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Project No. 777304

ERKReg The European Rare Kidney Disease Registry

Workpackage 02:

Deliverable Report D2.3: Layman`s Report

Start date of project: 2018-01-01 Duration: 36 months

Organisation name of lead contractor for this deliverable:

Partner 02: GuMed

This project has received funding from the European Union´s Health Programme # (2014-2020) Dissemination Level

PU Public X

PP Restricted to other programme participants (including the Commission Services)

RE Restricted to a group specified by the consortium (including the Commission Services)

CO Confidential, only for members of the consortium (including the Commission Services)

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Table of Content

1. What is the European Rare Kidney Disease Registry? ...................................................................... 3

2. What is ERKNet and its member and affiliated centres? ................................................................. 3

3. Where can I find the European Rare Kidney Disease Registry? ........................................................ 3

4. How is the Registry funded? ........................................................................................................... 4

5. What are the aims of the Registry? ................................................................................................. 4

6. How was the Registry setup? .......................................................................................................... 5

7. How does the Registry work? ......................................................................................................... 7

8. Which countries have contributed to the Registry so far? ............................................................... 8

9. How many patients have been enrolled into the Registry and which diseases do they represent .... 9

10. Who has access to information collected by the Registry? ........................................................ 10

11. How is information about the Registry made visible? ............................................................... 11

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1. WHAT IS THE EUROPEAN RARE KIDNEY DISEASE REGISTRY?

The Registry is an online database that collects important information concerning pa-tients dispersed all over Europe who have rare kidney diseases. The Registry is open to all committed ERKNet (European Reference Network of centres with rare Kidney Dis-eases) member centres and Affiliated Partners and interested centres from outside the Network who wish to enter their patients. Since its official launched in Oct 2018 the ERKReg has become the largest single database of patients with rare or complex kidney diseases assembled to date having reached nearly 8000 patient entries.

2. WHAT IS ERKNET AND ITS MEMBER AND AFFILIATED CENTRES?

ERKNet is the European Reference Network for Rare Kidney Diseases, a consortium of 33 expert paediatric and adult nephrology centres and patient representatives (ePAGs) in 12 European countries, which provides healthcare to more than 40,000 patients with rare disorders of the kidneys. Besides the 33 expert member centres, 15 have joined as affiliated centres to the expert centres. 30 further expert centres are expected to join the Network in 2021.

3. WHERE CAN I FIND THE EUROPEAN RARE KIDNEY DISEASE REGISTRY?

The Registry website can be accessed at its website www.registry.erknet.org. which con-tains a public and a protected domain for healthcare centres with access by authorization. The public part of the website contains information about the Registry’s mission and ob-jectives, data on the current number of patients enrolled by the centres and by disease group, annual registry reports, a section with useful documents (FAQ sheet, manual, or-phacode list of rare kidney diseases, ERKReg data dictionary, and patient informed con-sent forms) and Registry governance structure.

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4. HOW IS THE REGISTRY FUNDED?

The Registry was co-funded solely by the European Commission through a CHAFEA* Grant for a 3 year duration (2018-2020). ERKReg receives no further funding from industry or other institutions. The beneficiaries of the grant are ERKNet expert centres from Germany (Heidelberg), Holland (Amsterdam), France (Paris), Poland (Gdansk) and Spain (Barce-lona). *CHAFEA (Consumers, Health, Agriculture and Food Executive AgENCY) IS THE EXECUTIVE AGENCY trusted by the European Commission with the management of the EU Health Programme, a funding programme created to implement the EU health strategy. https://ec.europa.eu/chafea

5. WHAT ARE THE AIMS OF THE REGISTRY?

The Registry was created to • inform on the to date unknown number of patients with rare KIDNEY dis-

eases who are dispersed across Europe • optimize, unify and monitor the quality of patient care across Europe • find and inform patients when novel therapeutic opportunities arise • provide a platform for sub-registries of specific kidney diseases

Figure 1. Main aims of ERKReg - European Registry for Rare Kidney Diseases

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6. HOW WAS THE REGISTRY SETUP?

The central Registry office, embedded in the ERKNet Central Office in Heidelberg coordi-nates all efforts towards the establishment of the ERKNet Registry. These efforts initially focused on preparing universal ERN (European Reference Network) informed consent forms (ICF), which were provided by the European Commission in all European languages. These were re-approved by ERKNet member centres and when nec-essary by local Institutional Review Boards. (Fig. 2) By the end of the project, centers from all but one country had obtained approval resulting in a gradual increase in numbers of patients reported.

Figure 2. Ethics approval status

Once the final list of items was defined, the online registry portal was programmed. The core features of the portal encompass a searchable and filterable patient dashboard, data entry forms for basic and follow-up entries, a KPI (Key Performance Indicators)*statistics and benchmarking module. Key Performance Indicators are an extremely important part of the Registry as they enable monitoring of patient management performance at centers and will be used to improve and harmonize patient care throughout Europe. This feature enables each center to review its performance in comparison to that of the ERKNet aver-age.

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The structure of the registry allows also the integration of existing sub-registries (specify for a disease e.g. distal renal tubular acidosis (dRTA), pediatric SLE nephritis, cystynuria and others). Through a special ‘Cohort Finder’ tool researchers can count patients by diagnosis or af-fected gene enabling them to identify potential patients within the ERKReg community for conducting a study. This feature will greatly improve the network’s ability to identify patient cohorts for clinical research regarding both new diagnostic tools and trials with new pharmacotherapies. The concept of the Registry is illustrated in Fig. 3.

Figure 3. ERKReg start website. Concept.

Pediatric SLE

• Center administration• Disease demographics• Trial cohort information

• Monitoring of guidelineadherence, performanceand outcome Indicators

• Genotype-phenotype information• Natural history information• Best medical practice information

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IPDN Pediatric Dialysis

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ERKNetMembers

ERKNetAffiliated Partners

Other Centers

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7. HOW DOES THE REGISTRY WORK?

The Registry website is accessed at www.registry.erknet.org. The password-protected do-main takes ERKNet registry users to the centre-specific patient dashboard and data entry menu. Over 100 of physicians and nurses from 38 countries are dedicated to this task. They have been supported by an ERKNet Helpdesk Team composed of five young junior physicians working at ERKNet sites from different countries. Two registry meetings have been organized, assembling the ERKReg users to share their experience and discuss com-mon data entry issues (technical and content), one face-to-face meeting in 2019 and an on-line meeting in 2020 due to the COVID pandemic. (Figs 4, 5)

Figure 4. 1st ERKReg user meeting Figure 5. 2nd user meeting 17th Feb 2020 11th Nov 2019 (28 centres present) (online due to COVID pandemic)

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8. WHICH COUNTRIES HAVE CONTRIBUTED TO THE REGISTRY SO FAR?

The contributing centres are located in 21 countries, including Italy (n=11), Germany (n=6), Turkey (n=6), France (n=4), the Netherlands (n=2), Belgium (n=2), Greece (n=2), Spain (n=2), Slovenia (n=2), Austria, Czechia, Denmark, Hungary, Iran, Ireland, Latvia, Lith-uania, Poland, Russia, the UK, and the UAE (n=1 each). The participating healthcare providers comprise 27 ERKNet members centres, 6 Affili-ated Partner centres, and 16 external centres. ERKNet centres entered the vast majority (91.7%) of the ERKReg population, Affiliated Partner centres entries count for 5.5%, and the external centres entries count for 2.8% (Fig. 6)

Figure 6. Contributing centres to ERKReg. Circles represent the absolute number of patients entered. Country colours show the fraction of patients enters relative to the national population size. Total patient number by 17th February 2021.

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Patients enrolled

Supported by Bing© GeoNames , Mic ros oft, TomTom

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9. HOW MANY PATIENTS HAVE BEEN ENROLLED INTO THE REGISTRY AND WHICH DISEASES DO THEY REPRESENT

To date, more than 8,500 patients with rare kidney disease have been enrolled at 64 sites. 91.8% of patients are treated in highly specialized pediatric and adult nephrology ERKNet units. A smaller proportion is seen in ERKNet Affiliated Partner (5.3%) centers or an ex-ternal center from outside the network (2.8%).

Figure 7. The enrolment curve

A total of 97.1% of these 8,500 patients have an established kidney disease diagnosis. ORPHANET* codes were used to unify diagnosis between centres. There are 335 codes relevant for kidney diseases. There are 335 codes relevant for kidney diseases Structural disorders (CAKUT, Ciliopathies) and the glomerulopathies accounted for the largest groups concerning the total number and codes used.

* ORPHANET is a unique resource, gathering and improving knowledge on rare diseases so as to improve

the diagnosis, care and treatment of diseases classified as rare. It has introduced an unified coding system

as the ICD coding system in hospital use identifies only 355 disease out of 6,954 rare clinical entities listed

by Orphanet.

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Figure 8. Number of patients enrolled into the European Rare Kidney Disease Registry with number of paediatric/adult patients and basic diagnosis groups.

10. WHO HAS ACCESS TO INFORMATION COLLECTED BY THE REGISTRY?

Healthcare professionals, patients and the wider public have continuous access to infor-mation through the ERKReg Website (www.registry.erknet.org). The public part of the website also contains information a section with useful documents (FAQ sheet, manual, orphacode list of rare kidney diseases, ERKReg data dictionary, and patient informed consent forms) and Registry governance structure. Information on an-nual registry reports and data access requests are also posted for the public. The password-protected domain takes ERKNet registry users to the centre-specific pa-tient dashboard and data entry menu. Centres have access to a cohort finder tool and may apply for further data access. Semi-annual KPI (Key Performance Indicators) reports and sent to the ERKNet centre leads for review. Information is regularly disseminated to professionals via ERKNet Newsletters and Twitter. It is hoped that regular monitoring by the ERKNet investigators of their centres’ performance will impact their adherence to clinical guidelines positively and lead to improved treatment quality and patient out-comes. The registry will also target clinical research stakeholders (e.g. pharmaceutical industry, academic researchers) who can request information on specific disease populations that may be suitable candidates for participating in diagnostic and prognostic biomarker stud-ies, clinical trials, and translational research.

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11. HOW IS INFORMATION ABOUT THE REGISTRY MADE VISIBLE?

To address the patient community, an informative multilingual layman flyer about the Network´s activities and the Registry´s purpose has been designed (in English, German, French, Dutch, Italian, Polish, Spanish and Lithuanian). It is handed out to all patients at the time of attainment of informed consent. The flyers have been made available both in digital form and in printed versions to all ERKNet centres.

Figure 9. Flyer for patients with information on ERKNet and ERKReg.

Presentations informing about the ERKReg project are given at various regional and international nephrology and Rare Diseases conferences. ERKReg was selected for a poster presentation at the IPNA (International Pediatric Nephrology Asso-ciation) in Venice, Italy Sept. 2020, thereby reach-ing the world-wide rare kidney disease community. (Fig.10)