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Guidance for Researchers

1. What is Research and what is audit? p.1 2. About our research p.2 3. What is the National Institute of Health Research (NIHR) p.3 4. How to contact us p.4 5. Support the Research Office can offer p.5 6. Starting a research project-full guidance on application process p.6 7. Medical Records p.10 8. Considerations for trials involving human tissues p.10 9. Research Not Requiring Ethical Review p.10 10. Guidance from INVOLVE in paying research participants p.11 11. Using Patient information p.11 12. Training p.12 13. Appendix 1-Trust Research Review Board form p.13 14. Appendix 2-Guidance on writing a protocol p.14 15. Appendix 3-Patient Information sheet checklist p.17 16. Appendix 4-DH Guidance storage of Research Records p.18 17. Appendix 5-Who or What is a Sponsor? p.20 18. Appendix 6-NRES Guidance for defining Research, Audit and p.22

Service Evaluation 19. Appendix 7-CV Template p.23

1. What is Research & what is Audit?

What is Research?

Research is work that produces new generalisable results. Research starts with a question such as "is this treatment that I am carrying out the most effective available?”. The next step is to examine the existing knowledge; is there information available from experts and published papers? If there is, then apply the research knowledge to changing your practice - this is development.

If the knowledge is not available you have a potential research project, discuss it with your manager and contact us.

What is Audit

Audit is a slightly different activity in which clinical work is measured against a standard, lessons are learned and practice is changed. The process is repeated setting a new standard or target. Continuous improvement in quality is the aim.

Appendix 6 will give further guidance for defining whether your project is research, audit or a service valuation.

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2. About Our Research

Buckinghamshire Healthcare is funded to support research through the National Institute for Health Research (NIHR) www.nihr.ac.uk the NIHR provide funding to local research networks to fund partner Trusts to participate in national portfolio projects and increase activity by setting up new projects and applying for programme grants run by the NIHR. Our local network is the Thames Valley Comprehensive Local Research Network, (TVCLRN), further details can be accessed via this link www.ukcrn.org.uk and click on CLRNs and Thames Valley which will take you to our local site

Researchers are encouraged to look at the NIHR national portfolio database of projects for areas of interest and see if there are any projects open to new sites they would like to participate in. Participation leads to funding which will be reimbursed to areas where costs incurred. The link to the portfolio database is here: http://public.ukcrn.org.uk/search/ if you would like further assistance to access then please contact the research office

The Trust is keen to support own account funded research projects and the Research Office would like to support where possible and include success stories and findings in our annual Research Report.

We have on average 210 projects running at any one time of portfolio, (approximately 70%), own account, commercial and student projects.

As we are no longer funded to support non-portfolio research, any external student wishing to undertake research within the Trust will be charged a £400 fee for the set up and administration of their project.

The Trust manages research governance in accordance of the DH Research Governance Framework, which can be accessed on this link http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_4122427.pdf

Funding of Research From the funding the Trust Research Office receives from the TVCLRN the following costs are funded:

Research Governance and management staff (Research & Innovation Office)

Research Nurses

Additional pathology and radiology costs resulting from research

Additional inpatient/outpatient costs

Designated pharmacy staff (Clinical Trials Pharmacist and Clinical Trials Technicians)

Training costs where available.

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3. What is the National Institute of Health Research? An overview from the Clinical Research Network and what it provides ‘Clinical research is, and has always been, at the very heart of the NHS. Only by carrying out

research into "what works" can we continually improve treatment for patients, and understand

how to focus NHS resources where they will be most effective.

In 2006, the Department of Health set up the National Institute for Health Research to create a

world-class health system within the NHS, and the Clinical Research Network is part of this

wider organisation.

At the centre of what we do is the Portfolio – a collection of high-quality clinical studies that

benefit from the infrastructure provided by the Clinical Research Network. Many of these

studies are Randomized Controlled Trials - considered by many in the medical profession to

be the most robust form of clinical trial - although we also support other types of well-designed

research.

This is how, in practice, we provide an "infrastructure" to support our Portfolio studies:

We run CSP - a system through which researchers can apply for permission to run a

clinical study in the NHS. We are constantly working to speed up and simplify this

process, so that researchers can get a clinical study up and running quickly, with the

minimum of bureaucracy.

We fund research support posts in the NHS, and provide training, so that researchers

have access to experienced "front-line" staff, who can carry out the additional practical

activities required by their study such as obtaining patient consent for participation,

carrying out extra tests, and collecting the clinical data required for the research.

We provide funding to meet the costs of using facilities such as scanners and x-rays

that are needed in the course of the study, so that research activity adds value to

patient care.

And we provide practical help in identifying and recruiting patients onto Portfolio

studies, so that researchers can be confident of completing the study on time, and on

target.

Although the Clinical Research Network operates as one organisation, we are made up of a

number of different parts:

Cancer,

Dementia and Neurodegenerative Diseases,

Diabetes,

Medicines for Children,

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Mental Health

Stroke

A Primary Care Research Network to support research in this part of the health service

A Comprehensive Clinical Research Network, which covers all other disease areas.

You can read more about each of these by logging onto

http://www.crncc.nihr.ac.uk/about_us/about_us .

4. How to contact us

The Research & Innovation Office can be found in the Old Occupational Health Building at Stoke Mandeville Hospital. We have bi-monthly Research Office Business Meetings and if you would like to represent your specialty then please contact Sophie Hennessy on the details below as we would like representation from as many specialties as possible.

Clinical Lead Research Dr Matthew Burn Email: matthew.burn@buckshealthcare.nhs.uk Trust Research & Innovation Manager Denise Watson Telephone: 01296 316259/ 07825 281923 Email: denise.watson@buckshealthcare.nhs.uk Research Portfolio Delivery Manager, (GCP facilitator, supports research nurses, works with researchers to tackle recruitment barriers and supports new research areas) Jacqui Carr Telephone: 01296 316046/07825 281910 Email: jacqui.carr@buckshealthcare.nhs.uk Research Officer, (guides researchers through approval process until project given Trust approval) Sharon Lambert Telephone: 01296 316200 (Monday-Thursday)) Email: sharon.lambert@buckshealthcare.nhs.uk Research Office Administrator (Amendments, study closedown, invoicing, purchase orders and office administration) Sophie Hennessy Telephone 01296 316065 Email : sophie.hennessy@buckshealthcare.nhs.uk Research Data Officer (recruitment collection and reports) Hollie Hanson

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Telephone: 01296 316065 (Monday-Thursday) Email: hollie.hanson@buckshealthcare.nhs.uk Clinical Trials Pharmacist Bhavna Badiani Telephone: High Wycombe :01494-425753 Stoke Mandeville Hospital: 01296-316199 Amersham Hospital 01494-734359 Email: bhavna.badiani@bucskhealthcare.nhs.uk

5. Support the Research office can offer If you are interested in starting a research project or would like to collaborate with existing projects, the Research Office will be able to support you by:

Guiding you through research project processes

Advice on GCP training opportunities, (see section 10 for more information).

Offering support and guidance in your Research Ethics application

Offering advice in funding opportunities

Source resources through the National Institute of Health Research, (i.e. Research nurse hours)

Build a link with the Thames Valley Comprehensive Local Research Network to build the Trust National portfolio research within your specialty

Advice in writing a protocol

Advice in sourcing projects you can act as a Trust investigator

Notify you of Trust research awards including a doctorate grant

Support you through commercialisation of your innovations/intellectual property, (you would have a share of profit from any income generated as stated in Trust IP policy).

Role of the Research & Innovation Office for the Trust • Support researchers through the approval process • Manage research governance to the DH Research Governance Framework • Source funding opportunities • Identify potential areas for NIHR portfolio growth • Set up research nurses in new areas • Costing of all research and negotiate with commercial partners • Financial management of studies • Negotiate and draw up contracts (as well as material transfer agreements,

memorandum of understanding and confidentiality agreements • Negotiate and help exploit intellectual property • Provide GCP training • Manage research and innovation funding. • Monitoring and auditing of research to ensure meeting GCP and DH Governance

framework regulations • Manage delivery of portfolio studies • Annual Trust Research Grants • Investigate GCP breaches reported to the MHRA and report findings & preventions for

future • Risk assess innovation opportunities • Promote research to clinical groups

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The Research Office is here to promote and support researchers in their research activity to provide improved patient care based on evidence. We want to give all specialties the platform to showcase their research activity and find the resources to support this where applicable.Whatever your research interests may be we would like to hear about them. ALL RESEARCH ACTIVITY IN THE TRUST MUST BE REGISTERED WITH THE RESEARCH OFFICE AND ALL RESEARCHERS MUST HAVE CURRENT GCP TRAINING

6. Guidance

Starting a research project

If you are unsure your project is research then use the toolkit:

Is my study research? http://www.hra-decisiontools.org.uk/research/

Documents needed by the Research Office for a Research Project

The research office will ask you to apply to the Trust Research Review Board using the form attached as Appendix 1. The Research Office will be able to advise you of the meeting dates. The Board will review your proposal and offer guidance if needed or ratify your proposal. The Board consists of clinicians, clinical support and our patient public representative. This can be done alongside completing your ethics application

A copy of your ethics application as a pdf file

A copy of you protocol (advice below)

A copy of your patient information sheet and patient consent form (advice below)

Evidence of funding

Evidence of external sponsorship where applicable

Clinical trial agreement where applicable (external bodies and commercial companies will provide this if your research is in collaboration with them)

Agreement from support services that they have the capacity to support you proposal (e.g. radiology for additional scans or pathology for additional tests and other specialties agreement to support if their staff are to be involved)

Copy of the request to pharmacy (for trials involving medicine) or radiology (for trials involving radiation) if applicable-see below.

Copy of MHRA approval where trial involves an investigational medicinal product

Evidence of peer review

Copy of ethics approval once received

Copy of SSI with signatures as listed below

Details of any costing to be carried out

Guide of start date required.

Copy of proof of indemnity if applicable

Copy of C.V. and evidence of current GCP.

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Applying to Research Ethics Committee for Ethics approval

If your study involves any investigational medicinal product you should liaise with Pharmacy’s Clinical Trial’s pharmacist before proceeding through ethics.

The toolkit below will advise you if your study requires ethics.

Do I need ethics? http://www.hra-decisiontools.org.uk/ethics/

If you need further clarification then please contact the Research & Innovation Office.

If you require ethics Create an account on IRAS (Integrated Research Approval System), this will be the area where you apply to ethics to gain ethical approval. Follow this link to gain access (www.myresearchproject.org.uk)

All notices should be addressed to the Trust RM&G Manager in the Research Office. The application should be written with the lay person in mind as there will be people representing service users on the committee and others from different fields and professions.

See section 9 of this guidance for projects that do not require ethical review.

Ethics committees will require evidence of the Trust supporting the researcher, the chief investigator and the Trust representative (RM&G Manager) should sign the IRAS form. The authorisation signatures needed to be entered on the IRAS application are:

Chief Investigator (for main ethics application)

Principal Investigator (for local SSI)

Trust representative (Trust Research & Innovation Manager) (For main IRAS form and local SSI)

The checklist on the front of the IRAS form will list the documents you will need to submit with your ethics application.

Consent should be clearly addressed within the IRAS form specifically where patients are unable to consent for themselves and the options to withdraw consent if they become able to give consent. If this patient group is to be recruited then evidence of NIHR GCP training for Adults Lacking Capacity to Consent in Research should be submitted. The research team should follow Trust policy ‘6.8 Policy for Consent to Examination or Treatment’.

Once submitted a copy should be sent to the research office as a pdf file and a hard copy with signatures.

Protocol

The attached document, (Appendix 2) should give you some guidance on writing your research protocol, if you need further assistance then please contact the Research Office. The protocol must have a version number on each page, (as header or footer), you will need to list the protocol version number you are submitting to ethics on the checklist.

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Patient Information Sheet

The attached document, (Appendix 3) should give you some guidance on writing your patient information sheet, if you need further assistance then please contact the Research Office. Ethics committees are putting more emphasis on the Patient information sheet in issuing ethics approval. The patient information sheet should be written in language that patients, their family and friends can understand. It should be clear as to

the background of the study

the aim of the study

what will happen to them if they participate

reassurance their care will not be affected if they do not take part

what happens if they decide they no longer want to participate

what will happen to their treatment when the study finishes, (specifically when trial involves drugs)

how they can find out more about the study

contact details for any concerns they have including emergency numbers

how participants and their family can find out the results of the study.

Again version numbers must be included on the patient information sheet.

Funding

There should be no adverse financial impact on a department for supporting research. Research proposals should be costed by the divisional accountant for the researchers area. Commercial studies should be costed using the NIHR commercial trials costing template. For national portfolio studies support services will be reimbursed through the NIHR service support costs allocations which the Trust receives through the Thames Valley Local comprehensive Research Network. All costs are reimbursed to directorates through the provision of recruitment numbers from the Principal Investigator. Finance will transfer costs on a quarterly basis.

For commercial studies, where the template has been used with 90% levy as been applied, the departments will get their costs plus 54% (being 60% of the 90% levy), the Research award will receive 31%, (being 35% of the 90% levy) and finance will receive 5%. Income will be held in a revenue account for the specialty and coded to 509211-Income from Clinical Trials.

Funding for research projects should be carried forward between financial years for the duration of the study. Commercial Income can not be coded to charitable funds.

Sponsor

All research projects must have a recognised sponsor listed. The cost of undertaking activities

to fulfill the role of sponsor for non‐commercial NHS research is classified as a research

cost. The definition of ‘What is a Sponsor’ can be found in Appendix 5.

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Clinical Trial Agreement

As soon as possible the clinical trial agreement (where applicable), should be sent to the Research Office for review. It is recommended where possible that the Model Clinical Trial Agreement is adopted as it is an approved document for use in Trust research. For commercial trials the NIHR costing template should be used for the value of the contract.

Once the Research Office has reviewed and approved the contract, three copies will be sent to the CEO for signature. Once returned we will send the three copies to the sponsor and expect two back, one for the Research Office and one for the Trust lead investigator. It is important the Clinical Trial Agreement is provided to the Research Office as soon as possible as any negotiations required could hold up the approval time.

Verification of support

If your project involves the use of other support services or staff from other specialties, we will need to see confirmation of support from the heads of those departments. This could for example be that your project involves additional x-rays, the service manager will need to confirm they have the capacity and it will need to be confirmed how any additional costs will be covered.

Pharmacy Approval

Any trials involving medicines will need to be signed off by Pharmacy before Trust approval can be issued. Pharmacy will need:

Protocol

Patient information sheet

Copy of the Clinical trial agreement

Copy of MHRA approval

Copy of ethics approval

Once you have sent this to the Clinical Trials Pharmacist in Pharmacy at Stoke Mandeville Hospital, please let the Research Office know so the date can be recorded and monitored. Pharmacy will produce an Appendix A which they will sign and send to the Research Office if they are happy to support the trial.

The Research Office has a service level agreement in place where trials are to be approved in four weeks with set up in 80% of trials four weeks after approval date.

Radiology Approval

Any trials involving radiation will need to be signed off by Dr. Pramjeet Singh in Radiology for Stoke Mandeville and Paul Murphy for Wycombe before Trust approval can be issued. They will need to see:

Protocol

Patient information sheet.

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Once you have sent this to Radiology please let the Research Office know so the date can be recorded and monitored. Radiology will produce an Appendix B which they will sign and send to the Research Office.

MHRA approval

If your project involves new investigational medicines or use of existing medicines for other uses then the MHRA will need to approve the use. If you are registering a project of this nature please bear in mind the MHRA will charge an initial fee of approximately £280 and an annual fee of the same whist the trial is running. Further guidance can be found here: http://www.mhra.gov.uk/Howweregulate/Medicines/Inspectionandstandards/GoodClinicalPractice/Frequentlyaskedquestions/index.htm

7. Medical Records

Please see the attached DH guidance in storing data for research. Information on the storage of research records can be found in Appendix 4. Patients who have been involved in an interventional trial should have details of the project held on their main medical record file. This should include a copy of the patient information sheet, information stating the drugs involved, (pharmacy hold a trial file which list patients and their identification numbers to identify which arm of the trial the patient is on), a copy of the patient consent and contact details for the trial centre, local investigator and chief investigator. A yellow sticker must also be placed on the medical record to indicate the patient is/has involved in a clinical trial.

8. Human Tissue

Any research involving the collection of human tissue should be ethically approved and tissues used for this purpose only. The Trust does not hold a license for research with the Human Tissue Authority; therefore tissues can not be stored for non-ethically approved projects. If tissues are to be stored by a third party for non-ethically approved project under their research license then the Trust will require a Material Transfer Agreement to be completed to transfer ownership and relinquish all rights. The recipient will be responsible for the tissues disposal. It should be clear on the patient consent sheet and patient information sheet that samples for research other than the advised project may be stored by a third party. The Research Office can supply a Material Transfer Agreement.

The MRC give guidance on the attached link which you may find useful as a further resource http://www.mrc.ac.uk/Ourresearch/Ethicsresearchguidance/Useofhumantissue/index.htm

9. Research Not Requiring Ethical Review

Under GAfREC (Governance Arrangements for Research Ethics Committees) which came into effect 1 September 2011, the following studies no longer require review by a Research Ethics Committee but should still be registered and approved by local NHS Research Ethics Committees. The study types involving NHS Trust’s are:

Research involving staff recruited as research participants by virtue of their professional role.

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Research involving previously collected, non-identifiable tissue samples. Where research is limited to use of previously collected, non-identifiable material consisting of or including cells in accordance with the terms the donor consent. REC review would be required if:

i. consent fro research had not been given, or the research is not within the terms of the consent.

ii. The samples will be held on premises in England, Wales or Northern Ireland without a licence from the HTA to store relevant material for scheduled purposes

iii. The research also involves removal, storage or use of new samples from the living or the deceased

iv. The research also involves use of identifiable information held with the samples

Research involving acellular materials Research limited to use of human biological material not consisting of or including calls, (e.g. plasma, serum, DNA) is also excluded from REC review. REC review would be required if:

a) Collection of tissue samples from patients in order to extract acellular material for the research

b) Collection of information from patients c) Use of previously collected information from which patients could be identified

by the researchers d) Analysis of DNA in material from the living, where consent for research is not in

place from the person whose body manufactured the DNA.

Research involving previously collected, non-identifiable information REC review continues to be required for research involving collection of information from patients or service users. REC review is also still required for research involving use of previously collected information from which patients or service users could be identified by researchers outside the usual care team. However REC review is not required for:

o Use of previously collected, non-identifiable information. This exception also applies to research undertaken by staff within a care team using information previously collected in the course of care fro their own patients, provided that such data is anonymised or pseudonymised in conducting research. Such research would involve no breach of the duty of confidentiality owed by the care professionals

Further information can be found: http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_133993.pdf

10. Paying Participants in Research

Guidance from INVOLVE in the attached document should be followed if you are considering paying research participants including travel and subsistence. http://www.invo.org.uk/pdfs/PaymentGuideWEB240510.pdf

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11. Using Patient Information

The use of patient data must be in line with the Trust’s data protection policy. Where information is stored for research purposes the data is to be anonymised. How information is stored and is to be used should be stated clearly on the patient information sheet, consent form and the ethics submission. Should patient identifiable data be the only option for the study then a request should be sent to the Trust Caldicott Guardian copying the Trust Research & Innovation Manager in.

12. Training

Under the Medicines for Human Use (Clinical Trials) Act 2004, it is stated that clinical trials involving investigational medicinal products should be carried out under the guidance of ICH GCP (International Conference on Harmonisation Good Clinical Practice); this is laid out in schedule 2 of the act. (http://www.opsi.gov.uk/si/si2004/20041031.htm#28) ICH GCP is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve human subjects. Compliance with this standard provides public assurance that the rights, safety and well-being of trial subjects are protected; consistent with the principles that have their origin in the Declaration of Helsinki, and that clinical trials data are credible. The objective of the guideline is to provide a unified standard for the E.U., Japan and U.S. to facilitate the mutual acceptance of clinical trial data by the regulatory authorities in these jurisdictions. (GCP Training.org.uk) Where patients are to be recruited who lack capacity to consent evidence of NIHR training Adults Lacking Capacity to Consent in Research which can be found on the NIHR website. The MHRA will investigate GCP as part of their inspections, it is therefore required that staff involved in clinical trials of IMP’s are trained on the principles of GCP. The Research Office will arrange for GCP training days and will be open to all. If research staff work on NIHR portfolio studies they will also be able to do on line training. A record of researchers GCP training will be held in the research office. The Research Office now has an in house GCP facilitator, there will also be dates of GCP training within the Thames Valley that Trust staff may be able to attend, please ask the Research Office for more information. The Health Research Authority have recently issued a statement to state that GCP training is not required to be renewed every two years some however, some sponsors may still require two yearly updates.

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Appendix 1

RESEARCH REVIEW BOARD OUTLINE PROPOSAL FORM

1. Details of applicant(s)

Name(s)

Present position of principal applicant

Other staff

Contact address

Telephone

E-mail

------------------------------------------------------------------------------------------------------------------------------------ 2. Title of Project

3. Brief description of project (maximum 350 words).

4. Approximate capacity implications for Department, eg rooms, staff, other

support.

Staff: Equipment: Rooms: Support:

5. Approximate number of participants required.

6. Approximate cost and proposed source of funding.

7. Proposed duration of project (in years):

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PLEASE RETURN COMPLETED FORM TO DENISE WATSON RESEARCH & INNOVATION OFFICE SMH

Appendix 2

WRITING A RESEARCH PROTOCOL GUIDANCE NOTES FOR RESEARCHERS

Introduction A research protocol provides justification of a research study and a detailed plan of investigation. It is used by the researchers as a reference tool throughout the duration of the study and protects the research method from gradual change. It should be sufficiently detailed for any person with appropriate qualifications and experience to direct an equivalent project. It allows the Trust, peer reviewer, Research Ethics Committee, or statistical advisor to make a judgement about the scientific aspects of the study. All research studies in Buckinghamshire Healthcare NHS Trust must be protocol based. Contents of a Protocol The length and complexity of a scientific protocol will reflect the nature and scope of the project. It divides into two main sections, and examples of research documentation (information sheets, consent forms, etc.) should be appended. .

Preamble to protocol

A front page with full title, a protocol number (ISRCTN, EudraCT number, REC number, RXQ number) and a version number & date. If any protocol amendments are made, then the protocol version number and date must be updated accordingly.

A contents page, detailing all relevant section / sub-sections and page numbers.

A signature page which senior members of the research team sign / date to confirm that the version has been approved and is final. This should also apply to protocol amendments.

The authority sponsoring the study and the sources of funding

The study team contact details of the chief / principle investigators, research nurse / fellow, trial co-ordinators and statisticians.

A summary of the main study issues. It should repeat the title of the study and cover objectives, design, treatment schedule, treatment groups, study endpoints and a flowchart of the schedule.

Body of protocol

An introduction to the study, justifying why it is necessary (hypothesis) and showing evidence of a literature search. May include a general background, previous studies on similar topics, structure & mechanism of the drug / procedure being assessed, rationale for the study and any relevant pre-clinical issues. References should be cited.

A simply stated trial aim / objective that clearly defines the research question, with primary / secondary endpoints.

The population to be studied, along with a clear listing of the inclusion and exclusion criteria and how subjects will be identified.

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How has the sample size been determined? The significance level and power used in the calculation should be stated. Realistic estimates of expected accrual rates and duration of patient entry into the study on estimated sample size should be provided as well as expected drop-out rates. All parameters used in the sample size calculation should be fully justified. Will there be an interim analysis?

A detailed description of any randomisation procedure – the type of randomisation procedure to be used, allocation ratio, any stratification factors (with levels) and any other factors considered in the process. Other things to consider are where allocation codes are kept, will the process be manual or automated, who will assign the randomisation, how will it be documented, who will have access to break the code in case of emergency. If the study is double-blind, detail the procedure and allowable reasons for breaking the blind (eg. clinical management purposes, treatment of overdose).

The process for obtaining informed written consent from the subjects. What systems have been put into place to work with minors or subjects who require the use of a legal representative?

The study procedure / treatment of subjects A detailed description of how the study will be conducted and what is performed at each study visit, including examinations, blood tests, other investigations, questionnaires, assessments for efficacy, end-points and safety. If different arms of the study have different treatments / interventions, then this needs to be stated.

The study drug supply. How any drug will be supplied (off the shelf, from a pharmaceutical company), packaged and labelled. (Special pharmacy control procedures will be required for drugs not generally available.) When will the drug be dispensed to subjects and how will accountability be documented:? What medication the subject may / may not take during the study?

A statement defining the end of the study. A study involving long term follow-up (such as oncology studies) may be split into 2 parts: randomised to treatment (the study period from the first patient being randomised into the study up to the last patient completing study treatment) and follow-up of all patients (the date the last randomised patient started long term follow-up up to the last patient completing follow-up, as stated in the protocol).

An assessment of safety. All studies using drugs / devices must have a defined pharmacovigilance procedure in place. This section should included information on the collection of toxicity data, definitions of adverse events (AEs) / serious adverse events (SAEs) / suspected unexpected serious adverse drug reactions (SUSARs). How these are to be recorded during the study and then reported to the study team / ethics / sponsor / regulatory authority and within what timeframes. Who within the study team takes responsibility for ensuring this process is adhered to? The researcher should consider a process for recording adverse events / effects of minors / vulnerable subjects for other types of studies (questionnaire / interviews), as a change in the process of the study may be required to minimise this effect.

How issues around subject withdrawal from the study will be handled - withdrawal from study medication / intervention, withdrawal from study follow-up, withdrawal of subject consent and therefore possible further subject data use. Studies should have a case report form page that lists reasons for withdrawals and protocol deviations / violations. Who will be informed of the withdrawl?

Data recording. When and how case data will be recorded, and who will be responsible for this? How and where is source data is to be documented and who will have access to this?(Separate guidance is available on the storage and handling

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of confidential study data and documents, to comply with data protection legislation.) How will subject anonymity be maintained? How long will study data and documents will be archived?

Quality control / quality assurance – how aspects of this will be implemented for the study (e.g. data monitoring committee, data monitoring and ethics committee, review of adverse events).

A statement of the ethical considerations involved and indicating that there is compliance with the principles of the World Medical Association Declaration of Helsinki (October 2000) and MRC/ICH good clinical practice..

A statement defining the publication policy – when and where results will be published. Who will be able to publish results?

A copy of the patient information sheet and consent form. These should also be marked with the appropriate project references, version numbers and dates. (Guidance on drafting these documents is available separately.)

Details of any payments to be made to subjects.

Declaration of possibly conflicting interests/relationships of the researchers.

(Text based on the guidance published by The Leeds Teaching Hospitals NHS Trust.)

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Appendix 3

Checklist for writing a patient information sheet (These are the questions your patient information sheet should seek to answer.)

Has the information sheet a clear and unambiguous heading?

Is the word 'Research' in the title of the consent form, and is it in bold?

Is the language throughout the sheet easy to understand?

What is the purpose of the study?

Why has this patient been chosen?

Does the patient have to take part?

What happens if the patient takes part?

Research methods - randomised trial, blind trial, cross-over trial, placebo

What does the patient have to do?

What drug or procedure is being tested?

What are the alternatives for diagnosis or treatment?

What are the side effects of taking part?

What are the possible disadvantages and risks of taking part?

What are the possible benefits of taking part?

Are the expenses/payment entitlements explained?

What will happen if the patient does not want to carry on?

What if new information becomes available (during the study)?

What happens after the research study?

What will happen to any samples given?

Will any genetic tests be done?

What if something goes wrong?

Will patient confidentiality be maintained?

What will happen to the results of the study?

Who is organising and funding the research?

Who has reviewed the study?

Who can the patient contact for further information?

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Appendix 4

DH Guidance on Storage of Research Records The following legislation, policies and common-practice guidance apply to the retention of records relating to research carried out in the NHS:

Data Protection Act 1998 (DPA) - Schedule 1, Part 1, Principle 5. Personal data processed for any purpose or purposes shall not be kept for longer than is necessary for that purpose or those purposes. (Data Protection Act 1998 (DPA) - Schedule 1, Part 1)

The Medicines for Human Use (Clinical Trials) Amendment Regulations 20061 - sections 18 and 28. The sponsor and the chief investigator shall ensure that the documents contained, or which have been contained, in the trial master file are retained for 5 years after the conclusion of the trial ….. The sponsor and the chief investigator shall ensure that the medical files of trial subjects are retained for at least 5 years after the conclusion of the trial. An ethics committee shall retain all the documents relating to a clinical trial on which it gives an opinion for: (a) where the trial proceeds, at least three years from the conclusion of the trial: or (b) where the trial does not proceed, at least three years from the date of the opinion. (The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006)

1

These regulations amend The Medicines for Human Use (Clinical Trials) Regulations 2004.

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COMMISSION DIRECTIVE 2003/63/EC (brought into UK law by inclusion in The Medicines for Human Use (Fees and Miscellaneous Amendments) Regulations 2003) – section 5.2(c). As a list of technical requirements, the Directive was simply added to a list of Community provisions that had to be complied with. Marketing authorisation holders must arrange for essential clinical trial documents (including case report forms) other than subject’s medical files, to be kept by the owners of the data: — for at least 15 years after completion or discontinuation of the trial, — or for at least two years after the granting of the last marketing authorisation in the European Community and when there are no pending or contemplated marketing applications in the European Community, — or for at least two years after formal discontinuation of clinical development of the investigational product. Subject’s medical files should be retained in accordance with applicable legislation and in accordance with the maximum period of time permitted by the hospital, institution or private practice. The documents can be retained for a longer period, however, if required by the applicable regulatory requirements or by agreement with the sponsor. It is the responsibility of the sponsor to inform the hospital, institution or practice as to when these documents no longer need to be retained. The sponsor or other owner of the data shall retain all other documentation pertaining to the trial as long as the product is authorised.

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The final report shall be retained by the sponsor or subsequent owner, for five years after the medicinal product is no longer authorised. (COMMISSION DIRECTIVE 2003/63/EC)

Research Governance Framework for Health and Social Care – paragraph 2.3.5. Data collected in the course of research must be retained for an appropriate period, to allow further analysis by the original or other research teams subject to consent, and to support monitoring by regulatory and other authorities. (Research Governance Framework for Health and Social Care)

Governance Arrangements for NHS Research Ethics Committees (GAfREC) – paragraph 7.8. A REC should retain all relevant records for a period of at least three years after completion of a research project…… (Governance Arrangements for NHS Research Ethics Committees (GAfREC))

Good Research Practice (MRC Ethics Series, 2000, updated 2005) – paragraph 5.2.

Personal Information in Medical Research (MRC Ethics Series, 2000, updated 2003) – chapter 7.

Data Protection Act 1998 – Part IV, Section 33 (3).

MRC The guidance on storage and reuse of research data suggests keeping research records for between 20 and 30 years (see guidance for full details).

DPA Personal data which are processed only for research purposes in compliance with the relevant conditions may, notwithstanding the fifth data protection principle, be kept indefinitely. However, the view of the Patient Information Advisory Group (PIAG) is that Principle 5 should be adhered to where personal data are used with support under Section 60 of the Health and Social Care Act 2001, and that the proposed retention

period should be made explicit where the basis for access is consent.2

(Good Research Practice) (Personal Information in Medical Research) (Data Protection Act 1998 - Part IV, Section 33)

Other considerations It is common practice for records to be kept for various lengths of time, eg seven, eight or fifteen years. However, Principle 5 of the DPA should be born in mind. It is not legitimate to archive health records for historical purposes. If such records are no longer required for the purposes of providing care, then they should not be retained in identifiable form or used for other purposes, without patient consent or without support under Section 60 of the Health and Social Care Act 2001. 2

PIAG will be giving further consideration during 2007 to the issue of data retention, with a view to issuing revised guidance if appropriate.

Various organisations, eg sponsors, funders, regulatory bodies, ethics committees, trusts, universities, may stipulate how long records should be kept. However, meeting any of these requirements in relation to research involving the NHS must be consistent with UK law and DH guidance.

Additional information For aspects of records and research involving the NHS not covered above, please refer to DH’s Records Management: NHS Code of Practice. In case of any query, please email stella.barclay@dh.gsi.gov.uk

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March 2007

Appendix 5

Who or What is a Sponsor

‘An individual, company, institution, or organisation which takes responsibility for the

initiation, management and/or financing (or arranging the financing) of a clinical trial’ (ICH

GCP 1.53).

In the UK

The sponsor must:

a) be established in the European Community, or

b) have a legal representative who is so established (SI2004 NO 1031).

What is a legal representative in this context?

The legal representative must be establidhed and contactable within the European Economic

Area (European Union member states + Iceland, Liechtenstein & Norway.

The sponsor, legal representative of the sponsor, or person/organisation authorised by the

sponsor to make an application signs the application form when requesting a Clinical Trial

Authorisation from the Competent Authority.

The sponsor is responsible for selecting qualified investigators, providing them with the

information they need to conduct an investigation properly, ensuring that the investigation is

conducted in accordance with the protocol as approved by the Competent Authority and Ethics

Committee during the trial and at the end of the trial and ensuring that the Competent

Authority and The Ethics Committee and all participating investigators are promptly informed

of significant new adverse effects or risks with respect to the drug.

The responsibilities of the sponsor may be shared in one of two ways, under UK law

Joint responsibility-whereby two or more persons (whether individuals, companies,

institutions or organisations) are jointly responsible for all responsibilities, or

Allocated responsibility –whereby two or more persons each take on separate

responsibilities i.e. co-sponsorship. In this situation it is crucial to specify who is

responsible for what in a written agreement. In particular, the person responsible for

making the application for the clinical trial authorisation (CTA) and ethics committee

opinion has to specify in the CTA application who is responsible for:

o Requesting the CTA and ethics opinion (Part 3 of SI2004No1031)

o Good clinical Practice and the conduct of the Trial (once the CTA is granted)

[Part 4]

o Pharmacovigilance [Part 5]

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Under an allocated responsibility sponsor model, it should also be documented who is

responsible, once the CTA is granted, for sponsor responsibilities under Parts 3, 4 or 5 with

regard to substantial amendments.

The application form also enables sponsors to indicate who will be responsible for:

Monitoring

Investigator recruitment

Interactive voice response system (IVRS)-treatment randomisation

Data management

E-data capture

Suspected Unexpected Serious Adverse Reaction

Quality Assurance auditing

Statistical analysis

Medical writing

Other subcontracted responsibilities.

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Appendix 6

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Appendix 7

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.)

Diabetes Centre

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.)

Research experience: (Summary of research experience, including the extent of your involvement. Refer to any specific clinical or research experience relevant to the current application.)

Research training: (Details of any relevant training in the design or conduct of research, for example in the Clinical Trials Regulations, Good Clinical Practice, consent or other training appropriate to non-clinical research. Give the date of the training.)

Relevant publications: (Give references to all publications in the last two years plus other publications relevant to the current application.)

Signature: Date:

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