Use of Clinical Data Interchange Standards Consortium (CDISC) Standards for Real-world Data: Expert Perspectives From a Qualitative Delphi Survey.

BACKGROUND: Real-world data (RWD) and real-world evidence (RWE) are playing increasingly important roles in clinical research and health care decision-making. To leverage RWD and generate reliable RWE, data should be well defined and structured in a way that is semantically interoperable and consistent across stakeholders. The adoption of data standards is one of the cornerstones supporting high-quality evidence for the development of clinical medicine and therapeutics. Clinical Data Interchange Standards Consortium (CDISC) data standards are mature, globally recognized, and heavily used by the pharmaceutical industry for regulatory submissions. The CDISC RWD Connect Initiative aims to better understand the barriers to implementing CDISC standards for RWD and to identify the tools and guidance needed to more easily implement them. OBJECTIVE: The aim of this study is to understand the barriers to implementing CDISC standards for RWD and to identify the tools and guidance that may be needed to implement CDISC standards more easily for this purpose. METHODS: We conducted a qualitative Delphi survey involving an expert advisory board with multiple key stakeholders, with 3 rounds of input and review. RESULTS: Overall, 66 experts participated in round 1, 56 in round 2, and 49 in round 3 of the Delphi survey. Their inputs were collected and analyzed, culminating in group statements. It was widely agreed that the standardization of RWD is highly necessary, and the primary focus should be on its ability to improve data sharing and the quality of RWE. The priorities for RWD standardization included electronic health records, such as data shared using Health Level 7 Fast Health care Interoperability Resources (FHIR), and the data stemming from observational studies. With different standardization efforts already underway in these areas, a gap analysis should be performed to identify the areas where synergies and efficiencies are possible and then collaborate with stakeholders to create or extend existing mappings between CDISC and other standards, controlled terminologies, and models to represent data originating across different sources. CONCLUSIONS: There are many ongoing data standardization efforts around human health data-related activities, each with different definitions, levels of granularity, and purpose. Among these, CDISC has been successful in standardizing clinical trial-based data for regulation worldwide. However, the complexity of the CDISC standards and the fact that they were developed for different purposes, combined with the lack of awareness and incentives to use a new standard and insufficient training and implementation support, are significant barriers to setting up the use of CDISC standards for RWD. The collection and dissemination of use cases, development of tools and support systems for the RWD community, and collaboration with other standards development organizations are potential steps forward. Using CDISC will help link clinical trial data and RWD and promote innovation in health data science.

Evaluating the Coverage of the HL7 ® FHIR ® Standard to Support eSource Data Exchange Implementations for use in Multi-Site Clinical Research Studies.

The direct use of EHR data in research, often referred to as 'eSource', has long-been a goal for researchers because of anticipated increases in data quality and reductions in site burden. eSource solutions should rely on data exchange standards for consistency, quality, and efficiency. The utility of any data standard can be evaluated by its ability to meet specific use case requirements. The Health Level Seven (HL7 ® ) Fast Healthcare Interoperability Resources (FHIR ® ) standard is widely recognized for clinical data exchange; however, a thorough analysis of the standard's data coverage in supporting multi-site clinical studies has not been conducted. We developed and implemented a systematic mapping approach for evaluating HL7 ® FHIR ® standard coverage in multi-center clinical trials. Study data elements from three diverse studies were mapped to HL7 ® FHIR ® resources, offering insight into the coverage and utility of the standard for supporting the data collection needs of multi-site clinical research studies.

Visualizing and Validating Metadata Traceability within the CDISC Standards.

The Food & Drug Administration has begun requiring that electronic submissions of regulated clinical studies utilize the Clinical Data Information Standards Consortium data standards. Within regulated clinical research, traceability is a requirement and indicates that the analysis results can be traced back to the original source data. Current solutions for clinical research data traceability are limited in terms of querying, validation and visualization capabilities. This paper describes (1) the development of metadata models to support computable traceability and traceability visualizations that are compatible with industry data standards for the regulated clinical research domain, (2) adaptation of graph traversal algorithms to make them capable of identifying traceability gaps and validating traceability across the clinical research data lifecycle, and (3) development of a traceability query capability for retrieval and visualization of traceability information.

Current applications and future directions for the CDISC Operational Data Model standard: A methodological review.

INTRODUCTION: In order to further advance research and development on the Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model (ODM) standard, the existing research must be well understood. This paper presents a methodological review of the ODM literature. Specifically, it develops a classification schema to categorize the ODM literature according to how the standard has been applied within the clinical research data lifecycle. This paper suggests areas for future research and development that address ODM's limitations and capitalize on its strengths to support new trends in clinical research informatics. METHODS: A systematic scan of the following databases was performed: (1) ABI/Inform, (2) ACM Digital, (3) AIS eLibrary, (4) Europe Central PubMed, (5) Google Scholar, (5) IEEE Xplore, (7) PubMed, and (8) ScienceDirect. A Web of Science citation analysis was also performed. The search term used on all databases was "CDISC ODM." The two primary inclusion criteria were: (1) the research must examine the use of ODM as an information system solution component, or (2) the research must critically evaluate ODM against a stated solution usage scenario. Out of 2686 articles identified, 266 were included in a title level review, resulting in 183 articles. An abstract review followed, resulting in 121 remaining articles; and after a full text scan 69 articles met the inclusion criteria. RESULTS: As the demand for interoperability has increased, ODM has shown remarkable flexibility and has been extended to cover a broad range of data and metadata requirements that reach well beyond ODM's original use cases. This flexibility has yielded research literature that covers a diverse array of topic areas. A classification schema reflecting the use of ODM within the clinical research data lifecycle was created to provide a categorized and consolidated view of the ODM literature. The elements of the framework include: (1) EDC (Electronic Data Capture) and EHR (Electronic Health Record) infrastructure; (2) planning; (3) data collection; (4) data tabulations and analysis; and (5) study archival. The analysis reviews the strengths and limitations of ODM as a solution component within each section of the classification schema. This paper also identifies opportunities for future ODM research and development, including improved mechanisms for semantic alignment with external terminologies, better representation of the CDISC standards used end-to-end across the clinical research data lifecycle, improved support for real-time data exchange, the use of EHRs for research, and the inclusion of a complete study design. CONCLUSIONS: ODM is being used in ways not originally anticipated, and covers a diverse array of use cases across the clinical research data lifecycle. ODM has been used as much as a study metadata standard as it has for data exchange. A significant portion of the literature addresses integrating EHR and clinical research data. The simplicity and readability of ODM has likely contributed to its success and broad implementation as a data and metadata standard. Keeping the core ODM model focused on the most fundamental use cases, while using extensions to handle edge cases, has kept the standard easy for developers to learn and use.

ß-lactam-associated eosinophilic colitis.

A 42-year-old man with a history of childhood asthma presented with a 2-week history of watery diarrhoea and marked peripheral eosinophilia in the setting of recent use of cephalexin. His colonoscopy revealed patchy colitis. Biopsies were consistent with eosinophilic colitis. Two months later he received a course of amoxicillin resulting in recurrence of peripheral eosinophilia. Given the time-frame of ß-lactam administration to symptom onset and elimination of all other precipitating causes, he was diagnosed with ß-lactam-associated eosinophilic colitis. The patient's symptoms resolved and peripheral eosinophil count decreased with no specific treatment. Eosinophilic colitis is a rare heterogeneous condition, the pathogenesis of which is likely to be an interplay between environmental and genetic factors. It can be secondary to a helminthic infection or a drug reaction and has been associated with ulcerative colitis. If secondary causes of eosinophilic colitis have been excluded, the mainstay of treatment is with corticosteroids.

Educating international students about tuberculosis and infections associated with travel to visit friends and relatives (VFR-travel).

BACKGROUND: International students in Victoria, Australia, originate from over 140 different countries. They are over-represented in disease notifications for tuberculosis and travel-associated infections, including enteric fever, hepatitis A, and malaria. We describe a public health initiative aimed to increase awareness of these illnesses among international students and their support staff. METHODS: We identified key agencies including student support advisors, medical practitioners, health insurers, and government and professional organisations. We developed health education materials targeting international students regarding tuberculosis and travel-related infections to be disseminated via a number of different media, including electronic and printed materials. We sought informal feedback from personnel in all interested agencies regarding the materials developed, their willingness to deliver these materials to international students, and their preferred media for disseminating these materials. RESULTS: Education institutions with dedicated international student support staff and on-campus health clinics were more easily engaged to provide feedback and disseminate the health education materials than institutions without such dedicated personnel. Response to contacting off-campus medical practices was poor. Delivery of educational materials via electronic and social media was preferred over face-to-face education. CONCLUSIONS: It is feasible to provide health education messages targeting international students for dissemination via appropriately-staffed educational institutions. This initiative could be expanded in terms of age-group, geographic range, and health issues to be targeted.