BACKGROUND: The Network University Medicine projects are an important part of the German COVID-19 research infrastructure. They comprise 2 subprojects: COVID-19 Data Exchange (CODEX) and Coordination on Mobile Pandemic Apps Best Practice and Solution Sharing (COMPASS). CODEX provides a centralized and secure data storage platform for research data, whereas in COMPASS, expert panels were gathered to develop a reference app framework for capturing patient-reported outcomes (PROs) that can be used by any researcher.
OBJECTIVE: Our study aims to integrate the data collected with the COMPASS reference app framework into the central CODEX platform, so that they can be used by secondary researchers. Although both projects used the Fast Healthcare Interoperability Resources (FHIR) standard, it was not used in a way that data could be shared directly. Given the short time frame and the parallel developments within the CODEX platform, a pragmatic and robust solution for an interface component was required.
METHODS: We have developed a means to facilitate and promote the use of the German Corona Consensus (GECCO) data set, a core data set for COVID-19 research in Germany. In this way, we ensured semantic interoperability for the app-collected PRO data with the COMPASS app. We also developed an interface component to sustain syntactic interoperability.
RESULTS: The use of different FHIR types by the COMPASS reference app framework (the general-purpose FHIR Questionnaire) and the CODEX platform (eg, Patient, Condition, and Observation) was found to be the most significant obstacle. Therefore, we developed an interface component that realigns the Questionnaire items with the corresponding items in the GECCO data set and provides the correct resources for the CODEX platform. We extended the existing COMPASS questionnaire editor with an import function for GECCO items, which also tags them for the interface component. This ensures syntactic interoperability and eases the reuse of the GECCO data set for researchers.
CONCLUSIONS: This paper shows how PRO data, which are collected across various studies conducted by different researchers, can be captured in a research-compatible way. This means that the data can be shared with a central research infrastructure and be reused by other researchers to gain more insights about COVID-19 and its sequelae.

BACKGROUND: Interoperability between health information systems is a fundamental requirement to guarantee the continuity of health care for the population. The Fast Healthcare Interoperability Resource (FHIR) is the standard that enables the design and development of interoperable systems with broad adoption worldwide. However, FHIR training curriculums need an easily administered web-based self-learning platform with modules to create scenarios and questions that the learner answers. This paper proposes a system for teaching FHIR that automatically evaluates the answers, providing the learner with continuous feedback and progress.
OBJECTIVE: We are designing and developing a learning management system for creating, applying, deploying, and automatically assessing FHIR web-based courses.
METHODS: The system requirements for teaching FHIR were collected through interviews with experts involved in academic and professional FHIR activities (universities and health institutions). The interviews were semistructured, recording and documenting each meeting. In addition, we used an ad hoc instrument to register and analyze all the needs to elicit the requirements. Finally, the information obtained was triangulated with the available evidence. This analysis was carried out with Atlas-ti software. For design purposes, the requirements were divided into functional and nonfunctional. The functional requirements were (1) a test and question manager, (2) an application programming interface (API) to orchestrate components, (3) a test evaluator that automatically evaluates the responses, and (4) a client application for students. Security and usability are essential nonfunctional requirements to design functional and secure interfaces. The software development methodology was based on the traditional spiral model. The end users of the proposed system are (1) the system administrator for all technical aspects of the server, (2) the teacher designing the courses, and (3) the students interested in learning FHIR.
RESULTS: The main result described in this work is Huemul, a learning management system for training on FHIR, which includes the following components: (1) Huemul Admin: a web application to create users, tests, and questions and define scores; (2) Huemul API: module for communication between different software components (FHIR server, client, and engine); (3) Huemul Engine: component for answers evaluation to identify differences and validate the content; and (4) Huemul Client: the web application for users to show the test and questions. Huemul was successfully implemented with 416 students associated with the 10 active courses on the platform. In addition, the teachers have created 60 tests and 695 questions. Overall, the 416 students who completed their courses rated Huemul highly.
CONCLUSIONS: Huemul is the first platform that allows the creation of courses, tests, and questions that enable the automatic evaluation and feedback of FHIR operations. Huemul has been implemented in multiple FHIR teaching scenarios for health care professionals. Professionals trained on FHIR with Huemul are leading successful national and international initiatives.

Background: The COVID-19 pandemic has spurred large-scale, interinstitutional research efforts. To enable these efforts, researchers must agree on data set definitions that not only cover all elements relevant to the respective medical specialty but also are syntactically and semantically interoperable. Therefore, the German Corona Consensus (GECCO) data set was developed as a harmonized, interoperable collection of the most relevant data elements for COVID-19-related patient research. As the GECCO data set is a compact core data set comprising data across all medical fields, the focused research within particular medical domains demands the definition of extension modules that include data elements that are the most relevant to the research performed in those individual medical specialties. Objective: We aimed to (1) specify a workflow for the development of interoperable data set definitions that involves close collaboration between medical experts and information scientists and (2) apply the workflow to develop data set definitions that include data elements that are the most relevant to COVID-19-related patient research regarding immunization, pediatrics, and cardiology. Methods: We developed a workflow to create data set definitions that were (1) content-wise as relevant as possible to a specific field of study and (2) universally usable across computer systems, institutions, and countries (ie, interoperable). We then gathered medical experts from 3 specialties-infectious diseases (with a focus on immunization), pediatrics, and cardiology-to select data elements that were the most relevant to COVID-19-related patient research in the respective specialty. We mapped the data elements to international standardized vocabularies and created data exchange specifications, using Health Level Seven International (HL7) Fast Healthcare Interoperability Resources (FHIR). All steps were performed in close interdisciplinary collaboration with medical domain experts and medical information specialists. Profiles and vocabulary mappings were syntactically and semantically validated in a 2-stage process. Results: We created GECCO extension modules for the immunization, pediatrics, and cardiology domains according to pandemic-related requests. The data elements included in each module were selected, according to the developed consensus-based workflow, by medical experts from these specialties to ensure that the contents aligned with their research needs. We defined data set specifications for 48 immunization, 150 pediatrics, and 52 cardiology data elements that complement the GECCO core data set. We created and published implementation guides, example implementations, and data set annotations for each extension module. Conclusions: The GECCO extension modules, which contain data elements that are the most relevant to COVID-19-related patient research on infectious diseases (with a focus on immunization), pediatrics, and cardiology, were defined in an interdisciplinary, iterative, consensus-based workflow that may serve as a blueprint for developing further data set definitions. The GECCO extension modules provide standardized and harmonized definitions of specialty-related data sets that can help enable interinstitutional and cross-country COVID-19 research in these specialties.

The National Institute of Health (NIH) Genetic Testing Registry (GTR) provides a variety of information about genetic tests such as relevant methods, conditions, and performing laboratories. This study mapped a subset of GTR data to the newly developed HL7®-FHIR® Genomic Study resource. Using open-source tools, a web application was developed to implement data mapping and provides many GTR test records as Genomic Study resources. The developed system demonstrates the feasibility of using open-source tools and the FHIR Genomic Study resource to represent publicly available genetic testing information. This study validates the overall design of the Genomic Study resource and proposes two enhancements to support additional data elements.

BACKGROUND: Increasing digitalization in the medical domain gives rise to large amounts of health care data, which has the potential to expand clinical knowledge and transform patient care if leveraged through artificial intelligence (AI). Yet, big data and AI oftentimes cannot unlock their full potential at scale, owing to nonstandardized data formats, lack of technical and semantic data interoperability, and limited cooperation between stakeholders in the health care system. Despite the existence of standardized data formats for the medical domain, such as Fast Healthcare Interoperability Resources (FHIR), their prevalence and usability for AI remain limited.
OBJECTIVE: In this paper, we developed a data harmonization pipeline (DHP) for clinical data sets relying on the common FHIR data standard.
METHODS: We validated the performance and usability of our FHIR-DHP with data from the Medical Information Mart for Intensive Care IV database.
RESULTS: We present the FHIR-DHP workflow in respect of the transformation of \"raw\" hospital records into a harmonized, AI-friendly data representation. The pipeline consists of the following 5 key preprocessing steps: querying of data from hospital database, FHIR mapping, syntactic validation, transfer of harmonized data into the patient-model database, and export of data in an AI-friendly format for further medical applications. A detailed example of FHIR-DHP execution was presented for clinical diagnoses records.
CONCLUSIONS: Our approach enables the scalable and needs-driven data modeling of large and heterogenous clinical data sets. The FHIR-DHP is a pivotal step toward increasing cooperation, interoperability, and quality of patient care in the clinical routine and for medical research.

BACKGROUND: Vital signs have been widely adopted in in-hospital cardiac arrest (IHCA) assessment, which plays an important role in inpatient deterioration detection. As the number of early warning systems and artificial intelligence applications increases, health care information exchange and interoperability are becoming more complex and difficult. Although Health Level 7 Fast Healthcare Interoperability Resources (FHIR) have already developed a vital signs profile, it is not sufficient to support IHCA applications or machine learning-based models.
OBJECTIVE: In this paper, for IHCA instances with vital signs, we define a new implementation guide that includes data mapping, a system architecture, a workflow, and FHIR applications.
METHODS: We interviewed 10 experts regarding health care system integration and defined an implementation guide. We then developed the FHIR Extract Transform Load to map data to FHIR resources. We also integrated an early warning system and machine learning pipeline.
RESULTS: The study data set includes electronic health records of adult inpatients who visited the En-Chu-Kong hospital. Medical staff regularly measured these vital signs at least 2 to 3 times per day during the day, night, and early morning. We used pseudonymization to protect patient privacy. Then, we converted the vital signs to FHIR observations in the JSON format using the FHIR Extract Transform Load application. The measured vital signs include systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and body temperature. According to clinical requirements, we also extracted the electronic health record information to the FHIR server. Finally, we integrated an early warning system and machine learning pipeline using the FHIR RESTful application programming interface.
CONCLUSIONS: We successfully demonstrated a process that standardizes health care information for inpatient deterioration detection using vital signs. Based on the FHIR definition, we also provided an implementation guide that includes data mapping, an integration process, and IHCA assessment using vital signs. We also proposed a clarifying system architecture and possible workflows. Based on FHIR, we integrated the 3 different systems in 1 dashboard system, which can effectively solve the complexity of the system in the medical staff workflow.

Heterogeneity is a problem in storing and exchanging data in a digital health information system (HIS) following semantic and structural integrity. The existing literature shows different methods to overcome this problem. Fast healthcare interoperable resources (FHIR) as a structural standard may explain other information models, (e.g., personal, physiological, and behavioral data from heterogeneous sources, such as activity sensors, questionnaires, and interviews) with semantic vocabularies, (e.g., Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT)) to connect personal health data to an electronic health record (EHR). We design and develop an intuitive health coaching (eCoach) smartphone application to prove the concept. We combine HL7 FHIR and SNOMED-CT vocabularies to exchange personal health data in JavaScript object notion (JSON). This study explores and analyzes our attempt to design and implement a structurally and logically compatible tethered personal health record (PHR) that allows bidirectional communication with an EHR. Our eCoach prototype implements most PHR-S FM functions as an interoperability quality standard. Its end-to-end (E2E) data are protected with a TSD (Services for Sensitive Data) security mechanism. We achieve 0% data loss and 0% unreliable performances during data transfer between PHR and EHR. Furthermore, this experimental study shows the effectiveness of FHIR modular resources toward flexible management of data components in the PHR (eCoach) prototype.

Clinical Trial Recruitment Support Systems can booster patient inclusion of clinical trials by automatically analyzing eligibility criteria based on electronic health records. However, missing interoperability has hindered introduction of those systems on a broader scale. Therefore, our aim was to develop a recruitment support system based on FHIR R4 and evaluate its usage and features in a cardiology department. Clinical conditions, anamnesis, examinations, allergies, medication, laboratory data and echocardiography results were imported as FHIR resources. Clinical trial information, eligibility criteria and recruitment status were recorded using the appropriate FHIR resources without extensions. Eligibility criteria linked by the logical operation \"OR\" were represented by using multiple FHIR Group resources for enrollment. The system was able to identify 52 of 55 patients included in four clinical trials. In conclusion, use of FHIR for defining eligibility criteria of clinical trials may facilitate interoperability and allow automatic screening for eligible patients at multiple sites of different healthcare providers in the future. Upcoming changes in FHIR should allow easier description of \"OR\"-linked eligibility criteria.

BACKGROUND: An essential step in any medical research project after identifying the research question is to determine if there are sufficient patients available for a study and where to find them. Pursuing digital feasibility queries on available patient data registries has proven to be an excellent way of reusing existing real-world data sources. To support multicentric research, these feasibility queries should be designed and implemented to run across multiple sites and securely access local data. Working across hospitals usually involves working with different data formats and vocabularies. Recently, the Fast Healthcare Interoperability Resources (FHIR) standard was developed by Health Level Seven to address this concern and describe patient data in a standardized format. The Medical Informatics Initiative in Germany has committed to this standard and created data integration centers, which convert existing data into the FHIR format at each hospital. This partially solves the interoperability problem; however, a distributed feasibility query platform for the FHIR standard is still missing.
OBJECTIVE: This study described the design and implementation of the components involved in creating a cross-hospital feasibility query platform for researchers based on FHIR resources. This effort was part of a large COVID-19 data exchange platform and was designed to be scalable for a broad range of patient data.
METHODS: We analyzed and designed the abstract components necessary for a distributed feasibility query. This included a user interface for creating the query, backend with an ontology and terminology service, middleware for query distribution, and FHIR feasibility query execution service.
RESULTS: We implemented the components described in the Methods section. The resulting solution was distributed to 33 German university hospitals. The functionality of the comprehensive network infrastructure was demonstrated using a test data set based on the German Corona Consensus Data Set. A performance test using specifically created synthetic data revealed the applicability of our solution to data sets containing millions of FHIR resources. The solution can be easily deployed across hospitals and supports feasibility queries, combining multiple inclusion and exclusion criteria using standard Health Level Seven query languages such as Clinical Quality Language and FHIR Search. Developing a platform based on multiple microservices allowed us to create an extendable platform and support multiple Health Level Seven query languages and middleware components to allow integration with future directions of the Medical Informatics Initiative.
CONCLUSIONS: We designed and implemented a feasibility platform for distributed feasibility queries, which works directly on FHIR-formatted data and distributed it across 33 university hospitals in Germany. We showed that developing a feasibility platform directly on the FHIR standard is feasible.

BACKGROUND: The COVID-19 pandemic highlighted the importance of making research data from all German hospitals available to scientists to respond to current and future pandemics promptly. The heterogeneous data originating from proprietary systems at hospitals\' sites must be harmonized and accessible. The German Corona Consensus Dataset (GECCO) specifies how data for COVID-19 patients will be standardized in Fast Healthcare Interoperability Resources (FHIR) profiles across German hospitals. However, given the complexity of the FHIR standard, the data harmonization is not sufficient to make the data accessible. A simplified visual representation is needed to reduce the technical burden, while allowing feasibility queries.
OBJECTIVE: This study investigates how a search ontology can be automatically generated using FHIR profiles and a terminology server. Furthermore, it describes how this ontology can be used in a user interface (UI) and how a mapping and a terminology tree created together with the ontology can translate user input into FHIR queries.
METHODS: We used the FHIR profiles from the GECCO data set combined with a terminology server to generate an ontology and the required mapping files for the translation. We analyzed the profiles and identified search criteria for the visual representation. In this process, we reduced the complex profiles to code value pairs for improved usability. We enriched our ontology with the necessary information to display it in a UI. We also developed an intermediate query language to transform the queries from the UI to federated FHIR requests. Separation of concerns resulted in discrepancies between the criteria used in the intermediate query format and the target query language. Therefore, a mapping was created to reintroduce all information relevant for creating the query in its target language. Further, we generated a tree representation of the ontology hierarchy, which allows resolving child concepts in the process.
RESULTS: In the scope of this project, 82 (99%) of 83 elements defined in the GECCO profile were successfully implemented. We verified our solution based on an independently developed test patient. A discrepancy between the test data and the criteria was found in 6 cases due to different versions used to generate the test data and the UI profiles, the support for specific code systems, and the evaluation of postcoordinated Systematized Nomenclature of Medicine (SNOMED) codes. Our results highlight the need for governance mechanisms for version changes, concept mapping between values from different code systems encoding the same concept, and support for different unit dimensions.
CONCLUSIONS: We developed an automatic process to generate ontology and mapping files for FHIR-formatted data. Our tests found that this process works for most of our chosen FHIR profile criteria. The process established here works directly with FHIR profiles and a terminology server, making it extendable to other FHIR profiles and demonstrating that automatic ontology generation on FHIR profiles is feasible.