1. Navigating Research Governance, Ethics and Sponsorship
Andrew Johnston
Newcastle Joint Research Office

2. Overview Governance and Ethics - Why do we need it?
Setting up a research study
Funding & Design considerations
Research Sponsorship
Regulatory Authorisations
Local/site level Confirmation of Capacity & Capability
NIHR Portfolio
Good Clinical Practice (GCP)
Site files & Essential documentation
Source Documentation
Informed Consent
NuTH R&D figures

3. Some terms before we begin……..
GCP: Good Clinical Practice
Sponsor: Responsible Party for the Research
Recruitment: Sample Population Consented
Feasibility: Assessment of Capacity and Do-ability
REC: Research Ethics Committee
CTIMP: Clinical Trial of Investigational Medicinal Product
ATIMP: Advanced Therapy Investigational Medicinal Product
MHRA: Medicines and Healthcare products Regulatory Agency
HRA: Health Research Authority
ISF: Investigator Site File

4. Why do we need Research Governance?
Episodes in history have shaped the regulation of research
led to the introduction of governance and Good Clinical Practice (GCP)
World War II & Nuremberg Trials
(Declaration of Helsinki in the foundation of the ethical principles)
Tuskegee Syphilis Experiment
(US Study - 40 year study on progression of syphilis)
More recently……
Bristol and Alder Hey investigations into retained organs
- Research Governance Framework implemented in 2001
Northwick Park, UK - Monoclonal antibody drug, 6 participants required treatment for organ failure
Biotrial, France - Phase 1 endocannibanoid, neurodegenerative diseases and anxiety, 1 fatality, 5 others injured

5. Ethics, GCP & Governance
Ethics: Moral principles that govern a person's behavior or the conduct of an activity GCP: Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects Governance: Establishment of policies, and continuous monitoring of their proper implementation, by the members of the governing body of an organisation

6. The Process – setting up a research study at NuTH
What do I need to do?

7. Overview of the Application and Award process
Printed pack will include this overview and the numbered detailed steps – these documents are also available on the NJRO website.
The process for every project should follow the same process – the level of depth that will be needed at each point will depend on the PROJECT – Not the funder or the value.
The detail behind the numbered steps will guide the PI to the relevant people – from a NuTH perspective this includes the Funding Development Team (Nicola and Layla) and relevant Team Leads

8. Funding application Study design Funding Awarded Host site Review
**One-form must be completed – key to
accessing nJRO services
Choose an appropriate methodology & outcome
Provide justification of the sample size
Draw up a statistical analysis plan
Data Handling
Prepare and present interim reports
Research Sponsorship
& governance
Portfolio Adoption
Authorisations
Obtained
Authorisations
Obtained
Host site Review
(NHS Capability &
Capacity review)
Start study

9. Pre-application considerations - One-form must be completed
Who is the Sponsor?
What type of trial is it?
Does it involve a CTU?
Does it require specialised departments?
How many NHS Sites are involved?
What is the per patient cost?
Are there storage/transport costs?
Have the right NHS staff been involved?
Will the study be eligible for portfolio adoption?

10. Definitions of types of NHS costs:
Research Costs - the costs of the R&D itself that end when the research ends. They relate to activities that are being undertaken to answer the research questions – funded by the Grant / Fellowship NHS Support Costs - the additional patient care costs associated with the research, which would end once the R&D study in question had stopped, even if the patient care involved continued to be provided NHS Treatment Costs - the patient care costs, which would continue to be incurred if the patient care service in question continued to be provided after the R&D study had stopped – funded by usual commissioning sources NHS Excess Treatment Costs - an extra cost which is in addition to that of standard treatment

11. Funding application Study design Funding Awarded
Choose an appropriate methodology & outcome
Provide justification of the sample size
Draw up a statistical analysis plan
Data Handling
Prepare and present interim reports
Research Sponsorship
& governance
Trust SOP for Sponsorship process
Portfolio Adoption
Authorisations
Obtained
Authorisations
Obtained
NHS Permission
CSP Governance
Review
Start study

12. Sponsorship - Research Governance Framework (RGF)
The Research Governance Framework (RGF) was developed by the DoH to set out the principles, requirements and standards for healthcare research (2001).
Ethics
Science
Health & Safety
Information
Finance
Quality Research Culture
All research conducted in the NHS must have an identified Research Sponsor.
- an individual or organisation that takes on responsibility for ensuring proper arrangements to initiate, finance, monitor and manage a study -

13. NuTH Sponsorship review process
Requirements for sponsor review/risk assessment:
Funding in place
IRAS complete
Finalised Protocol + Associated Patient Docs
Link to NuTH delivery team
Additional considerations:
Insurance indemnity
Project Management / Delegation of duties
Statement of Activities / Schedule of events

14. Funding application Study design Funding Awarded Host Site Review
Choose an appropriate methodology & outcome
Provide justification of the sample size
Draw up a statistical analysis plan
Data Handling
Prepare and present interim reports
Research Sponsorship
& governance
Portfolio Adoption
Study
Authorisations
Authorisations
Obtained
HRA
Host Site Review
CSP Governance
Review
Start study

15. HRA Approval What they say…
HRA Approval is a relatively new process for the NHS in England It brings together the assessment of governance and legal compliance, undertaken by the HRA, with an independent REC opinion provided through the UK research ethics service.  
What they say…
The new system will simplify the approvals process for research, making it easier for research studies to be set up.
The elimination of duplicate application routes means that the answers to research questions about how to improve patient care or about new treatments will be answered quicker.

16. Authorisations Health Research Authority (HRA)
Assessment of governance and legal compliance
Research Ethics Committee (REC)
Look at the ethical issues that may arise from the research & ensure the participant has all the information required to make an informed decision.
Medicines and Healthcare products Regulatory Agency (MHRA)
The UK competent authority – approve the use of Investigational Medicinal Products and Devices
The Ionising Radiation (Medical Exposure) regulations 2000 (IRMER)
Ionising radiation (CT Scans, X-Ray) require a IRMER review from a radiation expert.
Administration of Radioactive Substance advisory Committee (ARSAC)
Radioactive substances used in research (MUGA Scans, PET Scans) – site specific
Confidentiality Advisory Group (CAG)
Patient information
NHS Trust Host Site Review
Each participating NHS Trust must issue Capability and Capacity confirmation

17. Funding application Study design Funding Awarded Host site review
Choose an appropriate methodology & outcome
Provide justification of the sample size
Draw up a statistical analysis plan
Data Handling
Prepare and present interim reports
Research Sponsorship
& governance
Portfolio Adoption
Authorisations
Obtained
Authorisations
Obtained
HRA
Host site review
CSP Governance
Review
Start study

18. Confirmation of Capacity & Capability
NHS Host Site Review
Confirmation of Capacity & Capability
Separate process to sponsorship review
Will be undertaken by each participating site
Must be submitted by local study team
Reviewed in parallel with regulatory approval.
Intended to review site capacity to undertake the research.

19. What is needed for a Host Site review?
HRA guidelines state that a minimum document pack should include:
Copy of IRAS Form (combined REC and R&D form) as submitted for HRA Approval
Protocol
Any amendments & updated documents
Participant information and consent documents
Statement of Activity relevant to the participating NHS organisation (non-commercially sponsored only) or Relevant template contract/model agreement
schedule of Events (non-commercially sponsored only)
Any other documents that the sponsor wishes to provide to the site to support the set up and delivery of the study
Copy of HRA Initial Assessment letter (if one is issued)
HRA Approval letter and final document versions (when issued)

20. Researcher submits to HRA REC Favourable Opinion
REC validation
Initial Assessment
Researcher may submit document set to Host sites
REC review
HRA assessment
Host site commences work on the confirmation and capacity review
REC Favourable Opinion
Collate approvals
What happens within the HRA
Ready for Review
Ensure enough info to take assessment forward
Provide the REC with confirmation of insurance arrangements, legal compliance, internal consistency, etc
Confirm to applicant AND sites that certain things are in place so that the next phase of setting study up can occur – ie that assessment and arrangements can formally be in place. Letter includes what agreement will be used, if a PI/Local Collaborator /none are needed, what HR arrangements are needed. Will also try to get to a point where we are clear about what the assessment will sort so that sites do not need to do.
HRA Approval

21. Confirmation of Capacity & Capability
To summarise…
Funding/Budget award
Sponsorship Review
Regulatory Approval
REC / HRA
Host Site Review
Confirmation of Capacity & Capability
Site Opens

22. The NIHR Portfolio
The National Institute for Health Research Clinical Research Network (NIHR CRN) Portfolio is a database of high-quality research studies that are eligible for support from the NIHR Clinical Research Network in England.
Automatically eligible:
Have some or all research funding provided by the NIHR, Other areas of central Government or NIHR non-commercial partners.
Fulfil the research definition “attempt to derive generalisable new knowledge by addressing clearly defined questions with systematic and rigorous methods”
Potentially eligible:
Commercial
Overseas Government
Overseas Charities

23. Good Clinical Practice (GCP)
GCP is an international ethical and scientific quality standard for the design, conduct, recording and reporting of trials that involve the participation of human subjects. Its purpose is to:
Ensure the protection of the rights and well being of research participants
Ensure that results of research are accurate and credible
The principles of Good Clinical Practice have their origin in the Declaration of Helsinki and apply to ALL research, not just clinical trials of medicinal products!

24. Informed Consent for Research
Informed consent is a three step process which involves: • The giving of study related information • The discussion and clarification of this information and • The taking of the subject’s written consent All individuals asked to consider taking part in research should be given the fullest possible information, presented in a form that is understandable. This must include, but is not limited to, the Participant Information Sheet (PIS) approved by a REC. ** Participants must be given enough time to read the information about the Research - this is usually at least 24 hours except in an acute or emergency setting

25. Source documentation Source data: Source documents: Case Report Forms:
Details of clinical findings, observations or other activities carried out as part of clinical trial. Source data are contained in source documents (original documents or certified copies)
copies of PIS and consent form to be filed in patient record
original to be stored in the site file
documented consent process & confirmation of eligibility
detail each study visit
Source documents:
Original documents, data and records (e.g. hospital records, clinical charts, laboratory notes, memoranda, subject diaries or evaluation checklists), pharmacy dispensing records, adverse event charts
Case Report Forms:
Data generated by clinical trials are normally recorded in Case Report Forms (CRFs). A CRF is a printed or electronic document designed to record all of the protocol defined data on individual participants in a CTIMP.
For further details please refer to the JRO website - SOP essential and source documentation guide (release date Nov. 2013)

26. Essential study documents
Trial Master File/Site file
Protocol
Ethics
Research and Development
Regulatory
Research Team
Participant Information (including subject log + original consent form
Data Collection
Safety
Pharmacy/Product-Related
10. Monitoring and Audit
11. Correspondence (except Trust & Ethics)

27. In summary….. Design Set-up Continuation Close-Down Publication
Question
Statistics
Feasibility/Consultation
Documents
Funding
Sponsor Input
Design
Approvals
Implement Processes
Coordinate Centres
Registration
Set-up
Monitoring
Amendments
Record keeping
Safety reporting
Data Queries
Continuation
Site Close down
Final Monitoring Visit
Archiving
Close-Down
Write up
Publish
Reports
Publication

28. HRA Website – Very Useful!
HRA Decision Tool
NIHR Website
NJRO Website

29. Get in touch…
Please visit our website for guidance: You can contact our Inbox: Or call: