Navigating Research Governance,
Ethics and Sponsorship
Andrew Johnston
Research Management & Governance (RM&G) Manager
Overview
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Governance and Ethics - Why do we need it?
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Funding your Project
Patient Carer Public Involvement (PCPI)
Research Sponsorship
Gaining Study Wide Regulatory Authorisations
Local/site level NHS R&D approval
HRA – Changing times
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NIHR Portfolio
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Good Clinical Practice (GCP)
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Site files & Essential documentation
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Source Documentation
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Informed Consent
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NuTH R&D figures
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
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)
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World War II & Nuremberg Trials
(Declaration of Helsinki in 1946 - the foundation of the ethical principles)
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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
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Northwick Park, UK - Monoclonal antibody drug, 6 participants required treated for organ failure
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Biotrial, France - Phase 1 endocannibanoid, neurodegenerative diseases and anxiety, 1 dead, 5
others injured
What is Ethics, GCP & Governance?
Activity: Discuss and produce a word cloud for:
• Ethics
• GCP
• Governance
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
The Process – setting up a research study at NuTH
What do I need to do?
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
Portfolio Adoption
Authorisations
Obtained
Authorisations
Obtained
CSP Governance
Review
NHS Permission
Start study
Points to Consider at Costing Stage
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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?
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
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
CSP Governance
Review
NHS Permission
Start study
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).
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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 -
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
Portfolio Adoption
Authorisations
Obtained
Authorisations
Obtained
CSP Governance
Review
HRA
NHS Permission
Start study
Authorisations
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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 **
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Medicines and Healthcare products Regulatory Agency (MHRA)
The UK competent authority – approve the use of Investigational Medicinal
Products and Devices
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The Ionising Radiation (Medical Exposure) regulations 2000 (IRMER)
Ionising radiation (CT Scans, X-Ray) require a IRMER review from a radiation
expert.
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Administration of Radioactive Substance advisory Committee (ARSAC)
Radioactive substances used in research (MUGA Scans, PET Scans) – site specific
Confidentiality Advisory Group (CAG)
Patient information
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NHS Trust R&D approval/NHS Permission
Each participating NHS Trust must issue NHS permission
REC & MHRA
National Research Ethics Serivce (NRES) Research Ethics Committees (RECs)
safeguard the rights, safety, dignity and well-being of people participating in
research in the National Health Service.
They review applications for research and give an opinion about the proposed participant
involvement and whether the research is ethical.
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80 RECs
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Different remits
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Proportionate review.
The Medicines and Healthcare products Regulatory Agency (MHRA) is the government
agency which is responsible for ensuring that medicines and medical devices
work, and are acceptably safe. The MHRA is an executive agency of the
Department of Health.
Involved with: Investigational Medicinal Product (IMP)
Advanced Therapeutic Medicinal Product (ATMP)
Devices
There is a cost associated with an application to MHRA.
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
Portfolio Adoption
Authorisations
Obtained
Authorisations
Obtained
CSP Governance
Review
HRA
NHS Permission
Start study
NHS Trust Permission
Why do we have R&D approval?
As detailed in section 3.10 of the Research Governance Framework:
It is the responsibility of organisations providing health or social care in England to be
aware of all research undertaken in their organisation, or involving participants, organs,
tissue or data obtained through the organisation.
This is achieved via Trust R&D who coordinate the review and issue permission on behalf of the
Trust (governance role to ensure patient safety, financial stability and legal protection for the NHS
organisation)
**For further information please visit our website - www.newcastlejro.org.uk/**
Trust R&D Risk Assessment
A risk assessment is performed for every study that goes to committee:
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Finance – all costs must be funded
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Support Departments - Pharmacy, Radiology, Labs, Ophthalmology…
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Insurance/Indemnity – management/conduct/design
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Study Agreements – use of model agreement is encouraged
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Publicity Risk to the Trust – will it attract media attention?
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Ethics & Regulatory Approvals
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Data – Caldicott approval, CAG, if necessary
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Tissue/IRMER/ARSAC
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Site Specific Assessment – staffing support, suitable facilities available?
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Monitoring Arrangements
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Pharmacy Details – exit strategy
NHS Trust Permission** – Local Process
** In 2015/16 NHS permission to be replaced with a single HRA approval which will be
England wide therefore removing the need to apply to Trusts on an individual basis
HRA changes ahead for
NHS R&D approval….
HRA Approval
• HRA Approval is 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.
HRA
Application received
REC validation
Initial Assessment
Pharmacy information
complete
REC review
HRA assessment
Pharmacy technical
assurance
REC Favourable
Opinion
Collate approvals
HRA Approval
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:
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Have some or all research funding provided by the NIHR, Other areas of central
Government or NIHR non-commercial partners.
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Fulfil the research definition “attempt to derive generalisable new knowledge by
addressing clearly defined questions with systematic and rigorous methods”
Potentially eligible:
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Commercial
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Overseas Government
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Overseas Charities
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!
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
Source documentation
Source data:
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)
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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)
Essential study documents
Trial Master File/Site file
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3.
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Protocol
Ethics
Research and Development
Regulatory
Research Team
Participant Information (including subject log + original
consent form
7. Data Collection
8. Safety
9. Pharmacy/Product-Related
10. Monitoring and Audit
11. Correspondence (except Trust & Ethics)
In summary…..
• Question
• Statistics
• Feasibility/Consultation
• Documents
• Funding
• Sponsor Input
Design
Set-up
• Approvals
• Implement
Processes
• Coordinate Centres
• Registration
•Monitoring
•Amendments
•Record keeping
•Safety reporting
•Data Queries
Continuation
Close-Down
•Site Close down
•Final Monitoring
Visit
•Data Queries
•Archiving
• Write up
• Publish
• Reports
Publication
What can I do to help?
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Ensure there is enough funding to cover costs of conducting the study:
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Identify all costs appropriately (AcoRD) on the NuTH Costing Tool
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NHS cannot subsidise Commercial research so must be fully funded in all
cases
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Clinical Director should be approached to cover ETCs or for studies using
departmental funding/staff time
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Approach support departments with any specific needs e.g. radiology
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Encourage the PI to do their part: signing/electronically authorising the SSI
form, signing the PI responsibility documents and answering any queries from
the risk assessment promptly.
Clinical Trial Agreements
 Always encourage use of the model agreement
 Send the contract to R&D as early as possible!
R&D Figures
NuTH are one of the largest research Trusts within the country!
Number
of active recruiting studies
486
Number
of patients recruited overall
15,101
Number
of patients recruited to portfolio studies
12,493
The
NuTH ranked 1st (last two quarters) for the percentage of
closed commercial trials recruiting patients
to time to target.
Get in touch…
Please visit our website for guidance:
www.newcastleJRO.org.uk
You can contact our Inbox:
Trust.R&D@nuth.nhs.uk
Or call us:
0191 2825959