes were converted to OMOP and implemented across the network. RESULTS: It was feasible to implement the common data model across sites, with laboratory data producing the greatest challenge due to local encoding. Sites were then able to execute the OMOP phenotype in less than one day, as opposed to weeks of effort to manually implement an eMERGE phenotype in their bespoke research EHR databases. Of the sites that could compare the current OMOP phenotype implementation with the original eMERGE phenotype implementation, specific agreement ranged from 100% to 43%, with disagreements due to the original phenotype, the OMOP phenotype, changes in data, and issues in the databases. Using the OMOP query as a standard comparison revealed differences in the original implementations despite starting from the same definitions, code lists, flowcharts, and pseudocode. CONCLUSION: Using a common data model can dramatically speed phenotype implementation at the cost of having to populate that data model, though this will produce a net benefit as the number of phenotype implementations increases. Inconsistencies among the implementations of the original queries point to a potential benefit of using a common data model so that actual phenotype code and logic can be shared, mitigating human error in reinterpretation of a narrative phenotype definition.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/diagnóstico , Registros Electrónicos de Salud , Recolección de Datos , Humanos , Informática Médica , National Human Genome Research Institute (U.S.) , Estudios Observacionales como Asunto , Evaluación de Resultado en la Atención de Salud , Fenotipo , Proyectos de Investigación , Programas Informáticos , Estados UnidosRESUMEN
BACKGROUND: Implementation of phenotype algorithms requires phenotype engineers to interpret human-readable algorithms and translate the description (text and flowcharts) into computable phenotypes - a process that can be labor intensive and error prone. To address the critical need for reducing the implementation efforts, it is important to develop portable algorithms. METHODS: We conducted a retrospective analysis of phenotype algorithms developed in the Electronic Medical Records and Genomics (eMERGE) network and identified common customization tasks required for implementation. A novel scoring system was developed to quantify portability from three aspects: Knowledge conversion, clause Interpretation, and Programming (KIP). Tasks were grouped into twenty representative categories. Experienced phenotype engineers were asked to estimate the average time spent on each category and evaluate time saving enabled by a common data model (CDM), specifically the Observational Medical Outcomes Partnership (OMOP) model, for each category. RESULTS: A total of 485 distinct clauses (phenotype criteria) were identified from 55 phenotype algorithms, corresponding to 1153 customization tasks. In addition to 25 non-phenotype-specific tasks, 46 tasks are related to interpretation, 613 tasks are related to knowledge conversion, and 469 tasks are related to programming. A score between 0 and 2 (0 for easy, 1 for moderate, and 2 for difficult portability) is assigned for each aspect, yielding a total KIP score range of 0 to 6. The average clause-wise KIP score to reflect portability is 1.37⯱â¯1.38. Specifically, the average knowledge (K) score is 0.64⯱â¯0.66, interpretation (I) score is 0.33⯱â¯0.55, and programming (P) score is 0.40⯱â¯0.64. 5% of the categories can be completed within one hour (median). 70% of the categories take from days to months to complete. The OMOP model can assist with vocabulary mapping tasks. CONCLUSION: This study presents firsthand knowledge of the substantial implementation efforts in phenotyping and introduces a novel metric (KIP) to measure portability of phenotype algorithms for quantifying such efforts across the eMERGE Network. Phenotype developers are encouraged to analyze and optimize the portability in regards to knowledge, interpretation and programming. CDMs can be used to improve the portability for some 'knowledge-oriented' tasks.
Asunto(s)
Registros Electrónicos de Salud/clasificación , Informática Médica/métodos , Algoritmos , Genómica , Humanos , Fenotipo , Estudios RetrospectivosRESUMEN
BACKGROUND: To improve the site selection process for clinical trials, we expanded a site survey to include standardized assessments of site commitment time, team experience, feasibility of tight timelines, and local medical community equipoise as factors that might better predict performance. We also collected contact information about institutional research services ahead of site onboarding. AIM: As a first step, we wanted to confirm that an expanded survey could be feasible and generalizable-that asking site teams for more details upfront was acceptable and that the survey could be completed in a reasonable amount of time, despite the assessment length. METHODS: A standardized, two-part Site Assessment Survey Instrument (SASI), examining qualitative components and with multiple contact list sections, was developed using a publicly accessible dashboard and later transferred to a REDCap platform. After multiple rounds of internal testing, the SASI was deployed 11 times for multicenter trials. Follow-up questionnaires were sent to site teams to confirm that an expanded survey instrument is acceptable to the research community and could be completed during a brief work shift. RESULTS: Respondents thought the SASI collected useful and relevant information about their sites (100%). Sites were "comfortable" (90%) supplying detailed information early in the site selection process and 57% completed the SASI in one to two hours. CONCLUSIONS: Coordinating centers and sites found the SASI tool to be acceptable and helpful when collecting data in consideration of multicenter trial site selection.
Asunto(s)
Ensayos Clínicos como Asunto , Humanos , Encuestas y Cuestionarios/normas , Ensayos Clínicos como Asunto/normas , Ensayos Clínicos como Asunto/métodos , Ensayos Clínicos como Asunto/organización & administración , Estudios Multicéntricos como Asunto/métodos , Estudios Multicéntricos como Asunto/normasRESUMEN
OBJECTIVE: Data from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups. RESULTS: Precise SNP tracking showed no sample swap errors within the clinical testing laboratories. In contrast, when comparing predicted sex-by-genotype to the provided sex on the test requisition, we identified 110 inconsistencies from 25,015 clinical samples (0.44%), that had occurred during sample collection or accessioning. The genetic sex predictions were confirmed using additional SNP sites in the sequencing data or high-density genotyping arrays. It was determined that discrepancies resulted from clerical errors (49.09%), samples from transgender participants (3.64%) and stem cell or bone marrow transplant patients (7.27%) along with undetermined sample mix-ups (40%) for which sample swaps occurred prior to arrival at genome centers, however the exact cause of the events at the sampling sites resulting in the mix-ups were not able to be determined.
Asunto(s)
Servicios de Laboratorio Clínico , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Trasplante de Médula Ósea , Genotipo , LaboratoriosRESUMEN
In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.
RESUMEN
Objective: Data from DNA genotyping via a 96-SNP panel in a study of 25,015 clinical samples were utilized for quality control and tracking of sample identity in a clinical sequencing network. The study aimed to demonstrate the value of both the precise SNP tracking and the utility of the panel for predicting the sex-by-genotype of the participants, to identify possible sample mix-ups. Results: Precise SNP tracking showed no sample swap errors within the clinical testing laboratories. In contrast, when comparing predicted sex-by-genotype to the provided sex on the test requisition, we identified 110 inconsistencies from 25,015 clinical samples (0.44%), that had occurred during sample collection or accessioning. The genetic sex predictions were confirmed using additional SNP sites in the sequencing data or high-density genotyping arrays. It was determined that discrepancies resulted from clerical errors, samples from transgender participants and stem cell or bone marrow transplant patients along with undetermined sample mix-ups.
RESUMEN
The electronic Medical Records and Genomics (eMERGE) Network assessed the feasibility of deploying portable phenotype rule-based algorithms with natural language processing (NLP) components added to improve performance of existing algorithms using electronic health records (EHRs). Based on scientific merit and predicted difficulty, eMERGE selected six existing phenotypes to enhance with NLP. We assessed performance, portability, and ease of use. We summarized lessons learned by: (1) challenges; (2) best practices to address challenges based on existing evidence and/or eMERGE experience; and (3) opportunities for future research. Adding NLP resulted in improved, or the same, precision and/or recall for all but one algorithm. Portability, phenotyping workflow/process, and technology were major themes. With NLP, development and validation took longer. Besides portability of NLP technology and algorithm replicability, factors to ensure success include privacy protection, technical infrastructure setup, intellectual property agreement, and efficient communication. Workflow improvements can improve communication and reduce implementation time. NLP performance varied mainly due to clinical document heterogeneity; therefore, we suggest using semi-structured notes, comprehensive documentation, and customization options. NLP portability is possible with improved phenotype algorithm performance, but careful planning and architecture of the algorithms is essential to support local customizations.
Asunto(s)
Registros Electrónicos de Salud , Procesamiento de Lenguaje Natural , Genómica , Algoritmos , FenotipoRESUMEN
OBJECTIVE: The Genomic Medicine Working Group of the National Advisory Council for Human Genome Research virtually hosted its 13th genomic medicine meeting titled "Developing a Clinical Genomic Informatics Research Agenda". The meeting's goal was to articulate a research strategy to develop Genomics-based Clinical Informatics Tools and Resources (GCIT) to improve the detection, treatment, and reporting of genetic disorders in clinical settings. MATERIALS AND METHODS: Experts from government agencies, the private sector, and academia in genomic medicine and clinical informatics were invited to address the meeting's goals. Invitees were also asked to complete a survey to assess important considerations needed to develop a genomic-based clinical informatics research strategy. RESULTS: Outcomes from the meeting included identifying short-term research needs, such as designing and implementing standards-based interfaces between laboratory information systems and electronic health records, as well as long-term projects, such as identifying and addressing barriers related to the establishment and implementation of genomic data exchange systems that, in turn, the research community could help address. DISCUSSION: Discussions centered on identifying gaps and barriers that impede the use of GCIT in genomic medicine. Emergent themes from the meeting included developing an implementation science framework, defining a value proposition for all stakeholders, fostering engagement with patients and partners to develop applications under patient control, promoting the use of relevant clinical workflows in research, and lowering related barriers to regulatory processes. Another key theme was recognizing pervasive biases in data and information systems, algorithms, access, value, and knowledge repositories and identifying ways to resolve them.
Asunto(s)
Informática Médica , Registros Electrónicos de Salud , Genoma Humano , Genómica , Humanos , Proyectos de InvestigaciónRESUMEN
Genome-wide association studies (GWASs) have enabled robust mapping of complex traits in humans. The open sharing of GWAS summary statistics (SumStats) is essential in facilitating the larger meta-analyses needed for increased power in resolving the genetic basis of disease. However, most GWAS SumStats are not readily accessible because of limited sharing and a lack of defined standards. With the aim of increasing the availability, quality, and utility of GWAS SumStats, the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) GWAS Catalog organized a community workshop to address the standards, infrastructure, and incentives required to promote and enable sharing. We evaluated the barriers to SumStats sharing, both technological and sociological, and developed an action plan to address those challenges and ensure that SumStats and study metadata are findable, accessible, interoperable, and reusable (FAIR). We encourage early deposition of datasets in the GWAS Catalog as the recognized central repository. We recommend standard requirements for reporting elements and formats for SumStats and accompanying metadata as guidelines for community standards and a basis for submission to the GWAS Catalog. Finally, we provide recommendations to enable, promote, and incentivize broader data sharing, standards and FAIRness in order to advance genomic medicine.
RESUMEN
Hypertension and obesity are the most important modifiable risk factors for cardiovascular diseases, but their association is not well characterized in Africa. We investigated regional patterns and association of obesity with hypertension among 30 044 continental Africans. We harmonized data on hypertension (defined as previous diagnosis/use of antihypertensive drugs or blood pressure [BP]≥140/90 mmHg/BP≥130/80 mmHg) and obesity from 30 044 individuals in the Cardiovascular H3Africa Innovation Resource across 13 African countries. We analyzed data from population-based controls and the Entire Harmonized Dataset. Age-adjusted and crude proportions of hypertension were compared regionally, across sex, and between hypertension definitions. Logit generalized estimating equation was used to determine the independent association of obesity with hypertension (P value <5%). Participants were 56% women; with mean age 48.5±12.0 years. Crude proportions of hypertension (at BP≥140/90 mmHg) were 47.9% (95% CI, 47.4-48.5) for Entire Harmonized Dataset and 42.0% (41.1-42.7) for population-based controls and were significantly higher for the 130/80 mm Hg threshold at 59.3% (58.7-59.9) in population-based controls. The age-adjusted proportion of hypertension at BP≥140/90 mmHg was the highest among men (33.8% [32.1-35.6]), in western Africa (34.7% [33.3-36.2]), and in obese individuals (43.6%; 40.3-47.2). Obesity was independently associated with hypertension in population-based controls (adjusted odds ratio, 2.5 [2.3-2.7]) and odds of hypertension in obesity increased with increasing age from 2.0 (1.7-2.3) in younger age to 8.8 (7.4-10.3) in older age. Hypertension is common across multiple countries in Africa with 11.9% to 51.7% having BP≥140/90 mmHg and 39.5% to 69.4% with BP≥130/80 mmHg. Obese Africans were more than twice as likely to be hypertensive and the odds increased with increasing age.
Asunto(s)
Hipertensión/epidemiología , Obesidad/epidemiología , Adulto , África/epidemiología , Anciano , Antihipertensivos/uso terapéutico , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Sobrepeso/epidemiología , Prevalencia , Factores de RiesgoRESUMEN
The eMERGE Network is establishing methods for electronic transmittal of patient genetic test results from laboratories to healthcare providers across organizational boundaries. We surveyed the capabilities and needs of different network participants, established a common transfer format, and implemented transfer mechanisms based on this format. The interfaces we created are examples of the connectivity that must be instantiated before electronic genetic and genomic clinical decision support can be effectively built at the point of care. This work serves as a case example for both standards bodies and other organizations working to build the infrastructure required to provide better electronic clinical decision support for clinicians.