Please find below the latest newsletter from the Joint Research Office.  This newsletter focuses on new developments in NHS R&D with guidance about the new R&D approval process, IRAS, NIHR Portfolio and CSP. 

• Newsletter 07-09

Research governance refers to a set of principles, standards, regulations and legislation to ensure good practice and reduce risks associated with research.  The fundamental principles of the Department of Health Research Governance Framework (RGF) are safety and protection of all those involved in research by respecting participants’ rights, dignity and confidentiality.  It provides a framework to ensure high quality research is conducted in the NHS, focusing on scientific quality, ethical and financial standards, allocation of responsibilities and robust monitoring arrangements.

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

The Research Governance Framework relates to all research in the NHS involving human participants (patients or staff as research participants), their organs, tissue or data/records.

The sections below give brief guidance to help you through the approvals process when beginning a research project involving the NHS and research governance issues related to research.   This guidance is currently being developed further and the final version will be available shortly. 

It also includes information about how to identify an appropriate Research Sponsor for your research as an essential requirement under the Department of Research Governance Framework.  The application process for gaining approval from Newcastle upon Tyne Hospitals NHS Foundation (NUTH FT) is described including information about the INIHR Clinical Research Portfolio and the links to the new Co-ordinated System for NHS Permission (CSP).  Certain approvals will be required for your research and this is dependent on the type of research you are conducting.  Clinical trials of Investigational Medicinal Products (ctIMPs), fall under the EU Clinical Trials Directive and must work within a specific statutory framework within the UK under the Medicines for Human Use (Clinical Trials) Regulations 2004 & Amendment Regulations 2006.  Separate information is provided for these studies.  

As an excellent reference document to provide a summary of websites to assist in all areas of research processing and approvals and research governance, see the NHS R&D Forum at:

http://www.rdforum.nhs.uk/workgroups/primary/pcinfoguide/introduction.htm

and download the latest Research Governance Guide

There are already a number of Standard Operating Procedures (SOPs) and Working Instructions (WIs) for research within the Newcastle Hospitals Trust and Newcastle University which are hosted by the Newcastle Biomedicine Clinical Research Platform website at: 

http://www.ncl.ac.uk/crp/collaboration/standardop/library/

 There is currently a SOP working group reviewing these SOPs and developing additional SOPs for use in research throughout the Trust and University.  The location of all existing and new SOPs will be available on this website shortly.

The Department of Health Research Governance Framework:

http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4108962

- requires all research within the NHS to have an identified Research Sponsor.  Please see the attached document to help you determine who should be Research Sponsor for your project when working with Newcastle Hospitals Trust or Newcastle University.

Once you have secured funding for your research project, there are a number of approvals required before research can be conducted in the UK subject to adherence to legislation and regulations.  It has become increasing confusing when applications for the various approvals should be made.  The approvals required depend on the nature of the research and the type of study you are conducting.  (see below for the process for NIHR Portfolio projects which are now processed through the CSP system). 

The important message is that applications for approvals can be processed in parallel under any system and investigators are encouraged to apply as early as possible to avoid delay.

Permission is required from each NHS Organisation involved in a research project.  If your research involves any of the following then the Newcastle Trust must approve your research before it begins:

• NUTH FT patients, their data or tissue
• NUTH FT staff as participants in research or their data or tissue
• NUTH FT facilities or premises

There is a NUTH Trust R&D Approvals Committee that reviews all new projects and carries out risk assessments (see below for the membership of the group and the Terms of Reference)

The Committee meets once a month with a deadline for submission of applications of 2 weeks before the meeting (see document below for dates).  Each project is risk assessed on behalf of the Trust in accordance with the DH Research Governance Framework (RGF) and other research regulations and legislation (see ‘Clinical trials of Investigational Medicinal Products (ctIMPs)’).  This risk assessment considers:

• Patient safety (ethics, appropriate approvals eg. MHRA,  attention to patient confidentiality and data protection)
• Scientific risk (independent peer reviewed)
• Financial risk (full economic costing)
• Investigator risk (NHS employment contracts or Honorary Research Contracts – linked to insurance/indemnity)
• Organisational risk:  Sponsorship arrangements

Outcome of the meeting:

• Recommend to approve
• Recommend to approve subject to further clarification of issues raised and/or final approvals from ethics/MHRA/Caldicott etc
• Recommend NOT to approve

The risk assessment is sent out the Chief or Principal Investigator within 2 weeks of the meeting.  Once issues have been resolved the research project is then sent for final approval. 

Research CANNOT begin in Newcastle upon Tyne Hospitals NHS Foundation Trust without a final letter of approval signed by the Trust CEO

R&D Committee dates 2010

To apply directly for Trust R&D approval at Newcastle Hospitals Trust please complete the following R&D Additional Information Form V3.0 Nov 2009 and provide the documentation requested on the checklist.  (Important note: For NIHR portfolio studies please see the section below and note that your approval needs to be processed through the Co-ordinated System for Permissions in the NHS – CSP.  Contact the R&D office to discuss this further)

PLEASE NOTE, TRUST R&D CANNOT BEGIN PROCESSING YOUR APPLICATION UNTIL YOU HAVE FUNDING FOR THE RESEARCH CONFIRMED

Please also note all documents are now to be submitted electronically to the following address: Trust.R&D@nuth.nhs.uk. (webmail users will need to copy this mail address into their message). Please DO NOT copy in other members of the R&D Staff into your submission email – the Trust R&D email account is checked twice a day for new applications and you will receive an acknowledgement email confirming receipt of your application. 

If you have a very large submission with large documents then these will be difficult to send in an email.  In these situations, you should save to disc or memory stick and send or bring these to our department.  The disc or memory stick will be returned to you once we have uploaded the documents.

You should also note that if your project has been adopted by the NIHR Portfolio then it must be processed through the centralised database available to all NHS R&D departments – this is called the Co-ordinated System for gaining NHS Permissions (CSP).  If your project is being processed through CSP you should inform R&D as many of the documents listed below will already be available to us in the central document repository in the CSP database.

The following documents are required for a valid application:

• R&D Additional Information Form (V3 July 2009) – please note, this form helps us to help you by providing additional information that we are unable to get from the NHS R&D form or the SSI form in the IRAS system.   By providing this additional information at this early stage we hope to be able to process your application as quickly as possible as this helps our support departments assess the project – this replaces the need for you to visit each support department to discuss your project and have them sign the SSI form  – click here to download the form
  
• Evidence of funding and a breakdown of costs at this site as well as any costings spreadsheet you may have (eg, from the Research Platforms, Industry Costing Template etc.)
• Latest study protocol which clearly shows the version number and date
• Latest Participant Information Sheet and Informed Consent form which clearly shows the version number and date (ideally we need this localised with Trust logo and local contact details – if you are unable to provide this at date of submission for R&D approval this can follow at a later date but please be aware we will need this for our records before final approval). 
• NHS R&D Form (generated via IRAS submit as XML file AND a PDF file) – click here see the guidance document about saving files as XML
• SSI Form (generated via IRAS submit as a PDF file).  This form should be signed by the local investigator or it can be electronically authorised through the IRAS system.  If it is a wet ink signature you can save the PDF form in IRAS, send this to us and then send a scanned copy or original copy of the signature page separately.  If electronically authorised through IRAS, once authorised by investigator, save as PDF and send this form to us.  Please note, you do not need to have the SSI form authorised by managers within the NHS organisation/support department prior to submission (Q23)  – we discuss the project with the support departments as part of our R&D Approvals Committee.
• CVs of the main investigator at this site and any other key staff at this site (eg, any co-investigator, lead research nurse—we do not require CVs of staff that do no have patient contact).  There is a recommended 2-page short CV template which is available through IRAS and which can be managed through this system.  In IRAS you will find the template under ‘my account’ tab and it can be easily updated and attached to applications. Alternatively see this CV template.
• For ALL commercial projects – we need a study agreement/contract (at least in draft).  This should be one of the nationally recognised model agreements between the NHS and industry (see:  http://www.ukcrc.org/regulationgovernance/modelagreements.aspx.  the finance section must be completed otherwise the study will not be suitable for review by the Approvals Committee. 
• For ALL clinical trials of Investigational Medicinal Products (ctIMP) studies where the Trust is NOT Sponsor (for both commercial and non-commercial studies) – we need a study clinical trial agreement with the sponsor (at least in draft).  Again this should be one of the nationally recognised model agreements for clinical trials either the commercial or non-commercial agreement depending on the sponsor  - also see http://www.ukcrc.org/regulationgovernance/modelagreements.aspx

Please submit the following documents if they are already available but these can follow at a later stage:

• Favourable opinion from NHS REC
• Approval letter from MHRA (if already granted)
• Caldicott approval (if already granted)
• Any evidence of other approvals necessary for your study

If you would like the Newcastle upon Tyne Hospitals NHS Foundation Trust to act as sponsor and need the original REC form signed please call us to arrange an appointment.

Caldicott approval can be sought by visiting http://intranet/dataprotection/Approval/notificationmain.asp if you have access to the Trust intranet site.  If not, please see the Caldicott section below and download the form – the form should be submitted to Richard Oliver as indicated. 

For commercially sponsored studies these projects should be pre-registered before full submission of the application to R&D to allow inform the necessary support departments (eg, Pharmacy) .  Please call the R&D office to arrange this.

If you are unsure about any of the above please call 0191 28 25959.

The final signed letter of approval from the Trust will not be granted until the R&D Approvals Committee has carried out the risk assessment and the R&D department has seen evidence of the various other approvals necessary to carry out your research

From 18^th November 2008, projects that have been adopted by the NIHR Clinical Research Network Portfolio are processed for NHS permissions and approvals in a different way.  The new system for approvals for portfolio studies only is the Co-ordinated System for gaining Permissions in the NHS (CSP).  These could be non-commercial studies or commercial studies that are eligible for adoption to the NIHR portfolio.

Non-commercial studies

Studies funded by NIHR partner organisations are eligible to be included in the NIHR Clinical Research Network Portfolio. NIHR partners are organisations that award funding for research that is of clear value to the NHS, in open national competition across England, with high quality peer review, and with strategic direction for the research they fund. Other well-designed studies funded by non-NIHR partner organisations, including investigator initiated studies, may be eligible for inclusion in the Portfolio via an NIHR adoption process. See http://www.ukcrn.org.uk/index/clinical/portfolio_new/P_eligibility.html for full details about eligibility criteria for portfolio adoption.

Commercial studies

Commercial studies (which are sponsored and funded by a commercial company) are also eligible for adoption to the portfolio to allow processing through the centralised CSP system.  Any commercial company that wants to access this process would approach and be assessed for adoption through a separate NIHR Industry Team – see http://www.ukcrn.org.uk/index/industry/collaborations.html for more details.

CSP Factsheet

Studies not eligible for portfolio adoption

Studies that are not eligible for portfolio adoption will NOT be processed through the new CSP system (eg, smaller studies funded by local charities, own or self-funded projects etc).  For these studies you MUST contact your local Research and Development Department to arrange approval for your study (see above for information about applying directly to Newcastle Trust R&D.

CSP - Key points:

• From 18th November 2008 researchers that want NEW non-commercial projects considered for NIHR portfolio adoption should apply for registration through the Portfolio Adoption Team at an early stage in the research process (NIHR is encouraging application to the NIHR portfolio adoption team at the bid stage but at the latest you should apply as soon as funding is confirmed).
• Registration for adoption to the portfolio is now via the Integrated Research Application System (IRAS) website at https://webmail.nuth.nhs.uk/exchweb/bin/redir.asp?URL=https://www.myresearchproject.org.uk/.  Investigators that want their study considered for portfolio adoption should complete the filter page at the IRAS website.  They must select ‘England’ at question 3a and then answer ‘yes’ at question 5a for processing through CSP.  This produces a Portfolio Adoption Form (PAF) in ‘project forms’ which should be completed and submitted to the NIHR portfolio team for consideration – see the attached CSP Factsheet for specific instructions.
• All studies adopted by the portfolio MUST be processed through the centralised CSP system (see the attached factsheet for the processes for single site and multi-site projects)
• If your study is adopted by the portfolio then the project is automatically logged with the CSP Unit and goes onto the CSP system awaiting all the necessary documentation

What happens next for portfolio projects being processed through CSP?

• The investigator needs to complete all of the necessary documentation (eg, REC application, R&D application form etc) on the IRAS website  (please note REC form still needs to be printed and signed by relevant parties for submission to REC with ‘wet ink’ signatures)
• These forms and all other supporting documents are uploaded to the CSP system for processing by R&D departments.
• All NHS Organisations involved in the project will be notified about the project via the CSP system which has been set-up in all Trust R&D departments.

Portfolio projects being processed in Newcastle upon Tyne Hospitals NHS Foundation Trust (NUTH FT) R&D

• Once NUTH FT receives information about a study via the CSP system, someone from R&D will contact the investigator to obtain any additional information required to allow R&D to process the application.
• Once all the information necessary for processing has been received, the project will be placed on the agenda of the next available Trust R&D approvals committee.
• The risk assessment and governance checks that form part of the R&D approvals meeting and follow-up processes form the basis of the CSP approvals process and R&D will log all the information necessary on the CSP system.
• Once all of the governance checks are complete and verified, then R&D will arrange the necessary letter of approval from the Trust and upload this to the CSP system – there is a ‘21 day clock’ for this final letter to be processed and issued.
• Therefore, in summary, for the investigator, the main difference to current practice is making sure that projects that are eligible are registered on the portfolio as soon and possible and therefore entered automatically on the CSP system for processing.
• We will do all we can to help investigators through the transition period as we all adjust to the new CSP system.  If you have any questions please contact Dr Lesley Hall at Newcastle Trust R&D (see below) or Mark Ryan-Daly at NTW CLRN - Mark.Ryan-Daly@nuth.nhs.uk – tele: 0191 2418842.

There is a particularly strict legal framework under the EU Clinical Trials Directive (transposed into UK law through the Medicines for Human Use Regulations 2004 and Amendment Regulations 2006) which applies to ctIMP studies.  If your study is a ctIMP then a Clinical Trial Authorisation (CTA) is required from the Medicines and Healthcare products Regulatory Agency (MHRA) at: http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&nodeId=723 .  You must also register your study with the European Clinical Trials database (EudraCT) at http://eudract.emea.europa.eu/ and obtain a unique EudraCT Number which must be recorded on all documentation.  This number is required before a submission can be made to MHRA. 

See the clinical trials toolkit at:  http://www.ct-toolkit.ac.uk/

Flowchart for ctIMP Approval

Completion of the documentation required to obtain a CTA can be extremely complex and involved.  Furthermore, the ongoing monitoring of ctIMPs is a statutory requirement of the EU Clinical Trials Directive and subsequent Good Clinical Practice (GCP) Regulations (see Good Clinical Practice (GCP) requirements below)

For ctIMPs which are commercially sponsored and funded the commercial Sponsor is responsible for making the necessary applications to MHRA and for the quality of the study documentation, safety monitoring and reporting for the study.  However, for non-commercial studies this responsibility lies with the non-commercial Sponsor.  This is a responsibility that is delegated to the Chief Investigator for the study.

It is now policy at Newcastle Hospitals Trust that any ctIMP for which the Trust is Research Sponsor, must provide evidence that there is appropriate support to assist in making the initial application to MHRA for the Clinical Trial Authorisation and for the ongoing monitoring of the study.  For studies being carried out as part of a larger research networks this type of support is now more commonly available.  However, for other studies the Trust would expect the researchers to enlist the services of an accredited Clinical Trials Unit to assist with the application for the CTA with MHRA and for the ongoing monitoring of the study. 

See this document for the expectations and obligations of PIs running ctIMPs

For studies which are not ctIMPs and therefore not subject to the regulations above, other approvals will still be required before research can begin.  As a minimum, these studies will require NHS Research Ethics Review and Trust R&D approvals from all trusts involved in the research.  (see below for information about applying for approval in Newcastle Hospitals Trust). 

There may be other approvals required depending on the type of research.  Consult the research governance guide:

http://www.rdforum.nhs.uk/workgroups/primary/pcinfoguide/introduction.htm

Non-ctIMP Studies Approvals Flowchart

Guidance on the approval of research involving ionising radiation is available on the NRES website at http://www.nres.npsa.nhs.uk/news-and-publications/news/approval-of-research-involving-ionising-radiation2/

Full guidance can be downloaded at this site explaining the requirements both for a favourable opinion from the main REC, including ethical consideration of radiation exposures, and local employers' approval for these exposures under the Ionising Radiation (Medical Exposure) Regulations 2000 ("IRMER"). The guidance aims to harmonise these procedures, facilitate communication and consultation between those concerned and avoid unnecessary duplication of effort.

For advice locally within Newcastle Trust please contact: 

Dr Ian Driver
Consultant Physicist
email:  Ian.Driver@nuth.nhs.uk

Not all of the projects undertaken are research. If your study is an audit or service evaluation then it would NOT be classified as research.  However, it can be difficult to differentiate between research, audit and service evaluation.  Useful guidance is provided by National Research Ethics Services (NRES) Guidance page –http://www.nres.npsa.nhs.uk/rec-community/guidance/#researchorauditcommunity/guidance/#researchoraudit.  If you go to this page under ‘Research or Audit’ there is a leaflet entitled ‘Defining Research Leaflet’. 

If you are still unsure whether your study is research or audit/service evaluation you can contact the Chair of your local REC by email with a description of your proposal (one side of A4 in length) and seek their opinion.  Alternatively you can send you A4 summary to NRES for an opinion (email: queries@nres.npsa.nhs.uk).

For clinical audit projects please contact the Trust’s Clinical Governance and Risk Department.

All research in the NHS requires a review by an NHS Research Ethics Committee.  This is made explicit in the Government Arrangements for NHS Research Ethics Committees (GAfREC) paragraph 3.1 states that ethical review from the appropriate NHS REC is required for any research proposal involving:

a) 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

b) individuals identified as potential research participants because of their status as relatives or carers of patients and users of the NHS, as defined above

c) access to data, organs or other bodily material of past and present NHS patients

d) fetal material and IVF involving NHS patients

e) the recently dead in NHS premises

f) the use of, or potential access to, NHS premises or facilities

g) NHS staff - recruited as research participants by virtue of their professional role.

See http://www.nres.npsa.nhs.uk/applicants/help/faq/do-i-need-ethical-approval/

No research involving any of the above can begin before a FULL favourable opinion has been obtained from an NHS Research Ethics Committee.  To apply for NHS ethical review please go to the IRAS website at:  https://www.myresearchproject.org.uk/ 

See the IRAS User Manual: https://www.myresearchproject.org.uk/Help/UsingIRAS.aspx

Remember the REC form requires ‘wet ink’ signatures before submission in hard copy to the REC.  If Newcastle Trust is Sponsor, the Declaration of Sponsor section must be signed by either Ms Amanda Tortice or Dr Lesley Hall on behalf of the Trust.  Contact the Joint Research Office (Research & Development) to arrange a time to have your form signed.

If your research falls outside the GafREC 3.1 remit it is often still advisable in most cases to seek an opinion from an NHS Research Ethics Committee especially if involving human subjects, tissue or data.  Most NHS RECs will review projects on request, especially those involving human subjects (eg, healthy volunteer studies that could be considered interventional).  For example, healthy volunteer studies taking blood or tissue samples, those involving x-rays or MRI scans, ETC.  For studies of this type within Newcastle University, the University will act as Sponsor and a representative of the BDD will sign the Declaration of Sponsor section on the ethics form (see Determining Sponsor document above). 

For all studies within the University of Newcastle that involve human subjects that will not be reviewed by an NHS REC must be reviewed by the University of Newcastle Ethics Committee

See: 

http://www.ncl.ac.uk/internal/finance/insurance/special_cover/human_subjects.htm

http://www.ncl.ac.uk/internal/finance/insurance/special_cover/clinical_trials.htm

All research projects that require insurance cover by the University of Newcastle must be reviewed by the insurance and Risk Manager, Mark Jackson (see below for contact details).  This is extremely important as the University insurance has exclusion clauses that must be checked and verified.

Mark Jackson
Insurance and Risk Manager
Newcastle University
Finance Office
6 Park Terrace
Newcastle upon Tyne
NE1 7RU
Tel: 0191 222 3913

Email:  mark.jackson2@newcastle.ac.uk

REC questions about insurance and indemnity

On the NHS REC application form there is a three part question regarding insurance and indemnity.  The following is a guide to complete this question.

1. Management

• If NUTH as Sponsor then NHS indemnity for patients and healthy controls

2 Design

• If an NHS organisation agrees to sponsor this does not over-ride the employer’s responsibility for professional activities eg: protocol writing.  Honorary clinical or honorary research contract relates only to clinical activity and duty of care – writing of protocols remains the responsibility of the substantive employer (eg, University)
• If all protocol authors are NHS then tick NHS.
• If all protocol authors are University staff should say something like this: ‘The legal liability of the employer will be Public Products and Employer’s Liability Policy held by the University’
• Where authors are split (NHS and University staff) then should say: ‘The legal liability of the sponsor and employer will be covered by either NHS indemnity or Public Products and Employer’s Liability Policy held by the University’

3 Conduct

• Where NUTH as Sponsor then NHS indemnity

FOR UNIVERSITY INSURANCE COVER YOU WILL REQUIRE A LETTER FROM THE UNIVERSITY INSURANCE OFFICER (TO BE SUBMITTED WITH YOUR ETHICS FORM TO THE RESEARCH ETHICS COMMITTEE. 

YOU DO NOT REQUIRE DOCUMENTARY EVIDENCE FOR NHS INSURANCE COVER.

Where the Newcastle Trust is acting as Research Sponsor for the research, the following details should be entered in the sponsor information section:

Name or ogranisation:

Newcastle upon Tyne Hospitals NHS Foundation Trust

Address: 

Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
Tele:  0191 2825959
Fax:  0191 2820064
Email:  Trust.R&D@nuth.nhs.uk

Sponsor's UK contact:

Ms Amanda Tortice
Newcastle upon Tyne Hospitals NHS Foundation Trust
Joint Research Office
4th Floor, Leazes Wing
Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
Tele:  0191 2825959
Fax:  0191 2824524
Email:  amanda.tortice@nuth.nhs.uk

Amanda Tortice is the Research Operations Manager and is the official contact person registered with REC.  However, either Amanda Tortice or Lesley Hall, Research Governance Manger, can sign the form on behalf of the Trust. Call the Joint Research Office to make an appointment for to have a REC form signed:  0191 2825959

Review of research databases by an NHS Research Ethics Committee is voluntary through the new system and under Research Governance Framework (RGF) there is no requirement for NHS research permission for the establishment of a research database or registry in the NHS.  It is because NHS permission is not required for databases that there is no identified Research Sponsor on new database review form (see the IRAS website at:  https://www.myresearchproject.org.uk/ and complete the filter form for access to form for research database review). 

Any subsequent research projects which conducted using the data from a research database or registry would require a full NHS Research Ethics Committee review and NHS R&D permission for each Trust involved.  Each study will require a separate review and application.

It should also be noted that where using patient data to set up a database or registry for research, the Trust Caldicott Guardian must give permission for this use and storage of data (see below for information about applying for Caldicott approval).

Participant Information sheets and Informed consent

 All participants must receive information about the study to allow them to make an informed decision about taking part.  This must be approved by the NHS Research Ethics Committee. 

 It is extremely important that the any changes to the Participant Information Sheet (PIS) and/or consent form are submitted for consideration through the appropriate amendment procedures to the REC (see above for amendments). 

 See the NRES website for examples and processes for designing Patient Information Sheets and Informed Consent forms: http://www.nres.npsa.nhs.uk/rec-community/guidance/#PIS

Version control of Patient Information Sheets and Informed Consent forms

It is vital that the correct version of the PIS and consent form are used at all times.  Where a PIS or consent form has been changed and approved through an amendment form REC, then a line should be put through the older version of both documents in the main file and the words ‘superseded by version....’ should be written across the page.  All other copies of the old PIS and consent should be removed from use and destroyed. 

Where necessary patients should be re-consented using the new PIS and consent form which is especially important when changes to these forms involve information that could affect the safety of participants.

 The informed consent forms should reference the correct version of the PIS to confirm that participant has received and read this information. 

 Informed consent is a three step process:

1. The giving of information (the Patient Information Sheet)
2. The discussion and clarification of the information (with adequate time to review information usually 24 hours)
3. Verbal and written consent (using the appropriate consent form)

 All participants entering into a research project MUST have given informed consent before any aspect of the project starts (interventional or non-interventional)

It is the responsibility of the Chief Investigator (CI) or Principle Investigator (PI) to ensure appropriate consent is taken for each participant.  However, sometimes this responsibility is delegated to an appropriate, suitably qualified member of the research team.  Anyone taking this responsibility should be fully trained and have a full understanding of the study and potential risks/benefits.

All training should be documented and the delegation of responsibility should also be clearly documented on the study delegation log.  All responsibilities allocated to each member of the research team should be documented clearly on this log. The log must be signed and dated by the CI/PI.

All those responsible for obtaining written informed consent must have a copy of their signed and dated CVs in the Trial Master File (TMF).

All consent forms must be signed and dated by the participant – it is not acceptable for the CI or person taking consent to date the form for the participant.  The participant should also initial (not tick) in each of the boxes to indicate they have read and understand each statement they are consenting to.

The consent form must be signed and dated by the CI or person taking consent at the same time as the participant signs and dates the consent form. 

The original signed consent form for each participant should be kept on the main file at the site (Trial Master File or Investigator Site File).  A photocopy (or carbon copy if specifically printed forms in triplicate are used) should be given to the participant and a copy placed on the patient’s medical notes.

The following basic rules should apply to consent forms:

1. Consent forms and Patient information Sheets must be on letterhead – the Newcastle Hospitals Trust logo should be included on letterhead or Trust letterhead should be used where patients of this Trust are the participants of the study
2. The consent form should reference the correct version number and date of the Patient Information Sheet
3. All statements to which the participant is agreeing should be initialled by the participant in the box at the end of the statement – this confirms they have read each statement.  Ticking these statements is not acceptable evidence as anyone could tick the box.
4. Form must be signed and dated by the participant (ie, so that it is clear that it in the participant’s handwriting)
5. Form must be signed and dated by the person taking consent at the same time that the participant signs.

It is a statutory requirement of the EU Clinical Trials Directive and subsequent amendments (Medicines for Human Use Regulations and Amendment Regulations in the UK) that clinical trials of Investigational Medicinal Products (ctIMPs) are conducted to Good Clinical Practice (GCP) standards (most commonly reference is made to IHC-GCP).  IHC-GCP is a set of internationally recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording and reporting ctIMPs that involve the participation of human subjects.  Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected and that the results of the clinical trial are credible and accurate.

To ensure that ctIMP studies are carried out to GCP standards, all staff involved in these studies must be GCP trained on a regular basis.  In Newcastle Hospitals Trust is it policy that investigators and staff must have completed a full face-to-face GCP training course and then that this training is updated through a refresher course every three years as a minimum.  This training is mandatory for ctIMP studies, in particular where NUTHFT acts as Sponsor for these studies.  This training is available on a rolling programme through Newcastle CRC using an accredited GCP trainer.  See the programme on the CRC website at: http://www.ncl.ac.uk/crc/training/trainingdays/item/forthcoming-events1

However it is good practice for researchers involved in non ctIMP studies to be aware of and work to Good Clinical Practice (GCP) standards in Research as outlined in the Research Governance Framework.  Therefore, from January 2008 Newcastle Trust is advising all new researchers attend the following three training days, GCP in research, legal issues and responsibilities and research ethics and consent before becoming actively involved in a research study.  The above mandate gained approval from the Joint Research Executive committee which oversees research conducted within Newcastle University and NUTHFT in November 2007. 

Again, see for information about research training days: http://www.ncl.ac.uk/crc/training/trainingdays/item/forthcoming-events1

GCP is also offered by the Comprehensive Local Research Network – please visit website at:  http://www.crncc.nihr.ac.uk/index/networks/comprehensive/clrns/northumberland.html

Or contact Mark Ryan-Daly at:  Mark.Ryan-Daly@nuth.nhs.uk

Many Research Sponsor tasks are delegated to the Chief Investigator or local Principal Investigator and then to members of the Research Team. These are outlined the document below.

Delegated Responsibilities

Depending on the level of direct contact with patients and/or direct bearing on their care, researchers may require an Honorary Research Contracts or a letter of access with the Trust.  The type of contract or letter required will be determined by the Human Resources department. 

At present, the same form issued in all cases (see Trust application form below).  However, if a person applying for an honorary research contract is employed by or studying at the University of Newcastle, then the application should be processed through the University of Newcastle in the first instance.  Please contact Daniel.stow@ncl.ac.uk ext 5428 for the relevant application form and procedures. 

For all other applications for Honorary Research Contracts please complete the form below and send directly to Trust R&D, Joint Research Office, 4^th Floor, Leazes Wing, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP.

Trust application for an Honorary Contract

What is patient identifiable information?

"All items of information which relate to an attribute of an individual should be treated as potentially capable of identifying patients and hence should be appropriately protected to safeguard confidentiality". (Caldicott Committee: Report on the review of patient-identifiable information, 1997)

These items include:

 or a combination of these pieces of information.

Approval from the Newcastle upon Tyne Hospitals NHS Foundation Trust Caldicott Guardian is required for research where data is used for any living patient (this also includes images, videos, charts etc).  An application should be made to the Caldicott Guardian for all use of NHS patient data even if you consider the data being held to be non-identifiable data.  It is the responsibility of the Caldicott Guardian to review the use of all data and determine if it is appropriately anonymised to ensure that this it non-identifiable.  If identifiable data is to be used then you must be able to justify the requirement for use of this data.  In addition, all databases created for the purposes of research to hold patient identifiable data must also be registered with the Trust for data protection purposes.   

Applications for Caldicott approval and to register a database can now be made using a single on-line application form.  At present this is only available on the Newcastle Trust intranet site but the Trust hopes to put this on the external internet site as soon as possible.  To access the form and guidance notes, go to the alphabetical site index on the intranet site and click ‘C’ for Caldicott.  On the Caldicott/Data Protection page click on the ‘Data Protection Notification’ button.  On the next page click ‘Data Protection and Caldicott Guidance’ document and read these notes before completing the application form.  To complete the on-line form click on ‘the ‘Data Protection and Caldicott Form’ button.  Using the ‘Send for Approval’ button at the bottom of the form, this is sent directly to the Caldicott and Data Protection team for consideration.  Once you have received approval for use of the data, you should inform R&D as this approval forms part of your overall Trust R&D approval.

If you are unable to access the Newcastle Trust intranet site then please make your Caldicott application using the paper application form below:

New Caldicott Form download

Amendments to a research project must be considered in all cases to determine if these are substantial or non-substantial amendments.

Definition of substantial and non-substantial amendments

The guidance below is from the NRES website:

The following amendments should normally be regarded as substantial:

• changes to the design or methodology of the study, or to background information affecting its scientific value;
• changes to the procedures undertaken by participants;
• any change relating to the safety or physical or mental integrity of participants, or to the risk/benefit assessment for the study;
• changes to study documentation such as participant information sheets, consent forms, questionnaires, letters of invitation, letters to GPs or other clinicians, information sheets for relatives or carers;
• a change of sponsor(s) or sponsor’s legal representative;
• appointment of a new chief investigator or key collaborator;
• a change to the insurance or indemnity arrangements for the study;
• inclusion of a new research site (not listed in the original application) in a study requiring site-specific assessment (SSA);
• appointment of a new principal investigator at a research site;
• a significant change to the definition of a research site requiring SSA;
• a change to the SSA-exempt status of a study;
• a change to the definition of the end of the study;
• any other significant change to the protocol or the terms of the REC application.

There will, however, be changes to the details of research that have no significant implications for participants or for the conduct, management or scientific value of the study and can be regarded as ‘non-substantial’ or ‘minor’ amendments.

Examples of non-substantial amendments might be as follows:

• correction of typographical errors in the protocol or other study documentation;
• other minor clarifications of the protocol;
• updates of the Investigator's Brochure (unless there is a change to the risk/benefit assessment for the trial);
• changes to the chief investigator’s research team (other than appointment of key collaborators);
• changes to the research team at particular trial sites (other than appointment of a new principal investigator);
• changes in funding arrangements;
• changes in the documentation used by the research team for recording study data;
• changes in the logistical arrangements for storing or transporting samples;
• inclusion of new sites in SSA-exempt studies;
• extension of the study beyond the period specified in the application form.

Changes to contact details for the sponsor (or the sponsor’s representative), chief investigator or other project staff are minor amendments but should be notified to the main REC for information. Changes to contact details for principal investigators should be notified both to the main REC and the relevant local REC.

For full information and guidance, please see the guidance at: http://www.nres.npsa.nhs.uk/applicants/after-ethical-review/amendments/

This describes the process for submitting amendments to the Research Ethics Committee and MHRA (for ctIMP studies).

In all cases, Trust R&D departments concerned should receive a copy of the amendment documents submitted to REC and MHRA (if applicable) as Trust R&D must also approve the amendment.

Any substantial amendment should not be implemented until approval has been received.

The definition of the end of trial or study should be included in your protocol.  This is usually the date of the last visit of the last patient taking part in the study and this includes follow-up visits or data collection as described in your protocol.  Any changes to the end of study must be treated as a substantial amendment to REC and MHRA (if relevant) - see Amendments above.

For clinical trials of Investigations Medicinal Products (ctIMPs) it is a statutory requirement (Article 10 (c) of the Directive 200/20/EC) that MHRA as the Competent Authority is notified of the end of the trial within 90 days or within 15 days if the Trial is terminated early or halted.  Notification of end of trial is a Research Sponsor responsibility which is usually delegated to the Chief Investigator.  For trials involving other countries, then the appropriate competent authorities in each member state should also be notified when the study ends in each country.  For further guidance see: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-10/11_ca_14-2005.pdf

The end of trial should be notified on the Annex 3 form available on at the following link. 

https://eudract.emea.europa.eu/eudract/endOfTrialForm.do

One form should be send to the competent authority (eg, MHRA), one form to the Research Ethics Committee and a copy to R&D.  It is the responsibility of the competent authority to record this on the EudraCT database. 

For other non-ctIMP studies it is the responsibility of the chief investigator to notify the main REC of the end of the project.  The NRES declaration of the end of a study form should be used and again a copy of this sent to R&D.  For further guidance see:

http://www.nres.npsa.nhs.uk/applicants/after-ethical-review/endofproject/

In both cases, the study will then be closed in R&D, a notification will be send to you confirming the file has been closed.

Once completed your study documentation should be archived appropriately.  See the following link for guidance from the Department of Health regarding retention of records and archiving of research documents for research within the NHS.

http://www.dh.gov.uk/en/Researchanddevelopment/A-Z/Researchgovernance/index.htm

It is a requirement of the Research Governance Framework that NHS Trusts regularly audit research projects being carried out within their organisation.  This is not only to protect the organisation but also to protect investigators and research teams by ensuring that research is compliant with regulatory requirements.  It also assists with preparation for external audit or inspection by competent authorities.

In Newcastle upon Tyne Hospitals NHS Foundation Trust, the yearly research audit schedule is developed by selecting a random 10% sample of all projects approved in the previous year. 

In addition to the 10% random sample, all clinical trials of Investigational Medicinal Products (ctIMPs) where the Trust acts as Research Sponsor will be audited.  This is in accordance with the responsibilities of a Research Sponsor for such studies regulated by the EU Clinical Trials Directive and Good Clinical Practice regulations.  It recognises that these studies are subject to external inspection by the MHRA at any time. 

Below is the Research Audit Policy for Newcastle Trust and guidance notes to help prepare for audit.

Audit Policy

Guidance notes for PIs for audit V3.0

Summary of type of event

The following summary is from the MHRA website at:  http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Clinicaltrials/Safetyreporting-SUSARSandASRs/index.htm

Terminology

Adverse event (or adverse experience):
Any untoward medical occurrence in a subject to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product;

Adverse drug reaction (ADR):
Any untoward and unintended response in a subject to an investigational medicinal product which is related to any dose administered to that subject;

Unexpected adverse reaction:
An adverse reaction the nature and severity of which is not consistent with the information about the medicinal product in question set out –

a) in the case of a product with a marketing authorization, 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.

Serious adverse event or serious adverse drug reaction or unexpected serious adverse reaction:
Any adverse event, adverse reaction or unexpected adverse reaction, respectively, that:

(a) results in death,
(b) is life-threatening,
(c) requires hospitalisation or prolongation of existing hospitalisation,
(d) results in persistent or significant disability or incapacity, or
(e) consists of a congenital anomaly or birth defect;

Important medical events that may not be immediately life-threatening or result in death or hospitalisation but may jeopardise the patient or may require intervention to prevent one of the other outcomes listed in the definition above should also be considered serious.

Further guidance on safety reporting can be found in http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-10/21_susar_rev2_2006_04_11.pdf

Reporting of SUSAR (Suspected, Unexpected, Serious Adverse Reaction.) 

 There is a legal requirement to report SUSARs within strict legal timelines to the Competent Authority (MHRA in UK) and to the Eurovigilance database. 

Fatal or life-threatening SUSARs

7 days requirement:

The competent authority and the Ethics Committee in the concerned Member States should be notified as soon as possible but no later than 7 calendar days after the sponsor has first knowledge of the minimum criteria for expedited reporting.  In each case relevant follow-up information should be sought and a report completed as soon as possible. It should be communicated to the competent authority and the Ethics Committee in the concerned Member States within an additional eight calendar days.

Non fatal and non life-threatening SUSARs

15 days requirement

All other SUSARs and safety issues must be reported to the competent authority and the Ethics Committee in the concerned Member States as soon as possible but no later than 15 calendar days after the sponsor has first knowledge of the minimum criteria for expedited reporting. Further relevant follow-up information should be given as soon as possible.

It is the Research Sponsor’s responsibility to report SUSARs.  You should make the sponsor aware of all SUSARs as soon as possible (within 24 hours).

See the guidance for reporting of Serious Adverse Reactions (SARs) and Serious Adverse Events (SAEs).  http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-10/21_susar_rev2_2006_04_11.pdf

It is the responsibility of the investigators and research team to review and monitor all incidents regularly and discuss them at Data & Monitoring Committee meetings and the discussions should be recorded in the minutes and kept as evidence of monitoring. 

Reporting of incidents to Newcastle Trust in different situation is as follows:

Where Newcastle Trust is Sponsor - incidents at Newcastle Trust site

• SUSARs - If the Trust is Sponsor, R&D need to know of a SUSAR at this site ASAP (within 24 hours) as the Trust as Sponsor has to report to the Competent Authority (CA) - MHRA and EuroVig database, with 7 days or 15 days depending on the type of incident
• SAEs and SARs where Trust is Sponsor at this site - SAEs and SARs should be reported to the MHRA and MREC as instructed on the NRES website.  R&D Should also receive a copy of SAEs and SARs for patients of Newcastle Trust we would like to know when they happen. 

Where Newcastle Trust is Sponsor - Incident at other sites (Not Newcastle Trust)

• SUSARs - As above, if Newcastle Trust is Sponsor R&D need to know of a SUSAR at any site ASAP (within 24 hours if possible) as the Trust as Sponsor has to report to the Competent Authority (CA) - MHRA and EuroVig database, with 7 days or 15 days depending on the seriousness of the SUSAR.
• SAEs and SARs where Newcastle Trust is Sponsor at other sites - SAEs and SARs should be reported to the MHRA and MREC as instructed on the NRES website.  R&D Should also receive a copy of SAEs and SARs for patients of Newcastle Trust

Where Newcastle Trust is NOT Sponsor - incident at Newcastle Trust site

• SUSARs – where Newcastle Trust is NOT Research Sponsor for a study, there is no requirement Newcastle Trust to report SUSARs, even if on the Newcastle Trust site.  The responsibility lies with the Sponsor (eg, the commercial company or other NHS organisation) to report the SUSAR to the Competent Authority. 
• If a SUSAR occurs then the investigator must get in touch with the Research Sponsor immediately (eg, commercial company or other NHS organisation) as the Research Sponsor must report within the strict legal guidelines.  However, please also let Newcastle Trust know by sending a copy of the SUSAR report so we can check the incident.  This is important for internal structures and monitoring where a serious incident has happened to one of Newcastle Trust’s.
• SAEs and SARs – where Newcastle Trust is NOT Sponsor but an SAE or SAR occurs at Newcastle Trust site, should be reported to the MHRA and MREC as instructed on the NRES website.  R&D Should also receive a copy of SAEs and SARs for patients of Newcastle Trust. 

Where Newcastle Trust is NOT Sponsor - Incident at other sites (not Newcastle Trust)

• SUSARs – if a SUSAR happens at another site and Newcastle Trust is NOT Sponsor, as above it is the responsibility of the Sponsor (eg, commercial companies or other NHS organisation) to report the SUSAR to the competent authority.  The study team at all sites should receive notification from the Research Sponsor when a SUSAR occurs at other sites as this might have an impact on safety of other participants on the study. 
• SAEs and SARs - for Serious Adverse events (SAEs) or adverse reactions (SARs) at other sites - all SAEs and SARs should be reported to the MHRA and MREC as instructed on the NRES website.

New developments - permissions within the NHS for carrying out research

General Research Governance Presentation

Research Governance including information about how to register for adoption to the NIHR portfolio and the new CSP centralised processing system for NHS permissions