Delivering with the Pharmaceutical Industry

1. Delivering with the Pharmaceutical Industry R Kaplan NCRN Associate Director

2. Benefits of Industry Research performed in UK • Healthcare industry invests more on R&D within UK than any other business sector (>£3 billion p.a.) • If a commercial trial – performed within the NHS – speeds licensing of an effective new agent . . . • Patients benefit directly, as well as sponsor • Future UK 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

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

4. Why UK Pharma and DHare applying pressure to UKCRN • Industry estimates out-of-pocket costs average $1.2M (~£0.6M) per study for each month delayed, plus $0.8-5.4M (£0.4-2.7M) per day in potential lost sales • UK performance has been declining for several years, while other areas of the world have improved dramatically • >90% of commercial trials opened in UK have had substantial delays in enrolment, and many fail to deliver target numbers • Global companies are not placing studies in UK • UK pharma affiliates are being forced to downsize

5. Industry Trials in UKCRN • Effective collaboration with the UK pharmaceutical, biotech & device industries is a founding principle of UKCRN • Trials need not come though or use the networks, but hopefully it will be advantageous to do so • UKCRN working with DH and industry partners to improve the clinical research environment for industry in the UK – and in the process improve the research environment for all clinical research • Scale & scope of the initiative  momentum for progress • Industry-led and investigator-led trials within the same overall portfolio

6. Importance of Industry Studies • The ‘industry’ portfolio within the NCRN has become an area of major DoH focus • This should include both commercial studies (industry developed) and investigator-led partnership studies • . . . pharma lobbying focuses on commercial • These trials need to be considered joint top priority with major national investigator-led trials

7. NCRN Industry Services: • Consultation • Feasibility • Costing & contracting • Governance & regulatory • Some elements of site set-up • Study delivery to targets

8. NCRN (& UKCRN) offer to companies for commercial trials • Reliable UK feasibility & site selection • Coordinated contact with network sites • Rapid access to new sites and patient populations • Systems for expediting start-up • Rapid site set up via streamlined costing & RM&G • Study delivery to promised targets: • Experienced and trained research staff • NCRN ‘badging’ of trials • Shared performance goals • Network monitoring and performance management • Effective troubleshooting & sharing of good practice

9. Standard agreements & contracts • Generic confidentiality agreements allow rapid assessment of feasibility • Adoption of the unaltered mCTA by companies and LRN/CLRN Trusts • Removes requirement of legal review from both sides • Reduces delays incurred through individual contract negotiations • Incorporates university sub-contracts • Company/network agreement to define responsibilities, timelines, study requirements and share performance goals • Standard, transparent costing methodology

10. Consistent & transparent costing guidelines ­ & costing template • Transparency of costing breakdowns, using a consistent method • Appropriately allocated overheads* and fees for capacity building • Consistent (rather than identical) costing for multi-centre studies • Pricing index for NHS research investigations (which also will inform activity based funding allocation) • Standard method of adjustment for locality differences • Overall goal: to fast-track cost negotiation of trials

11. Record to date • A few very small studies met their targets • Most of those with targets in the range of 50-120 are running well below their target accrual rates . . . but: • In most of the earliest NCRN adoptions, there was recognition that the studies were already in trouble • (thus companies were willing to try this very new approach) • In other cases, there have been continued very substantial delays for R&D (or other) approvals • Delayed UK or site start-up → little time to catch up before global trials finish • Many adopted trials experienced very substantial company/sponsor delays to study finalisation or activation after adoption and/or site selection • MHRA/FDA discussions, final design decisions, drug supply, etc. • But in many cases cause of company delay not communicated

12. Performance management of portfolio trials • Emphasis on feasibility assessment to accurately predict patient numbers and timelines • Inter-hospital referral within Network, and inter-Network referrals for studies • Overarching management of trial performance within local networks • Clear communication between industry and NHS staff to define roles, responsibilities and expectations • Assure appropriate incentives for all parties • Additional layer of support to ensure delivery

13. Performance management • RNMs and CC should agree site targets • Regular phone updates/discussions with sponsor’s trial manager • Regular e-mail interactions with RNMs for participating sites • Individual phone discussions with sites • Monitoring all activities via industry-tracking and portfolio databases • Pre site activation: • detailed checklist to cover all tasks associated with site selection, approvals and start-up, with assigned responsibilities – to be used as the basis for the sponsor-CC updates • After activation: • pro-forma for regularly assuring that sites, RNMs, sponsor, CC all have access to (identical) updated information & can effectively coordinate actions

14. PI Expression of Interest Form • For studyidentifierover the period _________: • How many patients do you anticipate enrolling? • ____________ • Divide the above by 3 and enter the number here: • ____________ • Or explain why you think you’ll do better than that: • ________________________________________ • ________________________________________ • ________________________________________

15. Performance management • RNMs and CC should agree site targets • Regular phone updates/discussions with sponsor’s trial manager • Regular e-mail interactions with RNMs for participating sites • Individual phone discussions with sites • Monitoring all activities via industry-tracking and portfolio databases • Pre site activation: • detailed checklist to cover all tasks associated with site selection, approvals and start-up, with assigned responsibilities – to be used as the basis for the sponsor-CC updates • After activation: • pro-forma for regularly assuring that sites, RNMs, sponsor, CC all have access to (identical) updated information & can effectively coordinate actions

16. Some key issues • Inadequate communication lines amongst companies, site investigators/staff, relevant RNMs, and CC • Coordinators may only communicate with sites, ignoring RNMs & CC • RNMs – and CC – sometimes unclear as to which sites were selected, and about agreed target accrual and accrual rate • To date, most selected sites have been those with well developed and mature commercial trials operations, staffed by individuals who have operated largely independently of the networks and their managers • The number of DGHs with commercial trials is small, yet these are the sites whose activity has been most boosted by NCRN

17. Some key issues (cont.) • NCRN portfolio is very large and until recently revolved primarily around investigator-initiated publicly funded research. This has led to an established and particular ethos and culture. • Many research staff and most clinicians have not yet fully absorbed the message about the critical role of industry studies and consequences for the UK if targets are not met • Might devolved architecture networks have a more difficult time in establishing influence over sites’ commercial trial performance? • Cross-network – and intra-network, cross-Trust – referral should be an important tool, but need to overcome organisational disincentives • Many continued challenges with pharmacy & imaging resources, staffing & capacity; ARSAC (radiation protection) licenses; R&D delays, contracting & costing (prior to new arrangements), etc.

18. Future for NCRN/Industry Links • Collaborative investigator-initiated (or investigator-influenced) studies are perhaps the most natural and consequential sphere of partnership • Phase II + Phase IV > Phase III • Emphasise potential shortening of total cycle time (the overall sequence from early trials → completion of Phase III)

19. Working in Partnership