1. Management Through Systems Vicki Latter Biomedicine Research & Development Unit University College London

2. –No database – no idea how many projects –No sponsorship system in place –Blanket insurance but new insurers wanted lists –Researchers naïve of governance, EUCTD and GCP –Safety procedures using NHS Trust polices –Trials being run on DDX rollovers –Protocols etc. didn’t meet ICH GCP –No Trial Master Files Gap analysis Jan – May 2004 UCL Biomedicine R&D Unit created October 2004 4 staff, now 5 and rising to 8

3. Non-commercial projects at UCL Registered –Active projects –Closed projects Not registered – DDX rollovers to CTAs –Estimated in May 2005 from NRRs to be ca. 625

4. Non-commercial projects registered TOTAL = 213 active projects International = 17 –Regulated trials = 15 –Governance studies = 2 UK only = 196 –Regulated trials = 52 –Mechanistic studies = 8 –Research governance studies = 85 –Insurance only = 26 (managed by PGIs) –Student projects = 25

5. Volume versus resource!!! Help researchers help themselves Access to comprehensive information Systems for sponsorship and insurance Help with IMP sourcing Nurture researchers through protocol and authorisation stages Provide SOPs, guides and templates TMF (SMF) training and monitoring

6. Raising awareness and providing information Presentations and seminars Cascade of communication Communications to administrators GCP training courses Enquiries – 35-45/week (Nov 05) Website - launched December 2006

7. http://www.ucl.ac.uk/biomed-r-d/ Homepage About us Research Governance Clinical Trials Forms and Procedures SOPs, Guides and Templates Frequently used acronyms What’s New?

8. http://www.ucl.ac.uk/biomed-r-d/ Funding Opportunities Reference Documents Useful Links Training Links UCL Biomedicine UCL Admin Feedback Site Map

9. http://www.ucl.ac.uk/biomed-r- d/clinicaltrials Clinical research – clinical trials & clinical studies What are the EU Clinical Trials Directive and the UK Clinical Trials Regulations? Other EU Directives and requirements that impact on all clinical trials Laws and guidelines relevant to clinical research Clinical Trials responsibilities – their legal impact International clinical trials

10. http://www.ucl.ac.uk/biomed-r- d/clinicaltrials Is my trial encompassed by the CT Regulations? What you must know if you are already conducting a clinical trial at UCL Planning a clinical trial? Click here to get started Authorisations before your trial can start Contracts and agreements before you can start Insurance and indemnity for clinical trials Trial initiation, conduct, pharmacovigilance and closure

11. Project Sponsorship and Registration Form Part A Admin info Part B Study/ trial details Part C Summary progress Part D Funding, partners, CROs Part E Sponsorship Authorisations Part F CT Regulations (UK, EU, non-EU) Part G IMP sourcing, pkg, labelling, storage Part H Pharmacy manufacture Part I Safety procedures

12. IMP Sourcing Ex-commercial stock – proprietary or generic Provided free of charge by pharmaceutical company – licensed or unlicensed, in UK, EU, non-EU Formulation by licensed IMP manufacturer Active ingredient –Licensed –Unlicensed Toll manufacture UCL manufacture

13. Management of project life cycle IMP Sourcing Feasibility, insurance and risk assessment Sponsorship and submissions Authorisations & agreements Trial commencement & conduct Data management, analysis and write up

14. Feasibility, insurance and risk assessment Validate project & insurance registration R&D Committee Review (sponsors in principle) feasibility insurance IMP sourcing outline protocol risk assessment facilities resources Apply for waiver to insurance restriction(s) Issue insurance confirmation letter Register on database Pass project to coordinator Update information Controlled documents

15. Sponsorship and submissions Issues sponsorship authorisation letters and initiates agreements Supports completion of COREC form Supports completion of CTA or equivalent Coordinator supports researcher on protocol, IB, SIS, ICF and other project tasks REC MHRA Guides SOPs Templates Controlled documents Precedent agreements

16. Authorisations & agreements Trust R&D approval CI completes Trust R&D Registration form Coordinator negotiates and issues agreements CI and sponsor receive approvals REC / MHRA approvals Legal support All agreements signed

17. Trial commencement & conduct Trial opens and enrols pts Subsequent monitoring contacts & visits 1st monitoring visit Coordinator issues Trial Master File and trains research team RECMHRA Guides SOPs forms SUSAR(s) reporting SOP Termination Annual Safety Report Guide RECMHRA

18. Document control system Project registration Sponsorship authorisation Agreements Information sheets GCP –SOPs –Guides –Templates Internal Standard Operating Procedures

19. Sponsorship Agreements Allocation Responsibilities allocated to sponsors for Parts 3,4 & 5 Delegation Any sponsor may delegate any or all duties (e.g. monitoring) An agreement should be signed by all sponsors and delegated persons to ensure clear assignment of duties and assignments should be included in the protocol Due diligence! (Regulation 51, Medicines for Human Use (Clinical Trials) Regulations 2004)

20. Interlocking agreements - UK Clinical Trial Site Agreement Pivotal Clinical Trial Agreement Sponsor with Lead NHS Trust CI acknowledge Framework Partnership Agreement UCL with Trust Clinical Trial Site Agreement Clinical Trial Site Agreement IMP from Pharmacy Funding Agreement

21. Interlocking agreements - UK Clinical Trial Site Agreement Pivotal Clinical Trial Agreement Sponsor with Lead NHS Trust CI acknowledge Head agreement with pharmaco Framework Partnership Agreement Clinical Trial Site Agreement Clinical Trial Site Agreement IMP from pharmaco Precedent agreements cannot be used if there is a head agreement Funding Agreement

22. International Issues Notice to applicants Questions and Answers January 2005 The sponsor may delegate any or all of his trial- related tasks/duties and functions to an individual, company...There must still be an overall sponsor for the trial. Any duties and functions that are delegated should be specified in writing. However the sponsor remains ultimately responsible for ensuring that the conduct of the trial and the final data generated by those trials comply with the requirements of Directive 2001/20/EC.

23. Interlocking agreements - international Clinical Trial Agreement Sponsor w. Lead Trust CI acknowledge Head agreement with pharmaco IMPs from pharmacos Sponsor with Country Coordinating Group Country Coord. Gp with Country Site Country Coord. Gp. with Country Site Side agreement with another pharmaco x n countries Sponsor with UK site Sponsor with UK site

24. Systems and processes to drive R&D management Help researchers to help themselves Provide clear unambiguous information Sponsorship and insurance registration forms Ensure quality protocol, SIS, ICF etc. Agreements defining allocated responsibilities and delegated duties Provide SOPs, guides and templates Maintain TMFs and monitor as required