UKCRC Registered Clinical Trials Unit Network
UKCRC CTU
Registration
CTU Workshop, January 2012
Presented by Professor Julia Brown
UKCRC Registered CTU Network
UKCRC Registered Clinical Trials Unit Network
Rationale for CTU Registration
• 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
UKCRC Registered Clinical Trials Unit Network
Rationale for CTU Registration (2)
• 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
UKCRC Registered Clinical Trials Unit Network
Aim of UKCRC CTU Registration
Identify high quality CTUs to support the delivery
of UK clinical research
Current Situation
UKCRC Registered Clinical Trials Unit Network
• 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
UKCRC Registered Clinical Trials Unit Network
System established for coordinated CTU
engagement in UKCRC Activities
Clinical
Studies
Groups
Consumers
48 CTUs currently registered
National
Initiatives
e.g.
RDC Project
Tissue Banking
Network of Trials Units
TU
TU
Individual
Investigators
TU
TU
TU
TU
TU
TU
TU
UKCRC
TU
Regulatory
Bodies
e.g.
DoH, EU
Experimental
Medicine
UKCRN
Coordinating Centre
Local Research
Networks
Training & Education
Trials Activity
30 full
18 provisional
UKCRC Registered Clinical Trials Unit Network
UKCRC Registration Process
• 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 Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
Key Achievements to Date
 Review of UK CTU Capacity
 NIHR NETS CC Pump Priming for CTUs
UKCRC Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
• 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
UKCRC Registered Clinical Trials Unit Network
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.
UKCRC Registered Clinical Trials Unit Network
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.
UKCRC Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
• 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)
UKCRC Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
International Review Panel
– Clinical epidemiology
– Clinical Trials Unit Director
– Experienced triallist
– Information Systems
– Trial Management
– Statistics
– Funder/ triallist
UKCRC Registered Clinical Trials Unit Network
International Review Committee Issues
–
–
–
–
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
UKCRC Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
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...’
UKCRC Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
Clinical Data Management Systems –
Recommendations
•
Create solid building blocks
–
–
•
Build supporting systems on these building blocks
–
–
•
•
•
Buy a commercial system
Use hosting service if possible
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
UKCRC Registered Clinical Trials Unit Network
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
UKCRC Registered Clinical Trials Unit Network
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)?
UKCRC Registered Clinical Trials Unit Network
Questions?