UKCRC Registered Clinical Trials Unit Network

1. UKCRC Registered Clinical Trials Unit Network UKCRC CTU Registration CTU Workshop, January 2012 Presented by Professor Julia Brown UKCRC Registered CTU Network

2. Unprecedented investment in clinical research in recent years - expansion in UK clinical trials portfolio Increase in volume accompanied by increased complexity (biomarker sub-studies, regulatory requirements, international collaboration, consumer involvement) NHS research infrastructure strengthened through introduction of clinical research networks CTUs recognised as critical component in successful clinical trial development and management However, little national coordination of CTU activity and no national strategy for involving CTUs with trials Rationale for CTU Registration

3. Funders recognise need to ensure UK has expertise and capacity for development and delivery of high quality clinical trials Needs of UK clinical research community: Capacity to support the anticipated increases in accrual and trials activity Expertise to respond to new approaches to trials and regulatory requirements Efficient, coordinated national system Clear and easy to access Rationale for CTU Registration(2)

4. Identify high quality CTUs to support the delivery of UK clinical research Aim of UKCRC CTU Registration

5. 1st UKCRC CTU Registration Call - March 2007 2nd UKCRC CTU Registration call- Spring 2009 Applications from any CTU in UK responsible for design, conduct and analysis of multi centre RCTs or other well designed studies Individual CTUs and collaborative groups eligible to apply Any disease area/topic Current Situation

6. System established for coordinated CTU engagement in UKCRC Activities 48 CTUs currently registered 30 full 18 provisional

7. Two levels of registration offered: Full Track record in design, conduct and analysis Presence of core team of expert staff Robust QA systems Long term viability Provisional Developing expertise but currently falls short of full complement of infrastructure, resource and experience for full registration Facilitatory process – identifying CTUs with well established, high quality systems and outputs as well as those on the way to achieving this UKCRC Registration Process

8. Key Achievements to Date • Development of Registered CTU website • Showcases 48 Registered CTUs • Clear point of access for investigators and funders • Promotes collaboration with CTUs – better quality research proposals and study delivery • Online search facility –disease area, methodology and study design, funding body

9. Key Achievements to Date • Review of UK CTU Capacity • NIHR NETS CC Pump Priming for CTUs

10. Key Achievements to Date • Cohesion and closer collaboration between CTUs • Creation of CTU Directors Committee facilitating strategic discussion on common issues with key national stakeholders • Creation of themed working groups • Information systems, Quality Assurance, Trial Management, Training & Professional Development • Regular routes of communication • SharePoint site, Monthly newsletter, JISCmail lists “Registration of Clinical Trials Units by an international panel and the subsequent establishment of collaborative structures between them have been major steps towards ensuring the quality and efficiency of UK led randomised controlled trials” Professor Adrian Grant, Chair of 2007 CTU Registration Process, Director of the NIHR Programme Grants for Applied Research

11. 2012 Process • Need to review currently registered units • Needs to open to new Units • Need to move to self funding basis • 2012 Registration process developed with Working Group Membership: Funders Sarah Rudkin, Arthritis UK (Chair), Michael Bowdery, Wales, Tom Walley, NETSCC CTU Representatives Julia Brown, Director UKCRC Registered CTU Network, Paula Williamson, Director CTRC Rhiannon Whitaker, Adrian Bloor, Director, Ian Ford, Lorraine Smith, Janet Darbyshire Clinical Research Network Jonathan Sheffield

12. Work programme • UK Registration Process with review of currently registered Units based on an International Panel Review model and annual review of status. • Networking opportunities between UKCRC Registered CTUs enabling: • common approaches to addressing issues across Registered CTUs resulting in optimisation of resources • facilitation of shared best practice amongst Registered CTUs including mentorship of developing CTUs resulting in increased quality systems and processes across the Registered CTUs • opportunities for CTUs to contribute to new developments and initiatives within the clinical research community (funders, networks, and regulators) • greater visibility of Registered CTUs providing easy access to information about their expertise to other stakeholders, particularly funders and clinical investigators • academic/industry partnerships to become more attractive resulting in increases in collaboration • development of more coordinated approach to the DMCs and TSCs Biannual CTU Directors meetings, biannual meetings for CTU Operational staff (Information Systems, statisticians and quality assurance representatives), continuation of existing communication routes – JISC Mail, ‘The Exchange’ Newsletter. In addition a new interactive website will be developed and maintained to facilitate information exchange between CTUs for all disciplines and levels of staff.

13. Work Programme (contd) • Creation and support for the following Working Groups:  • Industry To explore frameworks for facilitating and publicising collaborations with industry and small to medium enterprise and medical device companies. To share previous experiences of working with industry to achieve greater transparency and consistency into academic industry collaborations, addressing key issues such as IP and publications policy. • Core Infrastructure A UK-wide review of Registered CTU core infrastructure funding with the aim of mapping the availability of resources and expertise to support design and delivery of clinical trials. Interaction with a range of funders and host institutions to publicise the importance and benefits of core infrastructure funding in the delivery of cost effective high quality clinical trials • Costing Models Development of a standardised approach to costing studies. The aim of this initiative is to increase transparency, consistency and clarity in funding applications to assist both applicants and funding bodies. • Operational themed meetings -Quality Assurance, Information Systems and Statistics in order to share best practice and to help develop standard approaches to common issues.

14. Work Programme (contd) Representation of CTUs on national/ international groups and in national/international consultations • The Registered CTUs will be represented on key strategy and consultation groups (e.g. MHRA GCP Consultative Committee, MHRA/DoH/MRC Risk Assessment Working Group, NETSCC Trials Unit Advisory Group). CTU views on relevant consultations from national or international bodies e.g. the EU or MHRA will be collated and submitted. Publicity for the UKCRC Registered CTUs • A dedicated online resource presenting a branded identity and showcasing the Registered CTUs through an online directory of Registered CTU research interests and contact details. • Publicity material for funders, industry, small to medium enterprises, collaborators which showcases the Registered CTUs and highlights the importance of and benefits of engagement with Registered CTUs in terms of cost effective high quality delivery of clinical trials Focus for interaction with MRC Methodology Hubs Network and NIHR Research Design Services

15. What are CTUs getting from the network and the work programme? • Visible profile to facilitate access to and integration of UKCRC Registered CTUs with key stakeholders, in particular research funders (including industry), research networks, regulators, and investigators • Raising profile with and understanding of our collaborators, funders, host institutions • Focussed contact point facilitating engagement with stakeholders and ensuring CTUs have opportunity to contribute to key national initiatives and developments (eg MRC Methodology Hubs) • Efficiency and improvement in delivery through sharing best practice and SOPs • Avoidance of duplication of effort and standardising systems (e.g DIMs) • Peer support for common issues (SharePoint; JISCmail) • External recognition of quality – eligibility for new funding initiatives (e.g. NIHR CTU Pump Priming Funding) • Collaborative approach to addressing national issues (e.g. CTU capacity) • Networking with UK CTU Directors, for statisticians, IS, QA • Representation at national / international level • Mentoring (if required)

16. Funding model • Upfront fee for registration review (£500) • Review every 3 years with annual self assessment sign off • Annual maintenance fee to cover work programme • Amount to be adjusted depending on outcome of registration process • Likely to be around £2,000 per annum • Lean structure to keep costs down • Reviewed by working group

17. 2012 Registration Process • Key dates for review • Application process open Jan 2012 • Deadline for completed applications 5 April 2012 • Review early July 2012 • Outcome September 2012 • Application form available from website • Key differences • Simplified • Section 1 Overall summary • Details of 5 (3) open, in follow-up, analysis multi centre rcts, 1 in NIHR portfolio, at least 2 (1) open • 3 (1) trial publication of existing/closed trial - front page of each showing author contributions

18. 2012 Registration Process • Section 2 Staffing • Overall staffing, cvs of 2 (1) statisticians,2 (1) trial/project managers, 2 (1) IT person(s) • Section 3 Infrastructure • Statement of support from host institution • Details of how you ensure long term continuity • Section 4 Quality Assurance • List of Essential SOPs (8 new, deviations and serious breaches, urgent safety measures, sponsorship, system validation, database development, database change management, business continuity and disaster recovery) • How you manage quality assurance, risk assessment and monitoring

19. 2012 Registration Process • Section 5 Information Systems • How data is collected • Info on database systems and their management • Section 6 Statistics • Section 7 Extent of availability • Section 8 Signatures • Section 9 Collaborative Group information

20. International Review Panel • Clinical epidemiology • Clinical Trials Unit Director • Experienced triallist • Information Systems • Trial Management • Statistics • Funder/ triallist

21. Data management systems sub optimal Use of MS Access strongly discouraged Need for formally validated systems Quality management required development Key SOPs missing Quality Assurance required development Audit systems required development Risk assessment required development Need for local collaboration between Units Need for clarity on organisational arrangements and staff structures International Review Committee Issues

22. Clinical Data Management Systems - Requirements Functional • Does it do what I need? • Support allow entry and editing of data • Support RDC • Include library • Query/reporting • etc • And what ‘they’ (regulators) expect? • Audit trail • Robust backup • User access control • etc

23. Clinical Data Management Systems - Requirements System Validation • System itself • Functional specification • Evidence of (thorough) testing • Version control • Development methodology...with SOPs • Specific database implementation • Same as above, but at the database level. • List of CRFs, fields, skipping, category lookup lists, validation etc • Testing • Sign-off (with version control) • Methodology SOP ‘How we build databases...’

24. Clinical Data Management Systems – Options Bespoke • Flexible – but hard to control scope • Cheap ? – not really, very time heavy & need skilled prog staff (and keep them) • Do you want to be a software house? • High risk, difficult to achieve compliance • E.g. Visual Basic/C#, Access (care!, much better as front-end only) Commercial • Know what you are getting • Reduce validation burden (vendor responsible for part) • Restricted scope makes implementation (and building supporting systems & processes) easier • Cost – can be prohibitive • E.g. Medidata RAVE, Phase Forward Inform, Oracle Clinical, Infermed MACRO Free (?) • Cost – not really free, support & documentation often comes at a price • Quality – does the product have pedigree? who is already using it? • Consider validation carefully (where would the MHRA go hunting?) • E.g. Open Clinica, REDCap

25. Clinical Data Management Systems – Hosting Local • Hosted by CTU, or host organisation (e.g. Uni) • Need hardware, space, network connectivity (and security) – and skilled support staff • Difficult to build stable resource when small Remote (commercial) • Reduces need for dedicated servers etc, and support staff • Reduce validation burden on client, supplier will (should!) have SLAs • Cost (c.f. cost of good quality local hosting?) • Loss of control over data - where is it? How do I get at it? Is it even in the UK?! • ‘Pay as you go’ type cost model might be attractive to small units

26. Clinical Data Management Systems – Recommendations • Create solid building blocks • Buy a commercial system • Use hosting service if possible • Build supporting systems on these building blocks • Reporting • Analysis • Focus on the trial, be wary of technology for the sake of itself, and the ‘bleeding edge’ of IT • Expect to be asked to demonstrate regulatory compliance • Hard to achieve all this when starting out! • Consider open source, but be careful • Develop mentoring relationship with other CTU

27. Quality Assurance/ Audit • Examples of ‘best practice’; • SOP master file with signed and dated receipt from relevant personnel • Single person responsible for distribution, storage, archiving, collation of signatures for SOPs • Easy access to SOPs on web/intranet • Audit of SOP adherence • Formal risk assessment to lead monitoring and trial management for each trial • SOP training in place

28. Way forward: • Develop SOPs • Put in place robust plans for data management • Set up mentoring arrangement • Talk to local CTUs, develop collaborations • Wait for next call (2015)?

29. Questions?