1. Development of Haemodynamic Solutions in Renal Dialysis Venous Access Failure Mid-Term Review 3rd June Confidential

2. Welcome
Introductions
Programme Review

3. A joint industry-academia research programme to overcome the scientific and technical barriers to the understanding, development and adoption of technologies to combat the significant clinical problem of the failure of renal dialysis venous access.

4. Project Review
A joint industry-academia research programme to overcome the scientific and technical barriers to the understanding, development and adoption of technologies to combat the significant clinical problem of the failure of renal dialysis venous access.
The partnership is between the Universities of:
Dundee,
Limerick,
Queen Elizabeth Hospital Birmingham
and commercial partners:
Vascular Flow Technologies Ltd
Guerbet

5. Objectives of Mid-Term Co-Ordinators Report
Scientific – Graeme Houston
The scientific, technological or socio-economic reasons for carrying out the research
the research objectives of the network;
scientific highlights of the work so far
Partner Benefits
Transfer of Knowledge & Networking – Jerry Wyatt & Shona Matthew
secondment implementation vs Gantt chart planning
recruitment – new knowledge acquisition
network wide events and events open to external participants
benefits for each institution
Management – Jerry Wyatt & Shona Matthew
Financial aspects
any proposed re-orientations of the networks’ activities
dissemination
IPR
Impact – Graeme Houston
Benefits
Dissemination
Lasting collaborations
Complementary skills acquisition
Career development

6. The Problem Haemodialysis
The number of patients reaching end stage renal failure and requiring renal replacement therapy continues to increase at a rate of around 5% per year across Europe
Haemodialysis (HD) therefore remains a common treatment modality with over a quarter of a million patients on haemodialysis in Europe (ERA-EDTA Registry 2009)
This number which is double the number of patients on dialysis 15 years ago and is projected to continue to increase at 4-6% per year

7. The Problem Renal dialysis venous access (ReDVA) methods are:
arteriovenous fistula (AVF) formation,
arteriovenous graft (AVG) implantation or
central venous catheter (CVC) insertion

8. The Problem Renal dialysis venous access (ReDVA) problems:
AVF maturation variable
The AVF failure rate from multiple studies and at multiple sites at one year is around 50%,
AVG failure rates between 60-80% at one year.
Close surveillance of the AVF or AVG to avoid occlusion results in around 50% needing a procedure in the first year
CVC catheters associated with:
High mortality
High infection rates
Hospital attendances

9. ReDVA Failure
ReDVA long-term effectiveness limited by the formation of vessel
narrowing (stenosis) due to venous intimal hyperplasia (VIH)
Causes VIH:
Turbulence
Anatomical Geometry
Tissue Compliance mismatch
Tissue mediators VIH

10. ReDVA Failure
ReDVA long-term effectiveness limited by the formation of vessel
narrowing (stenosis) due to venous intimal hyperplasia (VIH)
Causes VIH:
Turbulence
Anatomical Geometry
Tissue Compliance mismatch
Tissue mediators VIH
Haemodynamics in ReDVA important but poorly understood.

11. Key Research Objectives
The development of new methods of assessment of ReDVA using imaging techniques - CT/MRI/Ultrasound
Flow rig simulations of ReDVA models
Computational fluid dynamics (CFD) of patient’s 3D geometries and observes flow patterns to predict wall stress patterns implicated with vascular occlusion.
Development and assessment of new vascular devices for ReDVA.

12. The Project Work Packages Lead Partner
1 Research Supervision and Management UNIVDUN
2 Data Mining and Prospective Data Sharing QEHB
3 New Methods of Assessment Using Imaging Techniques GU
4 Flow Rig Simulations of ReDVA Models UNIVDUN
5 Computational Fluid Dynamics Analysis UL
6 Serum Biomarkers of ReDVA Failure UNIVDUN
7 Mapping of Strategies of New Vascular Devices VFT

13. The Partners’ Expertise
University of Dundee (UNIVDUN): Cardiovascular interventions imaging, vascular biology and cardiovascular hemodynamic in a wide range of vascular conditions. UNIVDUN will co-ordinate the programme and contribute clinical imaging, flow rig analysis, ultrasound analysis.
University of Limerick (UNIVLIM): Cardiovascular fluid dynamics. UNIVLIM will co-ordinate the Computational Fluid Dynamics modelling and cellular/vascular models.
Queen Elizabeth Hospital Birmingham (QEHB): The largest UK renal replacement therapy unit with expertise in renal access imaging, salvage and the underlying mechanisms of venous intimal hyperplasia.
Vascular Flow Technologies Ltd (VFT): Global vascular graft products and cardiovascular fluid dynamics research. VFT will contribute commercial experience in the field of cardiovascular devices.
Guerbet (GU): Established expertise in contrast media, both for MRI and for CT. GU will bring competences about the safety and efficacy of its products to optimize the protocol of the study and help in the interpretation of the data.

14. Scientific Highlights
The development of new methods of assessment of ReDVA using imaging techniques.
Development protocols for Ultrasound and MRI imaging protocols
MRI assessment of peripheral veins , central veins prior to, immediately after ReDVA surgery or implantation and at follow-up

15. Scientific Highlights
Flow rig simulations of ReDVA models.
Computational fluid dynamics (CFD) .

16. Scientific Highlights
Development and assessment of new vascular devices.
Mapping of combination strategies of surgical technique, vascular devices and medical therapy to optimize vascular access long term patency for clinical trial evaluations.
Clinical literature reviews
Cochrane Reviews Approval
ERBP and ERA collaboration for new guideline development
Spiral central venous catheters
Spiral stents

17. UNIVDUN
MT Review Meeting 3rd June 2015

18. GU
MT Review Meeting 3rd June 2015

19. UL
MT Review Meeting 3rd June 2015

20. QEHB
MT Review Meeting 3rd June 2015

21. VFT
MT Review Meeting 3rd June 2015

22. Financial MT Review Meeting 3rd June 2015 ReDVA Budget Fellow Months
Fellow Months
Budget €
Initial Secondment
Initial recruitment
Current secondment
Current recruitment
Original
Current
QEHB 32 24 11 12
510407
220591
VFT 6 18
270628
207300 GU 16
149605
155198 UL 50 30
537846
771231 UD 36 48 39 60
Total
122
114
120
Difference
31391
MT Review Meeting 3rd June 2015

23. Benefits to each Institution
Limerick
Clinical Imaging Expertise
Ultrasound, MRI
Application of CFD in Commercial Development
MRI Contrast Agent
Protocol design
Pulse sequences
3D data
Different Fistula Models
Regulatory Processes
Guerbet
Clinical imaging expertise - vascular access: Ultrasound, MRI
Optimising imaging contrast products
Current Trends -Vascular Access Surgery. Impact of Failure
Flow Phantom Research
Interventional Devices
Data Mining
QEHB
Clinical Imaging and Surveillance of Vascular Access
US & MRI
MRI Contrast Media Research & Use
Data Mining Development – Regulatory Processes
Medical Interventional Device Research
MT Review Meeting 3rd June 15

24. Benefits to each Institution
VFT
Clinical Imaging Expertise
MRI & US
Current Trends in Vascular Access Surgery
Impact of VA Failure
Flow Phantom Research
CFD Research
Vascular Haemodynamics – Improving Patient Outcome
Medical Interventional Device Research
Dundee
Medical Device Research & Development
CFD in the application of medical device development
Commercial Approach
Vascular Access Surgery
MRI Contrast Agent
Data Mining
MT Review Meeting 3rd June 15

25. MT Review Meeting 3rd June 15
Milestones
Milestone
Name/Comment
Month
M1.1
Project website – Completed M3
M2.1
Clinical data mining & analysis - Completed
M12
M5.1
Imaging data collection – Continuing
M18 – M36
M3.1
Validation of US/MRI techniques
M24
M1.2
Fellow career development plans – Completed for all current ER’s and ESR’s
M30
MT Review Meeting 3rd June 15

26. MT Review Meeting 3rd June 15
Deliverables
Del No
Centre
Description of work
Completed by
Deadline
D6.1 UD
Serum Analysis
UNIVDUN
M12: Completed
D2.1
QEHB
Data collection & archiving
imaging
VFT/UNIVDUN/UNIVLIM
M18:Completed
D3.1 GU
Standardisation of US/MRI techniques across ReDVA centres.
GU/VFT/UNIVDUN/QEHB/UNIVLIM
M18: Completed
D4.1
UD/UL
Identification of different fistula models.
UNIVLIM/VFT
D5.1 UL
Acquisition of patient 3D MRI data
UNIVDUN/VFT
M18: Continuing towards M36
D3.2
Validation of imaging techniques across ReDVA centres (MRI,US)
GU/UNIVDUN/VFT/QEHB
M24: On target
D5.2
Construction of CFD meshes
VFT/UNIVLIM/UNIVDUN
MT Review Meeting 3rd June 15

27. Knowledge Transfer/Training
Opportunities Available to UL-VFT & UD-VFT Secondees, UD Recruit
Interventional Radiology Course
Session with Vascular Surgeon
Designing an MRI Protocol
MR Imaging Techniques – Pulse Sequences
Supercomputing Overview
Flow Rig Simulations
Ultrasound Techniques including Elastography
Developing a Pre-Clinical Model
CAD Stent Design
All secondees are actively encourage to attend course/conferences/meetings
MT Review Meeting 3rd June 15

28. Knowledge Transfer/Training
Opportunities Open to QEHB-GU & UD-GU Secondees
Cochrane training modules on systematic reviews and meta-analysis of diagnostic test accuracy studies (University of Amsterdam and University of Birmingham).
Cochrane author training module for diagnostic test accuracy systematic reviews (university of Birmingham)
Seminar and meeting with European Renal Association regarding guidelines group and data extraction from scientific literature.
Guerbet introductory program. 
Medical and regulatory affairs training
Theory of MRI and contrast agents.
MT Review Meeting 3rd June 15

29. Presentations Presentations 27 Presentations
British Society of Interventional Radiology
Vascular Access Society of Great Britain and Ireland
Annual Conference of the Bioengineering Section of the Royal Academy of Medicine in Ireland
World Congress of Nephrology
American Society of Nephrology
Vascular Access Society
Conference Sessions
VAS
Round table session – Outreach-ReDVA Project
VASA
Plenary Session

30. Publications
Less than two years into the project we have a number of publications submitted
to journals
Publications
Accepted: 2
Journal of Vascular Access & EJVES
Accepted pending minor revisions: 1
Journal of Vascular Access
Under peer review: 11
Various Journals

31. Workshops & Teleconferences
Paris April 2014
Novel and established methods of imaging vascular access (RR and SG)
Impact of VA failure on the patient and the NHS (SB)
The Scottish Renal registry (SB)
Factors affecting clinical decision making in VA (PS)
Paris July 2014
Handling large data and systematic reviews and EROS(Dr Evi Nagler, ERBP)
Birmingham October 2015
Under discussion - Focus on flow rig simulations and CFD?
Teleconferences
Regular teleconferences are held between ReDVA partners.
Nationwide data collaboration

32. Dissemination Public & Academic
Focus on transfer of knowledge and training for fellows
Many successes linked to our work – publications & presentations
The ReDVA website provides free availability of our results – abstracts, publications.
Collaborations emerging from ReDVA that may seed future funding applications
Commitment to outreach: Peers, Public and Patients……

33. Commitment to Outreach
Continuing commitment to outreach: Each centre to participate in two events
Month
Activity 12
Dundee Science Festival 18
Round Table Session (VAS) 20
Arts & Science Festival Birmingham 24
University of Dundee Open Day (CRC)
The ReDVA Website ReDVA Newsletters
MT Review Meeting 3rd June 15

34. Impact

35. Impact Key Impacts: ReDVA 2015-2017 New Secondee/ Recruitment
Guideline Development
Clinical Trial
Product Development – Pre-clinical assessment
Imaging Protocol Adoption
Dissemination

36. Impact
Dissemination Scientific Publications: Abstracts: US, EU, UK Accepted manuscripts: J Vasc Access Surg, J Biomech Eng Submitted Manuscripts: J Vasc Access Accepted Cochrane Review Public/Professional Engagement: Renal Patient Forum UK Renal Registry/ Kidney Research UK/NIHR Guideline Development: ERA and European Best Practice

37. External Collaborations
Academic:
Partners: Dundee, Limerick, Birmingham
External:
UK - Edinburgh, Belfast, Glasgow, Cardiff, London
EU – Amsterdam, Leipzig, Linz
US – Washington, Cinncinati
Clinical:
European Renal association/ ERBP Guideline Development
US Kidney Foundation/ Kidney Research UK
Commercial:
Partners: VFT, Guerbet
UK – Toshiba, Siemens
EU – H2020 submissions

38. Lasting Collaborations
Partner Benefits –Knowledge Exchange/Projects:
Collaborative Research – Academic/Commercial
Literature Review
Staff Development
Commercial Focus
Product Development
Market Research
Wider Benefits:
Scientific Meeting Presentation
Training Opportunities
Outreach – Public engagement

39. Skills Acquisition Partners Knowledge Transfer
Academic/Industrial partnerships
Clinical Data Handling
Basic Science Techniques
Commercial Focus
Product Development
Product Safety Assessment

40. Skills Acquisition Secondees and Recruits Clinical Research:
Clinical Trials
Registry Data
Clinical data Mining
Health Informatics
Guideline Development
Literature Review

41. Skills Acquisition
Secondees and Recruits Basic Research: Flow Rig Computational Fluid Dynamics Computer aided Design Prototype testing Regulatory Processes Imaging Research: Image Analysis Imaging Contrast Media Patient Risks

42. Career Development Secondees PhD Completion Clinical Researchers
Post Doctorate Training
Academic/Commercial Opportunities:
Project management
Accountability
Differences Academic/Commercial goals
Training Courses

43. Questions
Thank you for your attention.
Any questions?