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

Design of a Controlled Language for Critical Infrastructures Protection

We describe a project for the construction of controlled language for critical infrastructures protection (CIP). This project originates from the need to coordinate and categorize the communications on CIP at the European level. These communications can be physically represented by official documents, reports on incidents, informal communications and plain e-mail. We explore the application of traditional library science tools for the construction of controlled languages in order to achieve our goal. Our starting point is an analogous work done during the sixties in the field of nuclear science known as the Euratom Thesaurus.JRC.G.6-Security technology assessmen

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

A Kinematics-Based Testing Protocol to Study the Mechanics of the Human Lumbar Spine

The objective of this work was to develop a new kinematics-based testing protocol to quantify the axial and shear force components and rotational moment properties of the human cadaveric lumbar motion segment unit (MSU) in response to specific kinematic inputs. Modern, non-fusion spinal devices claim to treat degenerative disc disease better than traditional fusion surgery. Though there have been many biomechanical studies completed on these devices, there is still a debate over their efficacy. Conventional testing methods provide insight into the rotational properties of the MSU but lack the sensitivity or capacity to quantify lumbar MSU’s mechanical properties including shear and axial force components. There is a need for a new testing protocol capable of measuring the segmental properties of the lumbar MSU and to study the influence of non-fusion spinal devices on them. Seven human cadaveric lumbar MSUs were mounted in a custom designed spine robot and flexed or extended about six unique points of rotation located ¼, ½, and ¾ of the anterior-posterior depth of the intervertebral disc and at similar points located 5mm below the endplate of the subjacent body. The MSUs were rotated until a target bending moment of 8Nm was reached. Measurements of the shear force along the disc plane, axial force normal to the disc plane, bending moment, and sagittal rotation were used to determine the effects of different prescribed kinematic conditions on MSU mechanics. MSU rotations differed significantly between each rotational point. As the point of rotation moved from anterior to posterior, and from the disc midline to the end plate of the subjacent body, rotation increased. For flexion, significant differences in shear and axial forces occurred between rotational points at ¼ and ¾ depth of disc. During extension, shear and axial forces were significantly different between all rotational points along the disc plane. The results of this study show that the new kinematics-based testing protocol described herein has the capacity to detect significant differences in the segmental rotation and shear and axial forces for small perturbations in the MSU location of the center of rotation for both flexion and extension