17 December 2020

PVRI GoDeep progress report

IT infrastructure and software at the JLU Giessen

The PVRI GoDeep meta registry IT infrastructure is comprised of a central anonymised data repository and additional software components for establishing connections for up-to-date data transfers from any customised local PH registry or database.

The central server is hosted in the data centre of the Justus-Liebig University Giessen / Germany and managed by our local team of IT experts and data scientists. Access to the data and all analyses are governed by the use and access rules detailed in section Governance structure / Use and access rules on page 6.


Key aspect for the GoDeep to comply with heterogeneous regulatory and legislative restrictions around the world is to apply data protection in the strictest way possible. Our approach will only transfer completely de-identified and anonymised data. To eliminate possible reidentification through data analysis, algorithms for k-anonymity are applied. Any information which could be used for identification is censored or coarsened – e.g. only the birth decade is used instead of accurate birth dates.

With these measures, our data protection concept complies with all strict data privacy legislations, such as the European GDPR, the LGPD in Brazil, the CCPA in the USA, the PDPB in India, etc.

Data harmonisation and transfer using international standards

Existing PH registries around the world use different software for data entry into electronic patient records or electronic data capture software (e.g. Cerner ISH-MED, AGFA Orbis, PAHTool, REDCap, MS Access database, etc.) as well as different terminologies, granularity and possibly class definitions. In order to enter all data into the PVRI-GoDeep common database and to allow data analysis across different institutions/countries/continents, individual data harmonization must be performed. As a service, the PVRI-GoDeep competence team offers all participating centres to manage the harmonisation of parameters with the GoDeep central data dictionary.

Our central data dictionary is annotated and linked to international standard terminology codes like .e.g. LOINC for measurements, ICD-10 for comorbidities, ATC for medication, etc. To this end, individual mapping algorithms are created and adjusted together with the local data managers. With the mapping algorithms, our electronic interface allows regular (as standard quarterly) automatic data transfers to be performed semi-automatically minimal manual effort. In addition to the data points being annotated in international standards, also the transfer format is aligned to the current communication standard for medical data HL7 FHIR.

Data storage and analysis

Once the anonymised data transfers arrive at the PVRI central server, it is stored in three different established database formats. In its raw form, the data is stored in HL7 FHIR Bundle resources as specified by the international standardisation organisation for healthcare HL7. For distributing analysis algorithms, the data is also converted to the OMOP common data model specified by the Observational Health Data Sciences and Informatics (OHDSI) collaborative. Additionally, the i2b2 data warehouse software is used to allow easy access for GoDeep members to feasibility queries and simple analysis. All access to data is governed by the use and access rules detailed on page 7.

The continuous and consequent use of established standards for data annotation, transfer, representation and analysis as well as the public availability of the PVRI data dictionary allows us to meet the FAIR principles for scientific data management as close as possible with regard to the special characteristics of our data.


Coordination and development of the PVRI GoDeep registry is led by our team of researchers, physicians and computer scientists at the Justus-Liebig University Giessen.

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The team behind PVRI GoDeep at the Justus-Liebig-University Giessen: Kurt Marquardt, Werner Seeger, Patrick Fischer, Achim Michel-Backofen, Henning Gall, Tobiah Antoine, Raphael Majeed (from left to right)

Homepage PVRI GoDeep

For public relations and external communications, a public website was built and published at the domain https://pvri-godeep-registry.org. The website features basic information about our registry and the current participants as well as showcases for potential use of our global database.

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Governance structure / Use and access rules

Section 1 Definition, Status, Purpose

(1) These rules of procedure define the handling of clinical and patient-derived research data within PVRI-GoDeep.

(2) PVRI-GoDeep is a central PH Meta-Registry, run under the umbrella of the Pulmonary Vascular Research Institute (PVRI). It merges pseudonymised/anonymised PH patient related data from various local registries around the world run under the responsibility of PVRI members. It will be operated under the auspices of the University of Giessen/Giessen PH centre.

(3) Combining deep phenotyping with worldwide outreach, PVRI-GoDeep aims to offer insights into specific geographical and ethnical profiles of PH, to deepen the epidemiological, clinical and molecular understanding of this disease and to promote strategies for improved individualised treatment of PH patients.

(4) The data provided by PVRI-GoDeep will support academia to perform scientific projects in the field of PH. Pharmaceutical / commercial companies will be charged fee for access to PVRI-GoDeep data and / or analysis, thereby creating revenues exclusively devoted to support the PVRI mission and the registries entering their data into PVRI-GoDeep. All requests from academia or commercial companies are to be decided by the PVRI-GoDeep consortium, serving as Use and Access Committee.

(5) All activities will be performed in full compliance with current international legal standards and recommendations.

Section 2 Organisation

(1) PVRI-GoDeep is an entity of the PVRI. It is hosted at the Giessen University PH Centre, Germany. It's bodies are the PVRI-GoDeep consortium / Use and Access Committee, a Coordinator's Committee, the PVRI-GoDeep Competence Team and a Scientific Advisory Board

(1) The central organ of PVRI-GoDeep is the PVRI-GoDeep consortium which concurrently serves as Use and Access Committee (UAC). It is chaired by the Coordinator. Each local registry joining the PVRI-GoDeep consortium and entering its data into the PVRI-GoDeep repository delegates one member and has one vote in the PVRI-GoDeep consortium/UAC. This board decides on the rules of procedure for processing of data contained in the PVRI-GoDeep repository and on any request on PVRI-GoDeep data analysis by academic or commercial applicants. Decisions may be taken by way of written correspondence, during a face-to-face meeting, or by telephone/video conferencing. Decisions are made by majority vote.

(2) The Coordinator is a renowned PVRI member located at the Giessen University PH Centre. It will be appointed by the PVRI Executive Board for a term of three years, re-appointment is possible. (For the first three year term, Prof. Werner Seeger will serve this function). He/she heads the Coordinator's Committee, which includes the Central Data Manager (Chief Information Officer, CIO) of PVRI-GoDeep and the Chief Executive Officer of PVRI. This committee is responsible for the overall governance, strategic decisions, the PVRI-GoDeep budget and the contractual arrangements between the various worldwide registries and PVRI-GoDeep.

(3) For day-to-day business, the Coordinator is supported by the PVRI-GoDeep Competence Team. This is led by the CIO and includes (as a minimum) a biostatistician, a software developer, a PH physician expert and a documentation officer. It is responsible for content-related data management including the integration of data from the local registries into the central PVRI-GoDeep data repository, the execution of different queries, and the data export from PVRI-GoDeep for the retrieving researchers or commercial clients.

(4) A Scientific Advisory Board (SAB) will be installed, which is composed of the PVRI president, three members of the PVRI Board of Directors and four international experts representing competences adjuvant to the PVRI expertise. Such competences may include the fields of epidemiology, ethics, and data protection and privacy. Two of the international expert SAB members will be appointed by the PVRI-GoDeep Coordinator´s Committee, and two by the PVRI Executive Board. Each SAB member may serve for two 3-year periods and is expected to work on a voluntary basis. The SAB will meet annually. 

Section 3 Preconditions and Process for Feeding Data into the PVRI-GoDeep Repository

(1) Patient-derived data or related metadata from the local registries can only be entered into the central PVRI-GoDeep repository on the basis of a contract between the local registry (led by a PVRI member) and PVRI-GoDeep. Each local registry is still proprietor of its own data, but its authorities agree that a common data trunk (and further facultative modules) is fed into the central PH data repository provided by PVRI-GoDeep.

(2) The central PVRI-GoDeep repository operates in accordance with German/UK law, and with respect to any claims arising out of PVRI-GoDeep activity German/UK law shall apply. It operates under the responsibility of the University of Giessen Ethics Committee. A positive vote of this Ethics Committee is the prerequisite for the setup of PVRI-GoDeep according to these Use and Access Rules and for any changes/amendments of these rules. Moreover, each local registry documents that the feeding of pseudonymised or anonymised data into the central PVRI-GoDeep repository for unlimited storage (if not consent is withdrawn), central data analysis and data sharing within the PVRI-GoDeep consortium as well as with PVRI-GoDeep clients from academia or industry is approved by the respective local ethics committee and legal entity.

(3) The contract between PVRI-GoDeep and any local registry lays down the following obligations of the local registry: i) to comply with all specifications of the PVRI-GoDeep Use and Access Rules; ii) to comply with all applicable laws and regulation and internal provisions (including data privacy law, guidelines of Good Epidemiological Practice); iii) to enable automated periodical (quarterly) uploads of the registry data agreed on into the central PVRI repository and to agree to a comparison of the registry data with the original data (source data verification) carried out by an external monitor/auditor upon request; iv), iv) to inform the PVRI Coordinator's Committee of any protectable results to be taken care of upon central analysis of the PVRI-GoDeep data repository; v) not to disclose any confidential information received from PVRI-GoDeep to third parties. xxxx

(4) The contract between PVRI-GoDeep and any local registry lays down the following rights of the local registry: i) to download and analyse its own complete dataset contained in PVRI-GoDeep and to present or publish its own results without any restriction; ii) to have unrestricted permanent right to use the first level of data access to the entire PVRI-GoDeep data repository as laid down in section 4; iii) to have free of charge data access for any scientific project (second level of data access) granted by the entire PVRI-GoDeep consortium/UAC as defined in section 4; iv) to request anonymised comparisons of its local dataset versus all other centres (for quality control, reimbursement issues etc.); v) to designate contributors at the local centre as members of author groups for congress presentations and scientific papers arising from PVRI-GoDeep data repository analysis, depending on the specifications of the PVRI-GoDeep consortium/UAC for the individual scientific project (see section 4); vi) to terminate its participation at the PVRI-GoDeep data repository with immediate effect by means of written notification; in this case the respective data will be removed from the central data repository.

(5) The CIO and the PVRI-GoDeep competence team shall be responsible for the integration of data from the local registries into the central PVRI-GoDeep data repository. They will take care of the implementation of mapping algorithms for the harmonisation of variables and the establishment of an electronic interface, allowing automated periodical (quarterly) uploads into the central PVRI repository. 

Section 4 Process for the Use of Data

(1) The users of PVRI-GoDeep data include i) the members of the PVRI-GoDeep consortium/UAC, ii) Academia-based PVRI members and iii) PVRI-GoDeep clients from external academic organisations or industry.

(2) Two levels of access are defined:

The first level of data access operates via web browser and provides real-time results without written applications or review. The web based user interfaces (i2b2, tranSMART) are configured to limit the amount / granularity of data that can be accessed via this level. This level includes retrieval of patient counts of different categories (e.g. NYHA class, ethnicity, continent/country-dependent distribution, and combinations thereof) and to some extent multiple parameter analysis. Details of this level of access are defined by the PVRI-GoDeep consortium/UAC. This level will predominantly be used for data exploration and feasibility analysis to shape a specific project query to be operated on the second level of access.

The second level of data access allows unrestricted access to all available data for specific research questions. For this level, a data access request form needs to be submitted to the PVRI-GoDeep consortium/UAC serving as review board, which then decides whether access is granted. Moreover, this committee will define rules how to respect the contribution of the different local registries feeding their data into the central PVRI-GoDeep repository in case of publication. If access is granted, the applying party can choose whether to receive the raw data necessary for the specified research question or to make use of help from the PVRI-GoDeep competence team to perform the analysis

(3) Access authorisation and charge for access are defined as follows:

i) Members of the PVRI-GoDeep consortium/UAC have unrestricted permanent right to use the first level of data access. For the second level of data access, they have to shape a formalised draft proposal defining the scientific project, which is to be decided by the entire PVRI-GoDeep consortium/UAC. Moreover, this committee will define how to respect the contribution of the different local registries feeding their data into the central PVRI-GoDeep repository in case of publication of the scientific project under consideration and whether to take care of putative patent rights. If granted, data access is free of charge and the applying party can choose whether to receive the raw data necessary for the specified research question or to make use of the PVRI-GoDeep competence team to perform the analysis. After finalisation of the scientific project, a written report has to be committed to the PVRI-GoDeep consortium/UAC.

ii) Academia-based PVRI members may shape a short request for authorisation for the first level of PVRI-GoDeep data access for a limited period of time. If granted, its granularity will be defined and it will be free of charge. For the second level of data access, a formalised draft proposal defining the scientific project needs is to be submitted to the PVRI-GoDeep consortium/UAC serving as review board, which then decides whether access is granted. Moreover, this committee will define how to respect the contribution of the different local registries feeding their data into the central PVRI-GoDeep repository in case of publication and whether to take care of putative patent rights. If access is granted, the applying party can choose whether to receive the raw data necessary for the specified research question (data transfer agreement to be signed) or to make use of the PVRI-GoDeep competence team to perform the analysis. For access to data and / or analysis on this level, a fee will be charged, at a contribution towards expenses service charge (pay-for-query fee). Charging details will be decided by the Coordinator's Committee. After finalisation of the scientific project, a written report has to be committed to the PVRI-GoDeep consortium/UAC.

iii) For all requests from industry or external academic organisations (disclosure of the data to third parties), any authorisation for first or second level of data access demands a written request to be submitted to the PVRI-GoDeep consortium/UAC. This committee will decide, whether and to which extent (granularity) data access is granted. Any data transfer will be based on a detailed mutually signed data transfer agreement. Fee for access will be charged, with charge rates to be defined by the Coordinator´s Committee. As to data use by industry/pharmaceutical companies, the representative of each centre will have the possibility to exclude the anonymised data set of the individual centre from analysis. Moreover, there will no transfer of raw data to industry/pharmaceutical companies, but their access will be restricted to analysis of predefined questions the UAC agreed on.

(4) A state of the art bioinformatic/statistical tool set for analysis of the PVRI-GoDeep data set will be made available by the PVRI-GoDeep competence team. Moreover, this team strives to profit from the very large number of patients to apply innovative systems biology and medicine approaches, predictive modelling, artificial intelligence and deep learning technologies.

(5) General publication rules:

The PVRI-GoDeep consortium/UAC decides about the general publication strategy and its specifications for each scientific project undertaken with PVRI-GoDeep data. The following general principles will be followed: i) if a project proposed by an investigator becomes a scientific publication, the investigator will be offered first authorship (with all related responsibilities); ii) all local registries, from which data enter into the analysis underlying the publication, will be offered co-authorship; iii) numbers and position of co-authorship on the manuscript are decided based on the number of patients enrolled and the data quality provided. This refers to the patients eligible for a given analysis, not on the overall number of patients enrolled in the PVRI-GoDeep repository. The total number of authors will depend on the regulations of the target journal, but in general should not exceed 20 (the ICME rules for authorship apply).

(6) Use of PVRI-GoDeep revenue:

After the initial setup period, PVRI-GoDeep is expected to create revenue. All revenue will be used towards the running costs of this data repository. Should a surplus be generated, this will be used for scientific activities as agreed by the Coordinator’s Committee, who is responsible for the PVRI GoDeep budget, as outlined under section 2 (2). 

Section 5 Standards and Data Protection

(1) The main work steps related to the storage and analysis of data in the PVRI-GoDeep repository shall be subject to the principles of Good Laboratory Practice (GLP), Good Clinical Practice (GCP), and, where applicable, Good Epidemiological Practice (GEP); these steps shall be specified in the Standard Operating Procedures (SOPs) developed by the PVRI-GoDeep Competence Team.

(2) Any data stored in the PVRI-GoDeep repository may only be used for the purposes defined in section 4 and must not be shared with individuals or institutions beyond these predefined rules. This applies to all parties involved, i.e. employees, office-holders, and scientists/external parties granted access to PVRI-GoDeep data as defined in section 4. All users of anonymised or pseudonymized data are prohibited from taking measures to identify the persons examined. There must be a corresponding instruction. Any further procedures must be backed by way of additional specific approval of the ethics committee(s).

Section 6 Amendment to the Rules of Procedure

The PVRI-GoDeep consortium/UAC shall decide upon any amendments to these Rules of Procedure with a two-thirds majority after having adequately notified its members. A positive vote of the University of Giessen Ethics Committee is mandatory for any amendment.

Section 7 Provisions on Dissolution

(1) The operation of PVRI-GoDeep is bound to the continued existence of PVRI. The PVRI Executive Committee may decide upon the dissolution of PVRI-GoDeep in agreement with the PVRI Coordinator´s Committee.

(2) In the event that PVRI-GoDeep is dissolved, the data collected shall generally be assigned to the corresponding data-processing authorities, i.e. PVRI and the University of Giessen. These authorities will have to agree on any solution concerning the further storage/use of data and the financial obligations of PVRI-GoDeep (e.g. the salaries for the PVRI-Go-Deep competence team).

(3) If in this event any transfer/sale of the PVRI-GoDeep data or parts thereof to external organisations is considered, explicit agreement of the local registries feeding their data into PVRI-GoDeep for the respective data set is requested.

(4) Data that are no longer administrated upon dissolution must be deleted in accordance with any applicable provisions.

Section 8 Severability Clause

Any circumstances not covered by these Rules of Procedure for PVRI-GoDeep must be treated appropriately and in line with the Rules of Procedure, their purpose, the PVRI mission and the local data-gathering authorities.

Status of available data

The PVRI GoDeep dataset consists of ~250 parameters per baseline and follow up visit including detailed diagnosis classification, comorbidities, medication, RHC, PFT, Lab, etc. From the founding members, the connection of data from JLU Giessen and Imperial College London has been completed. The data from Johns Hopkins University has been connected partly and will be completed early 2021.

To date, detailed longitudinal data from a total of ~80.000 visits from ~10.000 patients is available in the PVRI GoDeep meta registry.

Participants and centres interested in joining

Currently, the main contributors of data in PVRI GoDeep are its founding members Imperial College London, Johns Hopkins University Baltimore and Justus-Liebig University Giessen. Many PH centres have declared their interest in joining and contributing data to PVRI GoDeep. We are currently in discussions and progress to connect the following additional PH centres:

  •        University Hospital Munich, Germany
  •        Golden Jubilee National Hospital, Glasgow, UK
  •        Sheffield Pulmonary Vascular Disease Unit, UK
  •        Mayo Clinic, Rochester, USA
  •        Amsterdam UMC, Netherlands
  •        Strazhensku Cardiology Institute, Kiev, Ukraine
  •        Universidade Federal de Sao Paulo, Brazil
  •        Hospital de Niños Santísima Trinidad, Cordoba, Argentina
  •        University Hospital Heidelberg, Germany
  •        Policlinico San Matteo Pavia, Italy
  •        University Hospital Graz, Austria
  •        Attikon University Hospital Athens, Greece
  •        University of Pittsburgh, USA
  •        University of Stanford, USA
  •        Karolinska Institute Stockholm, Sweden
  •        Aswan Heart Centre, Aswan, Egypt
  •        Freeman Hospital, Newcastle upon Tyne, UK
  •        National Jewish Health, Denver, USA
  •        Cleveland Clinic Florida, Ft. Lauderdale, USA
  •        Hackensack University Medical Centre, New Jersey, USA
  •        Brigham and Women’s Hospital, Boston, USA
  •        Policlinico Umberto, Rome, Italy
  •        Pablo Tobón Uribe Hospital, Medellin, Colombia
  •        University of Pennsylvania, Philadelphia, USA
  •        Clínica Comfamiliar, Pereira, Colombia
  •        Collaboration and concept sharing with PAH-ICON

Collaboration and concept sharing with PAH-ICON

PAH-ICON and PVRI GoDeep follow similar goals in enabling research and data science with PH cohorts. While PAH-ICON focuses on genotyping and PVRI GoDeep’s emphasis lies on deep phenotyping, both initiatives also overlap in these aspects. Therefore, a collaboration was started to harmonise the collected data set and enable patient record linkage for participating PH centres.

Together with PAH ICON, we are currently updating the specification of our deep phenotyping data set in joint video conferences. The resulting common data set will meet requirements of both PAH-ICON and PVRI GoDeep. Biomaterial and genotyping data obtained by PAH-ICON will be complemented by deep phenotyping data through PVRI GoDeep. While record linkage is not possible with our anonymised data set, the anonymisation process can be changed to pseudonymisation for patients enrolled in PAH-ICON before the transfer of data. As these patients will sign a specific informed consent to allow material and data transferred internationally, it is legally accepted to establish a link to the biomaterial during the data transfer. We thus plan to connect the PAH-ICON centres to our electronic interface for data transfer and to provide the corresponding phenotyping data to PAH-ICON free-of-charge – under the precondition that the participating centres will join PVRI GoDeep and contribute longitudinal data collection also for non-PAH-ICON patients in anonymised form.

Through this collaboration, PAH ICON will benefit from our detailed phenotyping data set and established data protection and data transfer infrastructure. On the other hand, our benefit lies in the PAH ICON participating PH centres joining our PVRI GoDeep meta registry and thus enlarging our pool of global deep phenotyping PH data.

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