Industry Research in the UKCRN (UK Clinical Research Network)

1. Industry Research in the UKCRN (UK Clinical Research Network) Dr H Howard Prof R Kaplan

2. Industry trials & UKCRN • Background of the UKCRC & the UKCRN • Organisation of UKCRN • Role of industry research in the UKCRN mission • Value of industry research to the NHS • Barriers • Work in progress • Way(s) forward

3. Industry Research in the UK • UK has strong history of clinical research – number of global and UK-based pharmaceutical, biotech & medical device companies engaged in research • Roughly 25% world’s top 100 medicines developed in UK • Now increasing global competition to attract investment from biomedical industry • US has commanding lead • Europe now competing with ‘new’ research locations for second place (e.g. India, China, Eastern Europe, S. America)

4. The Challenge for the UK • Industry under cost and time pressures: • New medicines typically take 12 years and ~£350m or more to develop • Companies under pressure to ensure reliable, on-time delivery of quality data, within budget • UK at risk of losing position as preferred research site due to lack of reliability factors critical to industry: • Timeliness – too many examples of Trust set-up abandoned by companies; non-recruiting Trusts; low recruiting Trusts • Cost – relative higher cost-of-living in UK accepted, but delayed Trust set-up & unreliable recruitment = avoidable additional cost • Quality – variations in data quality due to inconsistent training of research staff & standard procedures

5. BIGT, AMS, RPBWP Reports 10/03-03/04 - reports from Bioscience Innovation & Growth Team & Academy of Medical Sciences identified key areas in which UK could improve its competitiveness by building “mutually advantageous” collaboration between NHS and industry – followed by recommendations of RPBWP: • NHS Clinical Trials Network • Establish UKCRC to improve national health and increase national wealth • NHS research infrastructure • Clinical research facilities for experimental medicine • Incentives for research in the NHS • Clinical research programmes • Research workforce • Improved regulatory environment

6. UK Response • DoH announcement March 2004: £100m increase in NHS R&D funding (in England) by 2008 • UK Clinical Research Collaboration (UKCRC) established - new partnership between government, NHS, voluntary sector, private sector, and public • Objective: to transform the clinical research environment in the UK by - • Taking strategic oversight of clinical research • Identifying gaps in clinical research capability • Coordinating approaches between funding bodies to fill gaps and take advantage of opportunities • Providing leadership to develop the profile of the clinical research and enhance the research culture of the NHS • Monitoring progress in implementing plans and in achieving objectives

7. UKCRC workstreams • Building up the infrastructure in the NHS • Clinical Research Networks • Experimental Medicine, including development of national framework of clinical research facilities • Building up the research workforce • Phase 1 Academic Medicine • Phase 2 Other Researchers • Building up incentives for research in the NHS • Clinicians • NHS managers • Coordinating Research Funding Activity • Strategic analysis of clinical research funding in the UK • Develop joint initiatives in public health research • Develop coherent approaches to funding of network areas • Streamlining the Regulatory and Governance Processes

8. UK Clinical Research Network Aim: To take forward the UKCRC’s remit to develop a world-class health service infrastructure in the UK to support clinical research by facilitating the conduct of randomised trials of interventions (including prevention, diagnosis, treatment, and care) and other well designed studies. • Managed set of Clinical Research Networks, initially targeting six priority areas: • Cancer (NCRN) • Dementias & Neurodegenerative Disease (DeNDRoN) • Diabetes (DRN) • Medicines for Children (MCRN) • Mental Health (MHRN) • Stroke (SRN) • Research projects funded by both commercial & non-commercial organisations will be incorporated • UK-wide working & inclusion of primary care infrastructure are critical • Future intention to extend UKCRN to cover full spectrum of clinical need Six Topic-specific Clinical Research Networks (TCRNs)

9. NCRN Accrual (all & RCTs) *figures for 2004/05 are projections based on 8 months data

10. Comparison of recruitment into Myeloma VII and Myeloma IX 800 Myeloma VII recruitment 700 Myeloma IX Recruitment 600 Target 500 Number of patients 400 300 200 100 0 0 1 2 3 4 5 6 7 Year

11. NCRN Coordinating Centre DeNDRoN Coordinating Centre SRN Coordinating Centre DRN Coordinating Centre MHRN Coordinating Centre MCRN Coordinating Centre UKCRN Organisational Structure Local Research Networks (LRN) x 34 Local Research Networks (LRN) x 8 Local Research Networks (LRN) x 8 UKCRN Coordinating Centre Local Research Networks (LRN) x 8 Local Research Networks (LRN) x 8 Local Research Networks (LRN) x 8

12. UKCRN Coordinating Centre • National coordination of UKCRN activities • Conduit for addressing barriers to trials at national level • Development & provision of national systems & approaches to trial development & management • Central team of ~30-35 staff with leads for the different workstreams • Performance management of Topic-Specific Coordinating Centres • Financial management of UKCRN • Provides direct link with UKCRC Board/Partners • Note: not coordination of scientific plans/portfolios

13. Topic-Specific Coordinating Centres • Scientific portfolio development • Performance management of Local Research Networks • Provision of topic-specific training • Coordination of consumer involvement • Links with relevant trials units • Main point of contact with UKCRN Coordinating Centre • Communication with UKCRN Coordinating Centre about barriers to trials • Note: not coordinating the trials themselves

14. TCRN Coordinating Centres Professor Gary Ford Director, Stroke Research Network (Newcastle) Professor Rick KaplanActing Director, National Cancer Research Network (Leeds & MRC CTU) Professor Ros Smyth Director, Medicines for Children Research Network (Liverpool) Professor Til WykesDirector, Mental Health Research Network (Inst Psych & Manchester) Professor Martin RossorDirector, Dementias and Neurodegenerative Diseases Research Network (UCL & Newcastle) Professor Des JohnstonDirector, Diabetes Research Network (Imperial & Oxford)

15. Local Research Networks (LRNs) • Defined geographical area incorporating multiple acute & primary care Trusts • Allocated funding for staff: • Clinical Lead for Research • Research Network Manager • Research Nurses & other research staff • Admin support • Clinical support (e.g. pharmacy, radiology, pathology) • Close links with local service provision • University links • Network builds on and supplements existing local teams/infrastructure

16. Roll out of UKCRN Networks • Cancer (NCRN) – 34 Local Research Networks (LRNs) in England (41 across UK), established 2001 • Mental Health (MHRN) – 8 LRNs, established 2003 • Medicines for Children (MCRN) – LRNs to start April 2006 • Stroke (SRN) – LRNs to start ~May 2006 • Dementias and Neurodegenerative Disease (DeNDRoN) – some LRNs to start ~May 2006; others identified to follow • Diabetes (DRN) – LRNs to start ~May 2006

17. UKCRN Key Workstreams • Trials and Trials Unit Links • Regulatory and Governance • Industry Links • Primary Care Links • Experimental Medicine • Training and Education • Information Systems • Consumer Involvement

18. UKCRN Industry Team UKCRN Coordinating Centre • UKCRN Associate Director for Industry: Rick Kaplan • UKCRN Industry Lead: to be appointed • UKCRN Senior fellow - Industry: Helen Howard • UKCRN Senior fellow - Industry: Anne Davies NCRN Coordinating Centre • NCRN Industry Lead: Rick Kaplan DeNDRoN Coordinating Centre • DeNDRoN Industry Lead: Colin Dingwall DRN Coordinating Centre • DRN Industry Lead: Nishi Chatuverdi MCRN Coordinating Centre • MCRN Industry Lead: Tony Nunn MHRN Coordinating Centre • MHRN Industry Lead: Tony David SRN Coordinating Centre • SRN Industry Lead: Philip Bath Secondment Post(s)fromIndustry First to be appointed Spring 2006

19. Role of Industry Trials in UKCRN • Effective collaboration with the UK pharmaceutical, biotech & device industries is one of the founding principles of UKCRN • UKCRN will assist UKCRC partners in improving the clinical research environment for industry in the UK – and in the process improve the research environment overall • Scale & scope of the initiative  momentum for progress • Industry-led and investigator-led trials both belong in the portfolio

20. Benefits of Industry Research • If a commercial trial – performed in the NHS – speeds licensing of an effective new agent . . . • Both patients & sponsor benefit directly • Future patients benefit if access is speeded • Trial income contributes to a larger/better research infrastructure • Sponsor is likely to expand portfolio of work with NHS • If the company is UK-based, study leads to additional contribution to UK economy

21. Industry DH Charities MRC Funding of health-related R&D (from the House Select Committee report on the pharmaceutical industry 3/05)

22. What does Industry want/need from us? • Speed and reliable data, at reasonable cost • Speed, speed, speed: • Rapid study activation, completion of enrolment & availability of data • Efficient R&D and ethics approval & costing • Confidence that enrolment goals will be met • Confidence that the data quality will meet regulatory standards • ‘One-stop shop’ for series of agents and trials • Expert advice and ‘badging’ (but note that these are low on the list of importance)

23. Common concerns / obstacles • Delays & uncertainty of local R&D approvals • Aligning study time frame with (global) development plans • Will sites be able to deliver on enrolment commitments? • Will data meet all regulatory standards? • ‘One-stop shop’ possible? • Some key members of dispersed trial team may not be included in initial discussions • Delays in relation to funding & peer review decisions (partnership trials)

24. Industry partnership working Optimised partnerships will benefit from: • Establishing or strengthening industry relationships by successful delivery of contract trials • Ongoing partnerships across multiple projects, promoting: • Dialogue & strategic planning • Advance consultation • Collaboration on both early-phase and late-phase trials • Support & problem solving at coordinating centres • Central points of contact • Standardised agreements, contracts, costing, logistics

25. Some key objectives • Development of national framework for networks to carry out industry trials efficiently – and for industry to collaborate with networks (early and late trials) • Understanding barriers to industry involvement and developing solutions to address these barriers, e.g.: • Mandated application of standard processes for network studies: • mCTA and costing model • Streamlined multi-site R&D approval • Performance management of Trusts participating in network studies through development of clear metrics including: • Number of industry studies adopted • Study set-up time • Recruitment delivery according to mutually agreed targets • Data quality

26. Industry Road Map Group Industry sector • Peter Arnold (Smith+Nephew) • Alan Boyd (Ark Therapeutics) • Giles Campion (GE Healthcare) • Nick Deaney (MSD) • Stuart Dollow (GSK) • Joanna Nakielny (Eli Lilly) • Judith Syson (AstraZeneca) • Craig Stevenson (Pfizer) • Gwyn Thomas (Wyeth) • Anthony Walker (Onyvax) Department of Health • Louise Wood • Jill Dhell • Mark Lewis UKCRN • Colin Dingwall (DeNDRoN) • Nishi Chaturvedi (DRN) • Tony Nunn (MCRN) • Tony David (MHRN) • Philip Bath (SRN) • Anne Davies (UKCRN) • Helen Howard (UKCRN) • Rick Kaplan (NCRN/UKCRN)

27. Industry Roadmap Group goals - facilitating industry trials in networks Focus on: • Speed of commitment • Speed of trial set-up • Speed of delivery • Quality of data • Consistency of agreements & arrangements • Cost of service • Building up the basis for partnership working

28. Industry Road Map GroupHigh Priority Recommendations • A streamlined national R&D sign-off process for multi-centre trials (including honorary passport scheme) • Mandatory use of mCTA & a standardised costing method • Standing Trust/University contract agreements in place • Inclusion of commercially sponsored research in NHS metrics and targets • Integration of Primary Care into research networks • UK-wide working • Implementation of ‘comprehensive’ or ‘generic’ capacity • Ring-fenced clinician and clinic time and resources • Interface with Connecting for Health • Promotion of long-term collaborations, beyond single trials

29. Feasibility & Adoption Panels • Process developed for very rapid assessment by Topic Networks of commercial trial feasibility (availability of eligible patients, competing trials, clinician enthusiasm, etc.) • Standing panel of experienced trialists to assist Network in confirming suitability of trial • Does the trial have a genuine & testable hypothesis with a possible future benefit for patients as its major objective? • Is the statistical design valid and reasonable for the stated main objective & main hypothesis of the trial? • Has there been peer review of the trial & its design by experts independent of the company sponsor? • Pilot experience with this approach has been successful • Two-week turnaround can be accomplished

30. Opportunities for UKCRN • To embrace the challenge and develop a world-class health service infrastructure to support clinical research • To make the UK an attractive place for industry collaborations • To improve the speed of clinical trials • To network those involved in clinical trials • To provide a qualified and trained workforce to support national clinical research • To improve patient treatment and care

31. Our questions for this workshop Can the network initiative kick start the transition to highly standardised agreements & contracts? . . . by requiring for all network multi-centre trials that Trusts & Universities (& companies? . . .) sign up to : • uniform use of the mCTA? • uniform use a single implementation of the costing guidance for any single multi-centre trial? • a standard package for implementation of costing guidance across all UKCRN trials?

32. UKCRN Industry Team UKCRN Coordinating Centre • UKCRN Associate Director for Industry: Rick Kaplan • UKCRN Industry Lead: to be appointed • UKCRN Senior fellow - Industry: Helen Howard • UKCRN Senior fellow - Industry: Anne Davies NCRN Coordinating Centre • NCRN Industry Lead: Rick Kaplan DeNDRoN Coordinating Centre • DeNDRoN Industry Lead: Colin Dingwall DRN Coordinating Centre • DRN Industry Lead: Nishi Chatuverdi MCRN Coordinating Centre • MCRN Industry Lead: Tony Nunn MHRN Coordinating Centre • MHRN Industry Lead: Tony David SRN Coordinating Centre • SRN Industry Lead: Philip Bath Secondment Post(s)fromIndustry First to be appointed Spring 2006

33. www.ukcrn.org.uk