Michael G Kahn’s research while affiliated with University of Colorado and other places

Objectives Accurate record linkage (RL) enables consolidation and de-duplication of data from disparate datasets, resulting in more comprehensive and complete patient data. However, conducting RL with low quality or unfit data can waste institutional resources on poor linkage results. We aim to evaluate data linkability to enhance the effectiveness of record linkage. Materials and Methods We describe a systematic approach using data fitness (“linkability”) measures, defined as metrics that characterize the availability, discriminatory power, and distribution of potential variables for RL. We used the isolation forest algorithm to detect abnormal linkability values from 188 sites in Indiana and Colorado, and manually reviewed the data to understand the cause of anomalies. Result We calculated 10 linkability metrics for 11 potential linkage variables (LVs) across 188 sites for a total of 20 680 linkability metrics. Potential LVs such as first name, last name, date of birth, and sex have low missing data rates, while Social Security Number vary widely in completeness among all sites. We investigated anomalous linkability values to identify the cause of many records having identical values in certain LVs, issues with placeholder values disguising data missingness, and orphan records. Discussion The fitness of a variable for RL is determined by its availability and its discriminatory power to uniquely identify individuals. These results highlight the need for awareness of placeholder values, which inform the selection of variables and methods to optimize RL performance. Conclusion Evaluating linkability measures using the isolation forest algorithm to highlight anomalous findings can help identify fitness-for-use issues that must be addressed before initiating the RL process to ensure high-quality linkage outcomes.

Objectives The Multi-State EHR-Based Network for Disease Surveillance (MENDS) is a population-based chronic disease surveillance distributed data network that uses institution-specific extraction-transformation-load (ETL) routines. MENDS-on-FHIR examined using Health Language Seven’s Fast Healthcare Interoperability Resources (HL7® FHIR®) and US Core Implementation Guide (US Core IG) compliant resources derived from the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to create a standards-based ETL pipeline. Materials and Methods The input data source was a research data warehouse containing clinical and administrative data in OMOP CDM Version 5.3 format. OMOP-to-FHIR transformations, using a unique JavaScript Object Notation (JSON)-to-JSON transformation language called Whistle, created FHIR R4 V4.0.1/US Core IG V4.0.0 conformant resources that were stored in a local FHIR server. A REST-based Bulk FHIR $export request extracted FHIR resources to populate a local MENDS database. Results Eleven OMOP tables were used to create 10 FHIR/US Core compliant resource types. A total of 1.13 trillion resources were extracted and inserted into the MENDS repository. A very low rate of non-compliant resources was observed. Discussion OMOP-to-FHIR transformation results passed validation with less than a 1% non-compliance rate. These standards-compliant FHIR resources provided standardized data elements required by the MENDS surveillance use case. The Bulk FHIR application programming interface (API) enabled population-level data exchange using interoperable FHIR resources. The OMOP-to-FHIR transformation pipeline creates a FHIR interface for accessing OMOP data. Conclusion MENDS-on-FHIR successfully replaced custom ETL with standards-based interoperable FHIR resources using Bulk FHIR. The OMOP-to-FHIR transformations provide an alternative mechanism for sharing OMOP data.

Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data, but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to construct them automatically. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoint resources and abstraction algorithms), and benchmarks (e.g., prebuilt KGs). We evaluated the ecosystem by systematically comparing it to existing open-source KG construction methods and by analyzing its computational performance when used to construct 12 different large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability.

Precision medicine initiatives across the globe have led to a revolution of repositories linking large-scale genomic data with electronic health records, enabling genomic analyses across the entire phenome. Many of these initiatives focus solely on research insights, leading to limited direct benefit to patients. We describe the biobank at the Colorado Center for Personalized Medicine (CCPM Biobank) that was jointly developed by the University of Colorado Anschutz Medical Campus and UCHealth to serve as a unique, dual-purpose research and clinical resource accelerating personalized medicine. This living resource currently has more than 200,000 participants with ongoing recruitment. We highlight the clinical, laboratory, regulatory, and HIPAA-compliant informatics infrastructure along with our stakeholder engagement, consent, recontact, and participant engagement strategies. We characterize aspects of genetic and geographic diversity unique to the Rocky Mountain region, the primary catchment area for CCPM Biobank participants. We leverage linked health and demographic information of the CCPM Biobank participant population to demonstrate the utility of the CCPM Biobank to replicate complex trait associations in the first 33,674 genotyped individuals across multiple disease domains. Finally, we describe our current efforts toward return of clinical genetic test results, including high-impact pathogenic variants and pharmacogenetic information, and our broader goals as the CCPM Biobank continues to grow. Bringing clinical and research interests together fosters unique clinical and translational questions that can be addressed from the large EHR-linked CCPM Biobank resource within a HIPAA- and CLIA-certified environment.

Objectives In a randomized controlled trial, we found that applying implementation science (IS) methods and best practices in clinical decision support (CDS) design to create a locally customized, “enhanced” CDS significantly improved evidence-based prescribing of β blockers (BB) for heart failure compared with an unmodified commercially available CDS. At trial conclusion, the enhanced CDS was expanded to all sites. The purpose of this study was to evaluate the real-world sustained effect of the enhanced CDS compared with the commercial CDS. Methods In this natural experiment of 28 primary care clinics, we compared clinics exposed to the commercial CDS (preperiod) to clinics exposed to the enhanced CDS (both periods). The primary effectiveness outcome was the proportion of alerts resulting in a BB prescription. Secondary outcomes included patient reach and clinician adoption (dismissals). Results There were 367 alerts for 183 unique patients and 171 unique clinicians (pre: March 2019–August 2019; post: October 2019–March 2020). The enhanced CDS increased prescribing by 26.1% compared with the commercial (95% confidence interval [CI]: 17.0–35.1%), which is consistent with the 24% increase in the previous study. The odds of adopting the enhanced CDS was 81% compared with 29% with the commercial (odds ratio: 4.17, 95% CI: 1.96–8.85). The enhanced CDS adoption and effectiveness rates were 62 and 14% in the preperiod and 92 and 10% in the postperiod. Conclusion Applying IS methods with CDS best practices was associated with improved and sustained clinician adoption and effectiveness compared with a commercially available CDS tool.

Objective The Multi-State EHR-Based Network for Disease Surveillance (MENDS) is a population-based chronic disease surveillance distributed data network. Current data partners create institution-specific extraction-transformation-load (ETL) routines. MENDS-on-FHIR provides a standards-based ETL approach using Health Language Seven’s Fast Healthcare Interoperability Resources (HL7 ® FHIR ® ) and US Core Implementation Guide (US Core IG) compliant resources derived from the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). Materials and Methods The input data source was a research data warehouse (RDW) containing clinical and administrative data in OMOP CDM Version 5.3 format. OMOP-to-FHIR transformations, using a unique JavaScript Object Notation (JSON)-to-JSON language called Whistle, created FHIR R4.0.1/US Core IG V4.0.0 conformant resources that were stored in a local FHIR server. A REST-based Bulk FHIR $export request extracted FHIR resources to populate a local MENDS database. Results Eleven OMOP tables were used to create 10 FHIR/US Core compliant resource types. A total of 1.13 trillion resources were extracted and inserted into the MENDS repository. A very low rate of non-compliant resources was observed. Discussion OMOP-to-FHIR transformations passed validation with only minimal non-compliance issues. These resources provided the clinical and administrative data elements required by the MENDS surveillance use case. The Bulk FHIR application programming interface (API) enabled population-level data exchange using interoperable FHIR resources. The OMOP-to-FHIR transformation pipeline creates a FHIR “facade” for accessing OMOP data. Conclusion MENDS-on-FHIR successfully replaced custom ETL with standards-based interoperable FHIR resources using Bulk FHIR. The OMOP-on-FHIR transformations provide an alternative mechanism for sharing OMOP data.

Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to automatically construct them. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoints and abstraction algorithms), and benchmarks (e.g., prebuilt KGs and embeddings). We evaluate the ecosystem by surveying open-source KG construction methods and analyzing its computational performance when constructing 12 large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability.

Every scientist knows that research results are only as good as the data upon which the conclusions were formed. However, most scientists receive no training in methods for achieving, assessing, or controlling the quality of research data—topics central to clinical research informatics. This chapter covers the basics of acquiring or collecting and processing data for research given the available data sources, systems, and people. Data quality dimensions specific to the clinical research context are used, and a framework for data quality practice and planning is presented. Available research is summarized, providing estimates of data quality capability for common clinical research data collection and processing methods. This chapter provides researchers, informaticists, and clinical research data managers basic tools to assure, assess, and control the quality of data for research.KeywordsClinical research dataData qualityResearch data collectionProcessing methodsInformaticsManagement of clinical dataData accuracySecondary use