TBase - an Integrated Electronic Health Record and Research Database for Kidney Transplant Recipients

Summary

TBase combines an electronic health record with an innovative research database for kidney transplant recipients. TBase is built upon an in-memory database platform, connected to different hospital systems, and used for regular outpatient care. It automatically integrates all relevant clinical data including transplantation-specific data creating a unique research database.

Abstract

TBase is an electronic health record (EHR) for kidney transplant recipients (KTR) combining automated data entry of key clinical data (e.g., laboratory values, medical reports, radiology and pathology data) via standardized interfaces with manual data entry during routine treatment (e.g., clinical notes, medication list, and transplantation data). By this means, a comprehensive database for KTR is created with benefits for routine clinical care and research. It enables both easy everyday clinical use and quick access for research questions with highest data quality. This is achieved by the concept of data validation in clinical routine in which clinical users and patients have to rely on correct data for treatment and medication plans and thereby validate and correct the clinical data in their daily practice. This EHR is tailored for the needs of transplant outpatient care and proved its clinical utility for more than 20 years at Charité – Universitätsmedizin Berlin. It facilitates efficient routine work with well-structured, comprehensive long-term data and allows their easy use for clinical research. To this point, its functionality covers automated transmission of routine data via standardized interfaces from different hospital information systems, availability of transplant-specific data, a medication list with an integrated check for drug-drug interactions, and semi-automated generation of medical reports among others. Key elements of the latest reengineering are a robust privacy-by-design concept, modularity, and hence portability into other clinical contexts as well as usability and platform independence enabled by HTML5 (Hypertext Markup Language) based responsive web design. This allows fast and easy scalability into other disease areas and other university hospitals. The comprehensive long-term datasets are the basis for the investigation of Machine Learning algorithms, and the modular structure allows to rapidly implement these into clinical care. Patient reported data and telemedicine services are integrated into TBase in order to meet future needs of the patients. These novel features aim to improve clinical care as well as to create new research options and therapeutic interventions.

Introduction

Motivation for an integrated electronic health record and research database
Clinical research is based on the availability of high-quality data, regardless of whether classical statistical methods or Machine Learning (ML) techniques are used for analysis^1,2. In addition to routine data (e.g., demographic, laboratory, and medication data), domain-specific data (e.g., transplantation-relevant data) are required with high granularity^3,4. However, routine care at many university hospitals is performed with hospital information systems (HIS) that neither allow for systematic collection of research-specific data nor for easy data extraction of routine data^5,6,7. As a result, clinical researchers create specific research databases, which have a variety of problems including complex process of setting up a database, manual data entry, data protection issues, and long-term maintenance (Table 1). Limited amount of data, missing data, and inconsistencies are a major problem for clinical research in general and impede the use of ML technologies^{8,9,10,11,12,13}. These standalone research databases are usually focused on certain disease or patient aspects, not connected to other databases, and often discontinued after a certain period, resulting in inaccessible "data silos". Ultimately, high-quality, long-term data on various disease aspects are sparse. In the era of digital medicine there is an increasing need for a comprehensive electronic health record (EHR)^7,14,15, which enables easy documentation of domain-specific data and automated collection of routine data from the systems of inpatient and outpatient care.

These general considerations apply to transplantation medicine as well¹⁶. Hence, a complete documentation of the patient's medical history including all inpatient and outpatient treatments, clinical routine data as well as transplantation-specific data is necessary for successful follow-up care^17,18. Since ordinary HIS are static and focused on inpatient treatment, they cannot integrate transplantation-specific data, such as donor data, cold ischemia times, and human leukocyte antigens (HLA) data. However, these data are a basic prerequisite for transplantation research^19,20,21,22 as well as from long-term clinical care. While the initial hospital stay usually is only 1-2 weeks and processes as well as early outcomes after kidney transplantation are comparable between many transplant centers, lifelong post-transplant care is complicated and lacks a common structured approach. This motivates an integrated EHR and research database to capture the lifelong post-transplant patient journey.²³

In order to integrate these functionalities for routine care and research of KTR, an EHR named "TBase" was developed with the idea that the routine use for post-transplant care will create a unique research database with highest data quality (Table 2).

Design and Architecture
TBase is based on a typical client-server architecture. For development, the components and tools of SAP High Performance Analytic Appliance extended application advanced (SAP HANA XSA) were used. Based on the latest Hypertext Markup Language 5 (HTML5) web-technologies the EHR has been developed and tested for the Google Chrome Engine. This web engine is used by Chrome and the Microsoft Edge Browser and allows to use the EHR in the most frequently used web browsers²⁴ without the need for local installation. The applied technology enables a responsive web design and allows the web-based EHR to be used on all devices (PC, tablet, smartphone). The innovative high-performance development platform is composed of various components (Web IDE, UI5 and HANA DB) and has enabled us to rapidly implement the EHR project TBase with state-of-the-art software tools (Figure 1).

For the representation of patient data, a simple table structure was implemented for an intuitive and self-explanatory design of the EHR. For example, the patient table with the PatientID as the primary key is at the center of the table structure. Almost all tables (except individual sub-tables) are connected to this central table through PatientID (Figure 2).

Figure 3 shows part of TBase's table structure and the data types used in greater detail. The end user can access the data fields via graphical user interface (GUI), for which an example is shown in Figure 4.

This EHR contains all current patient data and is used for routine outpatient care. Important routine clinical data (e.g., laboratory data, medical results, radiology, microbiology, virology and pathology data, hospital data, etc.) are directly imported into TBase via standardized interfaces (e.g., on the basis of Health Level Seven (HL7) – a standard for digital communication in the healthcare sector²⁵). Transplant-specific data such as cold ischemia times, donor data, HLA data as well as follow-up notes, vital signs, medical reports and the medication list are entered by the users via GUI into the EHR. Before data are transferred to the database, an automated plausibility check is performed for prompt detection of erroneous data entry providing the option to correct immediately. In addition, data validation takes part during clinical routine in which clinical users routinely write reports and letters to patients and physicians. These letters must provide correct data (e.g., on medication, lab values and clinical remarks) for further treatment and medication plans. As a consequence physicians and patients constantly validate and correct the clinical data in their daily practice, a process resulting in high data quality. If data are entered via application programming interfaces (API) or other interfaces, plausibility checks are performed in the backend similarly to the plausibility checks in the frontend.

Frontend (GUI)
To implement the frontend, the UI5 Framework is used. This framework provides an extensive library for frontend elements as well as a variety of additional features such as multilingualism and graphical libraries for data visualization. Currently, TBase frontend elements are displayed either in English or German depending on the language setting of the browser.

A master-detail interface is used for the frontend to ensure a simple, intuitive page structure. The upper part of the viewing page consists of individual tabs for the detail pages (basic data, medical data, transplantation data, etc.). This master part remains unchanged regardless of which detail page is shown below (Figure 4). The detail view of each page enables an easy overview on the page topic.

For data manipulation, the EHR has different levels of user rights ("read", "write", "delete", and "administrator"). There is an "edit" level in addition to the "view" level, which can only be activated by users with higher rights than "read". If the user has the right to write, all input fields for data entry are activated and can be filled with data. Users with "delete" rights can delete data via a corresponding button, but only after confirmation through a pop-up window.

Database structure and interfaces
The development of TBase is performed in the development database. Extensive and detailed testing of all software changes such as new functionalities is carried out in the quality assurance database. Software updates that pass the quality control checks are transferred to the live system. For research purposes the live system is copied into the replication database, which can be queried via standard Open Database Connectivity (ODBC) interfaces (e.g., via open-source software R Studio). As there is no direct connection between replication and live system the data in the live system are protected from corruption, loss or manipulation of data. This modular structure and the clear separation of the four databases (development, quality assurance, live system and replication database), which are tailored to the specific needs of developers, researchers, and clinicians facilitates maintenance and data protection of sensitive patient data.

The EHR is fully integrated into the Data Infrastructure of Charité and relies on different interfaces for data import from various data sources. The interface to the HIS imports all relevant data such as administrative data, examinations, medications, laboratory findings and discharge letters. This interface connects both systems via a staging area. Here, all new data (data delta) are transferred from the HIS to TBase in real time. Patients are identified via a patient number or case number and the corresponding data from the HIS is imported (if not already available in TBase).

For outpatients, our laboratory partner provides the laboratory results via HL7 messages. These are deployed to a shared area in the laboratory system and picked up via an HL7 interface and imported into the EHR. For bi-directional communication and data exchange with KTR (via smartphone apps) and home nephrologists, a HL7 Fast Healthcare Interoperability Resource (HL7 FHIR) interface was implemented²⁶. This interface grants interoperability and flexibility for a safe data exchange with other data sources (e.g., Eurotransplant, patient apps) in the future.

User Management and Data Protection
TBase is based on user management at the application level. Thus, the user can only access the frontend of the application, but not the database itself. As described above, a four-stage authorization concept was chosen, reserving user management for those with administrative rights. Administrators use an "Identity Management Console" application to add new users from the Charité user pool for the TBase application and to maintain their user rights (Figure 5). Most users can access all patients in the database. However, it is possible to restrict access for specific users such as study monitors to a group of patients.

Using the commercial in-memory database platform a secure database technology that protects data with strategies such as application-level authorization, single sign-on (SSO), MIT-Kerberos protocol and Security Assertion Mark-up Language (SAML) is used. The platform secures communication, data storage, and application services using the latest encryption and testing techniques. All developments on the database are controlled by authorizations. This ensures the security of data by design at a high level. In addition, all data are kept behind the certified Charité firewall. In compliance with the latest European Union General Data Protection Regulation (EU GDPR) a robust data protection concept was implemented, including data flow diagrams, data protection risk assessment (DSFA) and authorization concept. All documents are laid down in a procedure directory of the Charité Data Protection Office.

Protocol

The protocol demonstrates the use of the electronic health record TBase, how to add data into the database, and how to extract them for research purposes. All steps are in accordance with the guidelines of the human research ethics committee of Charité – Universitätsmedizin Berlin. 1. Register a new patient and add basic patient data into TBase Upon registration, transfer the patient's basic data (name, birth date, and health insurance data) from the patient's hea…

Representative Results

TBase was first released in 1999 at Charité Campus Mitte and is in use ever since. For more than 20 years the TBase-EHR prospectively collects data from all KTR. Starting in 2001, the other transplant programs at Charité used TBase for the routine care of KTR and wait-listed patients as well. Since 2007, this EHR is in use for routine care of living donors and all patients in the department of nephrology. By providing the TBase software with its functionalities, which has been furthe…

Discussion

TBase combines a web-based EHR for specialized outpatient care of KTR with a research database, creating a comprehensive long-term database for patients with kidney disease^6,11,15,37. Regarding organizational structure, this is enabled by implementing a modern software design process as an institutional agent and including over 20 years of experience as developers, clinical users and researcher…

Materials

Developer platform SAP Web IDE	SAP SE
GUI Toolbox SAPUI5	SAP SE
In-memory database SAP-HANA	SAP SE
Interface Standard HL7	Health Level Seven International
Interface Standard HL7 FHIR	Health Level Seven International
RStudio	RStudio Inc.
TBase – Electronic Health Record	Charité – Universitätsmedizin Berlin
Webserver SAP-HANA XSA	SAP SE