the nuts & bolts of clinical research governance

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The Nuts & Bolts of Clinical Research Governance Catrina Forde, Senior Research Governance Manager

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Page 1: The Nuts & Bolts of Clinical Research Governance

The Nuts & Bolts of

Clinical Research Governance

Catrina Forde, Senior Research Governance Manager

Page 2: The Nuts & Bolts of Clinical Research Governance

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.

Page 3: The Nuts & Bolts of Clinical Research Governance

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.

Page 4: The Nuts & Bolts of Clinical Research Governance

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.

Page 5: The Nuts & Bolts of Clinical Research Governance

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

Page 6: The Nuts & Bolts of Clinical Research Governance

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...

Page 7: The Nuts & Bolts of Clinical Research Governance

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.

Page 8: The Nuts & Bolts of Clinical Research Governance

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

Page 9: The Nuts & Bolts of Clinical Research Governance

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

Page 10: The Nuts & Bolts of Clinical Research Governance

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

Page 11: The Nuts & Bolts of Clinical Research Governance

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

Page 12: The Nuts & Bolts of Clinical Research Governance
Page 13: The Nuts & Bolts of Clinical Research Governance
Page 14: The Nuts & Bolts of Clinical Research Governance

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.

Page 15: The Nuts & Bolts of Clinical Research Governance

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

Page 16: The Nuts & Bolts of Clinical Research Governance

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.

Page 17: The Nuts & Bolts of Clinical Research Governance
Page 18: The Nuts & Bolts of Clinical Research Governance

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/

Page 19: The Nuts & Bolts of Clinical Research Governance
Page 20: The Nuts & Bolts of Clinical Research Governance
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How can I decide if it is research?

Contact TASC Research Governance Office

[email protected]

[email protected]

TASC Joint R&D Office

Governance & Sponsorship

GCP Monitoring

PV/Safety

NHS Permissions

Legal

Finance

QA TCTU

Page 22: The Nuts & Bolts of Clinical Research Governance
Page 23: The Nuts & Bolts of Clinical Research Governance

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

Page 24: The Nuts & Bolts of Clinical Research Governance

Set-up : Study planning & funding

Identify a Funding Opportunity

Register the study with TASC & RIS/SFO using the PRF

[email protected]

[email protected]

Prepare & submit the application

Page 25: The Nuts & Bolts of Clinical Research Governance

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

Page 26: The Nuts & Bolts of Clinical Research Governance

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

Page 27: The Nuts & Bolts of Clinical Research Governance

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

Page 28: The Nuts & Bolts of Clinical Research Governance
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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

[email protected]

[email protected]

Page 30: The Nuts & Bolts of Clinical Research Governance

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

Page 31: The Nuts & Bolts of Clinical Research Governance

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

Page 32: The Nuts & Bolts of Clinical Research Governance

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

Page 33: The Nuts & Bolts of Clinical Research Governance
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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

Page 35: The Nuts & Bolts of Clinical Research Governance

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

Page 36: The Nuts & Bolts of Clinical Research Governance

IRAS : Integrated Research Application System

Page 37: The Nuts & Bolts of Clinical Research Governance
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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

Page 39: The Nuts & Bolts of Clinical Research Governance

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

Page 40: The Nuts & Bolts of Clinical Research Governance

http://www.crn.nihr.ac.uk/wpcontent/uploads/Fundersacademics/CSPamendmentsguidanceforRD_UK_v1_0.pdf

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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