Clinical Research Induction Pack for Nurses, Midwives and other

LEEDS TEACHING HOSPITALS NHS TRUST/UNIVERSITY OF LEEDS Clinical Research Induction Pack for Nurses and other Allied Health Professionals 29.3.12

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Clinical Research

Induction Pack

for Nurses, Midwives and other

Allied Health Professionals

Leeds Teaching Hospitals NHS Trust

&

University of Leeds

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

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

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

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


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THIS PAGE HAS BEEN INTENTIONALLY LEFT BLANK


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CONTENTS Page No

• Glossary and Further Resources - 4 • Introduction - 12 • Useful contacts - 13

SECTION A INDUCTION

• Clinical Research Nurse Induction programme - 15 o Local research induction - 18 o Induction Programme line manager sign off - 20 o Clinical Research Nurse Competency Tool - 21

SECTION B ESSENTIAL KNOWLEDGE

• Research & the NHS - 59 o LTHT R&I Strategy - 60

• National Institute of Health Research and the Networks - 65 • Research Governance - 68

o Declaration of Helsinki - 70 o Good Clinical Practice - 71 o Health Research Authority & Ethics - 73 o EU Directives, Statutory Instruments and MHRA - 74 o Roles & Responsibilities of Researchers & Organisations - 75 o Amendments - 79 o Safety - 83 o Human Tissue Act - 84 o Data Protection - 85 o Informed Consent - 86 o SOPs Standard Operating Procedures - 88

SOP training log & SOP template • Trial design - 92 • Case Report Forms - 94 • Essential Documents - 96

Appendices

I Clinical Research Forum Terms of References - 103 II Training Folder Template - 107 III Research CV template - 109 Authors: E. Giddings/D. Beirne Date of Review: March 2013.


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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


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obtained in the two groups are then compared to see if the investigational treatment is 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.


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Suspected Unexpected Serious Adverse Reaction (SUSAR)

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 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

Acknowledgements:

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

Debbie Beirne, Cancer Research UK Nurse Consultant & Assistant Director of Clinical Research, LTHT

Emma Giddings, Lead Nurse, West Yorkshire CLRN

Viv Dolby, Senior Midwife Researcher, LTHT

Suzanne Rogerson, Senior Research Nurse, LTHT

This document has been based on the Yorkshire Cancer Research Network’s Induction Pack and includes submissions from the following:

Neville Young QA Manager, Research & Development Dept LTHT


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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_117353

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


Developing the Role of the Clinical Academic Researcher in the Nursing, Midwifery and Allied Health Professionals.


Competency Framework for Clinical Research Nurses

http://www.rcn.org.uk/development/researchanddevelopment/rs/publications_and_position_statements/competencies

http://www.hm-treasury.gov.uk/ukecon_growth_index.htm�

http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_117353�


http://www.number10.gov.uk/wp-content/uploads/2011/12/8971-BIS-Life-Sciences-Prospectus-BMK_Spreads.pdf�

http://www.number10.gov.uk/wp-content/uploads/2011/12/8971-BIS-Life-Sciences-Prospectus-BMK_Spreads.pdf�

http://www.bis.gov.uk/assets/biscore/innovation/docs/s/11-1429-strategy-for-uk-life-sciences�





http://www.rcn.org.uk/development/researchanddevelopment/rs/publications_and_position_statements/competencies�

http://www.rcn.org.uk/development/researchanddevelopment/rs/publications_and_position_statements/competencies�


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Introduction

Welcome to your post in clinical research. The health research arena in LTHT and The University of Leeds is a dynamic and diverse one in which multiple disciplines and professions work collegiately and in partnership to deliver world class research for patient benefit.

There are strong and established areas of research activity in Oncology, Muscular-skeletal medicine and cardiovascular research, but also many more in surgery, general medicine, paediatrics and midwifery to name but a few. There is a wealth of research ongoing across the University and Trust in epidemiology, genetics, psychology and many other areas of health science.

You are therefore joining a team of colleagues who desire to improve the health outcomes for patients and the public by means of effective prevention, earlier detection, improved diagnostic markers, enhanced treatment techniques and novel therapeutics; drives their professional focus and commitment to delivering high quality, robustly evidenced health research.

Starting in a new role in research can be daunting, and you may find that whatever prior experience you come with does not seem of use, or where you once felt competent you now feel a novice again. This is a common experience for many and it is important to remind yourself that your skills and knowledge are extremely valuable to this role, but that there is much also to learn and new skills to develop and allow yourself the time to do so without undue pressure. A career in health related clinical research can be personally, intellectually and professionally very rewarding.

At the heart of a research nurse or allied professional role is patient care and advocacy. Research involving unlicensed medicinal products, invasive interventional studies and early phase clinical trials can be particularly challenging to deliver and therefore require research staff to be flexible, innovative, proactive and committed to successfully recruit and safely care for patients, and deliver the quality data required to inform and influence future practice.

We hope you find the information and guidance in this handbook a useful first reference point in your induction and start of your research career. Do not struggle in your new role but seek the support and advice of the R&D department and other research colleagues. A list of key contacts is included in this handbook.

Wishing you every success in your post

Debbie Beirne Emma Giddings Nurse Consultant for Clinical Research Lead Nurse Leeds Teaching Hospitals NHS Trust West Yorkshire CLRN


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Useful Contacts

Research & Development Department 34 Hyde Terrace Leeds LS2 9LN

T 0113 39 22878 F 0113 39 26397 E r&[email protected] http://www.leedsth.nhs.uk/sites/research_and_development/ Debbie Beirne Cancer Research UK Nurse Consultant & Assistant Director of Clinical Research Oncology Research Department Level 6, Bexley Wing St James’s University Hospital T 0113 206 7855 E [email protected] [email protected] West Yorkshire Comprehensive Local Research Network Leeds Innovation Hub 103 Clarendon Road Leeds LS2 9DF Emma Giddings Lead Nurse T 0113 384 5700 F 0113 384 5706 M 07534 274555 E [email protected] Visit the WYCLRN Website: www.westyorks.crncc.nihr.ac.uk

mailto:r&[email protected]�

http://www.leedsth.nhs.uk/sites/research_and_development/�

mailto:[email protected]�


http://www.westyorks.crncc.nihr.ac.uk/�


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SECTION A

Clinical Research Nurse Induction Programme

Local Research Induction

Line Management Induction Programme Sign Off

Clinical Research Nurse Competency Tool


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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.


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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:

• 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 Trust’s R&D Department also offer shorter Informed Consent workshops that are mandatory for any Trust employees who are involved in obtaining consent for clinical trials. The sessions take about an hour and delegates receive a certificate in Informed Consent at the end. Dates for forthcoming workshops can be found on their website:

http://www.leedsteachinghospitals.com/sites/research_and_development/Events.php#IC

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)

http://www.crncc.nihr.ac.uk/about�

http://www.leedsteachinghospitals.com/sites/research_and_development/Events.php#IC�

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


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Access to or use of:

• Centrifuge (with training on safe use of this equipment) • Fridge • Freezer • Lab space • Photocopier

Building Networks

It is important that you feel supported within your role and we recommend that you make the most of any opportunities to network with other research colleagues. The Clinical Research Forum at Leeds is open to all nurses and allied clinical trial personnel involved in research. The Forum meets quarterly and is supported by the R&D Department. This is a great opportunity to meet other research professionals to network, share ideas and problems, facilitate good practice across the group and keep up to date with national initiatives. (see appendix I)

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.


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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 LTHT/University of Leeds � 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

Clinical Research Induction Pack for Nurses, Midwives and other Allied Health Professionals Leeds Teaching Hospitals NHS Trust/University of Leeds

16 March 2012 version 1.1 Authors: E. Giddings, D. Beirne

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.


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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: This document forms part of the Clinical Research Nurse Induction Programme for LTHT. 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.


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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 participants 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


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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.


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Competence 2: To work within the regulations framework

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


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.


25

Competence 2: To work within the regulations framework 2.2 Contributes to the preparation of submissions for regulatory reviews


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.


26

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


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.


27

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


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


28

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


29

4.2 Contribute to effective and efficient use of resources


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.


30

4.3 Facilitate the delivery of clinical research


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.


31

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


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


32

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.


33

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


34

Review at Induction Date:

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

Target Level Band 5 1

Band 6 1

Band 7 2

Band 8 3

Identified Objectives:

To be actioned by:

Training needs identified:

To be actioned by:


35


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.


Band 6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


36


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.


Band 6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


37


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


Band 6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


38


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

4.1 Contribute to the development of safe clinical research.


Band 6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


39



4.2 Contributes to efficient use of resources.


Band 6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


40



4.3 Contributes to the delivery of clinical research.


Band 6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


41



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


Band 6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


42

Review at 6 months Date:

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

Target levels at 6 months

Band 5

1 Level Achieved

□ Band6 1

Band 7 2

Band 8 3

Evidence at 6 month review: Identified Objectives:

To be actioned by:


To be actioned by:


43


Competency 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.


To be actioned by:


To be actioned by:


Band 5

1 Level Achieved

□ Band6 1

Band 7 2

Band 8 3


44


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.


Band 5

1 Level Achieved

□ Band6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


45


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


Band 5

1 Level Achieved

□ Band6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


46


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



Band 5

1 Level Achieved

□ Band6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


47

Review at 6 months Date: Competence 4 - To apply professional knowledge and skills to facilitate efficient, safe and participants focused clinical research. 4.2 Contributes to efficient use of resources.


Band 5

1 Level Achieved

□ Band6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


48





Band 5

1 Level Achieved

□ Band6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


49





Band 5

1 Level Achieved

□ Band6 1

Band 7 2

Band 8 3


To be actioned by:


To be actioned by:


50


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


Band 5

2 Level Achieved

□ Band6 3

Band 7 3/4

Band 8 4


To be actioned by:


To be actioned by:


51


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.


To be actioned by:


To be actioned by:


Band 5

2 Level Achieved

□ Band6 3

Band 7 3/4

Band 8 4


52


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.


Band 5

2 Level Achieved

□ Band6 3

Band 7 3/4

Band 8 4


To be actioned by:


To be actioned by:


53


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


Band 5

2 Level Achieved

□ Band6 3

Band 7 3/4

Band 8 4


To be actioned by:


To be actioned by:


54





Band 5

2 Level Achieved

□ Band6 3

Band 7 3/4

Band 8 4


To be actioned by:


To be actioned by:


55

Review at 12 months Date: Competence 4 - To apply professional knowledge and skills to facilitate efficient, safe and participants focused clinical research. 4.2 Contributes to efficient use of resources.


Band 5

2 Level Achieved

□ Band6 3

Band 7 3/4

Band 8 4


To be actioned by:


To be actioned by:


56





Band 5

2 Level Achieved

□ Band6 3

Band 7 3/4

Band 8 4


To be actioned by:


To be actioned by:


57





Band 5

2 Level Achieved

□ Band6 3

Band 7 3/4

Band 8 4


To be actioned by:


To be actioned by:



SECTION B

RESEARCH – ESSENTIAL KNOWLEDGE


59

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 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

http://cdn.hm-treasury.gov.uk/2011budget_growth.pdf�




60

1. Vision “We will ensure the Leeds Teaching Hospitals NHS Trust is an internationally renowned centre of excellence for patient care, education and research”.

2. Purpose

The Trust undertakes research and promotes innovation because high quality clinical research and innovation improve clinical outcomes for patients.

3. Strategic Objectives

The strategy for research and innovation (R&I) aims to contribute to realising the goals of the Trust;

• To be the hospital of choice for patients and staff • To be a consistently high performing and influential healthcare provider • To achieve the best possible clinical outcomes for every patient, every time • To achieve academic excellence and expand the boundaries of healthcare

The core objectives of the R&I Strategy are to;

• offer patients opportunities to participate in research and increase the number of patients participating in studies

• increase the quality and value of research and innovation in the Trust • develop research capacity and capability by directing support for high quality research and

innovation • translate research findings and service innovations into benefits for patients and the Trust • make the Trust the NHS research and innovation partner of choice for industry

THE LEEDS TEACHING HOSPITALS NHS TRUST

RESEARCH AND INNOVATION STRATEGY


61

In order to realise these objectives, the Trust recognises;

• that research performance and innovation management speciality, should be embedded within normal Trust business and clinical governance processes, at directorate and divisional levels

• the value of a strong academic partnership with the University of Leeds • the value of research and innovation partnerships, including those with the Leeds Teaching

Hospitals Charitable Foundation, National Institute for Health Research (NIHR), Research Councils and other NIHR partners, medical charities, other academic institutions and industry

• that the Trust’s business development, education, training, performance management, estates and capital strategies should support the delivery of the R&I Strategy

4. Strategy Map

The R&I strategic intent is described as a strategy map, in which core aims are underpinned by objectives and enabling steps.

5. Review

This strategy will be subject to regular review, in partnership with patients, carers, clinicians, managers and the University of Leeds. The review process will include an annual horizon-scanning exercise.

Professor S W Smye

Director of Research & Development

April 2011



RESEARCH AND INNOVATION STRATEGY MAP

Visi

on

"We will ensure the Leeds Teaching Hospitals NHS Trust is an internationally renowned centre of excellence for patient care, education and research”.

By 2015, our distinctive ability to integrate research, innovation and clinical care will have secured a place among the top 5 performing Trusts in the UK

Stak

ehol

ders

and

pat

ient

s

Our patients expect to be offered the opportunity to participate in high quality, ethical, research which is relevant to their needs, and to benefit from research.

Our patients expect the Trust to be an innovative organisation, committed to developing and adopting innovation which aims to improve patient outcomes and service delivery.

The Trust expects to work collaboratively with the University of Leeds to undertake research and innovation which is internationally competitive and related to the goals of the National Institute for Health Research, including strong academic and industry partnerships.

Trust staff expect to be appropriately supported to develop and conduct high quality research and innovation


63

Key

ob

ject

ives

Monitor Trust, Divisional and Directorate performance against the R&I Strategy using R&I performance management toolkit which is integrated with core LTHT process

Maintaining LTHT position as one of top 5 recruiting NHS Trusts to NIHR Clinical Research Network portfolio studies in England.

The Trust will adopt a proportionate approach to managing risk in Clinical Trials and audit 30 research studies pa Informed by risk assessment

Raise awareness of the Patient, Public Involvement (PPI) agenda

Maximise NIHR funding by meeting appropriate government initiation and delivery benchmarks for NIHR Portfolio studies.

Secure NIHR Biomedical Research Unit and Centre (or equivalent) status in partnership with the University of Leeds

Secure NIHR Applied Programme Grants and other high quality grants from NIHR Partners, in partnership with the University of Leeds, growing non-commercial research income by 10% pa to achieve total portfolio valued at £30m.

Develop 5 new major industry research partnerships, growing commercial income by 10% pa

Secure £300k pa gross income from innovation deals (licences, patents) within 3 years

Establish 4 spin-out companies and sell one

Embed research and innovation in Trust business plan and exploit research as a factor in making LTHT “Hospital of Choice” by incorporating in marketing plan

Integrate the research and innovation strategy within the Trust’s organisational development strategy through its Managing for Success programme

Develop joint strategy for R&D with University of Leeds, through Biomedical and Health Research Centre.

Keep 4 key priority clinical areas under review;

- oncology

- musculoskeletal disease and dentistry

- cardiovascular disease

- cross-cutting technologies including clinical genetics.

Secure additional £5m investment from Cancer Research UK in Leeds Cancer Centre

Secure £3m BHF and other major investment in Multidisciplinary Cardiovascular Research Centre and secure NIHR Biomedical Research Unit or equivalent status

Secure £2m additional funding for Leeds Dental Institute Clinical Research Facility

Work with EPSRC Integrated Knowledge Centre in tissue engineering and regenerative medicine to increase leveraged industry funding

Work with University of Leeds to deliver 10 innovation challenges of the Wellcome Trust/EPSRC Tissue engineering and regenerative medicine centre, and identify 10 clinicians to contribute to Integrated Knowledge Centre

Achieve NIHR Faculty membership for 200 staff.

Secure funding for Experimental Cancer Medicine Centre

Develop Associate Clinical Professor model for selected staff

Secure funding for research PAs for staff recruiting to NIHR portfolio studies, for 200 staff

Create partnership with cohort of LTHT recognised research-active GPs

Work with University to develop Academic and Clinical Workforces by ensuring job planning and appraisal processes delivers protected time for appropriate R&D leaders and teams

Achieve 10 NIHR research fellowships per annum

Raise awareness of research to new starters in the Trust

Increase proportion of publications in highly-cited journals

Ensure NIHR Collaboration for Leadership in Applied Health Research and Care in partnership with the Universities of Leeds and York, achieves goals.

Work with Leeds City Council to deliver goals of Innovation City Leeds.


64

Enab

ling

st

eps

Review strategy regularly at R&D Forum, Senior Management Team and Joint Partnership Board

Develop integrated R&I performance toolkit, including specific targets for patient recruitment with Divisions and Directorates in conjunction with the WYCLRN, grant submissions and study status.

Work with the new Health Research Regulatory Agency to combine and streamline approvals using a national system of research governance.

Work with the WYCLRN using the NIHR Research Support Services principles to adopt a proportionate review of Clinical Trials.

Embed R&I in normal Directorate business via Directorate R&D Leads.

Manage R&D funding effectively, ensuring it is a managed element of Directorate budgets

Advise Leeds Teaching Hospitals Charitable Foundation in relation to high quality research funding

Develop a strong industry marketing plan for both pharmaceutical and device industries which is actively managed for the benefit of patients and the Trust, working with WYCLRN

Develop innovation implementation plan and metrics for innovation

Identify an Innovation champion for Trust

Work with Medipex to deliver series of innovation workshops for Trust staff

Implement R&I Communications Strategy

Provide workshops to researchers about the importance of involving patients in research.

Provide posters for research active departments explaining research is taking place in their area.

Work with the University of Leeds to provide research training to Directorate Managers and Research Leads

Promote the WY PPI forum in partnership with the NIHR Research Design Service, Yorkshire and the Humber

Ensure that Trust estate and capital programmes support high quality research and innovation.

Establish a joint R&D office with University of Leeds which includes developing joint business, governance and administrative processes with University.

Consider the creation of a West Yorkshire Academic Health Sciences Partnership

Manage investment in Clinical Trials Research Unit and Institute of Health Sciences to create research grant application capacity, by monitoring grant awards and FSF funding

Representation on steering groups of key clinical research activity, including NIHR Biomedical Research Unit in Musculoskeletal Disease, Cancer Research UK Cancer Centre and Multidisciplinary Cardiovascular Research Centre, and leadership of CLAHRC, EPSRC Integrated Knowledge Centre, and Wellcome Trust/EPSRC in tissue engineering and medical technologies

Record all Trust staff awarded higher degrees by research

Record details of all Trust staff with protected time for research, including funding, research outputs and impact.

Deliver NIHR Biomedical Research Unit in Musculoskeletal Disease goals by embedding BRU management in LTHT management process

Support development of Multidisciplinary Cardiovascular Research Centre goals by embedding management in LTHT management process.

Support delivery of Cancer Research UK Cancer Centre programme, including developmental areas, by embedding management in LTHT management process

Design a leaflet explaining research in the Trust and include this in new starter Induction packs.

Work with WYCLRN to create a pool of cross-speciality research nurses, appointing a lead research nurse and then reviewing line management arrangements for all research nurses

Develop and deliver series of seminars, workshops and other initiatives designed to support researchers in making high quality grant applications.

Establish a promotion day with the University of Leeds enabling clinicians and academics to meet and discuss partnership working.

Establish a joint group from the Directorates to work with Organisational Development and partners to develop research knowledge for the organisation as part of the Managing for Success programme.



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,

Stud

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anni

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•Advice on available facilities/ support staff

•Ideas on supporting clinicians

•Intelligence on local patient populations

Stud

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t-up •Systems to reduce

red-tape on multi-site studies

•Managing NHS R&D approval process

•Speeding up set-up times

Stud

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liver

y •Funding of facilities and people to carry out research

•Recruiting patients into studies

•Providing training for research staff

http://www.crncc.nihr.ac.uk/�

http://www.crncc.nihr.ac.uk/�


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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.

NIHR Infrastructure

Topics: 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.

Leeds Teaching Hospitals NHS Trust is represented by the West Yorkshire CLRN.

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)


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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 WYCLRN streamline the research management function for NIHR portfolio studies supported by the networks and provides the NHS infrastructure to support clinical research across all areas of disease and clinical need by:

• Managing Specialty Groups to give focused clinical expertise; • Having access to the national portfolio of studies; • Funding NHS Service Support Costs for portfolio studies.

2011/2012 budget of £13.1m 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

• Flexibility & Sustainability Funding (FSF) o Staff costs of researchers between portfolio grants o Staff costs of researchers who haven’t yet obtained portfolio funding, but are expected to

The WYCLRN provide funding for research posts across the region and the Lead Nurse has a remit 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 [email protected]

http://www.westyorks.crncc.nihr.ac.uk/�



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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

In 2001 (updated 205, annex updated 2008), the Department of Health (DH) published a set of guidelines entitled “Research Governance Framework for Health and Social Care”. This document provides the 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.

The Research Governance Framework is presented in five domains:

Research Governance Framework

Ethics

Science

Information

Financial & Intellectual

Policy

Health, safety and employment


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Each domain is underpinned with requirements in legislation and regulations; some of the main legal and regulatory documents are reviewed in this chapter. They are based on standards and established principles of good practice from recognised national and international authorities and professional organisations. The Research Governance Framework (RGF) defines standards, details responsibilities and accountability, outlines delivery systems and describes local and national monitoring systems.

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

Research Governance is for managers and staff, in all professional groups, no matter how senior.

Research Governance is an ongoing exercise that requires continuous monitoring to ensure that all projects adhere to the principles of research excellence.


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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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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 enforced in the UK in May 2004 (Clinical Trials Act 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).


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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.

http://www.dh.gov.uk/health/2011/12/creation-hra�

http://www.hra.nhs.uk/�


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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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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.


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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.


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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.


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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.


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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


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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


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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


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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


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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


84

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.

http://www.hta.gov.uk/�


85

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.

LTHT Data Protection Policy can be accessed on the Trust Intranet: http://lthweb/policies/policy.php?id+134

http://lthweb/policies/policy.php?id+134�


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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.


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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.


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STANDARD OPERATING PROCEDURES (SOPs) – Log & Template Departmental SOP log

SOP Number SOP Title Initials / Date

EQU_0014 Use & Maintenance of Sigma Centrifuge 2-16K (Clinical)

EQU_0015 Use & Maintenance of Labcold -20 Freezers

EQU_0017 Use an Maintenance of New Brunswick -80 Freezer

EQU_0018 Equipment Maintenance and Callibration

EQU_0024 Use and Maintenance of Labcold Refrigerator (clinical)

GOV_0006 Duties of speciality registrars with respect to clinical trials

GOV_0007 Emergency contact and out of hours procedure for clinical trials

GOV_0009 Duties of specialist trainees (ST1, ST2) with respect to clinical trials

GOV_0010 Clinical trial approval by clinical trials research approval board (CTRAB)

GOV_0011 The governance of clinical trials

GOV_0012 Regulatory Inspection

CLIN_0001 Blood collection for laboratory analysis

CLIN_0003 Gaining written, informed consent from patients in clinical trials

CLIN_0004 Storage of biological samples

CLIN_0006 Blood sampling for pharmacokinetic analysis

CLIN_0007 Recording vital signs

CLIN_0009 Measurement and recording of height and weight

CLIN_0010 Introduction of a new patient to the unit

CLIN_0011 Synchronised clocks for sample collection

CLIN_0012 Buccal Smear collection and storage

CLIN_0015 Packing and shipment of samples on dry ice

CLIN_0017 Urine collection for analysis

CLIN_0018 Collection of punch biopsies of normal skin

CLIN_0019 Using Recist measurement criteria

QMS_0001 Archiving and destroying documents

QMS_0002 Document preparation and control

QMS_0003 Quality management file


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SOP Number SOP Title Initials / Date

QMS_0004 Disaster recovery plan

QMS_0005 Quality Policy

QMS_0006 Documentation policy

PER_0001 Staff Induction

PER_0002 Staff training files

PER_0003 SOP training

ADM_0001 Updating PPM

ADM_0002 Putting new trial on PPM

ADM_0003 Site file management

ADM_0004 Management of study related correspondence


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Title:

Scope:

Doc. No: (to include version number)

Replaces:

Effective Date: Review Date:

Author: Date:

Authorised/

Approved by

Title Signature Date

Nurse Consultant

QA Manager

Document Change Control

Version No. Reason For Change Author Date

Training Implications; (Please tick appropriate box)

A

B

C

D

A = New Users – New procedure requiring documented assessment of competence B = Existing users - Modified procedure requiring documented reassessment of competence C = New Users - Familiarity with new procedure required (no assessment of competence necessary) D = Existing Users - Familiarity with changes required (no assessment of competence necessary)


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1. Introduction

2. Purpose

3. Associated Documents

4. Safety Requirements 5. Responsibilities

6. Equipment

7. Procedure


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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.


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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


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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.


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• 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.


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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

To document agreements

X

X

X

X

X X X


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Title of Document Purpose Located in Files of Investigator/ Institution

Sponsor

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

To document that the trial has been subject to IRB/IEC review and given approval/favourable opinion. To identify the version number and date of the document(s).

X

X

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


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Title of Document Purpose Located in Files of Investigator/ Institution

Sponsor

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

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


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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


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



100


Sponsor

Documentation of investigational products and trial related materials shipment

X X

Certificates of analysis for new batches of investigational products

X

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


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



101


Sponsor

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

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


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Sponsor

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

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

http://www.ich.org/LOB/media/MEDIA482.pdfBBC�


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Appendix I - LTHT Clinical Research Forum, Terms of Reference

Clinical Research Forum

Background

Translational and clinical research activity has been central to the Trust’s research strategy for some considerable time. Recent changes to the way in which the Department of Health (DOH) fund such activity has changed to more accurately reflect the output that is actually delivered locally. This funding may arise directly in the form of NIHR grant awards, or indirectly from the West Yorkshire Comprehensive Local Research Network in response to work carried out, for example, number of patients recruited; or pump prime the infrastructure required to support clinical research activity, e.g. pathology, pharmacy, radiology, research nurse support. In so doing it will improve the speed, quality and integration of research resulting in improved patient care.

In 2008 the Biomedical and Health Research Centre (BHRC) was established as a strategic partnership between the four science Faculties of the University of Leeds and the Leeds Teaching Hospitals NHS Trust. The centre will promote collaboration between basic sciences, translational, clinical and applied health research to create an internationally competitive centre of excellence in research. Academic excellence and Research and Innovation are a key goal for LTHT.

The BHRC in Leeds has been developed with the view that the strong science faculties which already have significant health care interests, working together with the Faculty of Medicine and Health and the NHS organisations in Leeds can deliver world-class research in response to global health care challenges.

Across LTHT there are personnel working in a variety of roles from research nurses, study coordinators, business managers and clinical trial administrators, to other allied health professionals whose role incorporates research activity. Whilst there are some well established teams across the Trust, others work in isolation or within very small teams will little support, or in some cases, research experienced professional line management.

In 2011 Leeds Teaching Hospitals NHS Trust made ‘Academic Excellence, Research and Innovation’ a fourth goal in recognition of the importance of maintaining a highly educated and skilled workforce to provide enhanced care and contribute to the evidence base of health and social care through world class research, in partnership with the University of Leeds.


104

Terms of Reference

The forum exists to offer peer support, facilitate knowledge transfer, education and training, alongside R&D, in order to develop and retain an expert clinical research workforce within LTHT and facilitate high quality research for the benefit of patients.

Aims of the forum

• To be a forum for nurses, Allied health professionals and administrative clinical trial personnel to meet and discuss issues related to CT activity, share concerns, problems and good practice.

• To facilitate networking together in an open and constructive environment • Develop common working guidelines and share standard operating procedures when appropriate • To ensure that all staff engaged in the area of clinial research remain up to date of the changes in

legislation/policies and procedures in conducting clinical research within the Trust/University and nationally

• To provide two way communication/ engagement with R&D in general matters relating to clinical trial activity and conduct within LTHT/University and be a forum for raising issues for discussion and providing valuable feedback.

• To promote research nursing as a career within LTHT/University • To be recognised as an expert resource to Nursing and Midwifery and AHP in matters relating to

research methodology, governance and conduct in human subjects • To promote/facilitate/encourage nurse led research projects amongst nurses and AHP within LTHT

Constituents of the Forum

• Allied health professionals who are engaged in clinical research projects as part of their role • All nurses employed in a research nurse capacity in whatever field of healthcare is encouraged to

participate in the forum • Staff employed as administrators/data managers/study coordinators within a clinical trial setting • Representatives from R&D in the Trust/University


105

Meetings

• Meetings are held quarterly. The venue will be across both main hospital sites of St James and LGI where a frequent direct shuttle service is in place.

• Meetings are facilitated and minuted with support from R&D department • The meeting is led by a chair. The position of Chair and deputy-chair will be for a period of two years,

followed by re-appointment from within the forum members • An agenda is circulated 2 weeks ahead of the meeting and items/suggestions for the agenda may be

taken by email or telephone to R&D or the Chair • Each meeting will be for two hours and include an educational presentation/talk or workshop of 30

minutes duration as part of our ongoing aim to inform and educate. Guest speakers will be arranged for meetings periodically as information needs are assessed. Members will also use this time to present the work of their area to share their experience and inform others, so that a broader awareness of the breadth of activity across the Trust and University is elucidated.

• Representation is sought from all research active areas of the Trust in order to foster a collaborative and effective working forum that serves its members and facilitates its aims.

• Refreshments of tea and coffee will generally be provided • People are requested to try to get to the meetings on time and plan to be there for the whole

meeting unless urgent matters arise. • Mobile telephones should be switched to silent mode during the meeting


106

Clinical Research

for patient benefit

Quality Assurance

Standards

Core Governance

Education & Training

SOPs

Guidelines

Registry of all research nurses and AHPs

National & local policies & frameworks

Professional development

Professional Leadership

Peer support

Nurse led research


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Staff Training File

Issued by: G. Langton

OCR

Approved by: D. Beirne

FRM_PER_0002_F1_1.0

Issue date: 27/01/12

Section of Oncology &

Clinical Research

St James Institute of Oncology

Training File

Name: Current Job Title: Start Date: Leave Date


108

1 Copy of job description

2 Signed and dated CV (Documented on the NRES CV template. Renewed annually, retain all versions)

3 Membership of professional associations (e.g. NMC, National or local cancer groups, RCN – include copy of official notification of membership/renewal)

4 Records of all research specific training (Including GCP certificates) -If not certificated, retain schedule/agenda/handouts

5 Records of all mandatory Trust specific training. (e.g. health and safety training) -If not certificated, retain schedule/agenda/handouts

6 Records of all other continuing education –courses/seminars/training sessions. (Include induction programme)

7 Copies of Publications/Presentations

8 Copies of professional and higher educational certificates

9 Departmental SOP log

10 Miscellaneous


109

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.

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


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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: