1. Update on the NIHR TMN, BRTC and the Hubs for TMR Athene Lane

2. Overview TMN history and past activities Planned activities BRTC Hubs for Trials Methodology Research

3. UK TMN history Network for trial managers on MRC trials Commenced in 1988 2003 joint funding HTA & MRC - 2010 Annual meetings with workshops (1999) Linking with new trial managers Steering group of TM & funders (2006 AL)

4. UK TMN activities One day workshops Project management, Practical GCP Writing study newsletters Website: http://www.tmn.ac.uk/http://www.tmn.ac.uk/ Trial management guide

5. Current status NIHR TMN reflecting funding changes NETSCC funding the network Base in Leeds CTU, CTRU: Vicky Napp Network coordinator tba Activities to resume in 2011

6. Planned activities? Eligibility: NIHR portfolio studies and EME Reinstate the annual meeting Update trial management guide Website and discussion board facility Newsletter, inc new trial developments Signpost TM relevant training opportunities

7. Bristol Randomised Trials Collaboration NCRI accredited and UKCRC registered CTU School of Social and Community Medicine Director: Alan Montgomery, Associate: AL Management group: statisticians, health economists and social sciences

8. Bristol Randomised Trials Collaboration Primary care especially mental health Cancer and other secondary care trials Qualitative research for trial design and conduct Complex trial designs enquiry-brtc@bristol.ac.uk

9. Bristol Randomised Trials Collaboration Primary care especially mental health Cancer and other secondary care trials Qualitative research for trial design and conduct Complex trial designs enquiry-brtc@bristol.ac.uk

10. Collaboration and innovation in Difficult or Complex randomised controlled Trials Rhiannon Macefield TMH Director: Jane Blazeby http://www.methodologyhubs.mrc.ac.uk/default.aspx

11. PRISMA flow diagram Records identified through database searching (Embase: 529, Medline: 536) Additional records identified through other sources n= 33 (Hand search of CT/CCT/CCT, referenced in other papers, personal knowledge) Records after duplicates removed (n =678) Records screened (n = 678) Records excluded (n = 526) Full-text articles assessed for eligibility (n =152) Full-text articles excluded (n = 117) Reasons inc: Safety monitoring only, central monitoring only, monitoring of specific procedure only e.g. radiotherapy QA, no monitoring details/ does not discuss monitoring methods, site visits excluded monitoring conduct, not full paper. (Waiting on 1 inter-lib loan) Articles included in review (n = 68)

12. Benefits of on-site monitoring Identified problems, e.g. procedural errors (weighing) and data inconsistencies Issues resolved quicker, e.g. increased recruitment Improved protocol adherence and GCP compliance Greater central & site staff interaction and between sites Shared best practice between sites Opportunities for additional training

13. Site monitoring disadvantages Costs ($800-1500/visit) or 0.1% annual budget NCI Staff time (1-2 days per visit) Environmental impact of travel to sites Visits created potential for staff friction or harassment Little evaluation of benefits or disadvantages “On-site monitoring is the only type intended to seek out sloppiness and fraud” (Cohen 1994)

14. Written report to CIs & PI within 12 weeks PRIME Site visits 1-2 days PRIME structure Problem solving meeting with senior nurse at close Review arranged 8 wks in advance Monitoring SOP & report template Utilise report at next review

15. PRIME site activities Observation of recruitment & follow-up appointments Major focus and most informative aspect Individual feedback – mentoring and training role CRF completion during/after appt

16. PRIME site activities Group meetings/orientation meeting Site recruitment and attrition Problem solving local issues Protocol adherence Data storage Site files Safety reporting Staff training

17. Monitoring report findings

19. PRIME advantages for a trial Focuses on trial staff, including as reviewers Standardises conduct across staff (including data collection) & shares good practice Assists with overall staff training Potential for study performance gains Early notice of any issues Improves GCP compliance, e.g. site file