Preparing an annotated gold standard corpus to share with extramural investigators for de-identification research.

OBJECTIVE: The current study aims to fill the gap in available healthcare de-identification resources by creating a new sharable dataset with realistic Protected Health Information (PHI) without reducing the value of the data for de-identification research. By releasing the annotated gold standard corpus with Data Use Agreement we would like to encourage other Computational Linguists to experiment with our data and develop new machine learning models for de-identification. This paper describes: (1) the modifications required by the Institutional Review Board before sharing the de-identification gold standard corpus; (2) our efforts to keep the PHI as realistic as possible; (3) and the tests to show the effectiveness of these efforts in preserving the value of the modified data set for machine learning model development. MATERIALS AND METHODS: In a previous study we built an original de-identification gold standard corpus annotated with true Protected Health Information (PHI) from 3503 randomly selected clinical notes for the 22 most frequent clinical note types of our institution. In the current study we modified the original gold standard corpus to make it suitable for external sharing by replacing HIPAA-specified PHI with newly generated realistic PHI. Finally, we evaluated the research value of this new dataset by comparing the performance of an existing published in-house de-identification system, when trained on the new de-identification gold standard corpus, with the performance of the same system, when trained on the original corpus. We assessed the potential benefits of using the new de-identification gold standard corpus to identify PHI in the i2b2 and PhysioNet datasets that were released by other groups for de-identification research. We also measured the effectiveness of the i2b2 and PhysioNet de-identification gold standard corpora in identifying PHI in our original clinical notes. RESULTS: Performance of the de-identification system using the new gold standard corpus as a training set was very close to training on the original corpus (92.56 vs. 93.48 overall F-measures). Best i2b2/PhysioNet/CCHMC cross-training performances were obtained when training on the new shared CCHMC gold standard corpus, although performances were still lower than corpus-specific trainings. DISCUSSION AND CONCLUSION: We successfully modified a de-identification dataset for external sharing while preserving the de-identification research value of the modified gold standard corpus with limited drop in machine learning de-identification performance.

Phenotyping for patient safety: algorithm development for electronic health record based automated adverse event and medical error detection in neonatal intensive care.

BACKGROUND: Although electronic health records (EHRs) have the potential to provide a foundation for quality and safety algorithms, few studies have measured their impact on automated adverse event (AE) and medical error (ME) detection within the neonatal intensive care unit (NICU) environment. OBJECTIVE: This paper presents two phenotyping AE and ME detection algorithms (ie, IV infiltrations, narcotic medication oversedation and dosing errors) and describes manual annotation of airway management and medication/fluid AEs from NICU EHRs. METHODS: From 753 NICU patient EHRs from 2011, we developed two automatic AE/ME detection algorithms, and manually annotated 11 classes of AEs in 3263 clinical notes. Performance of the automatic AE/ME detection algorithms was compared to trigger tool and voluntary incident reporting results. AEs in clinical notes were double annotated and consensus achieved under neonatologist supervision. Sensitivity, positive predictive value (PPV), and specificity are reported. RESULTS: Twelve severe IV infiltrates were detected. The algorithm identified one more infiltrate than the trigger tool and eight more than incident reporting. One narcotic oversedation was detected demonstrating 100% agreement with the trigger tool. Additionally, 17 narcotic medication MEs were detected, an increase of 16 cases over voluntary incident reporting. CONCLUSIONS: Automated AE/ME detection algorithms provide higher sensitivity and PPV than currently used trigger tools or voluntary incident-reporting systems, including identification of potential dosing and frequency errors that current methods are unequipped to detect.

Evaluating the impact of pre-annotation on annotation speed and potential bias: natural language processing gold standard development for clinical named entity recognition in clinical trial announcements.

OBJECTIVE: To present a series of experiments: (1) to evaluate the impact of pre-annotation on the speed of manual annotation of clinical trial announcements; and (2) to test for potential bias, if pre-annotation is utilized. METHODS: To build the gold standard, 1400 clinical trial announcements from the clinicaltrials.gov website were randomly selected and double annotated for diagnoses, signs, symptoms, Unified Medical Language System (UMLS) Concept Unique Identifiers, and SNOMED CT codes. We used two dictionary-based methods to pre-annotate the text. We evaluated the annotation time and potential bias through F-measures and ANOVA tests and implemented Bonferroni correction. RESULTS: Time savings ranged from 13.85% to 21.5% per entity. Inter-annotator agreement (IAA) ranged from 93.4% to 95.5%. There was no statistically significant difference for IAA and annotator performance in pre-annotations. CONCLUSIONS: On every experiment pair, the annotator with the pre-annotated text needed less time to annotate than the annotator with non-labeled text. The time savings were statistically significant. Moreover, the pre-annotation did not reduce the IAA or annotator performance. Dictionary-based pre-annotation is a feasible and practical method to reduce the cost of annotation of clinical named entity recognition in the eligibility sections of clinical trial announcements without introducing bias in the annotation process.

Web 2.0-based crowdsourcing for high-quality gold standard development in clinical natural language processing.

BACKGROUND: A high-quality gold standard is vital for supervised, machine learning-based, clinical natural language processing (NLP) systems. In clinical NLP projects, expert annotators traditionally create the gold standard. However, traditional annotation is expensive and time-consuming. To reduce the cost of annotation, general NLP projects have turned to crowdsourcing based on Web 2.0 technology, which involves submitting smaller subtasks to a coordinated marketplace of workers on the Internet. Many studies have been conducted in the area of crowdsourcing, but only a few have focused on tasks in the general NLP field and only a handful in the biomedical domain, usually based upon very small pilot sample sizes. In addition, the quality of the crowdsourced biomedical NLP corpora were never exceptional when compared to traditionally-developed gold standards. The previously reported results on medical named entity annotation task showed a 0.68 F-measure based agreement between crowdsourced and traditionally-developed corpora. OBJECTIVE: Building upon previous work from the general crowdsourcing research, this study investigated the usability of crowdsourcing in the clinical NLP domain with special emphasis on achieving high agreement between crowdsourced and traditionally-developed corpora. METHODS: To build the gold standard for evaluating the crowdsourcing workers' performance, 1042 clinical trial announcements (CTAs) from the ClinicalTrials.gov website were randomly selected and double annotated for medication names, medication types, and linked attributes. For the experiments, we used CrowdFlower, an Amazon Mechanical Turk-based crowdsourcing platform. We calculated sensitivity, precision, and F-measure to evaluate the quality of the crowd's work and tested the statistical significance (P<.001, chi-square test) to detect differences between the crowdsourced and traditionally-developed annotations. RESULTS: The agreement between the crowd's annotations and the traditionally-generated corpora was high for: (1) annotations (0.87, F-measure for medication names; 0.73, medication types), (2) correction of previous annotations (0.90, medication names; 0.76, medication types), and excellent for (3) linking medications with their attributes (0.96). Simple voting provided the best judgment aggregation approach. There was no statistically significant difference between the crowd and traditionally-generated corpora. Our results showed a 27.9% improvement over previously reported results on medication named entity annotation task. CONCLUSIONS: This study offers three contributions. First, we proved that crowdsourcing is a feasible, inexpensive, fast, and practical approach to collect high-quality annotations for clinical text (when protected health information was excluded). We believe that well-designed user interfaces and rigorous quality control strategy for entity annotation and linking were critical to the success of this work. Second, as a further contribution to the Internet-based crowdsourcing field, we will publicly release the JavaScript and CrowdFlower Markup Language infrastructure code that is necessary to utilize CrowdFlower's quality control and crowdsourcing interfaces for named entity annotations. Finally, to spur future research, we will release the CTA annotations that were generated by traditional and crowdsourced approaches.

Mining FDA drug labels for medical conditions.

BACKGROUND: Cincinnati Children's Hospital Medical Center (CCHMC) has built the initial Natural Language Processing (NLP) component to extract medications with their corresponding medical conditions (Indications, Contraindications, Overdosage, and Adverse Reactions) as triples of medication-related information ([(1) drug name]-[(2) medical condition]-[(3) LOINC section header]) for an intelligent database system, in order to improve patient safety and the quality of health care. The Food and Drug Administration's (FDA) drug labels are used to demonstrate the feasibility of building the triples as an intelligent database system task. METHODS: This paper discusses a hybrid NLP system, called AutoMCExtractor, to collect medical conditions (including disease/disorder and sign/symptom) from drug labels published by the FDA. Altogether, 6,611 medical conditions in a manually-annotated gold standard were used for the system evaluation. The pre-processing step extracted the plain text from XML file and detected eight related LOINC sections (e.g. Adverse Reactions, Warnings and Precautions) for medical condition extraction. Conditional Random Fields (CRF) classifiers, trained on token, linguistic, and semantic features, were then used for medical condition extraction. Lastly, dictionary-based post-processing corrected boundary-detection errors of the CRF step. We evaluated the AutoMCExtractor on manually-annotated FDA drug labels and report the results on both token and span levels. RESULTS: Precision, recall, and F-measure were 0.90, 0.81, and 0.85, respectively, for the span level exact match; for the token-level evaluation, precision, recall, and F-measure were 0.92, 0.73, and 0.82, respectively. CONCLUSIONS: The results demonstrate that (1) medical conditions can be extracted from FDA drug labels with high performance; and (2) it is feasible to develop a framework for an intelligent database system.

A sequence labeling approach to link medications and their attributes in clinical notes and clinical trial announcements for information extraction.

OBJECTIVE: The goal of this work was to evaluate machine learning methods, binary classification and sequence labeling, for medication-attribute linkage detection in two clinical corpora. DATA AND METHODS: We double annotated 3000 clinical trial announcements (CTA) and 1655 clinical notes (CN) for medication named entities and their attributes. A binary support vector machine (SVM) classification method with parsimonious feature sets, and a conditional random fields (CRF)-based multi-layered sequence labeling (MLSL) model were proposed to identify the linkages between the entities and their corresponding attributes. We evaluated the system's performance against the human-generated gold standard. RESULTS: The experiments showed that the two machine learning approaches performed statistically significantly better than the baseline rule-based approach. The binary SVM classification achieved 0.94 F-measure with individual tokens as features. The SVM model trained on a parsimonious feature set achieved 0.81 F-measure for CN and 0.87 for CTA. The CRF MLSL method achieved 0.80 F-measure on both corpora. DISCUSSION AND CONCLUSIONS: We compared the novel MLSL method with a binary classification and a rule-based method. The MLSL method performed statistically significantly better than the rule-based method. However, the SVM-based binary classification method was statistically significantly better than the MLSL method for both the CTA and CN corpora. Using parsimonious feature sets both the SVM-based binary classification and CRF-based MLSL methods achieved high performance in detecting medication name and attribute linkages in CTA and CN.

Large-scale evaluation of automated clinical note de-identification and its impact on information extraction.

OBJECTIVE: (1) To evaluate a state-of-the-art natural language processing (NLP)-based approach to automatically de-identify a large set of diverse clinical notes. (2) To measure the impact of de-identification on the performance of information extraction algorithms on the de-identified documents. MATERIAL AND METHODS: A cross-sectional study that included 3503 stratified, randomly selected clinical notes (over 22 note types) from five million documents produced at one of the largest US pediatric hospitals. Sensitivity, precision, F value of two automated de-identification systems for removing all 18 HIPAA-defined protected health information elements were computed. Performance was assessed against a manually generated 'gold standard'. Statistical significance was tested. The automated de-identification performance was also compared with that of two humans on a 10% subsample of the gold standard. The effect of de-identification on the performance of subsequent medication extraction was measured. RESULTS: The gold standard included 30 815 protected health information elements and more than one million tokens. The most accurate NLP method had 91.92% sensitivity (R) and 95.08% precision (P) overall. The performance of the system was indistinguishable from that of human annotators (annotators' performance was 92.15%(R)/93.95%(P) and 94.55%(R)/88.45%(P) overall while the best system obtained 92.91%(R)/95.73%(P) on same text). The impact of automated de-identification was minimal on the utility of the narrative notes for subsequent information extraction as measured by the sensitivity and precision of medication name extraction. DISCUSSION AND CONCLUSION: NLP-based de-identification shows excellent performance that rivals the performance of human annotators. Furthermore, unlike manual de-identification, the automated approach scales up to millions of documents quickly and inexpensively.

Building gold standard corpora for medical natural language processing tasks.

We present the construction of three annotated corpora to serve as gold standards for medical natural language processing (NLP) tasks. Clinical notes from the medical record, clinical trial announcements, and FDA drug labels are annotated. We report high inter-annotator agreements (overall F-measures between 0.8467 and 0.9176) for the annotation of Personal Health Information (PHI) elements for a de-identification task and of medications, diseases/disorders, and signs/symptoms for information extraction (IE) task. The annotated corpora of clinical trials and FDA labels will be publicly released and to facilitate translational NLP tasks that require cross-corpora interoperability (e.g. clinical trial eligibility screening) their annotation schemas are aligned with a large scale, NIH-funded clinical text annotation project.