By providing a central repository, PheKB enables improved development, transportability, and validity of algorithms for research-grade phenotypes using health care generated data.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver illness with a genetically heterogeneous background that can be accompanied by considerable morbidity and attendant health care costs. The pathogenesis and progression of NAFLD is complex with many unanswered questions. We conducted genome-wide association studies (GWASs) using both adult and pediatric participants from the Electronic Medical Records and Genomics (eMERGE) Network to identify novel genetic contributors to this condition. Methods: First, a natural language processing (NLP) algorithm was developed, tested, and deployed at each site to identify 1106 NAFLD cases and 8571 controls and histological data from liver tissue in 235 available participants. These include 1242 pediatric participants (396 cases, 846 controls). The algorithm included billing codes, text queries, laboratory values, and medication records. Next, GWASs were performed on NAFLD cases and controls and case-only analyses using histologic scores and liver function tests adjusting for age, sex, site, ancestry, PC, and body mass index (BMI). Results: Consistent with previous results, a robust association was detected for the PNPLA3 gene cluster in participants with European ancestry. At the PNPLA3-SAMM50 region, three SNPs, rs738409, rs738408, and rs3747207, showed strongest association (best SNP rs738409 p = 1.70 × 10 − 20). This effect was consistent in both pediatric (p = 9.92 × 10 − 6) and adult (p = 9.73 × 10 − 15) cohorts. Additionally, this variant was also associated with disease severity and NAFLD Activity Score (NAS) (p = 3.94 × 10 − 8 , beta = 0.85). PheWAS analysis link this locus to a spectrum of liver diseases beyond NAFLD with a novel negative correlation with gout (p = 1.09 × 10 − 4). We also identified novel loci for NAFLD disease severity, including one novel locus for NAS score near IL17RA (rs5748926, p = 3.80 × 10 − 8), and another near ZFP90-CDH1 for fibrosis (rs698718, p = 2.74 × 10 − 11). Post-GWAS and gene-based analyses identified more than 300 genes that were used for functional and pathway enrichment analyses.

Background Electronic health records (EHRs) are increasingly used for clinical and translational research through the creation of phenotype algorithms. Currently, phenotype algorithms are most commonly represented as noncomputable descriptive documents and knowledge artifacts that detail the protocols for querying diagnoses, symptoms, procedures, medications, and/or text-driven medical concepts, and are primarily meant for human comprehension. We present desiderata for developing a computable phenotype representation model (PheRM).Methods A team of clinicians and informaticians reviewed common features for multisite phenotype algorithms published in PheKB.org and existing phenotype representation platforms. We also evaluated well-known diagnostic criteria and clinical decision-making guidelines to encompass a broader category of algorithms.Results We propose 10 desired characteristics for a flexible, computable PheRM: (1) structure clinical data into queryable forms; (2) recommend use of a common data model, but also support customization for the variability and availability of EHR data among sites; (3) support both human-readable and computable representations of phenotype algorithms; (4) implement set operations and relational algebra for modeling phenotype algorithms; (5) represent phenotype criteria with structured rules; (6) support defining temporal relations between events; (7) use standardized terminologies and ontologies, and facilitate reuse of value sets; (8) define representations for text searching and natural language processing; (9) provide interfaces for external software algorithms; and (10) maintain backward compatibility.Conclusion A computable PheRM is needed for true phenotype portability and reliability across different EHR products and healthcare systems. These desiderata are a guide to inform the establishment and evolution of EHR phenotype algorithm authoring platforms and languages.

BackgroundManual eligibility screening (ES) for a clinical trial typically requires a labor-intensive review of patient records that utilizes many resources. Leveraging state-of-the-art natural language processing (NLP) and information extraction (IE) technologies, we sought to improve the efficiency of physician decision-making in clinical trial enrollment. In order to markedly reduce the pool of potential candidates for staff screening, we developed an automated ES algorithm to identify patients who meet core eligibility characteristics of an oncology clinical trial.MethodsWe collected narrative eligibility criteria from ClinicalTrials.gov for 55 clinical trials actively enrolling oncology patients in our institution between 12/01/2009 and 10/31/2011. In parallel, our ES algorithm extracted clinical and demographic information from the Electronic Health Record (EHR) data fields to represent profiles of all 215 oncology patients admitted to cancer treatment during the same period. The automated ES algorithm then matched the trial criteria with the patient profiles to identify potential trial-patient matches. Matching performance was validated on a reference set of 169 historical trial-patient enrollment decisions, and workload, precision, recall, negative predictive value (NPV) and specificity were calculated.ResultsWithout automation, an oncologist would need to review 163 patients per trial on average to replicate the historical patient enrollment for each trial. This workload is reduced by 85% to 24 patients when using automated ES (precision/recall/NPV/specificity: 12.6%/100.0%/100.0%/89.9%). Without automation, an oncologist would need to review 42 trials per patient on average to replicate the patient-trial matches that occur in the retrospective data set. With automated ES this workload is reduced by 90% to four trials (precision/recall/NPV/specificity: 35.7%/100.0%/100.0%/95.5%).ConclusionBy leveraging NLP and IE technologies, automated ES could dramatically increase the trial screening efficiency of oncologists and enable participation of small practices, which are often left out from trial enrollment. The algorithm has the potential to significantly reduce the effort to execute clinical research at a point in time when new initiatives of the cancer care community intend to greatly expand both the access to trials and the number of available trials.Electronic supplementary materialThe online version of this article (doi:10.1186/s12911-015-0149-3) contains supplementary material, which is available to authorized users.

Objectives (1) To develop an automated eligibility screening (ES) approach for clinical trials in an urban tertiary care pediatric emergency department (ED); (2) to assess the effectiveness of natural language processing (NLP), information extraction (IE), and machine learning (ML) techniques on real-world clinical data and trials.Data and methods We collected eligibility criteria for 13 randomly selected, disease-specific clinical trials actively enrolling patients between January 1, 2010 and August 31, 2012. In parallel, we retrospectively selected data fields including demographics, laboratory data, and clinical notes from the electronic health record (EHR) to represent profiles of all 202795 patients visiting the ED during the same period. Leveraging NLP, IE, and ML technologies, the automated ES algorithms identified patients whose profiles matched the trial criteria to reduce the pool of candidates for staff screening. The performance was validated on both a physician-generated gold standard of trial–patient matches and a reference standard of historical trial–patient enrollment decisions, where workload, mean average precision (MAP), and recall were assessed.Results Compared with the case without automation, the workload with automated ES was reduced by 92% on the gold standard set, with a MAP of 62.9%. The automated ES achieved a 450% increase in trial screening efficiency. The findings on the gold standard set were confirmed by large-scale evaluation on the reference set of trial–patient matches.Discussion and conclusion By exploiting the text of trial criteria and the content of EHRs, we demonstrated that NLP-, IE-, and ML-based automated ES could successfully identify patients for clinical trials.

ObjectiveCohort selection is challenging for large-scale electronic health record (EHR) analyses, as International Classification of Diseases 9th edition (ICD-9) diagnostic codes are notoriously unreliable disease predictors. Our objective was to develop, evaluate, and validate an automated algorithm for determining an Autism Spectrum Disorder (ASD) patient cohort from EHR. We demonstrate its utility via the largest investigation to date of the co-occurrence patterns of medical comorbidities in ASD.MethodsWe extracted ICD-9 codes and concepts derived from the clinical notes. A gold standard patient set was labeled by clinicians at Boston Children’s Hospital (BCH) (N = 150) and Cincinnati Children’s Hospital and Medical Center (CCHMC) (N = 152). Two algorithms were created: (1) rule-based implementing the ASD criteria from Diagnostic and Statistical Manual of Mental Diseases 4th edition, (2) predictive classifier. The positive predictive values (PPV) achieved by these algorithms were compared to an ICD-9 code baseline. We clustered the patients based on grouped ICD-9 codes and evaluated subgroups.ResultsThe rule-based algorithm produced the best PPV: (a) BCH: 0.885 vs. 0.273 (baseline); (b) CCHMC: 0.840 vs. 0.645 (baseline); (c) combined: 0.864 vs. 0.460 (baseline). A validation at Children’s Hospital of Philadelphia yielded 0.848 (PPV). Clustering analyses of comorbidities on the three-site large cohort (N = 20,658 ASD patients) identified psychiatric, developmental, and seizure disorder clusters.ConclusionsIn a large cross-institutional cohort, co-occurrence patterns of comorbidities in ASDs provide further hypothetical evidence for distinct courses in ASD. The proposed automated algorithms for cohort selection open avenues for other large-scale EHR studies and individualized treatment of ASD.

Background Early warning scores (EWS) are designed to identify early clinical deterioration by combining physiologic and/or laboratory measures to generate a quantified score. Current EWS leverage only a small fraction of Electronic Health Record (EHR) content. The planned widespread implementation of EHRs brings the promise of abundant data resources for prediction purposes. The three specific aims of our research are: (1) to develop an EHR-based automated algorithm to predict the need for Pediatric Intensive Care Unit (PICU) transfer in the first 24 hours of admission; (2) to evaluate the performance of the new algorithm on a held-out test data set; and (3) to compare the effectiveness of the new algorithm's with those of two published Pediatric Early Warning Scores (PEWS). Methods The cases were comprised of 526 encounters with 24-hour Pediatric Intensive Care Unit (PICU) transfer. In addition to the cases, we randomly selected 6,772 control encounters from 62,516 inpatient admissions that were never transferred to the PICU. We used 29 variables in a logistic regression and compared our algorithm against two published PEWS on a held-out test data set. Results The logistic regression algorithm achieved 0.849 (95% CI 0.753–0.945) sensitivity, 0.859 (95% CI 0.850–0.868) specificity and 0.912 (95% CI 0.905–0.919) area under the curve (AUC) in the test set. Our algorithm’s AUC was significantly higher, by 11.8 percent and 22.6 percent in the test set, than two published PEWS. Conclusion The novel algorithm achieved higher sensitivity, specificity, and AUC than the two PEWS reported in the literature.

This study adds to understanding of the genetic architecture of asthma in European Americans and African Americans and reinforces the need to study populations of diverse ethnic backgrounds to identify shared and unique genetic predictors of asthma.