1. Navigating Research Governance, Ethics and Sponsorship
Andrew Johnston
Research Management & Governance (RM&G) Manager

2. Overview Governance and Ethics - Why do we need it? Setting up a study
Funding your Project
NIHR Portfolio
Patient Carer Public Involvement (PCPI)
Research Sponsorship
Gaining Regulatory Authorisations
Local site set-up/Assess, Arrange and Confirm
HRA – Changing times
Running the study
Informed Consent
Source Documentation
Site files & Essential documentation
Good Clinical Practice (GCP)
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 ATMP: Advanced Therapy Investigational Medicinal Product MHRA: Medicines and Healthcare products Regulatory Agency HRA: Health Research Authority

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 treated for organ failure
Biotrial, France - Phase 1 endocannibanoid, neurodegenerative diseases and anxiety, 1 dead, 5 others injured

5. What is 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. 1. Design & Costings Funding application Study design
2. Identify research sponsor
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
3. Complete IRAS application
and proctocol
Research Sponsorship
& governance
Portfolio Adoption
Provide document set to
other sites/trusts for review
4. Submit for regulatory approval
HRA submission
NHS Governance
NHS Ethics
Researcher to respond to
queries/meet conditions
of approval
HRA approval
5. NHS site(s) confirm capacity
Start study

8. Points to consider at conception
What type of trial is it?
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?
Does it involve a CTU?
Who is the Sponsor?

9. 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

10. 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

11. 2. Identified research sponsor
1. Design &
Costings
Funding application
Study design
Funding Awarded
2. Identified research sponsor
Choose an appropriate methodology & outcome
Provide justification of the sample size
Draw up a statistical analysis plan
Data Handling
Prepare and present interim reports
3. Complete IRAS application
and proctocol
Research Sponsorship
& governance
Portfolio Adoption
Provide document set to
other sites/trusts for review
4. Submit for regulatory approval
HRA submission
NHS Governance
NHS Ethics
Researcher to respond to
queries/meet conditions
of approval
HRA approval
5. NHS site(s) confirm capacity
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. 4. Submit for regulatory approval
1. Design &
Costings
Funding application
Study design
Funding Awarded
2. Identified research sponsor
Choose an appropriate methodology & outcome
Provide justification of the sample size
Draw up a statistical analysis plan
Data Handling
Prepare and present interim reports
3. Complete IRAS application
and proctocol
Research Sponsorship
& governance
Portfolio Adoption
Provide document set to
other sites/trusts for review
4. Submit for regulatory approval
HRA submission
NHS Governance
NHS Ethics
Researcher to respond to
queries/meet conditions
of approval
HRA approval
5. NHS site(s) confirm capacity
Start study

14. Authorisations/Regulatory Approval
HRA 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.
** Proportionate Review **
HRA NHS review (Replaces R&D approval)
Assessment of governance and legal compliance
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 Sites
Confirm Capability and capacity

15. What can I do to help? Summary of main points to consider:
Finance – all costs must be funded
Support Departments - Pharmacy, Radiology, Labs, Ophthalmology…
Insurance/Indemnity – management/conduct/design
Study Agreements – use of model agreement is encouraged
Publicity Risk to the Trust – will it attract media attention?
Ethics, HRA, Regulatory Approvals
Data – Caldicott approval, CAG, if necessary
Tissue/IRMER/ARSAC – bio-banking
Site Specific requirements – staffing support, suitable facilities available?
Pharmacy Details – exit strategy

16. A recent
HRA replaces the need for Trust NHS R&D approval….

17. HRA Approval What they say…
HRA Approval is relatively the new process for the NHS in England that 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.

18. HRA Application received REC validation Initial Assessment
Pharmacy information complete
REC review
HRA assessment
Pharmacy technical assurance
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

19. 5. NHS site(s) confirm capacity
1. Design &
Costings
Funding application
Study design
Funding Awarded
2. Identified research sponsor
Choose an appropriate methodology & outcome
Provide justification of the sample size
Draw up a statistical analysis plan
Data Handling
Prepare and present interim reports
3. Complete IRAS application
and proctocol
Research Sponsorship
& governance
Portfolio Adoption
Provide document set to
other sites/trusts for review
4. Submit for regulatory approval
HRA submission
NHS Governance
NHS Ethics
Researcher to respond to
queries/meet conditions
of approval
HRA approval
5. NHS site(s) confirm capacity
Start study

20. 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!

21. 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

22. 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)

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

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

25. R&D Figures
NuTH is one of the largest research Trusts within the country!
Number of active recruiting studies: 295 (NuTH sponsored)
1211 (all studies) (commercial)
875 (non-commercial)
Number of patients recruited overall 2015/2016: 16,414
Number of patients recruited to portfolio studies 2015/2016: 12,122

26. Get in touch…
Please visit our website for guidance: (under revision) You can contact our Inbox: Or call us: