Biomedical Literature Mining and Knowledge Discovery of Phenotyping Definitions

Indiana University-Purdue University Indianapolis (IUPUI)Phenotyping definitions are essential in cohort identification when conducting clinical research, but they become an obstacle when they are not readily available. Developing new definitions manually requires expert involvement that is labor-intensive, time-consuming, and unscalable. Moreover, automated approaches rely mostly on electronic health records’ data that suffer from bias, confounding, and incompleteness. Limited efforts established in utilizing text-mining and data-driven approaches to automate extraction and literature-based knowledge discovery of phenotyping definitions and to support their scalability. In this dissertation, we proposed a text-mining pipeline combining rule-based and machine-learning methods to automate retrieval, classification, and extraction of phenotyping definitions’ information from literature. To achieve this, we first developed an annotation guideline with ten dimensions to annotate sentences with evidence of phenotyping definitions' modalities, such as phenotypes and laboratories. Two annotators manually annotated a corpus of sentences (n=3,971) extracted from full-text observational studies’ methods sections (n=86). Percent and Kappa statistics showed high inter-annotator agreement on sentence-level annotations. Second, we constructed two validated text classifiers using our annotated corpora: abstract-level and full-text sentence-level. We applied the abstract-level classifier on a large-scale biomedical literature of over 20 million abstracts published between 1975 and 2018 to classify positive abstracts (n=459,406). After retrieving their full-texts (n=120,868), we extracted sentences from their methods sections and used the full-text sentence-level classifier to extract positive sentences (n=2,745,416). Third, we performed a literature-based discovery utilizing the positively classified sentences. Lexica-based methods were used to recognize medical concepts in these sentences (n=19,423). Co-occurrence and association methods were used to identify and rank phenotype candidates that are associated with a phenotype of interest. We derived 12,616,465 associations from our large-scale corpus. Our literature-based associations and large-scale corpus contribute in building new data-driven phenotyping definitions and expanding existing definitions with minimal expert involvement

Generating Reliable and Responsive Observational Evidence: Reducing Pre-analysis Bias

A growing body of evidence generated from observational data has demonstrated the potential to influence decision-making and improve patient outcomes. For observational evidence to be actionable, however, it must be generated reliably and in a timely manner. Large distributed observational data networks enable research on diverse patient populations at scale and develop new sound methods to improve reproducibility and robustness of real-world evidence. Nevertheless, the problems of generalizability, portability and scalability persist and compound. As analytical methods only partially address bias, reliable observational research (especially in networks) must address the bias at the design stage (i.e., pre-analysis bias) including the strategies for identifying patients of interest and defining comparators. This thesis synthesizes and enumerates a set of challenges to addressing pre-analysis bias in observational studies and presents mixed-methods approaches and informatics solutions for overcoming a number of those obstacles. We develop frameworks, methods and tools for scalable and reliable phenotyping including data source granularity estimation, comprehensive concept set selection, index date specification, and structured data-based patient review for phenotype evaluation. We cover the research on potential bias in the unexposed comparator definition including systematic background rates estimation and interpretation, and definition and evaluation of the unexposed comparator. We propose that the use of standardized approaches and methods as described in this thesis not only improves reliability but also increases responsiveness of observational evidence. To test this hypothesis, we designed and piloted a Data Consult Service - a service that generates new on-demand evidence at the bedside. We demonstrate that it is feasible to generate reliable evidence to address clinicians’ information needs in a robust and timely fashion and provide our analysis of the current limitations and future steps needed to scale such a service

Repeatable and reusable research - Exploring the needs of users for a Data Portal for Disease Phenotyping

Background: Big data research in the field of health sciences is hindered by a lack of agreement on how to identify and define different conditions and their medications. This means that researchers and health professionals often have different phenotype definitions for the same condition. This lack of agreement makes it hard to compare different study findings and hinders the ability to conduct repeatable and reusable research. Objective: This thesis aims to examine the requirements of various users, such as researchers, clinicians, machine learning experts, and managers, for both new and existing data portals for phenotypes (concept libraries). Methods: Exploratory sequential mixed methods were used in this thesis to look at which concept libraries are available, how they are used, what their characteristics are, where there are gaps, and what needs to be done in the future from the point of view of the people who use them. This thesis consists of three phases: 1) two qualitative studies, including one-to-one interviews with researchers, clinicians, machine learning experts, and senior research managers in health data science, as well as focus group discussions with researchers working with the Secured Anonymized Information Linkage databank, 2) the creation of an email survey (i.e., the Concept Library Usability Scale), and 3) a quantitative study with researchers, health professionals, and clinicians. Results: Most of the participants thought that the prototype concept library would be a very helpful resource for conducting repeatable research, but they specified that many requirements are needed before its development. Although all the participants stated that they were aware of some existing concept libraries, most of them expressed negative perceptions about them. The participants mentioned several facilitators that would encourage them to: 1) share their work, such as receiving citations from other researchers; and 2) reuse the work of others, such as saving a lot of time and effort, which they frequently spend on creating new code lists from scratch. They also pointed out several barriers that could inhibit them from: 1) sharing their work, such as concerns about intellectual property (e.g., if they shared their methods before publication, other researchers would use them as their own); and 2) reusing others' work, such as a lack of confidence in the quality and validity of their code lists. Participants suggested some developments that they would like to see happen in order to make research that is done with routine data more reproducible, such as the availability of a drive for more transparency in research methods documentation, such as publishing complete phenotype definitions and clear code lists. Conclusions: The findings of this thesis indicated that most participants valued a concept library for phenotypes. However, only half of the participants felt that they would contribute by providing definitions for the concept library, and they reported many barriers regarding sharing their work on a publicly accessible platform such as the CALIBER research platform. Analysis of interviews, focus group discussions, and qualitative studies revealed that different users have different requirements, facilitators, barriers, and concerns about concept libraries. This work was to investigate if we should develop concept libraries in Kuwait to facilitate the development of improved data sharing. However, at the end of this thesis the recommendation is this would be unlikely to be cost effective or highly valued by users and investment in open access research publications may be of more value to the Kuwait research/academic community

Front-Line Physicians' Satisfaction with Information Systems in Hospitals

Day-to-day operations management in hospital units is difficult due to continuously varying situations, several actors involved and a vast number of information systems in use. The aim of this study was to describe front-line physicians' satisfaction with existing information systems needed to support the day-to-day operations management in hospitals. A cross-sectional survey was used and data chosen with stratified random sampling were collected in nine hospitals. Data were analyzed with descriptive and inferential statistical methods. The response rate was 65 % (n = 111). The physicians reported that information systems support their decision making to some extent, but they do not improve access to information nor are they tailored for physicians. The respondents also reported that they need to use several information systems to support decision making and that they would prefer one information system to access important information. Improved information access would better support physicians' decision making and has the potential to improve the quality of decisions and speed up the decision making process.Peer reviewe