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West Yorkshire Comprehensive Local Research Network

BRADFORD TEACHING HOSPITALS NHS TRUST

West Yorkshire Research

Induction Pack

for Nurses, Midwives and other

Allied Health Professionals

Name .........................................................................................................

Job Title .....................................................................................................

Department ................................................................................................

Start Date ..................................................................................................

Line Manager ............................................................................................

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CONTENTS ▼ = denotes local Trust information

Introduction▼

Research & the NHS

National Institute of Health Research and the Networks ▼

Trust R&I Strategy ▼

Research Governance

Declaration of Helsinki

EU Directives, Statutory Instruments and MHRA

Good Clinical Practice

Health Research Authority & Ethics

Roles & Responsibilities of Researchers & Organisations

Amendments

Safety

Human Tissue Act

Data Protection

Informed Consent

SOPs Standard Operating Procedures training log ▼

Clinical Research Nurse Induction programme

Local research induction

Induction Programme line manager sign off

Trial design

Case Report Forms

Essential Documents

Clinical Research Nurse Competency Tool

Appendices

I Clinical Research Forum Terms of References ▼ II Training Folder Template III Research CV template IV Glossary and Further Resources V Useful contacts ▼

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Acknowledgements:

The following were members of the Clinical Research Induction Working Group:

Angela Grange

Emma Giddings

Sue Williamson

Clive Nicholson

Heather Rostron

Victoria Drew

Linda Bamford

This document has been based on Leeds Teaching Hospitals NHS Trust Clinical Research

Nurse Induction Pack & Competency Framework and Yorkshire Cancer Research

Network’s Induction Handbook.

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Introduction

Welcome to the Bradford Institute for Health Research

The Bradford Institute for Health Research was established in 2007 as a unique research partnership between the primary and secondary care NHS Trusts in Bradford and Airedale and the universities of Bradford, Leeds and York. There is a real passion and commitment from the partners of the BIHR to harness the potential for expanding research in Bradford and establish the Bradford NHS community as a national leader in applied health research.

The BIHR has developed a strong track record in applied research and is a national centre of excellence in

a number of health priority areas. It provides a physical centre for academic and research staff

employed by the Trust as well as the Universities of Leeds and Bradford, and houses a number of these

staff.

Whatever your previous roles and experience, you will bring with you a variety of knowledge and skills. However, coming into the world of clinical research from hands-on care provision involves the development of new and different clinical skills, which is both exciting and challenging. As well as keeping your existing skills, additionally you will learn many new ones We hope you will find that the role of clinical research nurse is varied and interesting - everyday is different from the one before. Research nurses take part in a study from start to finish (they hear and learn about a completely new study, enrol patients and are there to see the results that will make a difference to the patient and their families in the future). Research nurses play a vital role in supporting patients throughout the course of the research, ensuring

clinical studies run smoothly and that participants are safe and fully informed. They may be responsible

for recruiting patients, gaining consent from patients to take part in a study, collecting data, carrying out

study-related clinical procedures and much more.

This booklet is designed to be a practical and informative resource to you. Take every opportunity to

obtain advice and support from your research colleagues and R&D Department.

Wishing you every success in your post,

Angela Grange

Lead Nursing Clinical Quality & Research/Trust Innovation Lead

Emma Giddings,

Lead Nurse WYCLRN

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RESEARCH AND THE NHS

Why engage in research

Studies suggest that patients who receive care in research-active institutions have better health

outcomes than patients who are treated in a non-research environment, so by joining the research

community you are actively helping to drive up the standard of healthcare for your patients. By

investigating the cause and course of diseases and how best to treat them, you are also helping to

establish ‘what works’ and build the body of evidence that can lead to a positive change in future care.

The importance of Research within the NHS

The Department of Health’s strategy to improve the health of the nation continues to place research at

the forefront of the NHS. The recent White Paper Equity and excellence: liberating the NHS (DH 2010)

highlights research in terms of quality, transparency and value for money, with the aim of achieving

health outcomes as good as anywhere else in the world. It aims to deliver quality care from evidence

based practice which is thoroughly researched. The NHS has a constant challenge to provide a service

that is up to date and efficient. Health research plays a key role in this service by using the evidence

from studies to support health strategies and changes in medical practice.

The NHS now has a thriving research culture that promotes fairness of access across England for patients

and health professionals to take part in multi-centre studies. As a member of a clinical research team

you will play a key role in contributing to this research culture through clinical trials and/or health

related research, therefore continually improving the quality and choices available for patients and

healthcare as a whole.

The Plan for Growth: http://cdn.hm-treasury.gov.uk/2011budget_growth.pdf

Liberating the NHS, Equity and Excellence:

http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH

_117353

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Supporting research to make patients, and the NHS, better

www.crncc.nihr.ac.uk

The NIHR Clinical Research Network (NIHR CRN) is part of the NIHR, specifically tasked with ensuring that

the infrastructure for research in the NHS enables studies to happen as quickly and efficiently as

possible including:

- Access to experienced Research Management and Governance staff who can advise on and

facilitate the governance aspects of undertaking clinical research in the NHS.

- Support to ensure studies can be successfully undertaken in the NHS.

In England, the Department of Health has determined that research studies (clinical trials and other well

designed studies which involve the NHS) that are funded by NIHR, other areas of Government and NIHR

non-commercial Partners are automatically eligible to be included in a database called the NIHR CRN

Portfolio (National Institute for Health Research Clinical Research Network Portfolio). In addition, other

studies, such as those that are commercially sponsored or those with industry funding that are led by a

local investigator, may be considered for inclusion in the NIHR CRN Portfolio by undergoing an adoption

process. ‘NIHR Portfolio studies’ have access to infrastructure support and funding for service support

costs via the NIHR.

Stu

dy p

lan

nin

g

•Advice on available facilities/ support staff

•Ideas on supporting clinicians

•Intelligence on local patient populations

Stu

dy s

et-

up

•Systems to reduce red-tape on multi-site studies

•Managing NHS R&D approval process

•Speeding up set-up times

Stu

dy d

elive

ry

•Funding of facilities and people to carry out research

•Recruiting patients into studies

•Providing training for research staff

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NIHR Infrastructure

Clinical Research Network

HQ

Comprehensive

(CCRN)

Cancer

(NCRN)

Diabetes

(DRN)

Dementia & neuro

(DeNDRoN)

Mental Health

(MHRN)

Medicines for

Children

(MCRN)

Primary Care

(PCRN)

Stroke

(SRN)

Topics Networks support research in the priority areas of Cancer, Diabetes,

Dementia & Neurodegenerative Diseases, Mental Health, Medicines for Children,

Stroke and Primary Care.

In addition to the topic specific research networks, the Comprehensive Clinical

Research Network (CCRN), comprising 25 Comprehensive Local Research

Networks, makes it possible for all patients and health professionals across

England to participate in clinical trials in all other areas of disease and clinical

need within the NHS.

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www.westyorks.crncc.nihr.ac.uk

“The West Yorkshire Comprehensive Local Research Network operates as part of the NIHR

Comprehensive Clinical Research Network in England. It is part of the National Institute for Health

Research and forms part of the UK Clinical Research Network. The Networks support and deliver high

quality clinical research studies.”

The role of West Yorkshire CLRN:

Provide support and signpost researchers during the planning, set up and delivery phase of a

study.

Research Management & Governance service through the Integrated Research Application

System (IRAS) and NIHR Co-ordinated System for gaining NHS Permission (NIHR CSP).

Support Local Specialty Groups to bring together researchers to provide a local focus for activity

in that disease area.

The NIHR CRN is committed to helping the life science industry deliver high quality research to

time and target in a well managed, efficient and cost effective environment. This is facilitated in

West Yorkshire through a dedicated industry manager, who provides a single point of contact for

all services.

2012/13 budget of £12.3m for West Yorkshire:

Service Support Costs

Clinical infrastructure (consenting patients/retrieving outcome data)

o Clinical sessions

o Research nurses

Key service support

o Pharmacy, Radiology, Pathology

o Translators, clinical trials coordinators, information managers

Research Capability Funding (RCF)

o Staff costs of researchers between portfolio grants

o Staff costs of researchers who haven’t yet obtained portfolio funding, but are expected

to imminently.

The WYCLRN provide funding for research posts across the region and the Lead Nurse role is to provide

leadership and support to this workforce. She can be contacted as below:

Emma Giddings, WYCLRN, 34 Hyde Terrace, Leeds, LS2 9LN. T 0113 392 3765 M 07534 274555 E E.K.Giddings@wyclrn.org.uk

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Yorkshire Cancer Research Network

The Yorkshire Cancer Research Network (YCRN) is 1 of 32 cancer networks across England which are co-ordinated by the National Institute for Health Research Cancer Research Network (NCRN). The NCRN is a part of the National Institute for Health Research (NIHR).

The NIHR supports and funds NHS research through the NCRN and five other Topic disease areas, a Primary Care Network and a Comprehensive Research Network ensuring all areas of research are covered.

The YCRN works closely with its two Comprehensive Local Research Networks – West Yorkshire and North & East Yorkshire & North Lincolnshire (WY CLRN & NEYNL CLRN). Additional CLRN funds supports the cancer clinical trials portfolio.

The YCRN is also part of the Yorkshire Cancer Network (YCN), which provides cancer care for a population of over 2.6 million people.

It embraces 7 acute hospitals:

Airedale NHS Foundation Trust Bradford Teaching Hospitals NHS Foundation

Trust Calderdale and Huddersfield NHS Foundation

Trust Harrogate and District NHS Foundation Trust Mid Yorkshire NHS Trust Leeds Teaching Hospitals NHS Trust York Teaching Hospitals NHS Foundation Trust

and several Primary Care Trusts (CCGs):

NHS Leeds North CCG

NHS Leeds West CCG

NHS Leeds South and East CCG

NHS Bradford City CCG

NHS Bradford Districts CCG

NHS Airedale, Wharfedale and Craven CCG

NHS Vale of York CCG

NHS Harrogate and Rural CCG

NHS Calderdale CCG

NHS Greater Huddersfield CCG

NHS North Kirklees CCG

NHS Wakefield CCG

What we do

The YCRN supports and funds research staff across the YCN to work on a large number of cancer clinical trials. The YCRN aims to:

Create a balanced and equitable local cancer clinical trial portfolio focusing on local Trust strengths ensuring NIHR recruitment targets are met.

Ensure timely and efficient clinical trial setup for network Trusts and improve the integration of these trials into clinical practice, ultimately resulting in improved patient care.

Raise research awareness in healthcare professional and service users groups Encourage patient and public involvement in the development of cancer clinical trials Provide and facilitate a comprehensive training and education programme

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Yorkshire Stroke Research Network

Yorkshire, North Yorkshire, East Yorkshire and North Lincolnshire (Scunthorpe and Goole)

The Yorkshire Stroke Research Network aims to improve the speed, quality, and integration of research,

ultimately resulting in improved patient care. We provide structures and support to local clinicians to get

involved in recruiting patients to high quality multicentre trials.

In 2012 the YSRN was named "Local Research Network of the Year" at the national SRN conference.

How the Network Works

We aim to provide a first class environment for stroke research and improve the care of people with

stroke and their carers. The YSRN operates through maximising autonomy for local clinicians. The

network provides the staff with training, advice, opportunities and resources to set-up and manage

trials, but clinicians decide which trials to run, based on their expert knowledge of local conditions,

interests and potential. Possible projects are discussed and presented at regular network meetings and

then quickly rolled out across an informed network.

Most of the resources of the network are devolved to local sites in the form of high-quality research

staff. These researchers are performance managed from the centre, but embedded in the local clinical

team.

The YSRN is proud to be a genuinely open network. YSRN network meetings are held jointly with the

West Yorkshire Stroke Group, the established clinical network, and are open to all. We have a broad

cross-section of people with an interest in stroke and stroke research on our Management, Executive

and Research Advisory (patient and carer) groups who are all consulted about our work and plans.

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Stroke Research Sites in the YSRN

The YSRN works mainly in stroke units in acute hospitals, but we also collaborate with other organisations to conduct research in, for example, primary care. We have staff based in the following organisations: Airedale NHS Trust

• Airedale General Hospital

Bradford Teaching Hospitals NHS Foundation

Trust

• Bradford Royal Infirmary

• St Luke’s Hospital

Calderdale & Huddersfield NHS Trust

• Calderdale Royal Hospital

• Huddersfield Royal Hospital

Harrogate and District NHS Foundation Trust

• Harrogate District Hospital

Hull and East Yorkshire NHS Foundation Trust

• Hull Royal Infirmary

• Castle Hill Hospital

• The Princess Royal Hospital

Leeds Teaching Hospitals NHS Trust

• Leeds General Infirmary

• St James’s University Hospital

• Chapel Allerton Hospital

Mid Yorkshire Hospitals NHS Trust

• Dewsbury and District Hospital

• Pinderfields General Hospital

• Pontefract General Infirmary

Northern Lincolnshire and Goole Hospitals NHS

Foundation Trust

• Diana, Princess of Wales Hospital, Grimsby

• Goole and District Hospital

• Scunthorpe General Hospital

Scarborough and North East Yorkshire Health Care

NHS Trust

• Scarborough General Hospital

York Hospitals NHS Foundation Trust

• York Hospital

The YSRN is Hosted by Bradford Teaching Hospitals NHS Foundation trust. For more information

contact:

Stephen Lock, YSRN Manager Yorkshire Stroke Research Network Bradford Institute for Health Research Temple Bank House Bradford Royal Infirmary Duckworth Lane Bradford BD9 6RJ T: 01274 383 425 F: 01274 382 768

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West Yorkshire research for CHildren

The West Yorkshire research for CHildren (WYCH) aims to develop research capacity using experience

from Greater Manchester Lancashire and south Cumbria MCRN (GMLC) to help local NHS staff and their

organisations to create a sustainable infrastructure to support paediatric research.

The West Yorkshire Comprehensive Local Research Network (WY CLRN) provided significant funding to

support new research nurses and medical time in all hospital Trusts in the area with recruitment

extending into primary care and the community for some studies.

WYCH supports National Institute for Health Research (NIHR) portfolio studies that fall under either

MCRN or Paediatric Specialty Group (PSG). Current MCRN and PSG portfolio studies can be found at the

NIHR CRN Clinical Research Portfolio webpage.

The WYCH team works closely with the GMLC team helping local clinical staff successfully set up and

deliver MCRN and PSG studies. The recruitment phase and other aspects of the study management

process are managed locally by the WYCH team.

The team:

11 Research Nurses and 1 Senior Research Nurse work across West Yorkshire, with nursing hubs in

Bradford and Leeds. Research Leads drive and champion paediatric research in all West Yorkshire District

General Hospitals and also in the speciality of neonatology. Most of the WYCH team are featured in the

photograph below.

Dr Tim Lee (far right) is a Consultant Paediatrician based at Leeds General Infirmary and is the West

Yorkshire MCRN lead. Heather Rostron (front 2nd right) is the West Yorkshire MCRN Senior Research

Nurse. The Leeds nurse team is led by paediatric oncology Senior Research Nurse Linda Phelan (5th right

back row) with Research Nurses: Becky Mottram (2nd right back row); Majorie Allen (3rd right front

row); Nicky Balatoni (4th left top row) and Jane Exall (3rd right top row). We also support Annabel Nixon

(2nd left top row) who is funded to work on an MCRN adopted Marfans Syndrome study. Our Bradford

hub comprises of Research Nurses Louise Akeroyd (front left) and Kelly Young (6th left top row) and we

have part time nurses based at Airedale Hospitals Trust; Mandy Swanepoel (5th left top row), Calderdale

and Huddersfield Hospitals Trust; Rachel Swingler (2nd left bottom row) and at Mid Yorkshire Hospitals

Trust; Gail Castle (4th right bottom row). Also, Sarah Rickard is our GMLC-MCRN Network Manager

(bottom right), and our WYCH Administrator is Stephanie Hill (3rd left top row).

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Contact us:

Heather Rostron; 0777 209 2410

Airedale

Dr Pronab Bala (pronab.bala@anhst.nhs.uk)

Mandy Swanepoel (mandy.swanepoel@anhst.nhs.uk) 01535 293934

Bradford

WYCH Office - 01274 382318

Louise Akeroyd (louise.akeroyd1@bthft.nhs.uk)

Kelly Young (Kelly.Young2@ bthft.nhs.uk)

Calderdale & Huddersfield

Rachel Swingler (Rachel.swingler@cht.nhs.uk) 077668 20793

Dr Lynne Terrett - 01484 342361

Leeds

WYCH Office – 0113 392 3995

Dr Tim Lee (tim.lee@leedsth.nhs.uk)

Majorie Allen (marjorie.allen@leedsth.nhs.uk)

Becky Mottram (rebecca.mottram@leedsth.nhs.uk)

Darren Hewett (darren.hewett@leedsth.nhs.uk)

Jane Exall (jane.exall@leedsth.nhs.uk)

Gill Jackson (gill.jackson@leedsth.nhs.uk)

Mid Yorkshire

Dr Kath Deakin (kathryn.deakin@midyorks.nhs.uk)

Gail Castle (gail.castle@midyorks.nhs.uk) 01924 543778

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▼Bradford Institute for Health Research

The BIHR has a particular focus on public health research, with major programmes including:

Born in Bradford – one of the world’s largest public health research projects following the lives of 10,000 families in the city.

Stroke and elderly care – hosting the regional stroke research network and one of the leading centres for elderly care research in the UK.

Patient safety – developing innovative solutions to improve the major public health issue of patient safety

Maternal and child health – a new centre covering obstetric trials, paediatric epidemiology and childhood obesity.

The BIHR has developed a strong track record in applied research and is a national centre of excellence in a number of health priority areas. In 2006 Bradford became the only centre in Yorkshire to win a clinical research network application with the £2 million Yorkshire Stroke Network.

During 2007-09 researchers in Bradford were successful in winning major National Institute for Health Research (NIHR) programme grants worth £5 million for:

rehabilitation, child health, delirium patient safety and a developmental programme grant in Quality and Safety

The BIHR also hosts the Born in Bradford research programme which has been successful in winning over £7 million in research grants over the last two years.

The Institute provides a physical centre for academic and research staff employed by the Trust and the

Universities of Leeds and Bradford and houses a number of these staff. In addition it provides the

following facilities for health care professionals in the Trusts:

1. Purpose-designed clinical research facility for all patients involved in commercial and non-commercial clinical trials, supported by high calibre, dedicated research nurses

The Bradford Institute for Health Research was established in 2007 as a unique research partnership between the primary and secondary care NHS Trusts in Bradford and Airedale and the universities of Bradford, Leeds and York. There is a real passion and commitment from the partners of the BIHR to harnessing the potential for expanding research in Bradford and establish the Bradford NHS community as a national leader in applied health research.

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2. A hub for all clinical researchers in Bradford across all disciplines. 3. An Exchange area where researchers can meet and network and share their research ideas and

expertise. 4. A formal meeting room for research training and research meetings and seminars 5. A Research Design Service for supporting grant development for clinical staff with new ideas.

The vision for the Bradford Institute for Health Research is to become a national centre for excellence in health research and to forge a unique research collaboration between the people of Bradford, the NHS community and the Universities of Leeds and Bradford. A strategy for the BIHR has been produced which details its strategic aims and objectives for the next five years. To summarise, its aims are:

To develop high quality research capacity across the Bradford research community. To undertake research programmes that will translate into real benefits for patients. To provide an opportunity for local people to share the benefits of participation and involvement

in healthcare research. To develop and attract the best researchers. To ensure high standards for research governance and minimise bureaucracy.

There will also be a number of activities that will be undertaken by the Institute:

Research governance support – the Bradford Teaching Hospitals NHS Foundation Trust’s Research Support and Governance Office is housed within the Institute and provides the full spectrum of research advice and support to researchers including advice on data protection, research passports and honorary contracts, approval processes and applications and quality assurance.

Research advice - methodological support and identification of grant opportunities Training and research events for researchers - research training is provided on subjects such as

research governance and GCP training but the Institute also hosts regular research meetings where staff can present their research. This latter activity not only encourages collaborations but will enable staff to learn about each other´s research activity.

Information to patients and public – within the Clinical Research Facility there is information resources for the patients and the public about research in the Trust and what they can expect if they get involved in a research project.

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Research Governance

All health and social care research arrived out in the UK is governed by strict regulations. They exist to

ensure that research is carried out consistently to high ethical and scientific standards, and to prevent

performance, adverse events where possible, research misconduct and fraud. They also help to ensure

that lessons are learned and shared when poor practice is identified. Organisations involved in clinical

research have a duty to foster a high quality research culture and individuals have a duty to ensure that

they, and those they manage, are appropriately qualified by training, education and experience for the

roles that they undertake.

Research Governance Framework

Research Governance Framework for Health and Social Care, 2001 (updated 2005) was published by

Department of Health (DH) to provide a practical framework for the governance of research in health

and social care in the UK. It applies to everybody involved in research (clinical and non-clinical)

undertaken by NHS staff using NHS resources. This includes research undertaken by industry, charities,

research councils and universities within the health and social care systems. The rules apply to

researchers, managers and staff in all professional groups, no matter how senior or junior, as well as to

research participants.

Research Governance Framework

Any research within the responsibilities of the Secretary of State for Health,

including any research conducted in the NHS in England.

CTIMPs and Non-CTIMPs

CTIMPs are also governed by UK Medicines for Human Use (Clinical Trials) Regulations

and overseen by the UK Competent Authority, the Medicines and Healthcare

Regulatory Agency (MHRA)

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The RGF outlines the key roles and responsibilities of both researchers and organisations that are

accountable for the proper conduct of a study. It requires that formal agreements are in place

describing the allocation of these responsibilities. Below are summaries of these roles and

responsibilities and a brief outline of how these are applied in practice.

Research Governance:

Sets standards

Defines mechanisms to deliver standards

Describes monitoring and assessments arrangements

Research Governance improves research quality and safeguards the public by:

Enhancing ethical and scientific quality

Promoting good practice

Reducing adverse incidents and ensuring lessons are learned

Preventing poor performance and misconduct

Research Governance is for all those who:

Participate in research

Host research in their organisation

Fund research proposals or infrastructure

Manage research

Undertake research

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Declaration of Helsinki

The Declaration of Helsinki is a landmark international agreement adopted in 1964 by the World Medical

Association recommending ethical standards in medical research. A fifth revision of this short document,

approved in 2000, addresses issues raised as a result of rapid expansion of biomedical research.

The key points of the Declaration of Helsinki are:

It is the duty of the physician to protect the life, health, privacy and dignity of the human subject.

Medical research involving human subjects must conform to generally accepted scientific

principles.

Effects on the environment and welfare of animals used for research must be considered.

Each experimental procedure should be fully described in a protocol and be considered by an

ethical review committee.

The research protocol should contain a statement of the ethical aspects

Medical research should be conducted by scientifically qualified personnel and supervised by a

clinically competent medical person.

Predictable risks and burdens should be weighed against foreseeable benefits for the subjects

and others.

Physicians should cease any investigations if the risks outweigh the potential benefits.

The importance of the objective should outweigh the risks and burden to the subject, especially

in healthy volunteer studies.

Medical research is only justified if there is reasonable likelihood that a population will be

benefited.

The subjects must be volunteers and fully informed participants.

The right of research subjects to safeguard their physical and mental integrity and privacy must

be respected.

Each potential subject must be adequately informed of and their freely given consent obtained

in writing.

Subjects in a dependant relationship with the research should be consented by an independent

physician.

For legally incompetent subjects, the investigator must obtain consent from a legally authorised

representative.

Where the legally incompetent subject is able to give assent to decisions about participation in

research, that assent should be obtained in addition to consent.

If research is intended on subjects who cannot consent, it must be justified to, and approved by,

the ethics committee.

Results of all trials conducted according to these principles should be accurately published and

made available.

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European Directive on Good Clinical Practice in Clinical Trials

The EU Directive of 2001 aims to harmonise and streamline clinical trials procedures throughout the

member states and to support GCP with a legislative framework. It relates to all intervention trials, both

academic and commercial.

The Directive relates to all trials involving medicinal products, and encompasses all personnel involved

with the clinical trial procedure.

The EU Directive was adopted by all Member States in February 2001 and was implemented in the UK in

May 2004 with the Medicines for Human Use (Clinical Trials) Act 2004 and subsequent Statutory

Instrument Amendments.

Guidance provided by the EU directive:

Properly obtained and documented informed consent must be obtained.

Adherence to data protection directive 95/46/EEC is required.

Indemnity and insurance to cover liability of Investigator and Sponsor is required.

Subjects must be given a contact point from where further information can be obtained.

Extensive details relating to the conduct of clinical trials using those unable to give consent.

A single ethics committee opinion is required for multi-centre studies.

60 days maximum is allowed for an ethics committee to provide an opinion (35 days for an

amendment).

Extensions to these approval times apply when studies involve gene/cell therapies.

A database with details of European trials and adverse events will be set up.

Adverse event reporting to be standardised.

GCP inspections to become mandatory.

Controls to be placed on the manufacture and labelling of investigational products.

Studies can be stopped in the event of sponsor and/or investigator non-compliance.

The EU Directive is applicable to all centres performing interventionist research trials. These include

academic institutions and those trial units supported by charities.

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Good Clinical Practice

Until 1997, there were several documents relating to good clinical practice (GCP). In 1997 an

international committee for the harmonization of good clinical practice (ICH-GCP) was formed to

produce a standard agreed by the European Union, Japan and the United States.

These guidelines were implemented in the participating countries, and had the advantage of facilitating

mutual acceptance of data by the regulatory authorities of those countries.

The first principle of the ICH-GCP guidelines is that:

“Clinical trials should be conducted in accordance with the ethical principles

that have their origin in the declaration of Helsinki and are consistent with GCP

and the applicable regulatory requirements.”

The ICH-GCP guidelines are very comprehensive and list responsibilities for all involved in research

activity. It includes specific sections listing responsibilities of ethics committees, Investigators and

Sponsors. There are also sections detailing the format of trial protocols, investigator brochures and

essential documents required for clinical trials.

The ICH-GCP guidelines were an attempt to unify GCP standards, but they were only ever guidelines, and

lacked the legal status needed to ensure that everyone adopted them. Although most sponsor

companies adopted the guidelines from the outset, there were some that did not. In particular,

academic research units found the workload cost implications were too great to implement the

guidelines. Also, some ethics committees were reluctant to adhere to the extra requirements that ICH-

GCP guidelines made of them, since they were not legally obliged to do so.

However, in 2000, the European Union issued a clinical trials directive that requires the adherence to the

principles of GCP. The EU Directive was transposed into UK law through the Medicines for Human Use

(Clinical Trials Act) Regulations, 2004.

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The Principles of ICH-GCP

1. Clinical trials shall be conducted in accordance with the ethical principles that have their origin in

the Declaration of Helsinki, and that are consistent with good clinical practice and the

requirements of the UK Regulations of Medicines for Human Use (Clinical Trials).

2. Before the trial is initiated, foreseeable risks and inconveniences have been weighed against the

anticipated benefit for the individual trial participant and other present and future patients. 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

shall prevail over interests of science and society.

4. The available non-clinical and clinical information on an investigational medicinal product shall

be adequate to support the clinical trial.

5. Clinical trials shall be scientifically sound, and described in a clear, detailed protocol.

6. A trial shall be conducted in compliance with the protocol that has a favourable opinion from an

ethics committee.

7. The medical care given to, and medical decisions made on behalf of, subjects shall always be the

responsibility of an appropriately qualified doctor or, when appropriate, of a qualified dentist.

8. Each individual involved in conducting a trial shall be qualified by education, training, and

experience to perform his or her respective task(s).

9. Subject to the other provisions relating to consent, freely given informed consent shall be

obtained from every subject prior to clinical trial participation.

10. All clinical trial information shall 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 shall be protected, respecting the

privacy and confidentiality rules in accordance with the requirements of the Data Protection Act

1998 and the law relating to confidentiality.

12. Investigational medicinal products used in the trial should be manufactured, handled and stored

in accordance with the principles and guidelines of 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 shall be

implemented.

Although the law only applies to CTIMP studies, the principles of ICH-GCP should be applied to all

clinical research studies (CTIMP and non-CTIMP). All research should be conducted to the highest

standard whether governed by the law, or not.

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Health Research Authority & Ethics http://www.dh.gov.uk/health/2011/12/creation-hra

The Health Research Authority (HRA) is a Special Health Authority (SpHA), completing one of the key

commitments made by the Government in the Plan for Growth towards rationalising and improving

health research regulation. Its central purpose is to protect and promote the interests of patients and

the public in health research. The HRA will co-operate with others to combine and streamline the current

approval system and promote consistent, proportionate standards for compliance and inspection. The

purpose of this is for the HRA to reduce the regulatory burden on research-active businesses, universities

and the NHS, and improve the efficiency and robustness of decisions about research projects.

In its initial form as a SpHA, the HRA has the National Research Ethics Service (NRES) at its core and has

taken on the functions, which have been the responsibility of the National Patient Safety Agency. In due

course, it will perform the Secretary of State’s function of approving the processing of patient

information for medical research.

Ethics

Research Ethics Committees (RECs) are the committees convened to provide independent advice to

participants, researchers, funders, sponsors, employers, care organisations and professionals on the

extent to which proposals for research studies comply with recognised ethical standards.

The purpose of a REC in reviewing the proposed study is to protect the dignity, rights, safety and well-

being of all actual or potential research participants. It shares this role and responsibility with others,

as described in the Research Governance Framework.

Ethical advice from the appropriate NHS REC is required for any research proposal involving:

Patients and users of the NHS. This includes all potential research participants recruited by

virtue of the patient or user’s past or present treatment by, or use of, the NHS. It includes NHS

patients treated under contracts with private sector institutions.

Individuals identified as potential research participants because of their status as relatives or

carers of patients and users of the NHS, as defined above.

Access to data, organs or other bodily material of past and present NHS patients.

Foetal material and IVF involving NHS patients.

The recently dead in NHS premises.

The use of, or potential access to, NHS premises or facilities.

NHS staff – recruited as research participants by virtue of their professional role.

23

Roles & Responsibilities of Researchers and Organisations

Review of research - An independent expert review of protocols is required. - A separate ethical review of the study is required. - All data must be available to inspection and auditing bodies from both internal and external

organisations. - The protocol must not change without formal agreement from those who gave appropriate

permission for the study. Funder of research - Ensures quality and value for money, based on research costs and any care or treatment costs and

makes arrangements for independent expert review. - Ensures funding is conditional on identifying a sponsor (usually a university or NHS Trust). - Provides assistance to any enquiry, audit or investigation of the funded work. Sponsor All clinical trials and studies: - Responsible for ensuring expert scientific and ethics reviews are carried out. - Puts in place arrangements to adhere to GCP (if no other person is specified) and ensures

arrangements are in place to be alerted to significant developments. - Takes appropriate urgent safety measures (with investigator). - Ensures arrangements are in place for compensation (indemnity/insurance arrangements). - Keeps records of all adverse events reported by investigators. - Ensures the Research Ethics Committee is notified when the trial has ended. Clinical Trials involving investigational medicinal products (CTIMP): - Ensures the EudraCT (European Clinical Trials Database) Number is obtained. - Competent Authority Authorisation is obtained (Chief Investigator). - Pharmacovigilance reporting and time frames are adhered to. - EudraCT and the Competent Authority are notified when trial has ended.

24

Chief Investigator - Is responsible for the design, management and reporting of the study for all sites. - Is responsible for ensuring that each investigator is aware of their legal duties and obligations. - Is responsible for ensuring the protocol is approved by relevant bodies, any pre-conditions are acted

upon, and that research follows the agreed protocol except in the case of urgent safety measures. - Undertakes duties delegated by the sponsor (usually working in conjunction with a clinical research

organisation CRO if it is a pharmaceutically funded trial). - Publishes the clinical study results as soon as possible following study completion. In a multi-centre

study, the chief investigator must ensure that the data from one centre is not published before the publication of the whole study without his/her consent, and must obtain Sponsor approval prior to publication.

Principal Investigator It is the responsibility of the PI to conduct the study according to the protocol and to ensure that he/she has the necessary patient population available to conduct the study within the period defined in the study protocol. The investigator also holds additional responsibilities: - To ensure that the study is performed in accordance with the International Good Clinical Practice

standards (ICH-GCP) and conforms with the principles of the Declaration of Helsinki (revised version 1996), all local laws and regulations concerning clinical studies.

- To submit the protocol, patient information sheet and consent form for local Research Management & Governance approval (R&D approval).

- To ensure that all staff involved in the study have a full understanding of the protocol and its requirements, and that their roles are documented on a study delegation log.

- To confirm subject eligibility according to the inclusion/exclusion criteria stated in the protocol. - To obtain and record subject consent. - To withdraw a subject from the clinical trial for any reason should this be thought to be in their best

interests. - To perform protocol directed medical care including assessment, examination and prescription of

study and support medication. - To ensure subject anonymity is maintained. - To ensure the completeness and accuracy of case report forms. - To agree to allow the monitor/auditor/inspector to have access to any or all of the study materials

needed for source data verification and proper review of study progress. - To report all safety events: SAEs, SARs, SUSARs as outlined in the protocol, including prompt

reporting to Sponsor to ensure further communication with MHRA/REC if applicable within the statutory timelines.

- To retain all essential documents as per NHS and Trust guidelines (usually a minimum of five years following the end of a study, at least two years after the approval of a marketing application, for a new drug, or longer if required by the regulator requirements).

- To comply with the study sponsor and regulatory authority requirements regarding the auditing of the study.

25

Co-investigator (Medical) The co-investigator is responsible for medical care of patients participating in research studies, working under the supervision of the principle investigator. The co-investigator is usually delegated the following responsibilities: - To ensure that the study is performed in accordance with ICH-GCP and conforms with the principles

of the Declaration of Helsinki (revised version 1996), all local laws and regulations concerning clinical studies.

- To confirm subject eligibility according to the inclusion/exclusion criteria stated in the protocol. - To obtain and record patient consent. - To withdraw a subject from the clinical trial for any reason should this be thought to be in their best

interest. - To perform protocol directed medical care including assessment, examination and prescription of

study and support medication. - To ensure subject anonymity is maintained. - To ensure the completeness and accuracy of case report forms. - To agree to allow the monitor/auditor/inspector to have access to any or all of the study materials

needed for source data verification and review of study progress. - To retain all essential documents as per NHS and Trust guidelines (usually a minimum of five years

following the end of a study, at least two years after the approval of a marketing application, for a new drug, or longer if required by the regulator requirements).

- To comply with the study sponsor and regulatory authority requirements regarding the auditing of the study.

Research Nurse/AHP/Midwife/Clinical Trials Officer/Practitioner The research nurse/AHP/Midwife/CTO is delegated responsibilities by the PI, these may include: - Preparing and submitting local regulatory approval applications. - Ensuring that they have attended an initiation meeting and received any appropriate training prior to

the trial commencement. - Co-ordinating the clinical trial in terms of patient screening, recruitment, entry into the trial via

randomisation if applicable and subsequent patient visits. - Checking patient eligibility according to the inclusion/exclusion criteria stated in the protocol in

collaboration with medical staff. - Collaborating with clinicians to assess patients and making treatment decisions according protocol. - Delivery of investigational agents/treatments and protocol directed care. - Handling, spinning, labelling, storage and shipping of blood and urine pharmacokinetic samples. - Ensuring that source documentation is a true reflection of decisions and actions taken for each

individual patient. - Completion of case report forms and ensuring relevant follow up data is collected (eg QoL data). - Monitoring and reporting all safety events: SAEs, SARs, SUSARs as outlined in the protocol, including

prompt reporting to Sponsor to ensure further communication with MHRA/REC if applicable within the statutory timelines.

- Liaising with the study sponsor regarding the conduct of the trial. - Educating patients/subjects and dissemination of trial related information to staff.

26

Data Managers/Research Assistants Non Clinical research support staff work closely with the research nurses and other members of the clinical team to ensure accurate and appropriate data collection. Their delegated responsibilities may include: - Ensuring that they have attended a site initiation meeting and received any appropriate training

necessary in order to conduct the trial safely and efficiently. - Entering subjects into clinical trials, utilising appropriate randomisation procedures when necessary. - Completing case report forms and other research records. - Ensuring that all data is available for monitoring visits. - Assisting with or completing submissions to Ethics/Research and Development. - Archiving all clinical trial related documents according to regulatory requirements. - Shipping blood and urine pharmacokinetic samples. - Entering data and updating fields/information within databases. Clinical Trials Pharmacist As the number and variety of trials continues to increase it is vital that there is a good communication between the sponsor, the research team and the trials pharmacist. This will ensure issues are raised and resolved at an early stage, allowing the trial to run smoothly and effectively. Early input from pharmacy in the planning of a clinical trial enables early recognition of potential pharmaceutical issues; pharmacy should be given a copy of the protocol at the earliest opportunity. The Clinical Trials Pharmacist will review: - The design of prescriptions so the correct trial supplies are ensured. - How the blinding of trial medication is to be achieved and maintained. - The requirement for documentation and record keeping. - Labelling requirements. - Drug receipt, delivery, reordering and stock checks. - The mechanism for continuation of supplies, if appropriate, once the trial period has finished. - Storage conditions for the trial medication. - Size of packaging, which has implications for storage space. - For parenterally administered products there may be a requirement for aseptic preparation. Organisations providing care - Must ensure the sponsor has assumed responsibility, research has been reviewed by appropriate

bodies, and that an authorised person has given written permission on behalf of the care organisation for the research to begin.

- Must arrange for researchers not employed by any NHS organisation to hold an NHS honorary contract.

- Must ensure adverse incidents are reported.

27

Substantial Protocol Amendments

Substantial amendments for MHRA approval:

During the conduct of a study it may be necessary to make changes to the study protocol. These may be

due to changes to the protocol, trial arrangements, the IMP and its manufacture, or if new data becomes

available that may affect the risks/benefits of the study or affect the safety of the subject.

The Sponsor is directly responsible for the processing of any amendments. At site the PI may carry out

urgent safety measures, such as temporarily halting the trial where subjects may be at risk, without prior

authorisation from the Sponsor. However this should be reported to the MHRA and Ethics Committee.

For all other substantial amendments, MHRA authorisation must be sought by the Sponsor before the

amendment is implemented.

All amendments should be processed using an Amendment Worksheet for version control purposes. All

amendments should also be recorded on an Amendment Log. These documents should be filed within

the Site File.

Guidance on what may be considered a substantial amendment is listed below:

Amendments related to the protocol

Purpose of trial

Design of trial

Informed consent

Recruitment procedure

Measures of efficacy

Schedule of samples

Addition or deletion of tests or measures

Number of participants

Age range of participants

Inclusion criteria

Exclusion criteria

Safety monitoring

Duration of exposure to the investigational medicinal product(s) (IMP)

Change of physiology of the IMP(s)

Change of comparator

Statistical analysis

28

Amendments related to the trial arrangements

Change of the principal investigator or addition of new ones (this means the lead investigator in each centre)

Change of the coordinating investigator

Change of the trial site or addition of new sites

Change of sponsor or legal representative

Change of the CRO assigned significant tasks

Change of the definition of the end of the trial

Amendments related to the IMP

Addition to stability data/change of expiry date

Change of formulation

Additional toxicology data

Change to route of synthesis

Manufacturer(s) of active substance

Manufacturing process of the active substance

Specifications of active substance

Manufacture of the medicinal product

Specification of the medicinal product

Specification of excipients where these may affect product performance

Shelf-life including after first opening and reconstitution

Major change to the formulation

Storage conditions

Test procedures of active substance

Test procedures of the medicinal product

Test procedures of non-pharmacopoeial excipients

29

Changes to clinical trial and human experience data where this is relevant to the ongoing trials (ie altered risk:benefit assessment) for example concerning:

Safety related to a clinical trial or human experience with the IMP

Results of new clinical pharmacology tests

New interpretation of existing clinical pharmacology tests

Results of new clinical trials

New interpretation of existing clinical trial data

New data from human experience with the investigational medicinal product

New interpretation of existing data from human experience with the investigational medicinal product

30

Non-substantial amendments

Non-substantial amendments do not have to be reported to the MHRA, but should be recorded

and be available upon request for inspection centrally and at the trial site. This would include

minor changes such as a change of telephone number.

Changes to non-clinical pharmacology and toxicology data where this is relevant to the ongoing trials (i.e. altered risk:benefit assessment. For example concerning:

Results of new pharmacology tests

New interpretation of existing pharmacology tests

Result of new toxicity tests

New interpretation of existing toxicity tests

Results of new interaction studies

31

Safety

Pharmacovigilance - “the recording and reporting of adverse events and reactions to medicinal products being used in a clinical trial”.

Throughout the duration of a clinical trial, data is collected to monitor the effects of the study and any

interventions on the participants, to ensure their safety and it is important to report any effects to

protect patients during the study. This information is collected and reviewed to assess the risk:benefit

ratio of any new treatments, or practices, used in a study and once it becomes standard care. For

example, the information leaflet that accompanies any medicines (giving information about the

medication and any possible side effects) has been produced from the safety information gathered

during and after the licensing of the drug.

Effects of study medication or interventions are recorded in the following categories:

Adverse Event (AE) - any untoward medical occurrence in a patient or clinical investigation subject administered a

pharmaceutical product and which does not necessarily have a causal relationship with this treatment

- protocol will specify whether it should be recorded on the CRF or not

Serious Adverse Event (SAE) Adverse events that: - result in death - are life-threatening - require in-patient hospitalisation or prolongation of existing hospitalisation - result in persistent or significant disability or incapacity - are a congenital anomaly or birth defect following maternal or paternal exposure - an event specified in the protocol as needing to be reported as serious - should be reported by fax to the sponsor within 24 hr of knowledge of event

Serious Adverse Reaction (SAR) - an event that is classed as serious and is consistent with the information provided about the

Investigational Medicinal Product - must be recorded in the CRF and reported annually to ethics and regulatory authorities

Suspected Unexpected Serious Adverse Drug Reactions (SUSAR) - if the nature or severity or frequency or outcome of the event is not consistent with the IMP

information - reporting of SUSARS must be expedited to main REC and MHRA

32

Human Tissue Act

Taken from Human Tissue Authority website – www.hta.gov.uk:

The Human Tissue Authority is an independent watchdog that protects public

confidence by licensing and inspecting organisations that store and use tissue for

purposes such as:

teaching about or studying the human body

carrying out post-mortem examinations

using human tissue to treat patients

carrying out research on human tissue

displaying human bodies or tissue in public (eg in a museum).

The HT Authority provides advice and guidance about the Human Tissue Act and the

Quality and Safety Regulations, (note: ‘Human Tissue Act 2006’ in Scotland).

Consent is the most important principle of the HT Act. Consent must be given for

bodies, body parts, organs and tissue to be stored and to be used for specific purposes

as set out in the HT Act and Q&S Regulations. The key principle of the HT Act is that a

person has the right to be asked for consent before any part of their body is used for

particular purposes. This applies whether the tissue comes from a living or a dead

person.

The HT Act uses the term ‘appropriate consent’ and this refers to the person who may give their consent. This could be the person from whom tissue is being taken, or if they are dead, by someone close to them, like a family member. For consent to be valid it must be given voluntarily and by a person who has the ability to make an informed decision. The person giving consent must also have the best information given to them so that they can make their decision. A person can also withdraw their consent at any time. An HTA licence is granted to an organisation if it shows it will comply with certain essential standards set down by the HTA. Organisations are inspected to check that they maintain good standards and follow appropriate procedures. Each licensed organisation has to nominate a person (Designated Individual) who will supervise the activities being carried out.

The Human Tissue Authority is funded by Department of Health and accountable to the

Secretary of State for Health.

33

Data Protection

Anyone processing personal data must comply with the eight enforceable principles of good practice.

They say that data must be:

Fairly and lawfully processed.

Processed for limited purposes.

Adequate, relevant and not excessive.

Accurate.

Not kept longer than necessary.

Process in accordance with the subject’s rights.

Secure.

Not transferred to countries without adequate protection.

Personal data covers both facts and opinions about the individual. It also includes information regarding

the intentions of the data controller towards the individual, although in some limited circumstances

exemptions will apply. With processing , the definition is far wider than before. For example, it

incorporates the concepts of obtaining, holding and disclosing.

The nature of research means that there is a large amount of paper and electronic data held about

research subjects.

All staff involved in research has a responsibility to their research subjects and their employer regarding

data protection.

All subject data should be stored in a secure room.

All subject data must be locked away if unattended.

No one should access subject data unless authorised to do so by research personnel and/or data

protection officer.

Subject confidentiality should be maintained by use of initials/numbers of on research material.

Electronic data must be password protected. In accordance with the Computer Security Policy.

Personal data that has the potential to identify research subjects should be kept in a secure

place.

Any concerns relating to data protection issues must be discussed with the departmental data protection

officer.

All staff should be stored in accordance with local NHS Trust policy.

34

Informed Consent

Within the context of clinical trials, valid informed consent may be regarded as:

The process by which a subject voluntarily confirms his/her willingness to participate in a particular

clinical trial, after having been informed of all aspects of the trial that are relevant to the subject’s

decision to participate.

When

It is morally and professionally unacceptable to perform any research related procedure on someone

without first obtaining their fully (valid) informed consent. The issue of valid informed consent has

prompted great discussion and thought, and really is a key issue in clinical research.

How

Informed consent should be obtained from subjects prior to any research related procedure being

performed. Consent is a continuous process not a one off event. Amendments or safety updates to a

study protocol and PIL will require re-consent of the patient/subject. Verbal consent during a study and

attendance at scheduled visits implies continued consent.

A designated Research Ethics Committee must have approved the consent process and

documentation for a particular study.

Informed consent form must be up to date and revised if new information becomes available

(must be re-approved by ethics committee if changed).

No coercion of subjects to participate.

Language of informed consent should be understandable and not cause subject to waive or

appear to waive or release investigator, institution or sponsor from responsibilities.

Inform subject of important information, including risks and side effects.

Language should be as non-technical as possible.

Allow subject time to review information before signing.

Allow time to answer questions and review issues raised by subject.

Consent form to be signed and dated by subject and person obtaining consent.

Subject must keep signed copy of consent.

Subject’s legal rights must be maintained.

It is essential to remember that even once a subject has signed an informed consent form, they can

withdraw from the trial at any time. It is the duty of the Investigator to reiterate this and reassure them

that they will not compromise their future medical care if they decide to withdraw.

35

Who

The issue of who should take consent has been debated at length. The guidance of the key GCP

documents, although helpful, is not clear.

The Declaration of Helsinki states: In any research on human beings, each potential subject must be

adequately informed of the aims, methods, anticipated benefits and potential hazards of the study and

the discomfort it may entail. He or she should be informed that they are at liberty to abstain from

participation in the study at any time. The Physician should then obtain the subjects freely given

informed consent, preferably in writing.

The EC guidelines state: The information to the patient should be given in oral and written form wherever

possible... and ... subjects must be allowed sufficient time to decide whether or not they wish to

participate.

It is widely acknowledged that other research personnel play a major role in the study team and are

often considered more approachable than the investigator. To this end, it would be foolish to exclude

them from the informed consent procedure/process. Although other research personnel may take part

in the consent process (explaining procedures, answering questions etc), responsibility for enrolling the

subject should lie with the investigator.

The investigator should ensure that subjects have fully understood what they are consenting to and sign

and date the consent form accordingly. Any research personnel involved in giving information during the

informed consent procedure should also sign the informed consent form.

This approach meets the criteria of the 3 key documents, and adheres to the Declaration of Helsinki. The

argument put forward by some, that the declaration is an old, almost obsolete document, is easily

refuted by the fact that it has had 5 separate reviews, (most recently 2000) and the informed consent

clause has not been changed and as such is considered appropriate.

36

STANDARD OPERATING PROCEDURES (SOPs) – Log

SOP Number SOP Title Review and understood

(date & initials)

37

SOP Number SOP Title Review and understood

(date & initials)

38

CLINICAL RESEARCH NURSE INDUCTION PROGRAMME

This Induction Pack forms part of the Clinical Research Nurse Induction Programme and includes

guidance to ensure that you and your line manager can:

Plan a comprehensive induction programme,

Gain an understanding of the core skills and knowledge needed to work in research;

Review the competencies and complete the Clinical Research Nurse Competency Tool, to set

learning objectives and identify training opportunities.

As a Clinical Research Nurse you will be providing specialist care that will have a potential benefit to your

patients as well as a benefit to future patients. The role of a Clinical Research Nurse is diverse, covers

many specialties and is increasingly becoming recognised as a specialty in its own right. It can be a

challenging role but is an opportunity to use the skills you have gained in clinical practice, combined with

new research skills that you will acquire that will establish your career as a Clinical Research Nurse.

You will be responsible for ensuring that your clinical trials are completed according to the study

protocol, that you perform any tasks which are delegated to you and that you have sufficient experience

and training to complete these tasks.

The most important elements of your role will be to provide a high standard of care and ensure patient

safety and to collect good quality data. The safety of your patients remains as important as it would in

a non-research role and poor data quality can affect the quality of the entire study.

This induction Pack is designed to give you the information you need at the outset. It aims to be a

comprehensive resource which you can refer back to throughout your career. It will form a foundation

to your learning and give you the opportunity to reflect upon this and signpost you to external resources

of further information, as your knowledge increases.

Training

In order to achieve your goals of patient safety and data quality and to adhere to legislative

requirements and research governance guidelines you will be required to complete Good Clinical

Practice (GCP) training. GCP training is mandatory for anyone working in clinical research. If you have

not completed GCP training before this is something that you will need to undertake as a priority during

the first month in post. GCP training can be undertaken as an online course or a full day classroom-

based course (NIHR Introduction to GCP) available several times per year within the Trust, University of

Leeds and through WYCLRN. Both ways have pros and cons but you may find it helpful to complete an

online course (which usually takes 3-4 hours) as soon as you can, followed by a full day course within the

first six months in post.

West Yorkshire CLRN offer a programme of training courses for clinical research nurses who are new to

research. This consists of 3 separate full day courses:

39

Introduction to GCP

Informed Consent

Introduction to Clinical Research

Details of these courses funded by the WYCLRN can be found on their website:

www.crncc.nihr.ac.uk/about us/ccrn/west yorks/news/training

The National Cancer Research Network has a training curriculum which can be viewed on

http://ncrndev.org.uk/index.php?option=com_content&task=view&id=142&Itemid=282 and can

sometimes be accessed by non-oncology researchers.

To record your professional development and to support the duties you are undertaking within your

studies it will be useful to set up a Training Folder (recommended inserts can be found in Appendix II).

This will demonstrate the experience you gain and training you complete as you progress through your

career. This should include a research CV (see appendix III) as well as copies of your GCP Certificate and

Informed Consent certificates as well as a copy of your job description.

Equipment

The equipment and resources that you will need to work in research will vary depending on the type of

studies you are involved in and whether or not research is new to your area or already established.

However, here is a suggestion of what you may find useful:

Desk, chair, PC, telephone

Fax machine (or access to a secure one)

Diary

Files to store any paper based data

Notebook and other general stationery items

Lockable filing cabinet(s)

Access to or use of:

Centrifuge (with training on safe use of this equipment)

Fridge

Freezer

Lab space

Photocopier

It is imperative that wherever possible research nurses or AHPs do not work in isolation. If you are a

lone worker in a particular area, please seek support and guidance from other experienced research

colleagues in other specialties. The R&D department and the Lead Nurse at WYCLRN can offer further

information.

40

Induction

It is important that you meet with your Line Manager to discuss the scope of your role, your previous

experience and ensure your Induction Programme covers all aspects of your role. Your Induction

Programme should include the following:

Familiarisation with working areas and induction into the building(s) as appropriate

Fire and evacuation procedures (attend Trust mandatory Fire Awareness Training)

Trust induction programme if new to Trust

ID badge and access procurement

Absence policy and arranging of annual leave

Clear understanding of line management and reporting

Information gathering around specialty area of practice, advice on key learning and sources of

appropriate information/courses

Allocation of a mentor or buddy for supervision and guidance

Familiarisation with data protection legislation and institutional policies

Internal governance procedures and quality assurance

Understanding the roles of RECs and R&D, and the statutory legislation for research governance

Understanding of research methods

How to describe randomisation and equipoise to potential subjects

Other trial related procedures, clinical and non-clinical

Introduction to multi-disciplinary team and attendance at MDT meetings where appropriate

Shadowing colleagues in clinical areas and for peer learning re research trial conduct

Introduction to blood sampling handling, processing, shipment

Dry ice handling and legislation/guidance

Familiarisation with departmental SOPs

Introduction to electronic information management systems

Participate in a monitoring visit

Pathway Co-ordinators (oncology)

Introduction to key staff:

Relevant consultants and wider medical team

Matron (or appropriate AHP line manager)

Directorate manager/faculty or R&D lead at University

R&D lead for specialty

Business Manager

Nursing and other local research colleagues

Outpatient or other patient areas to be utilised when conducting research

Administrative team and or wider research support staff as appropriate/available to your area

Example Induction Programme

Mon Tues Wed Thurs Fri

Week 1 Corporate Induction

– full day

Introduction to

Research Team

Local induction with

line manager

Meeting with PI

Meet with O/P

Clinic Sister

Visit by study

monitor

Meet with Lead

Nurse WYCLRN

Spend time with

Clinical Trials

Pharmacist

Study training with

research nurse

Week 2 Shadow Research

Nurse in clinic

NIHR Introduction to

GCP training

Attend new patient

clinic – OPD

Meet with CNS –

am

Shadow Research

Nurse in clinic

Attend Clinical

Research Forum –

12pm

Week 3 Lab training

Visit R&D Dept Attend Informed

Consent Training

Shadow Research

Nurse in clinic

Attend Inpatient

Service Team

Meeting

Week 4 Attend Directorate

Sisters meeting

Study training with

research nurse

SOP training with

line manager

Line Management Induction Programme Sign Off

Local Induction completed

Date:

Month 1 Induction Programme confirmed*

Date:

Competency Tool (Induction) reviewed and objectives set

Date:

Competency Tool (6 months) reviewed and objectives set

Date:

Competency Tool (12 months) reviewed and objectives set

Date:

Signature: Date: ______________________________

(Line Manager)

Signature: Date: ______________________________

(Research Nurse)

*It is your responsibility as well as your manager’s to ensure that you have a comprehensive Induction

Programme for the first month in post. This will be defined by the department you are based in and your

previous experience and therefore will need to be developed as part of your review.

43

Trial Design

Phases of Clinical Trials

Early Phase/Phase I Trials Phase 1 trials are the first test of a drug in humans; this typically involves a small number of participants in a gradual step wise approach, entering patients into dose cohorts, with careful assessment and evaluation before increasing the dose in further subjects. The main aim of such studies is to establish the safety profile, drug metabolism, disposition and tolerability in human subjects, building on existing preclinical data.

Phase II Trials Phase 2 trials aim to provide further safety information, adverse event management and information on drug activity (efficacy). These trials are normally used to determine dose regimens and obtain further safety data in a larger number of patients.

Phase III Trials Phase 3 trials are usually large scale comparative studies to look at the risks, benefits and side effects of a drug compared to or in combination with other drugs or placebo.

Phase IV Trials Phase 4 trials take place once the drug has been shown to be effective and has been granted a licence. These trials aim to find out how well the drug works when used more widely than in clinical trials, the long term risks and benefits and gain more information on the possible side effects and safety of the drug.

44

Clinical Trials Flow Chart

Team Review Feasibility assessment by team members

↓

Peer Review Written peer review to go with ethics submission (this will have been

done internally for commercially sponsored studies)

↓

Costing Resources, time, labs, tests etc

↓

Clinical Trial Review Process Obtain feedback from relevant staff and departments on their ability to

meet the requirements of the protocol

↓

ARSAC/IRMER Administration of Radioactive Substances Advisory Committee Ionising Radiation (Medical Exposure)Regulations

↓

EudraCT number Unique number issued or each trial from a database held by the

European Medicines Agency

↓

CTA Clinical trial agreement from the competent authority

(In the UK this is the MHRA)

↓

NHS Directorate or University Faculty Signoff

↓

IRAS process

↓

CSP Local R&D approval

45

Case Report Form Completion

A CRF is a record of all the data and other information on each subject required by the research protocol. The

ICH-GCP guidelines include strict guidance relating to CRF completion, as they are the official documentation

of the trial for the authorities. The CRFs, along with source documentation are closely examined in the event

of audit and inspection.

The CRF should collect necessary information about:

The enrolled subject.

Administration of the study drug or intervention.

Study specific procedures.

The outcome of any assessments.

Details of any adverse events, serious adverse events and SUSARs.

Only those personnel identified by the principal investigator should complete CRFs. These can include:

Co-investigators

Clinical trial practitioners

Research nurses/AHP

Anyone completing a CRF should have completed the signature delegation log in the Investigator file, and

provided a signed and dated copy of their CV.

CRFs should be completed as soon as possible after the associated visit/patient assessment to ensure that the

information is up to date and accurate. Before any monitoring or audit visits, it is essential to ensure that

CRFs are as up to date as possible.

There are guidelines to CRF completion with each study protocol. Some general points are given here for

reference.

Paper CRF

Always use a black ball point pen to complete paper CRFs.

If the CRF is on carbonless duplication paper, ensure that an appropriate separator is inserted.

Never leave blank spaces. If a section cannot be completed write, as appropriate, not known, not

certain, test not done.

46

All entries must be legible:

o Cross out incorrect entry with a single line, so that the original entry is still legible

o Enter the correct data

o Initial and data correction

o If it is not obvious, then give an explanation for alterations

The CRF for each patient MUST be signed off by the principle investigator to indicate that they believe

that they are complete and correct.

Electronic CRF

Adequate online training with the system to be used is required and will be facilitated by the study

sponsor.

A password will be issued to each individual authorised to access the system to enter data and should

be kept safe and never shared with others.

Data should be entered as soon as possible after the subjects scheduled visit.

Corrections and query resolution is auditable through the electronic system.

Provision is required at site to facilitate monitoring visits. And access to the electronic system.

Computers should not be left unattended with patient data on screen even though anonymised.

Adherence to the relevant data protection legislation is mandatory.

CRF completion is one of the most important roles of the clinical trials co-ordinator, as it is the only source of

data that will be received by the sponsor company. Therefore, accurate and thorough completion is essential.

Source documentation

Many items of data generated during routine and study related care episodes constitute source

documentation. For example, blood results, radiology reports, pharmacy prescriptions, letters in medical

notes, hand written notes in the patients record all constitute primary source data.

The development of study related source data sheets to capture relevant data items at designated study visit

time-points are helpful in ensuring that items are not overlooked or missed in error and can significantly

improve data quality overall. Such source sheets then also become primary source data and should be

retained with the subject’s medical notes for monitoring and data verification. If source data sheets are

created they need to be version controlled and signed and data on completion of primary data entry.

47

Essential Documents for the Conduct of a Clinical Trial

A Trial Master File (TMF) should be established before the start of a study. The TMF is a filing system, rather than a single file, that includes essential documents as defined by ICH-GCP that demonstrate the entire conduct of the study from beginning to end. Before the Clinical Phase of the Trial Commences During this planning stage the following documents should be generated and should be on file before the trial formally starts

Title of Document Purpose Located in Files of Investigator/ Institution

Sponsor

Investigator’s brochure To document that relevant and current scientific information about the investigational product has been provided to the investigator

X X

Signed protocol, amendments, sample case report forms

To document investigator and sponsor agreement to the protocol/amendment(s) and CRF

X X

Information given to trial subject: X X

Consent form (including all applicable translations)

Any other written information

Advertisement for subject recruitment

To document the informed consent To document that subjects will be given appropriate written information (content and wording) to support their ability to give fully informed consent To document that recruitment measures are appropriate and not coercive

X

X

X

Financial aspects of the trial To document the financial agreement between the investigator/institution and the sponsor for the trial

X X

Insurance statement (where required) To document that compensation to subject(s) for trial-related injury will be available

X X

Signed agreement between involved parties:

Investigator/institution and sponsor

Investigator/institution and CRO

Sponsor and CRO

Investigator/institution and authorities

To document agreements

X

X

X

X

X X X

Dated, documented approval/ favourable opinion of IRB/IEC:

To document that the trial has been subject to IRB/IEC review and given

X

X

48

Title of Document Purpose Located in Files of Investigator/ Institution

Sponsor

- protocol and any amendments - CRF (if applicable) - informed consent form(s) - any other written information to be

provided to the subject(s) - advertisement for subject recruitment

(if used) - subject compensation (if any) - any other documents given approval/

favourable opinion

approval/favourable opinion. To identify the version number and date of the document(s).

Institutional Review Board/ Independent Ethics Committee Composition

To document that the IRB/IEC is constituted in agreement with GCP

X X (where required)

Regulatory authorisation/approval/ notification of protocol (where required)

To document appropriate authorisation/approval/notification by the regulatory authority(ies) has been obtained prior to initiation of the trial in compliance with the applicable regulatory requirement(s)

X (where required)

X (where required)

Curriculum Vitae and/ or other relevant documents evidencing qualifications of investigator(s) and sub-investigator(s)

To document qualifications and eligibility to conduct trial and/or provide medical supervision of subjects

X X

Normal value(s) / range(s) for medical/laboratory/technical procedures and or tests included in the protocol

To document normal values and / or ranges of the tests results

X X

Medical laboratory/technical procedures/tests

- certification or - accreditation or - established quality control and/or

external quality assessment or - other validation

To document competence of facility to perform required test(s), and support reliability of results.

X (where

required)

X

Sample of labels attached to investigational product containers

To document compliance with applicable labelling regulations an appropriateness of instructions provided to the subjects.

X

Instructions for handling of investigational products and trial related materials

To document instructions needed to ensure proper storage, packaging, dispensing and disposition of investigational products and trial.

X X

49

Title of Document Purpose Located in Files of Investigator/ Institution

Sponsor

Shipping records for investigational products and trial related materials

To document shipment dates, batch numbers and method of shipment of investigational products and trial related materials. Allows tracking of product batch, review of shipping conditions, and accountability.

X X

Certificates of analysis of investigational products shipped

To document identity, purity and strength of investigational products to be used in the trial.

X

Decoding procedures for blinded trials To document how, in case of an emergency, identity of blinded investigational product can be revealed without breaking the blind for the remaining subjects’ treatment.

X

X(third party if

applicable)

Master randomisation list To document method for randomisation of trial population

X (third party if

applicable)

Pre-trial monitoring report To document that the site is suitable for the trial

X

Trial initiation monitoring report To document that trial procedures were reviewed with the investigator and the investigator’s trial staff

X X

50

During the Clinical Conduct of the Trial

Title of Document Purpose Located in files of Investigator/Institution

Sponsor

Investigators brochure updates To document that investigator is informed in a timely manner of relevant information as it becomes available

X X

Any revision to: - protocol/amendments and CRF - informed consent form - any other written information

provided to subjects - advertisement for subject

recruitment (if used)

To document revisions of these trial related documents that take effect during trial

X X

Dated, documented approval/favourable opinion of IRB/IEC of the following:

- protocol amendments - revision of - informed consent form - any other written information to

be provided to the subject - advertisement for subject

recruitment (if used) - any other documents given

approval/favourable opinion - continuing review of trial (where

required)

To document that the amendments and or revisions have been subject to IRB/IEC review and were given approval/favourable opinion. To identify the version number and date of the documents.

X X

Regulatory authorities authorisations/approvals/notifications where required for:

- protocol amendments and other documents

To document compliance with applicable regulatory requirements

X X (where required)

Curriculum vitae for new investigators and or sub-investigators

X X

Updates to normal values/ranges for medical/laboratory/technical procedures/tests included in the protocol

To document normal value and ranges that are revised during the trial

X X

Updates of medical/laboratory/technical procedures/tests

- certification or - accreditation or - established quality control and/or

external quality assessment or - other validation (where required)

To document that tests remain adequate throughout the trial period

X X (where required)

Documentation of investigational products and trial related materials shipment

X X

Certificates of analysis for new batches of X

51

Title of Document Purpose Located in files of Investigator/Institution

Sponsor

investigational products

Monitoring visit reports To document site visits by, and findings of, the monitor

X

Relevant communications other than site visits

- letters - meeting notes - notes of telephone calls

To document any agreements or significant discussion regarding trial administration, protocol violations, trial conduct, adverse event reporting

X X

Signed informed consent forms To document that consent is obtained in X accordance with GCP and protocol and dated prior to participation of each subject in trial. Also to document direct access permission.

X

Source documents To document the existence of the subject and X substantiate integrity of trial data collected. To include original documents related to the trial, to medical treatment, and history of subject.

X

Signed, dated and completed case report forms

To document that the investigator or authorised member of the investigator’s staff confirms the observations recorded.

X (copy) X (original)

Documentation of CRF corrections To document all changes/additions or corrections made to CRF after initial data were recorded

X (copy) X (original)

Notification by originating investigator to sponsor of serious adverse events and related reports

Notification by originating investigator to sponsor of series adverse events and related reports

X X

Notification by sponsor and/or investigator to regulatory authorities and IRB/IEC of unexpected serious adverse drug reactions and of other safety information

Notification by sponsor and/or investigator, where applicable, to regulatory authorities and IRB/IECs of unexpected serious adverse drug reactions and of other safety information.

X (where required)

X

Interim or annual reports to IRB/IEC and authorities

Interim or annual reports provided to IRB/IEC and to authorities

X X (where required)

Subject screening log To document identification of subjects who entered pre-trial screening

X X (where required)

Subject identification code list To document that investigator keeps a confidential list of names of all subjects allocated to trial numbers on enrolling in the trial. Allows investigator to reveal identity of any subject.

X

52

Title of Document Purpose Located in files of Investigator/Institution

Sponsor

Subject enrolment log To document chronological enrolment of subjects by trial number.

X

Investigational products accountability at the site

To document that investigational products have been used according to the protocol.

X X

Signature sheet To document signatures and initials of all persons authorised to make entries and/or corrections on CRFs

X X

Record of retained body fluids/tissue samples

To document location and identification of retained samples if assays need to be repeated.

X X

After completion or termination of the trial

Title of Document Purpose Located in files of

Investigator/Institution

Sponsor

Investigational products accountability at site

To document that the investigational products have been used according to the protocol. To document the final accounting of investigational products received at the site, dispensed to subjects, returned by the subjects, and returned to sponsor.

X X

Documentation of investigational product destruction

To document destruction of unused investigational products by sponsor or at site.

X (if destroyed at

site)

X

Completed subject identification code list To permit identification of all subjects enrolled in the trial in case follow up is required. List should be kept in a confidential manner and for agreed upon time.

X

Audit certificate (if available) To document that audit was performed.

X

Final trial close out monitoring report To document that all activities required for trial close out are completed, and copies of essential documents are held in the appropriate files.

X

Treatment allocation and decoding documentation

Returned to sponsor to document any decoding that may have occurred.

X

53

Title of Document Purpose Located in files of Investigator/Institution

Sponsor

Final report by investigator to IRB/IEC where required, and where applicable, to the regulatory authorities

To document completion of the trial. X

Clinical study report To document results and interpretation of trial.

X X

International Conference on Harmonisation of Technical Requirements for Registration of

Pharmaceuticals for Human Use (1996) ICH Harmonised Tripartite Guideline for Good Clinical Practice E6

(R1): http://www.ich.org/LOB/media/MEDIA482.pdfBBC

54

55

Clinical Research Nurse Competency Tool: Purpose of this document: This document has been developed to be a working tool for Clinical Research Nurses (CRNs) and their line managers to assess and review CRN competencies and is based directly on the Competency Framework for Clinical Research Nurses, A tool to promote patient safety and quality data (October 2011). Competencies are the essential skills and knowledge required by nurses to carry out their work in a safe and effective way. The competencies within this document have been identified as those unique to the role of a Clinical Research Nurse and are intended to provide clear guidance on the scope of this role and define the differences between bands 5 through to 8. How to use this document: During the first month in post the Clinical Research Nurse and their Line Manager should review the competencies together. The worksheets titled ‘Induction’ should be used to review the CRN competencies and should be used to identify personal objectives together with any training needs to form part of the CRN’s developmental plan. It is recommended that a review of the competencies is conducted at 6 months and again at 12 months using the ‘review worksheets’. The higher level of assessment target at 12 months demonstrates the level of knowledge and skills acquisition that should have occurred during the first 12 months in post.

What is a competency? The Competency Framework for Clinical Research Nurses defines competency as: “the ability to demonstrate the application of knowledge, understanding, practical and thinking skills to achieve effective performance in a professional or occupational role. This involves problem solving and

being sufficiently flexible to meet changing demands”. Further details on the use of competencies can be found in the Competency Framework.

56

The competencies

Competence 1

To demonstrate understanding of the background, political influence and strategy regarding clinical research in the UK

Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation

2.1 Understands the role and remit of research ethics committees in the UK

2.2 Contributes to the preparation of documentation and submissions of applications for ethical approval

Competence 3 To understand, apply and promote the principles and practice of

obtaining valid informed consent

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant-focused clinical research

4.1 Contributes to the development of safe clinical research

4.2 Contributes to efficient use of resources

4.3 Contributes to the delivery of clinical research

4.4 Contributes to the safe collection and storage of data and accurate completion of study documentation

57

Competence 1: To demonstrate understanding of the historical

background, political influence and strategy regarding clinical

research in the UK

Skills and behaviours Knowledge and understanding KSF

Understands the relevance of the historical development of clinical research to current research and policy.

Understands the current political context and relevant policy.

Champions the role of clinical research to the development of health, social care and the wealth of the nation.

Supporting and influencing the embedding of clinical research in NHS infrastructure / practice.

History of ethics related to clinical research [2-18].

Development of research ethics and governance [19-23].

Methodological developments in clinical research [24-27].

Political and strategic developments in clinical research [19, 28-34].

C1 C2 C3 C5 G5

Examples:

Band 5

Recognises the importance of acknowledging the historical context within which clinical research is undertaken.

Band 6 Articulates the significance of major historical events, publications and

policy developments in the evolution of clinical research, including political imperatives and government strategies.

Band 7 Demonstrates comprehensive knowledge and understanding of the historical context, political influence and strategic developments relating to the evolution of clinical research.

Band 8 Takes a leading role in supporting understanding of the historical and political context in which clinical research has developed and is currently being undertaken.

58

Competence 2: To work within the regulations framework

2.1 Understands the role and remit of research ethics committees in the UK

Skills and behaviours Knowledge and understanding KSF

Recognises the need to ensure

that appropriate ethical opinions and governance approvals are obtained before any research activities are undertaken.

Articulates understanding of regulatory requirements.

Undertakes relevant educational activities [35-40].

Structure and policy for the regulation of research [41-42].

Roles and responsibilities of RECs [19, 31-32, 43-47].

Structure and organisation of RECs and their membership [19, 41-44].

Structure and organisation of R&D Departments, their membership and their roles and responsibilities [31-32].

Processes for the submission of applications and their review [19, 29, 43-44, 46, 48-51].

Local policies and procedures related to ethical review and research governance [29, 31-32, 48].

Local and national policy developments [52-54].

Roles and responsibilities of investigators and other members of the research team [31-32].

Knowledge of procedures when breaches of protocol are identified or when fraud and misconduct is suspected [29, 39, 46, 48-49].

Actions required when processes to protect participant confidentiality are not followed.

C1 C2 C3 C5 G5

Examples:

Band 5 Understands the need for favourable ethical opinion and research and governance approval to be obtained before commencing research activities.

Has an awareness of the structure, roles and function of RECs and R&D Departments.

Knows how to raise concerns and report instances of protocol deviation.

Band 6 Contributes to the development of research protocols.

Has knowledge and understanding of structure, roles and function of RECs and R&D Departs.

Has Knowledge of local R&D policies and procedures.

Has familiarity with regulatory requirements.

Act as a knowledgeable resource and advisor to staff and researchers.

Contributes to supervision and meeting educational needs of staff.

Band 7 Provides comprehensive advice and guidance on matters relating to research ethics and governance.

Act as a resource to staff & contributes to the professional & educational development of staff.

Leads on the development and updating of local policies and procedures.

Leads on the professional and educational development of staff.

Band 8

Demonstrates leadership by:

Act as an expert resource to staff and researchers.

Leading on the professional and educational development of staff.

Ensuring appropriate reporting at the organisation executive board level.

Competence 2: To work within the regulations framework

2.2 Contributes to the preparation of submissions for regulatory reviews

59

Skills and behaviours Knowledge and understanding KSF

Aware of application processes and requirements for document management.

Leads or contributes to the preparation of paperwork and submission of applications.

REC and R&D application processes (IRAS) [19, 44, 55-57].

Other centralised permissions [58].

Key documentation required to support REC and R&D submissions [19, 56].

Protocol development.

Local review and reporting of research studies [59].

Clinical Research Agreements [60-61].

Risk assessment and feasibility.

Local and national policy developments.

Research sponsorship and researcher roles [31-32, 48, 56].

Professional responsibilities and potential for conflict with research role [62].

C1 C2 C3 C5 G5 HWB2

Examples:

Band 5 Articulates the importance of clear, complete and accurate submissions.

Familiar with application processes.

Band 6 Act as a knowledgeable resource for staff and researchers making applications for regulatory approvals.

Raises concerns and seeks to address incomplete, inaccurate or misleading documentation.

Contributes to supervision and meeting the educational needs of staff.

Band 7 Act as expert resource for staff and researchers preparing submissions for regulatory approval.

Prepares, or makes significant contribution to the preparation of applications for regulatory approval.

Contributes to the professional and educational development of staff and researchers.

Band 8 Ensuring that all processes, policies and standard operating procedures are in place.

Contributing to quality assurance.

Leading and taking responsibility for research in position of PI or CI.

60

Competence 3: To understand, apply and promote the principles and practice of

obtaining and maintaining valid informed consent

Skills and behaviours Knowledge and understanding KSF

Assures the provision of an environment conducive to obtaining valid informed consent.

Contributes to policy and practice development.

Aware of and is responsive to factors contributing to decision making during the consent process.

Assures patient safety by proactively managing any breaches of the informed consent process.

Principles of informed consent for participation in research [18, 63-65].

Roles of researchers, including CI and PI, in gaining and maintaining informed consent [31-32].

Role of research nurses [31-32, 40, 66-69].

Role of the REC [19, 42-43, 70-71].

Key information required in PIS and CF [19, 72-75].

Ongoing nature of informed consent.

Legal requirements related to gaining and maintaining valid informed consent, especially when participants lack capacity [76-80].

Local policies and procedures relating to gaining and maintaining valid informed consent.

C1 C2 C3 C4 C5 C6 HWB2 HWB3

Band 5 Effectively engages with research participants to ensure understanding of info about the

research.

Demonstrates an awareness of the factors contributing to a participant’s autonomous decision making during the consent process.

Complies with the informed consent processes as described in the approved protocol, including use of approved versions of PIS and CF.

Raises any concerns about the informed consent processes.

Recognises own learning needs and takes responsibility for maintaining up to date knowledge.

Provides evidence of training and understanding.

Recognises that informed consent is an ongoing process.

Band 6 Demonstrates a sound understanding of the need to identify issues which may impact on the process of gaining valid informed consent. Plans and implements actions to resolve these issues.

Receives informed consent when appropriate and as agreed in the approved protocol.

Supports participants through the consent process.

Band 7 Act as an expert resource to provide in-depth knowledge to acquire and maintain informed consent.

Contributes to the mentorship and monitoring of consent procedures.

Responsible for the reporting of poor consent processes that compromise patient safety and the study protocol.

Band 8 Demonstrates leadership by:

Attending and reporting to corporate boards regarding governance, policy and service development related to research.

Holding responsibility for the training and monitoring of correct consent processes in research.

Developing systems to ensure that correct procedures are adhered to.

Contributing to professional development and education of clinical research staff in the organisation.

Competence 4: To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research

61

4.1 Contribute to the development and facilitation of clinical research

Skills and behaviours Knowledge and understanding KSF

Has an understanding of the research designs and methodologies used in clinical research.

Understands the implications for practice of the regulatory and legal frameworks related to the planning, delivery and closure of clinical research studies.

Has a comprehensive knowledge and understanding of the regulatory and legal frameworks related to the planning, undertaking and closure of clinical research studies.

Encourage, appreciate and value the contribution of study participants in all areas of research activity.

The role of the National Institute of Health Research (NIHR) [48, 52, 81].

The need for Quality Assurance [82-83].

Phases of clinical research [84-85].

Different research study designs: including protocol design and development; sample size and power; inclusion and exclusion criteria; randomisation; blinding and unblinding [49, 81, 86-88].

Translational research [89-90].

Multi-centre studies.

Management processes from feasibility to closure [49, 91]

Pharmacovigilance [92-93].

Local, national and international dissemination of clinical research findings [94-97].

Relevant UK legislation [76, 98-103].

Professional codes of practice [62].

Roles of licensing authorities and the licensing of investigational products [29, 104-105].

Local requirements, policies and procedures.

C1 C2 C3 C5 G5

23

62

Examples:

Band 5 Consistently adheres to the study protocol design.

Raises concerns if design conflicts with regulatory frameworks and legal requirements or if research activities deviate from the study protocol.

Recognises own limitations and attends/completes relevant training (including GCP). Is supportive in the training of others.

Demonstrates an awareness of the need for patient and public involvement (PPI) in clinical research. This could include their involvement in any aspect of the research process.

Band 6 Act as a knowledgeable resource for staff, researchers, research participants and patients.

Contributes to the training and supervision of staff and researchers.

Contributes to the development of local policies related to all parts of the clinical research process.

Promotes and facilitates PPI in all aspects of clinical research.

Contributes to nurse led research.

Band 7 Act as an expert resource for staff, researchers, research participants and patients.

Demonstrates a detailed knowledge and understanding of different research designs and methodologies and the regulatory and legal frameworks related to clinical research studies.

Leads on the training and ensuring the appropriate supervision of staff.

Leading role in the development and updating of local policies and procedures.

Contributes to the development of national policies and procedures.

Leads in planning, conducting and supervising nurse led research.

Band 8 Demonstrates leadership by:

Playing an integral role in R&D for a, (locally, nationally and internationally).

Contributing strategically on all areas of clinical research.

Political astuteness.

Professional leadership.

Efficient and effective networking skills.

Further development of clinical research.

Prioritising competing needs.

Contributing to the professional development and education of clinical research staff and organisations.

Contributing to or leading clinical research.

25

63

4.2 Contribute to effective and efficient use of resources

Skills and behaviours Knowledge and understanding KSF

Has an awareness of the financial issues related to the planning and conducting of clinical research.

Recognises their role and contribution to the local and national strategic vision.

Funding of research studies [106].

Financial agreements [60-61].

Financial management during the course of a clinical research study [91].

Identification of costs [107].

Role of the research funder [31-32].

National and local research costing models.

Local employment policies and models of working.

C2 G5

Examples:

Band 5 Consistently operates within the financial constraints of the funding available for a clinical research study.

Alerts relevant personnel to potential escalating consumable and other costs associated with a clinical research study.

Is aware of different staff roles and responsibilities regarding resources.

Band 6 Contributes to the financial processes of planning, running and closing clinical research studies.

Band 7 Involved in the financial processes associated with coordinating research studies and grant applications.

Act as an expert resource for staff in relation to the financial management of clinical research studies.

Uses expert judgment in relation to competing demands for funding.

Involved in the management of staff as a resource.

Band 8 Demonstrates leadership by:

Building alliances and working partnerships.

Enhancing Institutional reputation

Skill mix review.

Contributing to the professional development of the workforce.

Contributing to the acquisition of grant income and identification of

other potential funding streams.

Cost recovery systems.

64

4.3 Facilitate the delivery of clinical research

Skills and behaviours Knowledge and understanding KSF

Contributes to the delivery of clinical research protocols as a member of the research team.

Understands the rationale behind adherence to ethical approved study protocols.

Demonstrates safe and effective care of patients and/or research participants in research.

Awareness of policies relating to Investigational Medicinal Products (IMP).

Recognise the importance of accurate and comprehensive source documentation.

Demonstrate a good understanding of GCP in relation to direct patient/participant care.

Local Medicines Policy.

Quality Assurance [82].

Standard Operating Procedures (SOPs) [108].

Relevant clinical skills in line with local procedures and national occupational standards [31-32].

Knowledge of research study protocol.

Processes for participant recruitment.

Risk Management.

Public involvement in research [87].

Importance of submitting recruitment figures to relevant bodies, including NIHR recruitment data [29, 52].

Local organisational policies and procedures.

C1 C2 C3 C5 Ik2 G5 G6

Band 5 Is able to correctly use and dispose of study supplies and equipment, in accordance with study protocol and relevant Standard Operating Procedures (SOPs).

Completes accurate paperwork associated with research study supplies.

Attends relevant training in relation to requirements of research study protocol.

Consistent application of relevant clinical and research skills.

Contributes to an active and effective research culture.

Band 6 Actively involved in the ordering of supplies, ensuring that resources (including staff and beds) are available for the effective conduct of the research study.

Ensures clear and accurate documentation is maintained on the arrival, use and disposal of research study supplies.

Advises staff and researchers, acting as a knowledgeable resource on matters relating to clinical practice and research, promoting an active and effective research culture.

Contributes to the development and training of staff and researchers.

Contributes to the development of SOPs.

Band 7 Takes a leading role in managing research studies.

Supports colleagues and researchers through the research study process, including clinical aspects associated with the research study.

Takes the lead on developing and updating SOPs.

Takes a leading role in activities of professional fora and networks.

Contribute to local recruitment strategies.

Band 8 Demonstrates leadership by: Having wider oversight and strategic vision.

Actively seeking to collaborate and share best practice to enhance delivery of clinical research.

Promoting effective recruitment strategies to increase recruitment in line with local/national targets.

4.4 Contribute to the safe collection and storage of data and accurate

completion of study documentation

65

Skills and behaviours Knowledge and understanding KSF

Undertakes, supervises and manages

the accurate and complete collection of data and insertion of data into Case Report Forms (CRFs) or other research storage formats.

Ensures the safe and secure storage of data.

Has a comprehensive understanding of the roles and responsibilities of key personnel within the clinical research environment.

Facilitating the monitoring process.

Ensures participant’s confidentiality.

Roles of those involved in all aspects of research [31-32, 66, 68, 109-111].

Data insertion techniques, including the use of electronic data entry.

Audio and other media as means of data.

Source document verification.

Fraud and misconduct [112].

Audit and monitoring of data [113].

The process of inspections [113].

Local and national policies and procedures relating to data collection and safe transfer [111, 114-120].

Local Caldicott guardian and local information governance policy [121].

Actions required when processes to protect confidentiality are not adhered to [116-117].

C1 C3 C5 Ik2 G5 HWB2

66

Examples:33 Band 5 Evidence of accurate and complete data collection and entry.

Adherence to requirements of ethically approved protocol.

Raises concerns if inaccurate or incomplete data entry is suspected.

Takes appropriate action in event of adverse events.

Contributes to the safe and secure storage of research data.

Consistently works within own role and adheres to the roles and responsibilities documentation.

Is aware of own role limitations and escalates up when necessary.

Understands the roles and responsibilities of others involved in clinical research.

Addresses non adherence to defined protocol/policies by timely and appropriate reporting.

Consistently adheres to requirements to protect confidentiality.

Raises concerns when processes to ensure confidentiality are not adhered to.

Band 6 Advises staff and researchers on data collection, data entry and safe data storage.

Responds to concerns if inaccurate or incomplete data entry is suspected.

Contributes to supervision and meeting the professional and educational needs of staff.

Contributes to study closure and archival preparation.

Act as a knowledgeable resource and contributes to the development and training of staff and researchers.

Contributes to the development and updating of local policies and procedures.

Band 7 Contributes to the development of local policies and procedures.

Ensures that local policies and procedures are followed by all members of the research team.

Contributes to the auditing and monitoring of research studies and responds to recommendations.

Takes an active lead in the setting up, coordination and management of clinical research studies.

Act as an expert resource for staff and researchers.

Takes an active role in developing and updating local and national policies and procedures.

Actively involved in local and national forums and networks related to clinical research and the nurse’s role in that clinical research.

Ensures that processes and procedures for ensuring participant confidentiality are developed and adhered to.

Band 8 Demonstrates leadership by:

Leading on the professional and educational development of staff.

Involvement in local implementation of national directives and policies.

Driving quality assurance measures and appropriate policies to enhance clinical research activity.

Involved in appropriate reporting at the organisational level.

67

Assessment Levels

Level 1 Is competent with assistance and supervision

Level 2 Is competent with supervision

Level 3 Is competent and autonomous with minimal assistance and supervision

Level 4 Supports, trains and supervises others

Band 5

Band 6

Band 7

Band 8

68

Induction Review Date

Competence 1 To demonstrate understanding of the background, political influence and strategy regarding clinical research in the UK

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

69

Induction Review Date

Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.1 Understands the role and remit of research ethics committees in the UK.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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Induction Review Date

Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.2 Contributes to the preparation of documentation and submissions of applications for ethical approval.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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Induction Review Date

Competence 3 To understand, apply and promote the principles and practice of obtaining valid informed consent.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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Induction Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.1 Contribute to the development of safe clinical research.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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Induction Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.2 Contributes to efficient use of resources.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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Induction Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.3 Contributes to the delivery of clinical research.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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Induction Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.4 Contributes to the safe collection and storage of data and accurate completion of study documentation.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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6 Month Review Date

Competence 1 To demonstrate understanding of the background, political influence and strategy regarding clinical research in the UK.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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6 Month Review Date

Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.1 Understands the role and remit of research ethics committees in the UK.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

6 Month Review Date

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Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.2 Contributes to the preparation of documentation and submissions of applications for ethical approval.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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6 Month Review Date

Competence 3 To understand, apply and promote the principles and practice of obtaining valid informed consent.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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6 Month Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.1 Contribute to the development of safe clinical research.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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6 Month Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.2 Contributes to efficient use of resources.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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6 Month Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participants focused clinical research. 4.3 Contributes to the delivery of clinical research.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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6 Month Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.4 Contributes to the safe collection and storage of data and accurate completion of study documentation.

Target Band 5 1 Band 7 2 Level achieved:

Band 6 1 Band 8 3

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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12 Month Review Date

Competence 1 To demonstrate understanding of the background, political influence and strategy regarding clinical research in the UK.

Target Band 5 2 Band 7 3 / 4 Level achieved:

Band 6 3 Band 8 4

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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12 Month Review Date

Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.1 Understands the role and remit of research ethics committees in the UK.

Target Band 5 2 Band 7 3 / 4 Level achieved:

Band 6 3 Band 8 4

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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12 Month Review Date

Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.2 Contributes to the preparation of documentation and submissions of applications for ethical approval.

Target Band 5 2 Band 7 3 / 4 Level achieved:

Band 6 3 Band 8 4

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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12 Month Review Date

Competence 3 To understand, apply and promote the principles and practice of obtaining valid informed consent.

Target Band 5 2 Band 7 3 / 4 Level achieved:

Band 6 3 Band 8 4

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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12 Month Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.1 Contribute to the development of safe clinical research.

Target Band 5 2 Band 7 3 / 4 Level achieved:

Band 6 3 Band 8 4

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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12 Month Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.2 Contributes to efficient use of resources.

Target Band 5 2 Band 7 3 / 4 Level achieved:

Band 6 3 Band 8 4

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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12 Month Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participants focused clinical research. 4.3 Contributes to the delivery of clinical research.

Target Band 5 2 Band 7 3 / 4 Level achieved:

Band 6 3 Band 8 4

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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12 Month Review Date

Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.4 Contributes to the safe collection and storage of data and accurate completion of study documentation.

Target Band 5 2 Band 7 3 / 4 Level achieved:

Band 6 3 Band 8 4

Evidence at review:

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:

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▼ Appendix I - Research Professional Forum, Terms of Reference

Aims of the Research Practice Network

To bring together nurses and midwives in the Trust who have an interest in research To raise the profile of research nurses and midwives in the Trust To act as a forum to discuss the managerial needs of research nurses and midwives in the

Trust To support the professional development and educational needs of Trust nurses and

midwives involved in research To develop the research capability and capacity of research nurses and midwives in the Trust To act as a forum to share best practice To act as a forum to present existing research projects and to share ideas for future projects

to strengthen the research profile in nursing and midwifery research in the Trust To promote the dissemination and translation of research findings into practice, locally,

nationally and internationally

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Training folder sections

In order to demonstrate your ongoing professional development

and research experience, it is recommended that you maintain a

training folder. The following headings are recommended for use

to organise this document:

1. Name and Position, Copy of Job Description

2. Signed and Dated CV

3. List of Professional Associations

4. GCP Training Certificates and Research Specific

Competencies

5. Publications and Presentations

6. Continuing Education and Professional Development Log

7. Trust Mandatory Training

8. Professional and Higher Educational Certificates

9. Miscellaneous

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Appendix III - Research CV Template

SUBMISSION OF CURRICULUM VITAE (CV) TO RESEARCH ETHICS COMMITTEES AND NHS R&D OFFICES

Guidance for applicants

Your CV needs to demonstrate that you are qualified by education, training and experience to

conduct the research.

A standard template for an investigator CV is set out below. This template would be suitable for

submission of CVs by:

Chief Investigators (for submission with main REC application)

Local Principal Investigators (for submission with the Site-Specific Information Form to RECs and NHS R&D offices)

Academic supervisors (for submission with student applications).

The template is issued as guidance and is not intended to be prescriptive. Use of the template is not

a requirement for a valid application.

The NRES Standard Operating Procedures state that CVs should be a maximum of 2 pages. This is

also guidance and is not an absolute requirement.

It is important that experience relevant to the specific research project is fully summarised, but the

overall document should be kept concise. It is not necessary to provide a complete record of the

applicant’s professional and academic background. In particular, CVs should not include lengthy lists

of publications.

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This template is recommended by NRES and the NHS R&D Forum for applications both for ethical review and R&D approval.

CURRICULUM VITAE

Name:

Present appointment: (Job title, department, and organisation.)

Address: (Full work address.)

Telephone number: Email address:

Qualifications:

Professional registration: (Name of body, registration number and date of registration.)

Previous and other appointments: (Include previous appointments in the last 5 years and

other current appointments.)

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Research experience: (Summary of research experience, including the extent of your

involvement. Refer to any specific clinical or research experience relevant to the current

application.)

Research training: (Details of any relevant training in the design or conduct of research, for

example in the Clinical Trials Regulations, Good Clinical Practice, consent or other training

appropriate to non-clinical research. Give the date of the training.)

Relevant publications: (Give references to all publications in the last two years plus other

publications relevant to the current application.)

Signature: Date:

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GLOSSARY AE

Adverse Event

ABPI

Association of the British Pharmaceutical Industry

ARSAC Administration of Radioactive Substances Advisory Committee

CF Consent Form

CI Chief Investigator

Clinical Trial

A clinical trial is a research study designed to methodologically answer specific questions about novel therapies, treatment techniques or new ways of using known treatment. Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people.

CRN Clinical Research Nurse

Clinical Trial Regulations

The Medicines for Human Use (Clinical Trials) Regulations 2004

Clinical Trial Authorisation

The authorisation from the MHRA as Competent Authority, in the UK to conduct a clinical trial of an investigational medicinal product (CTIMP).

Clinical Trial of an Investigational Medicinal Product (CTIMP)

Is any investigation in human subjects, other than non-investigational trial, intended to a) discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products; b) to identify any adverse reactions to one or more such products or c) to study absorption, distribution, metabolism and excretion of one or more such products with the object of ascertaining the safety or efficacy of those products.

Cohort

In epidemiology, a group of individuals with some characteristics in common.

Community-based Clinical Trial

A method of providing experimental therapeutics prior to final approval for use in humans, this procedure is used with very sick individuals who have no other treatment options. Often approval is on a case-by-case basis.

Complementary and Alternative Therapy

Broad range of healing philosophies, approaches, and therapies that Western (conventional) medicine does not commonly use to promote well-being or treat health conditions.

Confidentiality Regarding Trial Participants

Refers to maintaining the confidentiality of trial participants including their personal identity and all personal medical information. The trial participants consent to the use of their records for data verification purposes should be obtained prior to the trial and assurance must be given that confidentiality will be maintained.

Contraindication A specific circumstance when the use of certain treatments could be harmful.

Control Group The standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo (See Placebo and Standard Treatment).

CRA Clinical Research Associate (Monitor)

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CRF Case Report Form

CRO Contract Research Organisation

CRUK Cancer Research UK

CTA Clinical Trials Authorisation

CTC Common Toxicity Criteria

DMC

Data Monitoring Committee

Data Safety and Monitoring Board (DSMB)

An independent committee composed of community representatives and clinical research experts that review data while a clinical trial is in progress to ensure that participants are not exposed to undue risk. A DSMB may recommend that a trial be stopped if there are safety concerns or if the trial objectives have been achieved.

Diagnostic Trials Refers to trials that are conducted to find better tests or procedures for diagnosing a particular disease or condition. Diagnostic trials usually include people who have signs or symptoms of the disease or illness being studied.

Dose-ranging Study A clinical trial in which two or more doses of an agent (such as a drug) are tested against each other to determine which dose works best and is least harmful.

Double-blind Study A clinical trial design in which neither the participating individuals nor the study staff knows which participants are receiving the experimental drug and which are receiving the placebo (or another therapy). Double-blind trials are thought to produce objective results, since the expectations of the doctor and the participants about the experimental drug do not affect the outcome (See Blind, Single-Blind Study and Placebo).

Drug-Drug Interaction

A modification of the effect of a drug when administered with another drug, the effect may be an increase or a decrease in the action of either substance, or it may be an adverse effect that is not normally associated with either drug.

ECMC Experimental Cancer Medicines Centre

Efficacy The maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed.

Eligibility Criteria Summary criteria for participant selected; includes inclusion and exclusion criteria (See Inclusion and Exclusion Criteria).

EMEA European Medicines Evaluation Agency

EORTC European Organisation for Research and Treatment of Cancer

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EU Directive Directive 2001/20 EC of the European Parliament and the Council of the European Union relating to the implementation of good clinical practice in the conduct of the clinical trials of medicinal products for human use.

EudraCT European Drug Regulation authorities in Clinical Trials

Expanded Access Refers to the distribution of experimental drugs to participants who are failing on currently available treatments for their condition and who are also unable to participate in ongoing clinical trials.

Food and Drug Administration (FDA)

The US Department of Health and Human Services agency responsible for ensuring the safety and effectiveness of all drugs, biologics, vaccines and medical devices, including those used in the diagnosis, treatment and prevention of HIV infection, AIDS and AIDS-related opportunistic infections. The FDA also works with the blood banking industry to safeguard the US national blood supply.

GCP Good Clinical Practice

GLP Good Laboratory Practice

GMP Health Research Authority

Good Manufacturing Practice The HRA works closely with the MHRA and NIHR creating a unified approval process and to promote proportionate standards for compliance and inspection within a consistent national system of research governance

Hypothesis A supposition or assumption advanced as a basis for reasoning or argument, or as a guide to experimental investigation.

Inclusion/Exclusion Criteria

The medical or social standards determining whether a person may or may not be allowed to enter a clinical trial, these criteria are based on such factors as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions. It is important to note that inclusion and exclusion criteria are used to identify appropriate participants and keep them safe.

Informed Consent The process of learning the key facts about a clinical trial before deciding whether or not to participate. It is also a continuing process throughout the whole of the study to provide information to participants. To help someone decide whether or not to participate, the doctors and nurses involved in the trial explain the details of the study.

Informed Consent Document

A document that describes the rights of the study participants, and includes details about the study, such as its purpose, duration, required procedures and key contacts. Risks and potential benefits are explained in the informed consent document. The participant then decides whether or not to sign the document. Informed consent is not a contract and the participant may be withdrawn from the trial at any time.

ICH GCP International Conference on Harmonisation – Good Clinical Practice

ICR Institute of Clinical Research

Investigational Medicinal Product (IMP)

A pharmaceutical form of an active substance or placebo being tested, or to be tested, or used, or to be used, as a reference in a clinical trial, and includes a medicinal product which has a marketing authorisation but is, for the purposes of the trial:

a) Used to assembled (formulated or packaged) in a way different from the form of the product authorised under the authorisation;

b) Used for an indication not included in the summary of product characteristics under

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the authorisation for that product; c) Used to gain further information about the form of that product as authorised

under the authorisation.

Investigator’s Brochure (IB)

A document containing a summary of the clinical and non-clinical data relating to an investigational medicinal product which are relevant to the study of the product in human subjects.

IRAS

Integrated Research Application System

IRMER Ionising Radiation Medical Exposure Regulations

KSF Knowledge and Skills Framework Lead Site In the case of a multi-site study, the site for which the Chief Investigator is also the Principal

Investigator.

Medicines and Healthcare products Regulatory Agency (MHRA)

Is the competent authority for the UK in relation to the EU Directive and the Clinical Trials Regulations. MHRA (Devices) is the competent authority for the UK in relation to the Medical Devices Regulations 2002.

NHS National Health Service

NIGB National Information Governance Board

NIHR National Institute of Health Research

NIHR CSP NIHR Coordinated System for gaining NHS permission

National Research Ethics Centre

Directorate within the National Patient Safety Agency that provides help and leadership for RECs by co-ordinating the development of operational and infrastructure arrangements in support of their work. This includes implementing standards to ensure national consistency, providing training for REC members and Co-ordinators, identifying IT solutions for procedural management and establishing regional REC centres to manage RECs.

Open Label Trial A clinical trial in which doctors and participants know which drug or treatment is being administrated.

Peer Review Review of a clinical trial by experts chosen by the study sponsors. These experts review the trial for scientific merit, participant safety and ethical considerations.

PIS

Participant information sheet

PPI

Patient and public involvement

Pharmacokinetics The process of absorption, distribution, metabolism and excretion of a drug or vaccine.

Placebo A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatments effectiveness.

Placebo Controlled Study

A method of investigation of drugs in which an inactive substance is given to one group of participants, while the drug that is being tested is given to another group. The results obtained in the two groups are then compared to see if the investigational treatment is

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more effective in treating the condition.

Principal Investigator (PI)

The investigator responsible for the research site where the study involves specified procedures requiring site-specific assessment. There should be one PI for each research site. In the case of a single-site study, the CI and the PI will normally be the same person.

Protocol A document that describes the objectives, design, methodology, statistical considerations (or other methods of data analysis) and organisation of a research study.

Quality of Life Trials Refers to trials that explore ways to improve comfort and quality of life for individual’s chronic illness.

Randomisation A method by which study participants are assigned to a treatment group. Randomisation minimises the differences among groups by equally distributing people among the trial arms.

Randomised Trial A study in which participants are randomly assigned to one of two or more treatment arms of a clinical trial.

R&D

Research and Development

REC

Research Ethics Committee

Serious Adverse Event (SAE)

Serious adverse event, an untoward occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity or consists of a congenital anomaly or birth defect.

Single Blind A study in which one party, either the investigator or participant is unaware of what medication the participant is taking.

Site Specific Assessment (SSA)

An assessment of the suitability of the investigator, site and facilities made for any study with a Principal Investigator at each research site. The application for SSA should be made by the Principal Investigator using the Site-Specific Information (SSI) Form. In the case of a multi-site study, the outcome of the SSA should be notified to the main REC within 25 days.

SOP Standard Operating Procedure

Sponsor The person who takes on ultimate responsibility for the initiation, management and financing (or arranging the financing) of a clinical trial.

Standard Treatment A treatment currently approved, in wide use and considered to be effective in the treatment of a specific disease or condition.

Statistical significance

The probability that an event or difference occurred by chance or alone. In clinical trials, the level of statistical significance depends on the number of participants studied and the observations made, as well as the magnitude of differences observed.

Serious Adverse Reaction (SAR)

A serious adverse reaction in a CTIMP that results in death; is life-threatening; requires hospitalisation or prolongation of existing hospitalisation; results in persistent or significant disability or incapacity; or consists of a congenital anomaly or birth defect.

Suspected Unexpected Serious Adverse Reaction

A SUSAR is a CTIMP which is unexpected, meaning that its nature and severity are not consistent with the information about the medicinal product in question set out:

a) In the case of a product with a marketing authorisation, in the summary of product

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(SUSAR) characteristics for that product; b) In the case of any other investigational medicinal product, in the investigator’s

brochure relating to the trial in question.

TMF

Trial Master File

TSF Trial Site File

UKCRC United Kingdom Clinical Research Collaboration

Further resources:

NIHR Clinical Research Network

www.crncc.nihr.ac.uk/about_us

NIHR Clinical Research Portfolio

www.crncc.nihr.ac.uk/about_us/processes/portfolio

Search the NIHR portfolio database

www.crncc.nihr.ac.uk/about_us/processes/portfolio/p_search

Primary Care Research Network (PCRN)

www.crncc.nihr.ac.uk/about_us/pcrn

Mental Health Research Network:

www.mhrn.info/

Dementias and Neurodegenerative Diseases Research Network

www.crncc.nihr.ac.uk/about_us/dendron

Diabetes Research Network

www.crncc.nihr.ac.uk/about_us/drn

National Cancer Research Network

www.ncrn.org.uk/

Yorkshire Cancer Research Network

www.ycrn.org.uk

Yorkshire Stroke Network

yorkshire.uksrn.ac.uk

Yorkshire Cancer Network

www.yorkshire-cancer-net.org.uk

MHRA

www.mhra.gov.uk/index.htm

Clinical Trials Toolkit

www.ct-toolkit.ac.uk/

IRAS (Integrated Research Application System)

www.myresearchproject.org.uk

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Further Reading:

Plan for Growth

http://www.hm-treasury.gov.uk/ukecon_growth_index.htm

Liberating the NHS, Equity and Excellence

http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_117

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The Strategy for UK Life Sciences

http://www.number10.gov.uk/wp-content/uploads/2011/12/8971-BIS-Life-Sciences-Prospectus-

BMK_Spreads.pdf

A "prospectus" entitled Investing in UK Health and Life Sciences

http://www.bis.gov.uk/assets/biscore/innovation/docs/s/11-1429-strategy-for-uk-life-sciences

The NHS Chief Executive's review: Innovation Health and Wealth - Accelerating Adoption and Diffusion

http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_131299

Developing the Role of the Clinical Academic Researcher in the Nursing, Midwifery and Allied Health

Professionals.

http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_132968

Competency Framework for Clinical Research Nurses

http://www.rcn.org.uk/development/researchanddevelopment/rs/publications_and_position_statements/co

mpetencies

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Useful Contacts

Research Support and Governance Office Bradford Institute for Health Research Temple Bank House Bradford Royal Infirmary Duckworth Lane Bradford BD9 6RJ T: (01274) 366808/ 364687/ 383418 E: Bradfordresearch.application@bradfordhospitals.nhs.uk

The Research Governance Manager jane.dennison@bradfordhospitals.nhs.uk

Angela Grange Lead Nurse Clinical Quality & Research/Trust Innovation Lead Bradford Institute for Health Research Temple Bank House Bradford Royal Infirmary Duckworth Lane Bradford BD9 6RJ T 01274 366809 M 07968 472411 E angela.grange@bthft.nhs.uk

West Yorkshire Comprehensive Local Research Network 34 Hyde Terrace Leeds LS2 9LN Emma Giddings Lead Nurse T 0113 392 23765 M 07534 274555 E E.K.Giddings@wyclrn.org.uk Visit the WYCLRN Website: www.westyorks.crncc.nihr.ac.uk