1. UCL Clinical Trials Unit Launch 12 July 2012 UCL CTU Launch 12 July 20121

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3. UCL CTU Structure, Aims and Objectives Professor Peter Brocklehurst UCL CTU Launch 12 July 20123

4. UCL CTU Structure, Aims and Objectives CTU staff structure Mission statement UKCRC registration Trial types Linked centres UCL CTUs Collaborative CTU development Governance groups UCL CTU Launch 12 July 20124

5. CTU Director Peter Brocklehurst Deputy Director & Head of Clinical Trial Operations Sue Tebbs Clinical Trials Operations Project Manager Training Nicola Muirhead Clinical Trials Manager RAPs Simon Clawson Clinical Trials Operations Project Manager QA Michelle Tetlow Clinical Trials Operations Project Manager Methodology Julie Bakobaki INFANT Research Midwife Linda Mottram INFANT Trial Co-ordinator Jacqueline Coleman INFANT Trial Data Co-ordinator Abigail Howarth INFANT Trial Administrator Michael Franklyn BUMPES Senior Research Midwife Lynn Lynch BUMPES Trial Co-ordinator Laura Custins BUMPES Trial Data Co-ordinator TBC Health Economist Laura Vallejo-Torres CTU Manager Alan Bailey PA to SMT Clare Torud Head of Statistics Caroline Dore Principal Statistician TBC Statistician TBC Head of Research, Teaching & Learning and Developments, Advanced Information Services Centre (AISC) Anthony Peacock IT Manager Steve Hibbert IT Programmer Philip Bakobaki Professor of Epidemiology & Public Health Steve Morris Academic Reporting Line UCL CLINICAL TRIALS UNIT ORGANISATION CHART UCL CTU Launch 12 July 2012 5

6. UCL CTU Vision To establish a world-class clinical trials unit to conduct high impact trials across a broad range of clinical specialties UCL CTU Launch 12 July 20126

7. UCL CTU Mission Statement The UCL Clinical Trials Unit will design, conduct, analyse and report high quality clinical trials and other well designed studies that fit with the research strategies of UCL In pursuit of this Mission, the UCL Clinical Trials Unit will – Develop partnerships with clinical investigators at all relevant institutions – Promote a trial governance structure that supports a compliant, risk-based, proportional approach to the application of regulations – Provide clinical trials leadership and expertise across the whole range of activities required to deliver trials from concept to dissemination and implementation of research findings – Employ highly experienced staff with diverse research interests and expertise in clinical trial methodology to enhance the effectiveness of the research pathway The UCL CTU will accomplish its mission through CTU staff and collaborators supporting adoption of its policies and procedures UCL CTU Launch 12 July 20127

8. UKCRC registration Submitted for provisional registration April 2012 Result expected by September 2012 UCL CTU Launch 12 July 20128

9. Trial types that may be considered by CTU Randomised controlled trials – Two-arm – Multi-arm – Adaptive designs Factorial trials Cluster randomised trials All phases – Clinical Research Facility UCL CTU Launch 12 July 20129

10. Trial types that may be considered by CTU Drugs (IMPs) Devices Surgery Lifestyle interventions (exercise, smoking cessation etc) Information provision Organisational change etc UCL CTU Launch 12 July 201210

11. Other study designs Large observational studies – muticentre studies that require primary data collection Where data collection systems have to be quality assured to a standard required of clinical trials UCL CTU Launch 12 July 201211

12. Linked Centres The CTU has established a hub and spoke arrangement with linked trial centres The details of this relationship may vary depending on the facilities, resources and experience of the linked centre but the governing principles remain the same Linked Centre Clinical Trial Lead acts as a conduit UCL CTU Launch 12 July 201212

13. Linked Centres Hub and Spoke Model Current Linked Centres UCL CTU Queen Square GOSH ENT Royal National Orthopaedic Hospital Moorfields Eye Hospital UCL CTU Launch 12 July 201213

14. Linked centres UCL CTU hub main roles  Provides staff, skills and infrastructure expected within a registered CTU  Provide overarching SOPs  Provides or outsources IT for CTU trials: trial database, randomisation, SAE database, trial management systems  Leads the design and delivery of UCL CTU hub trials Linked centres spoke roles  Comply with overarching SOPs  Have hub support at the appropriate level depending on local staff/skills and infrastructure  Perform gap analysis of what is available locally and what hub can provide  Methods of how to address the gaps identified will be for discussion with linked centres and is likely to be a mixture of hub support, locally available resources supplemented by appointments on trial grants UCL CTU Launch 12 July 201214

15. UCL CTUs Collaborative UCL Clinical Trials Unit – Director Peter Brocklehurst CRUK & UCL Cancer Trials Centre – Director Jonathan Ledermann PRIMENT – Directors Michael King and Irwin Nazareth MRC CTU – Director Max Parmar Aim to share – a number of best practices – training UCL CTU Launch 12 July 201215

16. CTU Development Development of areas of expertise – eg Surgery Methodology – In collaboration with MRC Methodology Hub – Training in methodology eg PhD students Teaching UCL CTU Launch 12 July 201216

17. Governance UCL CTU Launch 12 July 201217

18. CTU Oversight Groups UCL Research Board Scientific Advisory Board (SAB) Senior Management Team (SMT) Quality Management Group (QMG) Protocol Review Committee (PRC) Trial Prioritisation Committee (TPC) UCL CTU Launch 12 July 201218

19. Scientific Advisory Board (SAB) Reports into UCL Research Advisory Board Functions Help shape the overall strategic direction of the UCL Clinical Trials Unit and linked Trial Centres Review progress towards the UCL CTU key objective of becoming a world class clinical trials unit delivering high impact trials that fit with the research strategies of UCL SLMS Review scientific performance of the UCL CTU Make suggestions on how to improve performance of the UCL CTU and linked Trial Centres Outputs Provide advice and feedback to the UCL Research Advisory Board, the UCL CTU Senior Management Committee and the Trial Prioritisation Committee to inform strategic decision making UCL CTU Launch 12 July 201219

20. Senior Management Team (SMT) Reports into Scientific Advisory Board (SAB) Functions Providing strategic leadership, direction and management of the CTU Advise the Unit Director on Unit strategy and its implementation Review the costs and value for money performance of the Unit, including budget performance Review the interactions and collaborations between CTU and other bodies Oversee development and training within the Unit Outputs To update the sponsor on the UCL CTU trials portfolio To provide reports to the Scientific Advisory Board (SAB) UCL CTU Launch 12 July 201220

21. Trial Prioritisation Committee (TPC) Reports into Senior Management Team (SMT) Functions Review requests for trial collaborations Reviews are conducted pre grant application To advise the applicant, using a phased approach, whether: It is an important scientific question It is fundable It is feasible to be adopted and conducted through the UCL CTU Outputs To develop and approve the UCL CTU trials portfolio To provide detailed feedback/advice to Investigators as appropriate UCL CTU Launch 12 July 201221

22. Quality Management Group (QMG) Reports into Senior Management Team (SMT) Functions Review, advise and approve Trial Risk Assessments and Quality Management Plans Manage reports of potential Serious Breaches (SB) Advise the Unit Director on the Quality Management strategy Receive and review any major concern with regard to trial conduct Oversee the development of a Unit Quality Assurance programme Outputs To provide a quarterly aggregate summary report to the Sponsor To respond to any relevant queries raised by the Sponsor To provide details of documentation reviewed or SBs when required To feedback to Investigators as appropriate UCL CTU Launch 12 July 201222

23. Reports into Quality Management Group Responsibilities Advise on the content/format of protocols adopted by the CTU Highlight major concerns after review of the content/format of protocols Provide feedback to Investigators from PRC recommendations Provide summary report of recommendations to UCL CTU QMG Manage the protocol template and associated guidance Membership Chair - Senior Clinical Operations Project Manager for Methodology Deputy Chair – Principal Research Associate (Health Economics) Permanent members with clinical, statistical and trial management expertise Other input will be sought as appropriate for individual trials UCL CTU Launch 12 July 201223

24. Trials and Functional Groups Susan Tebbs UCL CTU Launch 12 July 201224

25. Overview Functional Groups Trial portfolio New trial adoption process UCL CTU Launch 12 July 201225

26. Research area: methodology To improve patient outcomes through the timely collection of high quality, reliable, valid, cost effective data on which treatment recommendations are based.  Identifying and finding solutions to common problems in the design, conduct, analysis, interpretation and reporting of clinical trials and studies  Developing methods to improve trial conduct and quality  Adding to the available evidence on the most effective and appropriate methodological practice  Implementing the solutions through input to trial protocol and operational development, and through enhanced training of trial staff UCL CTU Launch 12 July 201226

27. Health Economics  Health Economics component on clinical trial is increasingly demanded by funding bodies  Is intervention under evaluation value for money?  Trial design: Interventions being compared, appropriate measure of effectiveness outcome, time horizon, etc.  Data collection: Information on health care resource utilisation, unit costs, health-related quality of life, patient costs, etc.  Analysis: Cost-effectiveness model, extrapolation, imputation of missing values, uncertainty, value of additional information analysis, etc. UCL CTU Launch 12 July 201227

28. Statistical Involvement  Review of collaboration requests  Study design  Choice of outcome measures  Sample size calculation  Randomisation  Select method and test the implementation  Trial conduct  Member of the trial team  Protocol and CRF development  Trial Monitoring  Analysis, reporting and dissemination UCL CTU Launch 12 July 201228

29. The QA role at UCL CTU To ensure compliance with Clinical Trial Regulations, GCP and unit SOPs and Policies:  Review of quality-related documents e.g. risk assessment and quality management and monitoring plans  Audit e.g. if planned inspection  Writing UCL CTU SOPs and Policies  Ensure compliance across unit with UCL CTU SOPs and Policies  Review of monitoring reports and assistance with corrective and preventative action plans  Inspection preparation, involvement and follow-up  Assistance with any particular problems/document review before submission for approvals UCL CTU Launch 12 July 201229

30. Training in the Clinical Trials Environment Summary objective  to enable CTU staff to be qualified by training to carry out their role in the Unit and to maintain comprehensive, auditable records Primary functions:  Identify performance gaps  Develop and deliver training  Source external training  Maintaining training records UCL CTU Launch 12 July 201230

31. IT at CTU Database application – Macro 4 Randomisation – Tenalea Document Management – EDGE UCL CTU Launch 12 July 201231

32. Current Funded Trials INFANT BUMPES RAPS COMPARE Crohns Imaging Study HT Trial UCL CTU Launch 12 July 201232

33. Other Trials Funded 6 Not funded or adopted 10 Adopted & gone/going to grant application 5 New trial enquiries 5 UCL CTU Launch 12 July 201233

34. New Trials Seeking CTU adoption/collaboration? At least 3 months before the application deadline Apply using the Collaboration Request Form available on the website Send to enquiries@ctu.ucl.ac.ukenquiries@ctu.ucl.ac.uk UCL CTU Launch 12 July 201234

35. New trial adoption process First steps  CI/deputy or Clinical Trial Lead(CTL) (from linked centres) completes a Collaboration Request Form Available on request or on line Reference # allocated  Triggers letter from CTU to CI/CTL acknowledging Receipt of proforma Informing of TPC meeting date that the trial will be reviewed Advising CI/CTL that they (or delegate) should attend Sending slide set for presentation  Call from CTU senior staff to discuss suitability and clarify any immediate issues 35UCL CTU Launch 12 July 2012

36. New trial adoption process TPC 1 st Review meeting – Short presentation by Investigator – TPC has opportunity to discuss with Investigator – TPC completes a report template Importance of scientific question Is it feasible Is it fundable (in the opinion of the TPC) 36UCL CTU Launch 12 July 2012

37. Supported UCL CTU Interested in developing the trial Letter to CI/CTL plus project proposal document CTU Project Manager allocated PM completes Initial high level risk assessment with the Investigator More Information Requested More information required to make a decision Feedback to CI/CTL from CTU Director/Deputy Director or TPC Chair Then reviewed again by TPC Not Supported Not supported Feedback to CI/CTL With summary recommendations or comments 1st TPC Review ~ outputs UCL CTU Launch 12 July 201237

38. Supported UCL Sponsorship requested? Yes  submission to UCL sponsorship office If agreed then proceeds to funding submission If no – then sponsor’s office responds to CI No  CI/CTL confirms sponsorship arrangement and agreement by UCL Not Supported Not supported Feedback to CI/CTL 2 nd TPC Review – feasibility of conduct 2 possible options based on risk assessment UCL CTU Launch 12 July 201238

39. New trial adoption process If funding successful: – 3 rd TPC review Amount of award? Has it changed? Amendments to the design required? Is the CTU still able to manage the trial? 39UCL CTU Launch 12 July 2012

40. Last TPC review Last TPC review 2 possible optionsSupported Trial staff recruited CTU completes a final risk assessment Develop protocol Approvals Trial governance structures established (TSC/IDMC) Not Supported Feedback to CI/CTL CI to find an alternative CTU TPC may recommend approaching a more appropriate UCL CTU or body CTU will notify other UCL CTU or body of recommendation UCL CTU Launch 12 July 201240

41. Working with the CTU Collaboration – Design – Grant application – Delivery Flexibility Aim – To develop & deliver high quality trials to improve patient care – Trials that are compliant with the regulations UCL CTU Launch 12 July 201241

42. Questions UCL CTU Launch 12 July 201242

43. Steve Hibbert UCL CTU Website http://www.ucl.ac.uk/ctu UCL CTU Launch 12 July 201243

44. Navigating to the website Navigating to the website Two useful pages Two useful pages  How to contact us  How to work with us Other information on the website includes; staff profiles and current research areas. UCL CTU Launch 12 July 201244

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50. Questions UCL CTU Launch 12 July 201250