The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies.

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for.

A FHIR has been lit on gICS: facilitating the standardised exchange of informed consent in a large network of university medicine.

BACKGROUND: The Federal Ministry of Education and Research of Germany (BMBF) funds a network of university medicines (NUM) to support COVID-19 and pandemic research at national level. The "COVID-19 Data Exchange Platform" (CODEX) as part of NUM establishes a harmonised infrastructure that supports research use of COVID-19 datasets. The broad consent (BC) of the Medical Informatics Initiative (MII) is agreed by all German federal states and forms the legal base for data processing. All 34 participating university hospitals (NUM sites) work upon a harmonised infrastructural as well as legal basis for their data protection-compliant collection and transfer of their research dataset to the central CODEX platform. Each NUM site ensures that the exchanged consent information conforms to the already-balloted HL7 FHIR consent profiles and the interoperability concept of the MII Task Force "Consent Implementation" (TFCI). The Independent Trusted Third-Party (TTP) of the University Medicine Greifswald supports data protection-compliant data processing and provides the consent management solutions gICS. METHODS: Based on a stakeholder dialogue a required set of FHIR-functionalities was identified and technically specified supported by official FHIR experts. Next, a "TTP-FHIR Gateway" for the HL7 FHIR-compliant exchange of consent information using gICS was implemented. A last step included external integration tests and the development of a pre-configured consent template for the BC for the NUM sites. RESULTS: A FHIR-compliant gICS-release and a corresponding consent template for the BC were provided to all NUM sites in June 2021. All FHIR functionalities comply with the already-balloted FHIR consent profiles of the HL7 Working Group Consent Management. The consent template simplifies the technical BC rollout and the corresponding implementation of the TFCI interoperability concept at the NUM sites. CONCLUSIONS: This article shows that a HL7 FHIR-compliant and interoperable nationwide exchange of consent information could be built using of the consent management software gICS and the provided TTP-FHIR Gateway. The initial functional scope of the solution covers the requirements identified in the NUM-CODEX setting. The semantic correctness of these functionalities was validated by project-partners from the Ludwig-Maximilian University in Munich. The production rollout of the solution package to all NUM sites has started successfully.

The generic Informed Consent Service gICS®: implementation and benefits of a modular consent software tool to master the challenge of electronic consent management in research.

BACKGROUND: Defining and protecting participants' rights is the aim of several ethical codices and legal regulations. According to these regulations, the Informed Consent (IC) is an inevitable element of research with human subjects. In the era of "big data medicine", aspects of IC become even more relevant since research becomes more complex rendering compliance with legal and ethical regulations increasingly difficult. METHODS: Based on literature research and practical experiences gathered by the Institute for Community Medicine (ICM), University Medicine Greifswald, requirements for digital consent management systems were identified. RESULTS: To address the requirements, the free-of-charge, open-source software "generic Informed Consent Service" (gICS®) was developed by ICM to provide a tool to facilitate and enhance usage of digital ICs for the international research community covering various scenarios. gICS facilitates IC management based on IC modularisation and supports various workflows within research, including (1) electronic depiction of paper-based consents and (2) fully electronic consents. Numerous projects applied gICS and documented over 336,000 ICs and 2400 withdrawals since 2014. DISCUSSION: Since the consent's content is a prerequisite for securing participants' rights, application of gICS is no guarantee for legal compliance. However, gICS supports fine-granular consents and accommodation of differentiated consent states, which can be directly exchanged between systems, allowing automated data processing. CONCLUSION: gICS simplifies and supports sustained IC management as a major key to successfully conduct studies and build trust in research with human subjects. Therefore, interested researchers are invited to use gICS and provide feedback for further improvements.

Assessment of scalability and performance of the record linkage tool E-PIX® in managing multi-million patients in research projects at a large university hospital in Germany.

BACKGROUND: The identity management is a central component in medical research. Patients are recruited from various sites, which requires an error tolerant record linkage method, to ensure that patients are registered only once. In large research projects or institutions, the identity management has to deal with several thousands or millions of patients. In environments with large numbers of patients the register process could lead to high runtimes caused by record linkage. The Central Biomaterial Bank of the Charité (ZeBanC) searched for an identity management solution, which can handle millions of patients in large research projects with an acceptable performance. The goal of this paper was to simulate the registration of several million patients using the E-PIX service at Charité - Universitätsmedizin Berlin. The E-PIX service was evaluated in terms of needed runtimes, memory requirements, and processor utilization. A total of at least 20 million patients had to be registered. The runtimes to register patients into databases with various sizes should be examined, and the maximum number of patients, which the E-PIX service could handle, should be determined. METHODS: Tools were set up or developed to measure the needed runtimes, the memory used and the processor usage to register patients into various sizes of databases. To generate runtimes close to reality, modified patient data based on transposed real patient data were used for the simulation. The transposed patient data were sent to E-PIX to measure the runtimes of the registration process. This measurement was repeated for various database sizes. RESULTS: E-PIX is suitable to manage multi-million patients within a dataset. With the given hardware, it was possible to register a total of more than 30 million patients. It was possible to register more than 16 thousand patients per day into this database. CONCLUSIONS: The E-PIX tool fulfills the requirements of the Charité to be used for large research projects. The use of E-PIX is intended for the research context in the Charité.

MAGIC: once upon a time in consent management-a FHIR® tale.

BACKGROUND: The use of medical data for research purposes requires an informed consent of the patient that is compliant with the EU General Data Protection Regulation. In the context of multi-centre research initiatives and a multitude of clinical and epidemiological studies scalable and automatable measures for digital consent management are required. Modular form, structure, and contents render a patient's consent reusable for varying project settings in order to effectively manage and minimise organisational and technical efforts. RESULTS: Within the DFG-funded project "MAGIC" (Grant Number HO 1937/5-1) the digital consent management service tool gICS was enhanced to comply with the recommendations published in the TMF data protection guideline for medical research. In addition, a structured exchange format for modular consent templates considering established standards and formats in the area of digital informed consent management was designed. Using the new FHIR standard and the HAPI FHIR library, the first version for an exchange format and necessary import-/export-functionalities were successfully implemented. CONCLUSIONS: The proposed exchange format is a "work in progress". It represents a starting point for current discussions concerning digital consent management. It also attempts to improve interoperability between different approaches within the wider IHE-/HL7-/FHIR community. Independent of the exchange format, providing the possibility to export, modify and import templates for consents and withdrawals to be reused in similar clinical and epidemiological studies is an essential precondition for the sustainable operation of digital consent management.

Data privacy management and data quality monitoring in the German Centre for Cardiovascular Research's multicentre TranslatiOnal Registry for CardiomyopatHies (DZHK-TORCH).

AIMS: The multicentric TranslatiOnal Registry for CardiomyopatHies (TORCH) of the German Centre for Cardiovascular Research aims to recruit 2300 patients with non-ischemic cardiomyopthies. METHODS AND RESULTS: The investigations were performed after standard operating procedures. The data are collected in standardized electronic case report forms provided by the data holding of the central data management of the German Centre for Cardiovascular Research using secuTrial (interActive Systems GmbH, Berlin, Germany). The personal-identifying data and informed consent are collected, stored, and quality-checked by the independent Trusted Third Party in Greifswald. The quality management of the medical data is performed by the data and quality centre Greifswald. In December 2014, the recruitment for TORCH has started. Currently, data and biomaterial from about 1397 patients and more than 74 500 biomaterial aliquots were collected. Regular study centre-specific quality reports address completeness and plausibility of data and provide detailed information about current missing or implausible data entries to improve the data quality by using a query management in addition. CONCLUSIONS: A regular quality control and reporting improve the data quality in TORCH and will support high-quality data analysis and the translation of research results into routine care.