OBJECTIVE: To build natural language processing (NLP) strategies to characterize measures of genetic counseling (GC) efficiency and classify measures according to phase of GC (pre- or post-genetic testing). MATERIALS AND METHODS: This study selected and annotated 800 GC notes from 7 clinical specialties in a large academic medical center for NLP model development and validation. The NLP approaches extracted GC efficiency measures, including direct and indirect time and GC phase. The models were then applied to 24 102 GC notes collected from January 2016 through December 2023. RESULTS: NLP approaches performed well (F1 scores of 0.95 and 0.90 for direct time in GC and GC phase classification, respectively). Our findings showed median direct time in GC of 50 minutes, with significant differences in direct time distributions observed across clinical specialties, time periods (2016-2019 or 2020-2023), delivery modes (in person or telehealth), and GC phase. DISCUSSION: As referrals to GC increase, there is increasing pressure to improve efficiency. Our NLP strategy was used to generate and summarize real-world evidence of GC time for 7 clinical specialties. These approaches enable future research on the impact of interventions intended to improve GC efficiency. CONCLUSION: This work demonstrated the practical value of NLP to provide a useful and scalable strategy to generate real world evidence of GC efficiency. Principles presented in this work may also be valuable for health services research in other practice areas.

OBJECTIVE: Building upon our previous work on predicting chronic opioid use using electronic health records (EHR) and wearable data, this study leveraged the Health Equity Across the AI Lifecycle (HEAAL) framework to (a) fine tune the previously built model with genomic data and evaluate model performance in predicting chronic opioid use and (b) apply IBM's AIF360 pre-processing toolkit to mitigate bias related to gender and race and evaluate the model performance using various fairness metrics. MATERIALS AND METHODS: Participants included approximately 271 All of Us Research Program subjects with EHR, wearable, and genomic data. We fine-tuned 4 machine learning models on the new dataset. The SHapley Additive exPlanations (SHAP) technique identified the best-performing predictors. A preprocessing toolkit boosted fairness by gender and race. RESULTS: The genetic data enhanced model performance from the prior model, with the area under the curve improving from 0.90 (95% CI, 0.88-0.92) to 0.95 (95% CI, 0.89-0.95). Key predictors included Dopamine D1 Receptor (DRD1) rs4532, general type of surgery, and time spent in physical activity. The reweighing preprocessing technique applied to the stacking algorithm effectively improved the model's fairness across racial and gender groups without compromising performance. CONCLUSION: We leveraged 2 dimensions of the HEAAL framework to build a fair artificial intelligence (AI) solution. Multi-modal datasets (including wearable and genetic data) and applying bias mitigation strategies can help models to more fairly and accurately assess risk across diverse populations, promoting fairness in AI in healthcare.

OBJECTIVE: Given the importance AI in genomics and its potential impact on human health, the American Medical Informatics Association-Genomics and Translational Biomedical Informatics (GenTBI) Workgroup developed this assessment of factors that can further enable the clinical application of AI in this space. PROCESS: A list of relevant factors was developed through GenTBI workgroup discussions in multiple in-person and online meetings, along with review of pertinent publications. This list was then summarized and reviewed to achieve consensus among the group members. CONCLUSIONS: Substantial informatics research and development are needed to fully realize the clinical potential of such technologies. The development of larger datasets is crucial to emulating the success AI is achieving in other domains. It is important that AI methods do not exacerbate existing socio-economic, racial, and ethnic disparities. Genomic data standards are critical to effectively scale such technologies across institutions. With so much uncertainty, complexity and novelty in genomics and medicine, and with an evolving regulatory environment, the current focus should be on using these technologies in an interface with clinicians that emphasizes the value each brings to clinical decision-making.

OBJECTIVE: The study sought to develop and apply a framework that uses a clinical phenotyping tool to assess risk for recurrent preterm birth. MATERIALS AND METHODS: We extended an existing clinical phenotyping tool and applied a 4-step framework for our retrospective cohort study. The study was based on data collected in the Genomic and Proteomic Network for Preterm Birth Research Longitudinal Cohort Study (GPN-PBR LS). A total of 52 sociodemographic, clinical and obstetric history-related risk factors were selected for the analysis. Spontaneous and indicated delivery subtypes were analyzed both individually and in combination. Chi-square analysis and Kaplan-Meier estimate were used for univariate analysis. A Cox proportional hazards model was used for multivariable analysis. RESULTS: : A total of 428 women with a history of spontaneous preterm birth qualified for our analysis. The predictors of preterm delivery used in multivariable model were maternal age, maternal race, household income, marital status, previous caesarean section, number of previous deliveries, number of previous abortions, previous birth weight, cervical insufficiency, decidual hemorrhage, and placental dysfunction. The models stratified by delivery subtype performed better than the naïve model (concordance 0.76 for the spontaneous model, 0.87 for the indicated model, and 0.72 for the naïve model). DISCUSSION: The proposed 4-step framework is effective to analyze risk factors for recurrent preterm birth in a retrospective cohort and possesses practical features for future analyses with other data sources (eg, electronic health record data). CONCLUSIONS: We developed an analytical framework that utilizes a clinical phenotyping tool and performed a survival analysis to analyze risk for recurrent preterm birth.

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.

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.

The American Medical Informatics Association convened the 2014 Health Policy Invitational Meeting to develop recommendations for updates to current policies and to establish an informatics research agenda for personalizing medicine. In particular, the meeting focused on discussing informatics challenges related to personalizing care through the integration of genomic or other high-volume biomolecular data with data from clinical systems to make health care more efficient and effective. This report summarizes the findings (n = 6) and recommendations (n = 15) from the policy meeting, which were clustered into 3 broad areas: (1) policies governing data access for research and personalization of care; (2) policy and research needs for evolving data interpretation and knowledge representation; and (3) policy and research needs to ensure data integrity and preservation. The meeting outcome underscored the need to address a number of important policy and technical considerations in order to realize the potential of personalized or precision medicine in actual clinical contexts.

OBJECTIVE: Clinicians' ability to use and interpret genetic information depends upon how those data are displayed in electronic health records (EHRs). There is a critical need to develop systems to effectively display genetic information in EHRs and augment clinical decision support (CDS). MATERIALS AND METHODS: The National Institutes of Health (NIH)-sponsored Clinical Sequencing Exploratory Research and Electronic Medical Records & Genomics EHR Working Groups conducted a multiphase, iterative process involving working group discussions and 2 surveys in order to determine how genetic and genomic information are currently displayed in EHRs, envision optimal uses for different types of genetic or genomic information, and prioritize areas for EHR improvement. RESULTS: There is substantial heterogeneity in how genetic information enters and is documented in EHR systems. Most institutions indicated that genetic information was displayed in multiple locations in their EHRs. Among surveyed institutions, genetic information enters the EHR through multiple laboratory sources and through clinician notes. For laboratory-based data, the source laboratory was the main determinant of the location of genetic information in the EHR. The highest priority recommendation was to address the need to implement CDS mechanisms and content for decision support for medically actionable genetic information. CONCLUSION: Heterogeneity of genetic information flow and importance of source laboratory, rather than clinical content, as a determinant of information representation are major barriers to using genetic information optimally in patient care. Greater effort to develop interoperable systems to receive and consistently display genetic and/or genomic information and alert clinicians to genomic-dependent improvements to clinical care is recommended.

OBJECTIVE: Pharmacogenomics evaluations of variability in drug metabolic processes may be useful for making individual drug response predictions. We present an approach to deriving 'phenotype scores' based on existing pharmacogenomics knowledge and a patient's genomics data. Pharmacogenomics plays an important role in the bioactivation of tamoxifen, a prodrug administered to patients for breast cancer treatment. Tamoxifen is therefore considered a model for many drugs requiring bioactivation. We investigate whether this knowledge-based approach can be applied to produce a phenotype score that is predictive of the endoxifen/N-desmethyltamoxifen (NDM) plasma concentration ratio in patients taking tamoxifen. MATERIALS AND METHODS: We implement a knowledge-based model for calculating phenotype scores from patient-specific genotype data. These data include allelic variants of genes encoding enzymes involved in the bioactivation of tamoxifen. We performed quantile linear regression to evaluate whether six phenotype scoring algorithms are predictive of patient endoxifen/NDM plasma concentration ratio, and validate our scoring methods. RESULTS: Our model illustrates a knowledge-based approach to predict drug metabolism efficacy given patient genomics data. Results showed that for one phenotype scoring algorithm, scores were weakly correlated with patient endoxifen/NDM plasma concentration ratios. This algorithm performed better than simple metrics for variation in individual and multiple genes. DISCUSSION: We discuss advantages of the model, challenges to its implementation in a personalized medicine context, and provide example future directions. CONCLUSIONS: We demonstrate the utility of our model in a tamoxifen case study context. We also provide evidence that more complicated polygenic models are needed to represent heterogeneity in clinical outcomes.

In pursuing personalized medicine, pharmacogenomic (PGx) knowledge may help guide prescribing drugs based on a person's genotype. Here we evaluate the feasibility of incorporating PGx knowledge, combined with clinical data, to support clinical decision-making by: 1) analyzing clinically relevant knowledge contained in PGx knowledge resources; 2) evaluating the feasibility of a rule-based framework to support formal representation of clinically relevant knowledge contained in PGx knowledge resources; and, 3) evaluating the ability of an electronic medical record/electronic health record (EMR/EHR) to provide computable forms of clinical data needed for PGx clinical decision support. Findings suggest that the PharmGKB is a good source for PGx knowledge to supplement information contained in FDA approved drug labels. Furthermore, we found that with supporting knowledge (e.g. IF age <18 THEN patient is a child), sufficient clinical data exists in University of Washington's EMR systems to support 50% of PGx knowledge contained in drug labels that could be expressed as rules.

Knowledge gained in studies of genetic disorders is reported in a growing body of biomedical literature containing reports of genetic variation in individuals that map to medical conditions and/or response to therapy. These scientific discoveries need to be translated into practical applications to optimize patient care. Translating research into practice can be facilitated by supplying clinicians with research evidence. We assessed the role of existing tools in extracting answers to translational research questions in the area of genomic medicine. We: evaluate the coverage of translational research terms in the Unified Medical Language Systems (UMLS) Metathesaurus; determine where answers are most often found in full-text articles; and determine common answer patterns. Findings suggest that we will be able to leverage the UMLS in development of natural language processing algorithms for automated extraction of answers to translational research questions from biomedical text in the area of genomic medicine.