Three Essays on Enhancing Clinical Trial Subject Recruitment Using Natural Language Processing and Text Mining

Patient recruitment and enrollment are critical factors for a successful clinical trial; however, recruitment tends to be the most common problem in most clinical trials. The success of a clinical trial depends on efficiently recruiting suitable patients to conduct the trial. Every clinical trial research has a protocol, which describes what will be done in the study and how it will be conducted. Also, the protocol ensures the safety of the trial subjects and the integrity of the data collected. The eligibility criteria section of clinical trial protocols is important because it specifies the necessary conditions that participants have to satisfy. Since clinical trial eligibility criteria are usually written in free text form, they are not computer interpretable. To automate the analysis of the eligibility criteria, it is therefore necessary to transform those criteria into a computer-interpretable format. Unstructured format of eligibility criteria additionally create search efficiency issues. Thus, searching and selecting appropriate clinical trials for a patient from relatively large number of available trials is a complex task. A few attempts have been made to automate the matching process between patients and clinical trials. However, those attempts have not fully integrated the entire matching process and have not exploited the state-of-the-art Natural Language Processing (NLP) techniques that may improve the matching performance. Given the importance of patient recruitment in clinical trial research, the objective of this research is to automate the matching process using NLP and text mining techniques and, thereby, improve the efficiency and effectiveness of the recruitment process. This dissertation research, which comprises three essays, investigates the issues of clinical trial subject recruitment using state-of-the-art NLP and text mining techniques. Essay 1: Building a Domain-Specific Lexicon for Clinical Trial Subject Eligibility Analysis Essay 2: Clustering Clinical Trials Using Semantic-Based Feature Expansion Essay 3: An Automatic Matching Process of Clinical Trial Subject Recruitment In essay1, I develop a domain-specific lexicon for n-gram Named Entity Recognition (NER) in the breast cancer domain. The domain-specific dictionary is used for selection and reduction of n-gram features in clustering in eassy2. The domain-specific dictionary was evaluated by comparing it with Systematized Nomenclature of Medicine--Clinical Terms (SNOMED CT). The results showed that it add significant number of new terms which is very useful in effective natural language processing In essay 2, I explore the clustering of similar clinical trials using the domain-specific lexicon and term expansion using synonym from the Unified Medical Language System (UMLS). I generate word n-gram features and modify the features with the domain-specific dictionary matching process. In order to resolve semantic ambiguity, a semantic-based feature expansion technique using UMLS is applied. A hierarchical agglomerative clustering algorithm is used to generate clinical trial clusters. The focus is on summarization of clinical trial information in order to enhance trial search efficiency. Finally, in essay 3, I investigate an automatic matching process of clinical trial clusters and patient medical records. The patient records collected from a prior study were used to test our approach. The patient records were pre-processed by tokenization and lemmatization. The pre-processed patient information were then further enhanced by matching with breast cancer custom dictionary described in essay 1 and semantic feature expansion using UMLS Metathesaurus. Finally, I matched the patient record with clinical trial clusters to select the best matched cluster(s) and then with trials within the clusters. The matching results were evaluated by internal expert as well as external medical expert

Using Neural Networks for Relation Extraction from Biomedical Literature

Using different sources of information to support automated extracting of relations between biomedical concepts contributes to the development of our understanding of biological systems. The primary comprehensive source of these relations is biomedical literature. Several relation extraction approaches have been proposed to identify relations between concepts in biomedical literature, namely, using neural networks algorithms. The use of multichannel architectures composed of multiple data representations, as in deep neural networks, is leading to state-of-the-art results. The right combination of data representations can eventually lead us to even higher evaluation scores in relation extraction tasks. Thus, biomedical ontologies play a fundamental role by providing semantic and ancestry information about an entity. The incorporation of biomedical ontologies has already been proved to enhance previous state-of-the-art results.Comment: Artificial Neural Networks book (Springer) - Chapter 1

LeafAI: query generator for clinical cohort discovery rivaling a human programmer

Objective: Identifying study-eligible patients within clinical databases is a critical step in clinical research. However, accurate query design typically requires extensive technical and biomedical expertise. We sought to create a system capable of generating data model-agnostic queries while also providing novel logical reasoning capabilities for complex clinical trial eligibility criteria. Materials and Methods: The task of query creation from eligibility criteria requires solving several text-processing problems, including named entity recognition and relation extraction, sequence-to-sequence transformation, normalization, and reasoning. We incorporated hybrid deep learning and rule-based modules for these, as well as a knowledge base of the Unified Medical Language System (UMLS) and linked ontologies. To enable data-model agnostic query creation, we introduce a novel method for tagging database schema elements using UMLS concepts. To evaluate our system, called LeafAI, we compared the capability of LeafAI to a human database programmer to identify patients who had been enrolled in 8 clinical trials conducted at our institution. We measured performance by the number of actual enrolled patients matched by generated queries. Results: LeafAI matched a mean 43% of enrolled patients with 27,225 eligible across 8 clinical trials, compared to 27% matched and 14,587 eligible in queries by a human database programmer. The human programmer spent 26 total hours crafting queries compared to several minutes by LeafAI. Conclusions: Our work contributes a state-of-the-art data model-agnostic query generation system capable of conditional reasoning using a knowledge base. We demonstrate that LeafAI can rival a human programmer in finding patients eligible for clinical trials

Bigram feature extraction and conditional random fields model to improve text classification clinical trial document

In the field of health and medicine, there is a very important term known as clinical trials. Clinical trials are a type of activity that studies how the safest way to treat patients is. These clinical trials are usually written in unstructured free text which requires translation from a computer. The aim of this paper is to classify the texts of cancer clinical trial documents consisting of unstructured free texts taken from cancer clinical trial protocols. The proposed algorithm is conditional random Fields and bigram features. A new classification model from the cancer clinical trial document text is proposed to compete with other methods in terms of precision, recall, and f-1 score. The results of this study are better than the previous results, namely 88.07 precision, 88.05 recall and f-1 score 88.06

Advanced Methods for Entity Linking in the Life Sciences

The amount of knowledge increases rapidly due to the increasing number of available data sources. However, the autonomy of data sources and the resulting heterogeneity prevent comprehensive data analysis and applications. Data integration aims to overcome heterogeneity by unifying different data sources and enriching unstructured data. The enrichment of data consists of different subtasks, amongst other the annotation process. The annotation process links document phrases to terms of a standardized vocabulary. Annotated documents enable effective retrieval methods, comparability of different documents, and comprehensive data analysis, such as finding adversarial drug effects based on patient data. A vocabulary allows the comparability using standardized terms. An ontology can also represent a vocabulary, whereas concepts, relationships, and logical constraints additionally define an ontology. The annotation process is applicable in different domains. Nevertheless, there is a difference between generic and specialized domains according to the annotation process. This thesis emphasizes the differences between the domains and addresses the identified challenges. The majority of annotation approaches focuses on the evaluation of general domains, such as Wikipedia. This thesis evaluates the developed annotation approaches with case report forms that are medical documents for examining clinical trials. The natural language provides different challenges, such as similar meanings using different phrases. The proposed annotation method, AnnoMap, considers the fuzziness of natural language. A further challenge is the reuse of verified annotations. Existing annotations represent knowledge that can be reused for further annotation processes. AnnoMap consists of a reuse strategy that utilizes verified annotations to link new documents to appropriate concepts. Due to the broad spectrum of areas in the biomedical domain, different tools exist. The tools perform differently regarding a particular domain. This thesis proposes a combination approach to unify results from different tools. The method utilizes existing tool results to build a classification model that can classify new annotations as correct or incorrect. The results show that the reuse and the machine learning-based combination improve the annotation quality compared to existing approaches focussing on the biomedical domain. A further part of data integration is entity resolution to build unified knowledge bases from different data sources. A data source consists of a set of records characterized by attributes. The goal of entity resolution is to identify records representing the same real-world entity. Many methods focus on linking data sources consisting of records being characterized by attributes. Nevertheless, only a few methods can handle graph-structured knowledge bases or consider temporal aspects. The temporal aspects are essential to identify the same entities over different time intervals since these aspects underlie certain conditions. Moreover, records can be related to other records so that a small graph structure exists for each record. These small graphs can be linked to each other if they represent the same. This thesis proposes an entity resolution approach for census data consisting of person records for different time intervals. The approach also considers the graph structure of persons given by family relationships. For achieving qualitative results, current methods apply machine-learning techniques to classify record pairs as the same entity. The classification task used a model that is generated by training data. In this case, the training data is a set of record pairs that are labeled as a duplicate or not. Nevertheless, the generation of training data is a time-consuming task so that active learning techniques are relevant for reducing the number of training examples. The entity resolution method for temporal graph-structured data shows an improvement compared to previous collective entity resolution approaches. The developed active learning approach achieves comparable results to supervised learning methods and outperforms other limited budget active learning methods. Besides the entity resolution approach, the thesis introduces the concept of evolution operators for communities. These operators can express the dynamics of communities and individuals. For instance, we can formulate that two communities merged or split over time. Moreover, the operators allow observing the history of individuals. Overall, the presented annotation approaches generate qualitative annotations for medical forms. The annotations enable comprehensive analysis across different data sources as well as accurate queries. The proposed entity resolution approaches improve existing ones so that they contribute to the generation of qualitative knowledge graphs and data analysis tasks