1. UK Clinical Research Network (UKCRN) Delivering with the Pharmaceutical Industry R Kaplan NCRN Associate Director

2. UK Clinical Research Network (UKCRN) 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.) 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... If a commercial trial – performed within the NHS – speeds licensing of an effective new agent... Patients benefit directly, as well as sponsor Patients benefit directly, as well as sponsor Future UK patients benefit if access is speeded Future UK patients benefit if access is speeded Trial income contributes to a larger/better research infrastructure Trial income contributes to a larger/better research infrastructure Sponsor is likely to expand portfolio of work with NHS Sponsor is likely to expand portfolio of work with NHS If the company is UK-based, study leads to additional contribution to UK economy If the company is UK-based, study leads to additional contribution to UK economy

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

4. UK Clinical Research Network (UKCRN) Why UK Pharma and DH are 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 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 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 >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 Global companies are not placing studies in UK UK pharma affiliates are being forced to downsize UK pharma affiliates are being forced to downsize

5. UK Clinical Research Network (UKCRN) Industry Trials in UKCRN Effective collaboration with the UK pharmaceutical, biotech & device industries is a founding principle of 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 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 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 Scale & scope of the initiative  momentum for progress Industry-led and investigator-led trials within the same overall portfolio Industry-led and investigator-led trials within the same overall portfolio

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

7. UK Clinical Research Network (UKCRN) NCRN Industry Services: Consultation Consultation Feasibility Feasibility Costing & contracting Costing & contracting Governance & regulatory Governance & regulatory Some elements of site set-up Some elements of site set-up Study delivery to targets Study delivery to targets

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

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

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

11. UK Clinical Research Network (UKCRN) Record to date A few very small studies met their targets 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: 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 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) (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 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 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 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. MHRA/FDA discussions, final design decisions, drug supply, etc. But in many cases cause of company delay not communicated But in many cases cause of company delay not communicated

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

13. UK Clinical Research Network (UKCRN) Performance management RNMs and CC should agree site targets RNMs and CC should agree site targets Regular phone updates/discussions with sponsor’s trial manager Regular phone updates/discussions with sponsor’s trial manager Regular e-mail interactions with RNMs for participating sites Regular e-mail interactions with RNMs for participating sites Individual phone discussions with sites Individual phone discussions with sites Monitoring all activities via industry-tracking and portfolio databases Monitoring all activities via industry-tracking and portfolio databases Pre site activation: 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 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: After activation: pro-forma for regularly assuring that sites, RNMs, sponsor, CC all have access to (identical) updated information & can effectively coordinate actions pro-forma for regularly assuring that sites, RNMs, sponsor, CC all have access to (identical) updated information & can effectively coordinate actions

14. UK Clinical Research Network (UKCRN) Some key issues Inadequate communication lines amongst companies, site investigators/staff, relevant RNMs, and CC Inadequate communication lines amongst companies, site investigators/staff, relevant RNMs, and CC Coordinators may only communicate with sites, ignoring RNMs & 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 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 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 The number of DGHs with commercial trials is small, yet these are the sites whose activity has been most boosted by NCRN

15. UK Clinical Research Network (UKCRN) 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. 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 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? 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 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. Many continued challenges with pharmacy & imaging resources, staffing & capacity; ARSAC (radiation protection) licenses; R&D delays, contracting & costing (prior to new arrangements), etc.

16. UK Clinical Research Network (UKCRN) Working in Partnership Working in Partnership Working in Partnership Working in Partnership