the nuts & bolts of clinical research governance
TRANSCRIPT
The Nuts & Bolts of
Clinical Research Governance
Catrina Forde, Senior Research Governance Manager
What is research governance?
… the broad range of regulations, principles and standards
of good practice that exist to achieve, and continuously improve,
research quality across all aspects of healthcare
in the UK and worldwide.
Who does research governance apply to?
… everyone connected to healthcare research, whether as a
Chief Investigator, Care Professional, Researcher, support staff,
funders, sponsors, regulatory authorities.
What is healthcare research?
… any health-related research which involves
humans (patients or volunteers),
their tissue and/or NHS data.
… generally occurs ‘in or through’ the NHS and may occur
in a social care or community setting.
Examples of healthcare research
Analysis of data from patient medical notes
Observations
Conducting surveys
Using non-invasive imaging
Using blood or other tissue samples
Inclusion in trials or other interventions of drugs, devices,
surgical procedures or other treatments
2012ON46 Clinical Data Collection for SPECIALS.
2014PC01* Urinary iodide levels following exposure to contrast media - a feasibility study.
2014PZ01 The Relationship between Trauma and Medically Unexplained Symptoms.
2014DM02 Effect of short duration high intensity sprint intervals to prevent late onset post-exercise hypo...
2012EP08 Modifying Alcohol Consumption to Reduce Obesity (MACRO): developing and feasibility testing of a complex community-based intervention for men.
2013PQ06 EDOCALD WP5: Validation of optical imaging in the diagnosis of pathology in the oral mucosa.
2013GA05 Can a negative FIT test avoid routine surveillance colonoscopy?
2013NG07 Brain Responses to Rewards and Losses in Social Drinkers.
2012ON26 Automatic analysis of dysplasia in optical projection tomography of colorectal polyps.
2014DE02 Exploring the feasibility of conducting a randomised controlled trial to test the impact of a computer-assisted online cognitive-behaviour therapy intervention for child
dental anxiety.
2014DE04 Fracture resistance of tooth roots filled with bioceramic materials.
2013GR03 How do older Heart Failure patients manage their medication?
2014GR05 Psychometric evaluation of the IoRN.
2014PZ06 Improving mobility and confidence in care home residents.
2014NS05 Exploring nurses' and patients' knowledge of heart failure.
2014PO01 GoSHARE-ADR
2013OB14 A study to evaluate the normal concentrations of maternal plasma lactate, serum C-reactive protein and procalcitonin following normal parturition in low risk
pregnancies.
2014PA01 Paediatric European Risperidone Studies: Observational pharmacovigilance study
2012NE02 ReDVA study - Haemodynamic assessment of arteriovenous fistula formation.
2013ON23 MULTIPROS study.
2014NG03 A reinforcement learning model of striatal dysfunction in dystonia
2013DE06 Research Tooth Collection - Dundee Dental School.
2014ON38 Lifestyle questionniare - patients with increased CRC risk.
2014SA05 Random urinary 5HIAA: New diagnostic test for early acute appendicitis.
2014RC04* The European Bronchiectasis Registry
2013DM14 BNP for Personalised Primary Prevention in Diabetes.
2014MO01 Preparing Exercise and Physical Activity as a Complex Intervention for Chronic Pain.
2014DS13 Staphylococcus aureus associated with Atopic eczema - Pilot study.
2014ON22 Living Well - a feasibility study to assess the impact of a lifestyle intervention in people attending family history clinics with an increased risk of colorectal and breast
cancer.
2015CV04 SPD555-802: Cohort study of the relative incidence of major cardiovascular events among patients initiating Prucalopride Versus a matched comparator cohort.
2014MH16 Understanding the use of mobile technology by people with depression.
2014CV01 Dynamic Lycra Orthoses as an adjunct to upper limb rehabilitation after stroke.
2015OS01 Prevalence of intimate partner violence (IPV) in orthpaedic trauma presenting at UK orthopaedic.....
2015NG03 Avoidance in Anxiety.
2014GA05 Comparison of starches and non-starch polysaccharides on the structure and metabolic activities...
Healthcare Research
…all clinical research in Tayside
is approved and managed via TASC.
… whether sponsored
by NHS Tayside and/or the University of Dundee
or sponsored externally.
Purpose of Research Governance
Safeguard participants in research – dignity, rights, safety and wellbeing
Minimise risk & reduce adverse incidents
Improve ethical and scientific quality
Monitor practice and performance
Promote good clinical practice (GCP)
Protect investigators - by providing a clear framework to work within
The RGF sets standards, details the responsibilities of key people involved in
research and outlines the process for achieving governance.
http://www.gov.scot/Topics/Research/by-topic/health-community-care/chief-scientist-office/6864/6933
Why do we need a Framework?
‘Any proposal relating to human subjects including volunteers
that cannot be considered as an element of accepted
clinical management or public health practice and that involves either
(i) physical or psychological intervention or observation, or
(ii) collection, storage and dissemination of information relating to
individuals.”
World Health Organization, Governance, rules and procedures, WHO Manual XVII
What is GCP?
‘… an international ethical and scientific quality standard for
the design, conduct and record of research
involving humans.
Compliance with this standard provides public assurance that the rights,
safety and well being of trial subjects are protected... and that the
clinical trial data and reported results … are credible’.
Each individual or organisation with a defined/delegated role
in clinical research must adhere to GCP.
TASC GCP training
http://www.tasc-research.org.uk/research/gcp-online-
TASC GCP Training Policy
http://www.tasc-research.org.uk/research/for-researchers/policies
ICH GCP - 13 Core Principles
1. Clinical trials should be conducted in accordance with ethical principles that have their origin in the Declaration
of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).
2. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against anticipated benefit
for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits
justify the risks.
3. The rights, safety and well-being of the trial subjects are the most important considerations and should prevail
over interest of science and society.
4. The available non-clinical and clinical information on an investigational product should be adequate to support
the proposed clinical trial.
5. Clinical trials should be scientifically sound, and described in clear, detailed protocol.
6. A trial should be conducted in compliance with the protocol that has received prior institutional review board
(IRB)/ independent ethics committee (IEC) approval/favourable opinion.
7. The medical care given to, and medical decisions made on behalf of subjects should always be the responsibility
of a qualified physician or, when appropriate, of a qualified dentist.
8. Each individual involved in conducting a trial should be qualified by education, training, and experience to
perform his or her respective task(s).
9. Freely given informed consent should be obtained from every subject prior to clinical trial participation.
10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate
reporting, interpretation and verification.
11. The confidentiality of records that could identify subjects should be protected, respecting the privacy and
confidentiality rules in accordance with the applicable regulatory requirement(s).
12. Investigational products should be manufactured, handled and stored in accordance with applicable Good
Manufacturing Practice (GMP). They should be used in accordance with the approved protocol.
13. Systems with procedures that assure the quality of every aspect of the trial should be implemented.
WHO GCRP - 14 Core Principles
Principle 1: Ethical Conduct
Principle 2: Protocol
Principle 3: Risk Identification
Principle 4: Benefit-Risk Assessment
Principle 5: Review by Independent Ethics Committee/Independent Review Board
Principle 6: Protocol Compliance
Principle 7: Informed Consent
Principle 8: Continuing Review/Ongoing Benefit-Risk Assessment
Principle 9: Investigator Qualifications
Principle 10: Staff Qualifications
Principle 11: Records
Principle 12: Confidentiality/Privacy
Principle 13: Good Manufacturing Practice
Principle 14: Quality Systems
Handbook for Good Clinical Research Practice (2002)
http://apps.who.int/prequal/info_general/documents/GCP/gcp1.pdf
Is my project research?
Not all projects undertaken within the NHS are research.
Research - primary aim to to derive generalisable new knowledge
Audit & Service Evaluation - primary aim to measure standards of care
Projects not classified as research
are not managed as research within the NHS
and will not require NHS R&D permission.
How can I decide if it is research?
Health Research Authority (HRA)
Is my study research?
http://www.hra-decisiontools.org.uk/research/
Do I need NHS REC approval?
http://www.hra-decisiontools.org.uk/ethics/
How can I decide if it is research?
Contact TASC Research Governance Office
TASC Joint R&D Office
Governance & Sponsorship
GCP Monitoring
PV/Safety
NHS Permissions
Legal
Finance
QA TCTU
Research Governance Office
Primary functions
• Protocol review and development
• Risk assessment
• Sponsorship approval
• Approval of protocol amendments
• Management of adverse incidents/events
• Management of breaches to GCP or the protocol
• Ensure compliance with GCP
Set-up : Study planning & funding
Identify a Funding Opportunity
Register the study with TASC & RIS/SFO using the PRF
Prepare & submit the application
Set-up : Approvals
1. Sponsorship – TASC RGO
2. Favourable ethical opinion – NHS REC
3. NHS R&D permission – TASC Approvals Office
The RGFs oblige all healthcare research conducted
within the NHS in the UK to have these approvals.
TASC SOP 29 Approvals for Clinical Research
TASC SOP 28 Approvals for CTIMPs
Who is the Sponsor?
An individual, organisation or group taking on responsibility for securing the
arrangements to initiate, manage and finance a clinical research study.
The University of Dundee and NHS Tayside act as Co-Sponsor
for research initiated by UoD or NHST Investigators
Sponsorship Process
Review of Protocol and associated study docs
:study design and conduct
•Insurance, indemnity & contracts
•Statistics & Data Management
• Confidentiality & Data Protection
•Pharmacovigilance & Safety Planning
• IMP Accountability
•GCP Monitoring & GCP Training Requirements
•SOPs – TASC, Local, Network
•Caldicott Guardian Approval and NHS Research Passport
Issue of Sponsorship Letter
The NHS Research Passport
… to allow non-NHS staff to obtain an Honorary Research Contract or Letter
of Access in order to carry out research in the NHS.
… a common system of pre-engagement checks which conform to the
standards required by all NHS bodies, so are therefore transferrable across
NHS Boards & Trusts.
TASC Contacts
High Risk Clinical Research
•CTIMPs
•medical device investigations – non CE marked devices, CE marked but for use in
a new indication, invented locally, devices combined with medicinal products
•radiotherapy trials
•surgery trials
•transplantation trials
•transfusion trials
•trials with cell therapy
•children < 5 yrs
• >5000 participants
•pregnant women
•contraception & conception
•gene therapy
• BBVs & CJD/vCJD
• a.n. other eg adults with incapacity
Ethics
• A favourable ethical opinion must be in place before
NHS R&D permission can be provided and research can commence
• Proportionate review is available - No Material Ethical Issues Tool http://www.hra.nhs.uk/resources/applying-to-recs/nhs-rec-proportionate-review-service/
• Where NHS REC review is not required, review is via an
independent REC eg UoD REC
• NHS REC review can be requested either by the Sponsor or
Investigator where substantive ethical issues are involved
The requirement for ethical review is defined in
1. The Research Governance Frameworks
ALL TYPES OF CLINICAL RESEARCH
2. The Medicines for Human Use (Clinical Trials) Act 2004
CTIMPs
3.The Medical Device Regulations
non-CE marked or outwith their CE indication
4. The International Conference on Harmonisation Good Clinical Practice
ICH GCP
NHS R&D Permission
• Sponsorship and a favourable ethical opinion must be in place
before NHS R&D permission can be provided and research can
commence
• Seek this approval in parallel to NHS REC review.
• Single-site in NHS Tayside : submit to TASC NHS Approvals Team
• Multi-site : submit to NHS Research Scotland (NRS CC) http://nhsgrampian.org/nhsgrampian/nrspcc.jsp
IRAS
IRAS “is a single system for applying for the permissions and approvals
for health and social care / community care research in the UK.”
IRAS “captures the information needed for the relevant approvals from
the following review bodies”
NHS Research Ethics Committees
Administration of Radioactive Substances Advisory Committee (ARSAC)
Gene Therapy Advisory Committee (GTAC)
Medicines and Healthcare products Regulatory Agency (MHRA)
Ministry of Justice
National Information Governance Board (NIGB)
National Offender Management Service (NOMS)
Social Care Research Ethics Committee
NHS R&D offices
IRAS : Integrated Research Application System
Investigator Responsibilities
Investigators must comply with the protocol and with GCP
Investigators must submit to REC, Sponsor and lead NHS R&D Office
• Annual Progress Reports
• Safety Reports
• End of Study/Trial Form
• End of Study Report
Investigators Must
Seek approvals for amendments from Sponsor, REC and NHS R&D Office(s)
(TASC SOP30: TASC SOP26)
• Report any potential serious breaches to protocol or to GCP
to Sponsor via the RGO.
(TASC SOP24: TASC SOP25)
• Establish and maintain a Study/Trial Master File and retain all study documentation
• (TASC SOP45)
• Establish and maintain a Data Management System
• (TASC SOP33)
If it isn’t written down, it didn’t happen
http://www.crn.nihr.ac.uk/wpcontent/uploads/Fundersacademics/CSPamendmentsguidanceforRD_UK_v1_0.pdf
Standards Regulations Guidelines
International
ICH GCP
WHO Handbook for GCRP
EU-wide
Clinical Trials Directive (2001/20/EC)
Medical Devices Directive (93/42/EEC)
UK-wide
Medicines for Human Use (Clinical Trials) Act 2004
The Medical Devices Regulations 2002
Human Tissue Act 2004
Data Protection Act 1998
NHS Caldicott Guardian Approval
GMC Good Practice in Research & Consent to Research
RCN Guidance on Consent to Research
Scotland-wide
Human Tissue (Scotland) Act 2006
Adults with Incapacity (Scotland) Act 2000
Age of Legal Capacity (Scotland) Act 1991
Scottish Executive Health Department Research Governance Framework for Health &
Community Care 2001 (2006)
NHS Scotland Code of Practice on Protecting Patient Confidentiality