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.

We Know What You Agreed To, Don't We?-Evaluating the Quality of Paper-Based Consents Forms and Their Digitalized Equivalent Using the Example of the Baltic Fracture Competence Centre Project.

INTRODUCTION: The informed consent is the legal basis for research with human subjects. Therefore, the consent form (CF) as legally binding document must be valid, that is, be completely filled-in stating the person's decision clearly and signed by the respective person. However, especially paper-based CFs might have quality issues and the transformation into machine-readable information could add to low quality. This paper evaluates the quality and arising quality issues of paper-based CFs using the example of the Baltic Fracture Competence Centre (BFCC) fracture registry. It also evaluates the impact of quality assurance (QA) measures including giving site-specific feedback. Finally, it answers the question whether manual data entry of patients' decisions by clinical staff leads to a significant error rate in digitalized paper-based CFs. METHODS: Based on defined quality criteria, monthly QA including source data verification was conducted by two individual reviewers since the start of recruitment in December 2017. Basis for the analyses are the CFs collected from December 2017 until February 2019 (first recruitment period). RESULTS: After conducting QA internally, the sudden increase of quality issues in May 2018 led to site-specific feedback reports and follow-up training regarding the CFs' quality starting in June 2018. Specific criteria and descriptions on how to correct the CFs helped in increasing the quality in a timely matter. Most common issues were missing pages, decisions regarding optional modules, and signature(s). Since patients' datasets without valid CFs must be deleted, QA helped in retaining 65 datasets for research so that the final datapool consisted of 840 (99.29%) patients. CONCLUSION: All quality issues could be assigned to one predefined criterion. Using the example of the BFCC fracture registry, CF-QA proved to significantly increase CF quality and help retain the number of available datasets for research. Consequently, the described quality indicators, criteria, and QA processes can be seen as the best practice approach.

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.

3LGM2IHE: Requirements for Data-Protection-Compliant Research Infrastructures-A Systematic Comparison of Theory and Practice-Oriented Implementation.

OBJECTIVES: The TMF (Technology, Methods, and Infrastructure for Networked Medical Research) Data Protection Guide (TMF-DP) makes path-breaking recommendations on the subject of data protection in research projects. It includes comprehensive requirements for applications such as patient lists, pseudonymization services, and consent management services. Nevertheless, it lacks a structured, categorized list of requirements for simplified application in research projects and systematic evaluation. The 3LGM2IHE ("Three-layer Graphbased meta model - Integrating the Healthcare Enterprise [IHE] " ) project is funded by the German Research Foundation (DFG). 3LGM2IHE aims to define modeling paradigms and implement modeling tools for planning health care information systems. In addition, one of the goals is to create and publish 3LGM2 information system architecture design patterns (short "design patterns") for the community as design models in terms of a framework. A structured list of data protection-related requirements based on the TMF-DP is a precondition to integrate functions (3LGM2 Domain Layer) and building blocks (3LGM2 Logical Tool Layer) in 3LGM2 design patterns. METHODS: In order to structure the continuous text of the TMF-DP, requirement types were defined in a first step. In a second step, dependencies and delineations of the definitions were identified. In a third step, the requirements from the TMF-DP were systematically extracted. Based on the identified lists of requirements, a fourth step included the comparison of the identified requirements with exemplary open source tools as provided by the "Independent Trusted Third Party of the University Medicine Greifswald" (TTP tools). RESULTS: As a result, four lists of requirements were created, which contain requirements for the "patient list", the "pseudonymization service", and the "consent management", as well as cross-component requirements from the TMF-DP chapter 6 in a structured form. Further to requirements (1), possible variants (2) of implementations (to fulfill a single requirement) and recommendations (3) were identified. A comparison of the requirements lists with the functional scopes of the open source tools E-PIX (record linkage), gPAS (pseudonym management), and gICS (consent management) has shown that these fulfill more than 80% of the requirements. CONCLUSIONS: A structured set of data protection-related requirements facilitates a systematic evaluation of implementations with respect to the fulfillment of the TMF-DP guidelines. These re-usable lists provide a decision aid for the selection of suitable tools for new research projects. As a result, these lists form the basis for the development of data protection-related 3LGM2 design patterns as part of the 3LGM2IHE project.

The COVID-19 Data Exchange Platform of the German University Medicine.

COVID-19 has challenged the healthcare systems worldwide. To quickly identify successful diagnostic and therapeutic approaches large data sharing approaches are inevitable. Though organizational clinical data are abundant, many of them are available only in isolated silos and largely inaccessible to external researchers. To overcome and tackle this challenge the university medicine network (comprising all 36 German university hospitals) has been founded in April 2020 to coordinate COVID-19 action plans, diagnostic and therapeutic strategies and collaborative research activities. 13 projects were initiated from which the CODEX project, aiming at the development of a Germany-wide Covid-19 Data Exchange Platform, is presented in this publication. We illustrate the conceptual design, the stepwise development and deployment, first results and the current status.

Advanced nursing practice and interprofessional dementia care (InDePendent): study protocol for a multi-center, cluster-randomized, controlled, interventional trial.

BACKGROUND: A redistribution of tasks between specialized nurses and primary care physicians, i.e., models of advanced nursing practice, has the potential to improve the treatment and care of the growing number of people with dementia (PwD). Especially in rural areas with limited access to primary care physicians and specialists, these models might improve PwD's quality of life and well-being. However, such care models are not available in Germany in regular healthcare. This study examines the acceptance, safety, efficacy, and health economic efficiency of an advanced nursing practice model for PwD in the primary care setting in Germany. METHODS: InDePendent is a two-arm, multi-center, cluster-randomized controlled intervention study. Inclusion criteria are age ≥70 years, cognitively impaired (DemTect ≤8) or formally diagnosed with dementia, and living in the own home. Patients will be recruited by general practitioners or specialists. Randomization is carried out at the physicians' level in a ratio of 1:2 (intervention vs. waiting-control group). After study inclusion, all participants will receive a baseline assessment and a follow-up assessment after 6 months. Patients of the intervention group will receive advanced dementia care management for 6 months, carried out by specialized nurses, who will conduct certain tasks, usually carried out by primary care physicians. This includes a standardized assessment of the patients' unmet needs, the generation and implementation of an individualized care plan to address the patients' needs in close coordination with the GP. PwD in the waiting-control group will receive routine care for 6 months and subsequently become part of the intervention group. The primary outcome is the number of unmet needs after 6 months measured by the Camberwell Assessment of Need for the Elderly (CANE). The primary analysis after 6 months is carried out using multilevel models and will be based on the intention-to-treat principle. Secondary outcomes are quality of life, caregiver burden, acceptance, and cost-effectiveness. In total, n=465 participants are needed to assess significant differences in the number of unmet needs between the intervention and control groups. DISCUSSION: The study will provide evidence about the acceptance, efficacy, and cost-effectiveness of an innovative interprofessional concept based on advanced nursing care. Results will contribute to the implementation of such models in the German healthcare system. The goal is to improve the current treatment and care situation for PwD and their caregivers and to expand nursing roles. TRIAL REGISTRATION: ClinicalTrials.gov NCT04741932 . Registered on 2 February 2021.

[Secondary Use of Electronic Medical Record Data from Primary Health Care is Feasible: Report from RADAR Project]. / Sekundäre Nutzung von hausärztlichen Routinedaten ist machbar ­ Bericht vom RADAR Projekt.

Objectives It is difficult to obtain longitudinal 'real world' data from ambulatory medical care in Germany in a systematic way. Our vision is a large German research data repository featuring representative, anonymized patient and outpatient health care data, longitudinal, continuously updated and across different providers, offering a perspective of linking secondary care data or additional data obtained from research cohorts, for example patient reported data or biodata, and will be accessible for other researchers. Here we report specific methods and results from the RADAR project.Methods Survey of legislation, design of technical processes and organisational solutions, with a feasibility study to evaluate technical and content functionality, acceptability and performance fitness for health services research questions.Results In 2016, a multi-disciplinary scientific team initiated the development of a privacy protection and IT security concept for data exported from the electronic medical records (EMR) of physicians' practices in line with the European General Data Protection Regulation. Technical and organisational requirements for lawful research infrastructure were developed and executed for use in a specific case, namely ̒oral anticoagulation'. In 7 Lower Saxonian general practices, 100 patients were selected by their physician and their data - reduced to 40 essential data fields - extracted from EMR via a mandatory software interface after informed consent. Still in the practice, the data were split into identifying or medical data. These were encrypted and transferred either to a trusted third party (TTP) or to a data repository, respectively. 75 patients who met our inclusion criteria (minimum of one year of oral anticoagulation treatment) received a quality-of-life questionnaire via the TTP. Of the 66 returns, 63 responses were then linked to the EMR data in the repository.Conclusion Results from RADAR project proved the technical and organisational feasibility of lawful, pseudonymised data acquisition and the linkage of questionnaires to EMR data. The protecting concepts privacy by design and data minimization (Art. 25 GDPR with Recital 78) were implemented. Without informed consent, secondary use of routine data from ambulatory care which are sufficiently anonymized but still meaningful is all but impossible under current German law.

Designing and piloting a generic research architecture and workflows to unlock German primary care data for secondary use.

BACKGROUND: Medical data from family doctors are of great importance to health care researchers but seem to be locked in German practices and, thus, are underused in research. The RADAR project (Routine Anonymized Data for Advanced Health Services Research) aims at designing, implementing and piloting a generic research architecture, technical software solutions as well as procedures and workflows to unlock data from family doctor's practices. A long-term medical data repository for research taking legal requirements into account is established. Thereby, RADAR helps closing the gap between the European countries and to contribute data from primary care in Germany. METHODS: The RADAR project comprises three phases: (1) analysis phase, (2) design phase, and (3) pilot. First, interdisciplinary workshops were held to list prerequisites and requirements. Second, an architecture diagram with building blocks and functions, and an ordered list of process steps (workflow) for data capture and storage were designed. Third, technical components and workflows were piloted. The pilot was extended by a data integration workflow using patient-reported outcomes (paper-based questionnaires). RESULTS: The analysis phase resulted in listing 17 essential prerequisites and guiding requirements for data management compliant with the General Data Protection Regulation (GDPR). Based on this list existing approaches to fulfil the RADAR tasks were evaluated-for example, re-using BDT interface for data exchange and Trusted Third Party-approach for consent management and record linkage. Consented data sets of 100 patients were successfully exported, separated into person-identifying and medical data, pseudonymised and saved. Record linkage and data integration workflows for patient-reported outcomes in the RADAR research database were successfully piloted for 63 responders. CONCLUSION: The RADAR project successfully developed a generic architecture together with a technical framework of tools, interfaces, and workflows for a complete infrastructure for practicable and secure processing of patient data from family doctors. All technical components and workflows can be reused for further research projects. Additionally, a Trusted Third Party-approach can be used as core element to implement data privacy protection in such heterogeneous family doctor's settings. Optimisations identified comprise a fully-electronic consent recording using tablet computers, which is part of the project's extension phase.

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.

Establishing an Interoperable Clinical Trial Information System Within MIRACUM.

In the long-run we wish to demonstrate the power of linking clinical trial information to routine health records for straightforward patient recruitment - not only at each single hospital but in a large German consortium (called MIRACUM). In such architecture a hospital wide clinical trial registry (CTR) plays a major role. All such site specific CTR however, also need to be interoperable and support automated data provision for a central MIRACUM wide trial registry. Based on a survey of already existing trial information systems at each partner site and a comparison of their functionality, a joint requirement specification was created, a minimal MIRACUM wide trial core dataset was defined and an architecture was designed in which each MIRACUM partner could keep their autonomous system decision. Partners could however also join forces in a cooperative enhancement of a new open source trial registry. Thus, sites with no trial registry could be supported by the others and synergies used. Finally, the newly developed CTR will allow modular site specific add-ons and can also take over the function of the MIRACUM wide trial registry. In this paper we describe the process, how such a consortium-wide CTR was designed and developed, while always keeping cross-site interoperability as a major requirement.

Robotic waterjet wound debridement - Workflow adaption for clinical application and systematic evaluation of a novel technology.

OBJECTIVE: We evaluated the clinical potential of a novel robotic system for autonomous performance of waterjet wound debridement. SUMMARY BACKGROUND DATA: Within the last decade, waterjet wound debridement has proven to be a valid alternative to the conventional approach using sharp spoons and scalpel. METHODS: The DLR MIRO robot using the DLR MICA instrument for robotic surgery was adapted for actuation of an ERBEJET 2 flexible endoscopic waterjet probe. Waterjet debridement of various wound shapes and sizes using a porcine skin model was compared between this novel robotic system and a control group of human medical professionals with regard to wound area cleaned by the waterjet, off-target area, and procedural time. RESULTS: After the wound area was registered in the robotic system, it automatically generated a cleaning path and performed debridement based on generated surface model. While the robotic system demonstrated a significant advantage for the covered wound area (p = 0.031), the average off-target area was not significantly different from human controls. Human participants had high variability in cleaning quality across users and trials, while the robotic system provided stable results. Overall procedural time was significantly lower in trials performed by humans. CONCLUSIONS: Robotic waterjet wound debridement is a promising new technological approach compared to the current clinical standard of interventional wound therapy, providing higher efficiency and quality of wound cleaning compared to human performance. Additional trials on more complicated wound shapes and in vivo tissue are necessary to more thoroughly evaluate the clinical potential of this technology.

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.

Toolbox for Research, or how to facilitate a central data management in small-scale research projects.

BACKGROUND: In most research projects budget, staff and IT infrastructures are limiting resources. Especially for small-scale registries and cohort studies professional IT support and commercial electronic data capture systems are too expensive. Consequently, these projects use simple local approaches (e.g. Excel) for data capture instead of a central data management including web-based data capture and proper research databases. This leads to manual processes to merge, analyze and, if possible, pseudonymize research data of different study sites. RESULTS: To support multi-site data capture, storage and analyses in small-scall research projects, corresponding requirements were analyzed within the MOSAIC project. Based on the identified requirements, the Toolbox for Research was developed as a flexible software solution for various research scenarios. Additionally, the Toolbox facilitates data integration of research data as well as metadata by performing necessary procedures automatically. Also, Toolbox modules allow the integration of device data. Moreover, separation of personally identifiable information and medical data by using only pseudonyms for storing medical data ensures the compliance to data protection regulations. This pseudonymized data can then be exported in SPSS format in order to enable scientists to prepare reports and analyses. CONCLUSIONS: The Toolbox for Research was successfully piloted in the German Burn Registry in 2016 facilitating the documentation of 4350 burn cases at 54 study sites. The Toolbox for Research can be downloaded free of charge from the project website and automatically installed due to the use of Docker technology.

mosaicQA - A General Approach to Facilitate Basic Data Quality Assurance for Epidemiological Research.

BACKGROUND: Epidemiological studies are based on a considerable amount of personal, medical and socio-economic data. To answer research questions with reliable results, epidemiological research projects face the challenge of providing high quality data. Consequently, gathered data has to be reviewed continuously during the data collection period. OBJECTIVES: This article describes the development of the mosaicQA-library for non-statistical experts consisting of a set of reusable R functions to provide support for a basic data quality assurance for a wide range of application scenarios in epidemiological research. METHODS: To generate valid quality reports for various scenarios and data sets, a general and flexible development approach was needed. As a first step, a set of quality-related questions, targeting quality aspects on a more general level, was identified. The next step included the design of specific R-scripts to produce proper reports for metric and categorical data. For more flexibility, the third development step focussed on the generalization of the developed R-scripts, e.g. extracting characteristics and parameters. As a last step the generic characteristics of the developed R functionalities and generated reports have been evaluated using different metric and categorical datasets. RESULTS: The developed mosaicQA-library generates basic data quality reports for multivariate input data. If needed, more detailed results for single-variable data, including definition of units, variables, descriptions, code lists and categories of qualified missings, can easily be produced. CONCLUSIONS: The mosaicQA-library enables researchers to generate reports for various kinds of metric and categorical data without the need for computational or scripting knowledge. At the moment, the library focusses on the data structure quality and supports the assessment of several quality indicators, including frequency, distribution and plausibility of research variables as well as the occurrence of missing and extreme values. To simplify the installation process, mosaicQA has been released as an official R-package.

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.

Extending the Capability of Using a Waterjet in Surgical Interventions by the Use of Robotics.

In waterjet surgery, a thin high-pressure jet is used for dissections and surface abrasion of soft tissue. This selective preparation method preserves nerves and vessels, whereas the surrounding soft tissue is washed away. OBJECTIVE: The aim of this study is to enhance the application field of this technique by resolving technological limitations. METHODS: A technical task definition of handling a hand-guided waterjet applicator is derived from the literature. All reported procedures require to follow a trajectory superimposed with an oscillating movement. By introducing a robotic system and a specialized kinematic approach, the limited dexterity of the waterjet applicator is increased. Additionally, the system provides assistance by automatically performing parts of the task. RESULTS: The method is applied to two different procedures: a minimally invasive dissection and a surface abrasion for open medical treatments. On the basis of experiments with gelatine phantoms, the performance of the method is shown for both procedures. CONCLUSION: In the minimally invasive use case, the reachability limited by the conventional manual tools is extended by the capabilities of the robotic system. Simultaneously, the handling is simplified by automation of the superimposed oscillation. In the surface abrasion case, a dense coverage of the treated area is achievable. The risk of cross infections could be reduced by spatial separation of patient and staff. SIGNIFICANCE: Thus, the waterjet technology can be fully integrated into robotic surgery systems and benefit from their inherent abilities.

A workflow-driven approach to integrate generic software modules in a Trusted Third Party.

BACKGROUND: Cohort studies and registries rely on massive amounts of personal medical data. Therefore, data protection and information security as well as ethical aspects gain in importance and need to be considered as early as possible during the establishment of a study. Resulting legal and ethical obligations require a precise implementation of appropriate technical and organisational measures for a Trusted Third Party. METHODS: This paper defines and organises a consistent workflow-management to realize a Trusted Third Party. In particular, it focusses the technical implementation of a Trusted Third Party Dispatcher to provide basic functionalities (including identity management, pseudonym administration and informed consent management) and measures required to meet study specific conditions of cohort studies and registries. Thereby several independent open source software modules developed and provided by the MOSAIC project are used. This technical concept offers the necessary flexibility and extensibility to address legal and ethical requirements of individual scenarios. RESULTS: The developed concept for a Trusted Third Party Dispatcher allows mapping single process steps as well as individual requirements and characteristics of particular studies to workflows, which in turn can be combined to model complex Trusted Third Party processes. The uniformity of this approach permits unrestricted re-combination of the available functionalities (depending on the applied software modules) for various research projects. CONCLUSION: The proposed approach for the technical implementation of an independent Trusted Third Party reduces the effort for scenario specific implementations as well as for maintenance. The applicability and the efficacy of the concept for a workflow-driven Trusted Third Party could be confirmed during the establishment of several nationwide studies (e.g. German Centre for Cardiovascular Research and the National Cohort).

Cohort profile: Greifswald approach to individualized medicine (GANI_MED).

BACKGROUND: Individualized Medicine aims at providing optimal treatment for an individual patient at a given time based on his specific genetic and molecular characteristics. This requires excellent clinical stratification of patients as well as the availability of genomic data and biomarkers as prerequisites for the development of novel diagnostic tools and therapeutic strategies. The University Medicine Greifswald, Germany, has launched the "Greifswald Approach to Individualized Medicine" (GANI_MED) project to address major challenges of Individualized Medicine. Herein, we describe the implementation of the scientific and clinical infrastructure that allows future translation of findings relevant to Individualized Medicine into clinical practice. METHODS/DESIGN: Clinical patient cohorts (N > 5,000) with an emphasis on metabolic and cardiovascular diseases are being established following a standardized protocol for the assessment of medical history, laboratory biomarkers, and the collection of various biosamples for bio-banking purposes. A multi-omics based biomarker assessment including genome-wide genotyping, transcriptome, metabolome, and proteome analyses complements the multi-level approach of GANI_MED. Comparisons with the general background population as characterized by our Study of Health in Pomerania (SHIP) are performed. A central data management structure has been implemented to capture and integrate all relevant clinical data for research purposes. Ethical research projects on informed consent procedures, reporting of incidental findings, and economic evaluations were launched in parallel.