Sponsorship of Research Avoiding chaos & confusion

1. Sponsorship of ResearchAvoiding chaos & confusion Bob LobleyResearch & Development ManagerRoyal Liverpool & Broadgreen UniversityHospitals NHS Trust Chris CounsellResearch & Development ManagerUniversity Hospital Birmingham NHS Foundation Trust

2. Background • Research Governance Framework (DoH 2001) • EU Clinical Trials Directive (2001/20/EC) • Medicines for Human Use (Clinical Trials) Regulations 2004 • RGF 2nd edition (April 2005) But there is • widespread confusion about what is involved • conflict about who is responsible • wide variation in practice

3. Roles & responsibilities

4. Basic Principles What … • All research in Health & Social Care must have a sponsor • Overall responsibility for initiation, management & conduct of study • Legal liability for conduct of Clinical Trial of IMP • Must be identified at outset (required by MHRA, REC, many funders) • Candidates are employer, NHS organisation or funder • Significant problem area – uncertainty, misunder-standing, inadequate communication and resources

5. Who can Sponsor? • Legal entity (organisation or individual) • Sole sponsor – single organisation accepts all responsibilities • Joint sponsors – several organisations accept all responsibilities (joint & several liability) • ‘Co-sponsors’ – several organisations divide responsibilities between them (not recognised elsewhere in EU)

6. Legal responsibilities – CTIMP • Regulatory permissions • authorisations & ethical review • Research conduct • GCP, provision of IMPs • Pharmacovigilance • adverse event reporting, SUSARs N.B. Sponsor may delegate duties but retains overall responsibility AND due diligence is a defence

7. Responsibilities – RGF • Respect for dignity, rights, safety and well-being of participants • Independent peer review to assure scientific quality and value for money of research • Appropriate ethics committee or independent ethics reviewer has given a favourable opinion • Expertise and experience of researchers and access to the necessary resources • Ensuring collection of high quality data, appropriate data analysis and necessary data protection

8. Responsibilities – RGF • Study arrangements are consistent with the Research Governance Framework • Organisations and individuals involved in the research agree (and document) the division of responsibilities between them • Written agreements between parties regarding management and monitoring of the study • All clinical trials are registered

9. Responsibilities – RGF • Appropriate compensation arrangements are in place for negligent (and non-negligent) harm • Arrangements for alerting the sponsor and other stakeholders of significant developments regarding the safety of individuals or scientific direction • Arrangements for concluding the study and disseminating the findings N.B. These should be recorded in study-specific agreements!

10. Problem Areas • Finding a Sponsor – NHS trust or HE institution? • Sole or group sponsorship? • Student (educational/vocational) research • International studies ??? • Assigning and documenting responsibilities e.g. authorisation, monitoring, pharmacovigilance • Delays to commencement of research …

11. Potential Solutions • Framework Agreements: high level, between established partners • Specific memorandum • Sponsorship agreements: study- and site-specific! But: • Agreements important 1st step but not sufficient • Implementation & communication are key: • common/joint processes & procedures • sharing information from outset (no surprises)

12. Sponsorship Memorandum Initially: • Univ: Trust should sponsor all clinical research involving patients, specimens or information • Trust: Univ should sponsor all academically- led research BUT many projects fall into both categories!

13. Sponsorship Memorandum (2) For all joint research: • Trust & Univ will together determine who will act as sponsor on case-by-case basis • Trust & Univ will each register as a sponsor with DoH • Prior written agreement by both parties required when study is to be co-sponsored by Trust & Univ • MoU on Sponsorship to replace corresponding section of Framework Agreement with Univ

14. Sponsorship Memorandum (3) Where … • All investigators are employed by Trust- Trust will normally be sole sponsor • One or more investigators is University employee holding Honorary Trust Contract - Trust will normally co-sponsor with Univ • None of investigators is Trust employee and no Trust patients or staff are subjects in research - Trust will normally not be a sponsor

15. Co-sponsorship Arrangements Division of responsibilities: Part 3: authorisations & ethical review (Univ) Part 4: GCP and conduct of research (Trust) Part 5: Pharmacovigilance (Trust) (www.rlbuht.nhs.uk/research)

16. Sponsorship document suite • Drafted by R&D Forum working group, led by Brenda Zinober & Bob Lobley • Designed to provide advice, guidance & model agreements for sponsorship of non-commercial R&D • Comprising: • Principles • Questions & Answers • Model sponsorship agreement (legal) • Model sponsorship agreement (non-legal)

17. Sponsorship Agreements Considerations: • Several different types of Agreement already in use • Inconsistency between documents is potential source of delay • Better to adapt existing agreements than reinvent wheels Legal vs. non-legal: • Legal agreements strongly disfavoured by DH & research community but already being used • DH/UKCRC to persuade universities to avoid use of legal agreements for non-commercial R&D • Aim to produce small set of model Agreements (legal and non-legal)

18. Model Agreement (Legal) Purpose: • to provide a standard, legal contract between Sponsor(s) and individual sites, especially for Clinical Trials of IMPs • for studies where one or more of parties is notan NHS organisation • suited to studies involving financial or other transactions between parties • suitable for single or multiple site studies

19. Model Agreement (Legal) Content (12 pp): • sets out roles & responsibilities of Sponsor(s) and site organisation • specifies obligations of parties, including confidentiality, publication rights, intellectual property rights, duration & termination arrangements, etc. • specifies activities that site must perform • specifies financial arrangements, provision of drugs, etc. (where appropriate) • other contractual essentials

20. Model Agreement (Legal) Schedules: • protocol & funding agreement (if applicable) • responsibilities of parties, including governance requirements & legal responsibilities under CT Regulations • services to be provided by site • programme of work to be performed • financial arrangements (where applicable)

21. Model Agreement (non-legal) Purpose: • to provide a standard, bilateral agreement setting out sponsorship arrangements between NHS sponsor & study site • for studies where legal contract inappropriate e.g. between NHS organisations • for studies that are not clinical trials under the Clinical Trials Regulations 2004 • suitable for single or multiple site studies

22. Model Agreement (non-legal) Content (6 pp): • sets out roles & responsibilities of Sponsor(s) and site organisation in brief • covers obligations of confidentiality, monitoring requirements, liabilities, intellectual property rights, publication rights, duration of study, termination arrangements, etc. in brief

23. Model Agreement (non-legal) Appendices – templates for: • the allocation of responsibilities between parties • the responsibilities of investigators • monitoring arrangements • model site file

24. Sponsorship scenarios • Single centre study with Framework Agreement or Memorandum between NHS & academic partners • letter confirming acceptance of standard arrangements for sponsorship • Clinical trials of IMP with legal & contractual obligations • Sponsorship agreement (legal?) • All other studies • Sponsorship agreement (non-legal)

25. Conclusions • Sponsorship isa challenge • Progress dependent on • close liaison/formal agreements between research partner(s) • appropriate resources & expertise • common/joint processes & procedures • Good guidance, e.g. from MRC & NHS R&D Forum • R&D Office alwaysgets the blame!