National Institute for Health Research Coordinated System for gaining NHS Permission (NIHR CSP)

Transcription

1 National Institute for Health Research Coordinated System for gaining NHS Permission (NIHR CSP) Operating Manual Please check the CCRN Portal for the latest version. Version: 5.2 Status: Consultation in Use Effective: July 2012 Version: 5.2

2 Table of Contents 1. INTRODUCTION Purpose Scope OVERVIEW NIHR CSP PROCESS NIHR CSP from the Investigator Perspective NIHR CSP from the NIHR Clinical Research Network Coordinating Centre Perspective NIHR CSP from the Lead CLRN Perspective NIHR CSP from the Participating CLRN Perspective NIHR CSP from the NHS Organisation Perspective CSP Module KEY CSP PROCESS DETAILS Receipt and Validation of Submissions Use of a Single SSI Form Governance Criteria CSP Governance Quality Assurance Governance Reports and Liaison with NHS Organisations Authorised Signatories Standard Correspondence CSP Module Document Repository Site-specific Assessment Communications Flow within CSP GOVERNANCE REVIEW Governance Review Recording Comments for Governance Criteria ABANDONING OR SUSPENDING STUDIES IN CSP Abandoning Studies in CSP Prior/Post Governance Review Abandoning Studies in CSP during the Governance Review Suspending Studies in CSP Delays to the Governance Review ARRANGEMENTS FOR INDUSTRY STUDIES Version 5.2 i

3 6.1. Support for Industry from the Clinical Research Networks Role of the CLRN Industry Manager Communication Channels Industry Funded/Non-Industry Sponsored Studies ARRANGEMENTS FOR DEVOLVED ADMINISTRATION STUDIES UK Wide Coordination Lead NHS R&D Contact in England with Additional NHS Research Sites or NHS Participant Identification Centres (PICs) in Scotland, Wales or Northern Ireland Secondary Care Lead NHS R&D Contact in England with Additional NHS Research Sites or NHS PICs in Northern Ireland Primary Care Lead NHS R&D Contact in Scotland (NRS Permissions CC), Wales (NISCHR PCU) or Northern Ireland Secondary Care with Additional NHS Research Sites or NHS PICs in England Lead NHS R&D Contact in Northern Ireland Primary Care with Additional NHS Research Sites or NHS PICs in England Handling of Amendments/Revised R&D Forms PARTICIPANT IDENTIFICATION CENTRES (PICs) Background and Principles Governance Review for a Participant Identification Centre NHS Agreement to Act as a Participant Identification Centre Correcting a Study Record when Participant Identification Centres have not been Identified Correctly at R&D Submission Validation HANDLING OF REVISED R&D SUBMISSIONS Introduction Processing of Revised R&D Submissions Figure 1 Decision Tree for Submitting Revised Forms (Researcher Contact) Figure 2 Decision Tree for Revised R&D Form Received without being Requested STUDY AMENDMENTS Version 5.2 ii

4 10.1. Impact of Amendments on NHS Organisations Principles for Handling Amendments Responsibilities Processing of Amendments Amendment Submission Documentation STANDARD CORRESPONDENCE Portfolio Application Form Correspondence R&D Submission Correspondence Site Specific Information (SSI) Submission Correspondence CSP Governance Review Correspondence Abandoning and Suspending Studies Correspondence Study Amendments Correspondence Correspondence for Studies Involving Devolved Administrations Correspondence relating to handling of revised R&D Forms PERFORMANCE MANAGEMENT CSP metrics calculation LEGAL RESPONSIBILITIES ON-GOING STUDY MANAGEMENT (XML FILES) APPENDIX 1. USE OF A SINGLE SITE SPECIFIC INFORMATION (SSI) FORM 1 APPENDIX 2. GOVERNANCE CRITERIA BY STUDY TYPE... 1 APPENDIX 3. GOVERNANCE CRITERIA REVIEW PROCEDURE... 1 Section 1 Review criteria for research sites... 3 F. INITIAL ASSESSMENT... 3 G. RISK ASSESSMENT (RISK TO PARTICIPANTS)... 4 H. RISK ASSESSMENT (RISK TO STUDY)... 8 I. RISK ASSESSMENT (RISK TO ORGANISATION) J. RISK ASSESSMENT (RISK TO RESEARCHER) K. LEGAL COMPLIANCE L. APPROVALS AND AUTHORISATIONS Section 2 - Review criteria for Participant Identification Centres Version 5.2 iii

5 APPENDIX 4. COMMON EXAMPLES OF CRITERIA FOR STUDY OR SITE STATUS OF SUSPEND... 1 APPENDIX 5. REASONS FOR DELAY IN COMPLETION OF REVIEW... 1 APPENDIX 6. DEVOLVED ADMINISTRATION CONTACTS... 1 APPENDIX 7. AMENDMENT SUMMARY FORM GLOSSARY... i DOCUMENT CONTROL... viii Version 5.2 iv

6 1. INTRODUCTION 1.1. Purpose The Operating Manual for the National Institute for Health Research Coordinated System for gaining NHS Permission (NIHR CSP) defines the: Business processes for NIHR CSP for a range of study types Role of the CSP Unit (CSPU) and Comprehensive Local Research Networks (CLRNs) in the conduct of NIHR CSP Specific components of NIHR CSP and how they should be conducted The governance review that should be undertaken for different study types. Version 5.2 is a consultation in use document that is released as an interim manual for release 1 of the CSP Module. With the update of the CSP Module to version 2.0, NIHR CSP Operating Manual Version 6.0 will be released Scope The Operating Manual provides direction to the CSPU and CLRNs in the conduct of the NIHR CSP process. In addition, the Operating Manual provides assurance to NHS organisations regarding the processes and procedures which underpin NIHR CSP. The Operating Manual will be updated over time to reflect the refinements and clarifications that are identified as the process becomes embedded. The Operating Manual describes the standard process for gaining NHS Permission for research supported by the NIHR. In the event that an alternative process is required due to exceptional circumstances, for example, in order to expedite urgent public health research, supplementary documentation detailing the alternative process will be issued separately by the NIHR Clinical Research Network. Version

7 2. OVERVIEW NIHR CSP PROCESS NIHR CSP is a system which standardises and streamlines the process of gaining NHS Permission (also known as R&D approval) for commercial or non-commercial clinical research studies in England. NIHR CSP was introduced in November 2008 and represented a significant change in the way in which NHS Permission for research was provided for NIHR Clinical Research Network (CRN) portfolio-eligible research. Over time the process will continue to develop in order to further streamline the NHS Permission process for clinical research in the NHS. NIHR CSP is used for all commercial and non-commercial studies which are either automatically eligible or adopted into the NIHR CRN Portfolio, and studies supported through NIHR Biomedical Research Units (BRUs), Biomedical Research Centres (BRCs), and NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRCs). For noncommercial studies automatically included or adopted onto the NIHR CRN Portfolio, NHS Permission obtained through NIHR CSP permits access to NHS service support resources. Information about eligibility to the NIHR CRN Portfolio is provided on the NIHR CRN website. 1 NIHR CSP is also used to process study protocol amendments, or the addition of new sites, for studies that have already gained NHS Permission through NIHR CSP. NIHR CSP is funded by the Department of Health via the Comprehensive Clinical Research Network (CCRN). It operates as a partnership between central teams in the NIHR CRN, the 25 Comprehensive Local Research Networks (CLRNs) and the NHS organisations that make up the membership of each CLRN. Each CLRN funds a research management and governance (RM&G) workforce whose role is to assist investigators in obtaining permission for their studies from NHS organisations. Whether working with or on behalf of CLRN NHS member organisations, the role of CLRNfunded RM&G staff is to: Advise and assist investigators on the regulatory approvals their studies require Assist investigators to obtain internal authorisations within NHS organisations which feed into the NHS Permission process Undertake the governance review required for a study and work with investigators and NHS organisations to resolve difficulties Provide evidence of the outcome of the research governance review and work with NHS organisations to issue the NHS Permission Letter Ensure that studies gain NHS Permission as quickly as possible whilst being consistent with strong governance. The benefits of NIHR CSP to investigators are: Efficient process for gaining NHS Permission 1 See Version

8 Support and advice from the CLRNs Access to NHS service support for non-commercial studies Single point of access, via the Integrated Research Application System (IRAS). The benefits of NIHR CSP to NHS organisations are: A centralised system through which applications for NHS Permission from NIHR CRN Portfolio studies can be received Assurance that studies comply with all the necessary regulations and standards required for clinical research in the NHS A way of recording any identified risks, and the mitigations against those risks, so that NHS organisations can give informed permission for the research to take place within their organisation Clarity concerning the provision of the resources required to undertake the research within that organisation. As healthcare providers and employers, NHS organisations have a wide range of legal responsibilities that they take seriously. The role of RM&G staff is to support researchers in ensuring that these responsibilities are met in relation to each study that is conducted through the organisation. Research ethics committees consider the safety, rights and dignity of participants. The sponsor is primarily responsible for ensuring that the design, procedures and analysis of the study will produce scientifically high quality data and results. The role of the NHS organisation is to ensure that the delivery of the study in that organisation will be able to comply with the approved design and procedures. This will in turn enable the organisation to meet its responsibilities for the participants safety, rights and dignity and to produce high quality data. Investigators can apply for NHS Permission using NIHR CSP in parallel with their applications to the National Research Ethics Service (NRES), the Medicines and Healthcare Products Regulatory Agency (MHRA) and other regulatory bodies. However NHS Permission will not be granted by NHS organisations until all other regulatory approvals are in place. Application to these bodies must be through IRAS. The time taken for a study to pass through NIHR CSP is dependent on the time taken for other approvals to be obtained and for contracts and agreements to be negotiated. It is expected that commercial investigators using NIHR CSP will use the unmodified model agreements found on the NIHR website 2, otherwise they may experience a delay while legal review is sought. NHS Permission for research is required from each NHS organisation. Each NHS organisation is a separate legal entity and must provide that permission on a per site basis. Neither the CSP Unit (CSPU) nor the CLRNs can give NHS Permission for a research study; their role is to facilitate and support the process in a coordinated way. 2 See suite of model agreements on the NIHR website Version

9 Studies adopted onto the NIHR CRN Portfolio which are either led from or have sites in Scotland, Wales and Northern Ireland are able to use NIHR CSP for their English sites. Mechanisms exist to work with centralised systems in the devolved administrations where they have been established. Some studies use Participant Identification Centres (PICs) to assist recruitment. These are identified in Part C of the R&D Form in IRAS. NHS organisations need to agree to their participation in that capacity. NIHR CSP also facilitates this function. NIHR CSP is supported by a number of linked information systems within the NIHR CRN Coordinating Centre of which CSP Module is the central system. Over time these information systems will be developed to increase their functionality and interactivity with other information systems supported by the NIHR NIHR CSP from the Investigator Perspective Investigators gain access to NIHR CSP through IRAS 3. IRAS holds the standard dataset that investigators need in order to apply for a range of regulatory approvals including Ethics and NHS Permission. Once the IRAS dataset is complete, investigators can automatically generate the relevant application forms they need. Questions in the IRAS Project Filter are used to route applicants in IRAS to the relevant forms and submission process to apply for NHS Permission through NIHR CSP. When completing the project filter in IRAS, the investigator indicates at question 3a that the lead site is in England, and selects yes at either questions 5a or question 5b, to indicate that he/she wishes to use NIHR CSP. For studies that were created in IRAS prior to the launch of the CSP Module (version 3.2 or below/prior to the 18 July 2011 and updated), it is not currently possible to electronically submit through IRAS. These submissions are instructed to be sent to CSPU (forms in pdf and xml formats, checklist and documents) where these are created manually for processing in the CSP Module. It is anticipated that electronic submissions for these studies will be enabled in the autumn of 2012 prior to the release of Operating Manual v6.0. The work of the Chief Investigator and/or Principal Investigator is often delegated to a study coordinator Submission of a Portfolio Application Form or PAF The first stage starts with the submission of a short Portfolio Application Form (PAF) (see for information). This is submitted electronically to the CSP Module from IRAS. 100% NIHR-infrastructure funded studies in all study sites in BRCs, BRUs, CLAHRCs or NIHR Research Centre for Patient Safety and Service Quality are able to use NIHR CSP, although they are not included on the NIHR CRN Portfolio as they do not require clinical infrastructure service support. These studies will select 'yes' to question 5a in the new IRAS project filter and will not be required to complete a PAF. The PAF allows the Portfolio Application Team (PAT) to judge whether or not the study is potentially eligible to use NIHR CSP. Note that the R&D Form is required before the full eligibility assessment can be made. The PAF can be submitted at any time between the application for grant funding and the point at which the study is ready to apply for NHS Permission. The optimum time would be as soon as the investigator has confirmation that 3 Access to IRAS is from Version

10 he/she has been awarded the grant, but before the IRAS dataset for regulatory submissions has been completed. A CLRN is appointed to lead on the study. The Lead CLRN is usually, but not necessarily, the CLRN which geographically covers the employing institution of the Chief Investigator. If the study is commercially sponsored, receipt of the PAF alerts the NIHR CRN Industry Team that a commercial study has been submitted so they can support the sponsor through the process of study adoption to the NIHR CRN Portfolio and set up in NHS sites. Alternatively adoption of the commercial study may have occurred at an earlier point, through direct interaction with the NIHR CRN Industry Team. If the study is sponsored by a non-commercial organisation, receipt of the PAF alerts the Lead CLRN of a potential study in their area. This is so they can support the Chief Investigator through the process once the outcome of any necessary grant applications is known Submission of the NHS R&D Application The NHS R&D application is submitted electronically to NIHR CSP from IRAS. The application (form and associated documents required for the submission as detailed within the IRAS R&D Form Checklist) is validated to ensure it is complete and that funding for the study is secured. Some documents, such as approvals from regulatory bodies, may not be available at the time of submitting the R&D Form and need to be provided to the Lead CLRN as soon as they are available. These are indicated in the IRAS R&D Form Checklist 'Documents required for NHS Permission' section. The R&D Form and all supporting documents are made available to all the CLRNs/NHS organisations with sites listed in Part C of the R&D Form. The CSP Module uses the NHS Organisational Data Service (ODS) codes to accurately route information from IRAS through to the CSP Module, so that sites have advance warning of the study and can support Principal Investigators at those sites with study set up. In many cases it will be the CLRNfunded RM&G staff working within or on behalf of those sites that will access this information. The Lead CLRN will review those governance criteria that are applicable to the study as a whole (study-wide governance criteria) and share the outcome of that review with all sites listed in Part C of the R&D Form. The Chief Investigator will work with the Lead CLRN to resolve any governance issues that arise Submission of a Site Specific Information Application for each NHS Site The Chief Investigator will coordinate the Site Specific Information (SSI) Applications required by the study for the different sites involved. An SSI application is submitted electronically to NIHR CSP from IRAS, usually by the Principal Investigator at each site, but sometimes supported by the Study Coordinator. The application (form and associated documents required for the submission as detailed within the IRAS SSI Form Checklist) is validated by the CLRN-funded RM&G staff to ensure that it is complete. CLRN-funded RM&G staff working within or on behalf of NHS organisations, alongside other CLRN or Topic-specific Clinical Research Network (TCRN) or Primary Care Research Network (PCRN) staff, work with the Principal Investigator/Study Coordinator to assist with Version

11 study set up in the NHS site, obtain all necessary internal authorisations, and ensure there is clarity over resources and contracts. CLRN-funded RM&G staff, working within or on behalf of NHS organisations, undertake the local governance review required for the study. The Principal Investigator will work with them to resolve any governance issues that arise NIHR Clinical Research Network Portfolio Currently NIHR CSP is available to NIHR CRN Portfolio studies and other NIHR supported studies only. Studies are included on the NIHR CRN Portfolio either automatically on the basis of their funder, or following a formal adoption process to assess their suitability. Full details of the criteria used to determine whether a study is eligible for the NIHR CRN Portfolio are available online. 4 Note: Confirmation of acceptance onto the NIHR CRN Portfolio is not completed in NIHR CSP until the Portfolio Team has confirmed that the study is to be included on the NIHR CRN Portfolio, following an assessment based on information within the R&D Form, and this has been recorded and communicated to the relevant CLRNs Automatically Eligible Studies Non-commercial studies which are funded by an NIHR Partner organisation are automatically eligible for the NIHR CRN Portfolio. A study must have secured full research funding in order to be confirmed as eligible for the NIHR CRN Portfolio Studies Requiring Adoption Non-commercial Non-commercial studies with confirmed funding from organisations which are not NIHR Partner organisations are potentially eligible for the Portfolio. To be included in the NIHR CRN Portfolio, potentially eligible studies must undergo a formal adoption process, managed by the appropriate TCRN, PCRN or CCRN Studies Requiring Adoption Commercial Commercial studies (commercially sponsored and funded) are potentially eligible for the NIHR CRN Portfolio through the NIHR CRN Industry Feasibility and Adoption Process (coordinated by the NIHR CRN Industry Team in collaboration with TCRNs, PCRN and CCRN). These are required to complete a Feasibility and Adoption Submission form to be considered for inclusion in the NIHR CRN Portfolio. This form is available from the CLRN Industry Manager or on the NIHR CRN Coordinating Centre website. All industry studies are potentially eligible for inclusion in the NIHR CRN Portfolio and will continue through the CSP process unless the industry team advises PAT that the study will not be adopted Other Studies Supported by the National Institute for Health Research 4 Version

12 NIHR-funded studies in NIHR BRCs, BRUs, CLAHRCs or NIHR Research Centre for Patient Safety and Service Quality are expected to use CSP NHS Permission When both study-wide and local governance reviews for a specific site or PIC are complete, a Governance Report will be produced which summarises the outcome of the governance reviews and the supporting documents used as evidence. This report can be used to confirm to the NHS Permission signatory that all criteria have been reviewed and to highlight any identified risks or issues. Alternatively the NHS Permission signatory may access the governance review directly through the CSP Module. The NHS Permission signatory then issues the NHS Permission Letter to the Principal Investigator, copied to the Chief Investigator (or Study Coordinator, if applicable) and the research can begin only at that site. Suggested minimum requirements for the letter of NHS Permission for research are published by the NHS R&D Forum Studies not Achieving NHS Permission through NIHR CSP In cases where a study does not satisfy all the applicable NIHR CSP governance criteria to a satisfactory standard, or the investigator withdraws the study, the study will exit NIHR CSP. It is then the decision of that NHS organisation whether or not to give permission for the study. Studies exiting NIHR CSP will not be eligible to access NHS service support resources provided by the CLRNs, TCRNs or PCRN. If the study exited because a regulatory governance criterion was not satisfied, then it is unlikely that the study will be given permission. However, if the study has exited NIHR CSP because it was not adopted onto the NIHR CRN Portfolio, an NHS organisation may agree to give permission to the study if all NHS service support costs are provided by the research team or funder NIHR CSP from the NIHR Clinical Research Network Coordinating Centre Perspective Staff employed by the NIHR CRN Coordinating Centre have a key role to play in the management of a study through the NIHR CSP process CSP Management Group The CSP Management Group is responsible for the oversight of NIHR CSP and associated processes, for ensuring it delivers benefits for investigators and NHS organisations, and for on-going development and improvement of business processes. In certain situations, a single SSI Form may be used for all sites or a sub-set of sites. Requests to use a single SSI Form are currently considered by the CSP Management Group prior to their use on the study. These circumstances are set out in APPENDIX 1USE OF A SINGLE SITE SPECIFIC INFORMATION (SSI) FORM. In these cases, only study-wide documents are required. Participating CLRNs are notified by of their involvement. 5 Version

13 Portfolio Application Team PAT is responsible for receiving studies into NIHR CSP and recording whether or not studies are eligible to use NIHR CSP. It provides the link between NIHR CSP and the NIHR CRN Portfolio Team NIHR CRN Portfolio Team The NIHR CRN Portfolio team is responsible for the oversight of automatically included studies and coordinating the adoption of certain categories of studies onto the NIHR CRN Portfolio. The team is also responsible for managing studies in the NIHR CRN Portfolio. NIHR CSP and the NIHR CRN Portfolio are closely linked CSP Unit CSPU is responsible for the flow and management of studies through the NIHR CSP process. It has an overview of the study across all sites and provides a central information hub through which study information is shared across all NHS sites and the NIHR CRN. CSPU performance manages the progress of a study through the system and provides a support service for CLRN-funded RM&G staff working on the study. The main functions of CSPU are: Assigning an R&D Applications Facilitator (RAF) to the study Validating the R&D submission Acting as a communications channel for issues the Participating CLRNs are having with the study, so the Lead CLRN can resolve them with the Chief Investigator/Study Coordinator Identifying delays in the system and following up with CLRNs to identify causes, working with the CLRNs to provide possible solutions CSP Helpdesk The CSP Helpdesk (crncc.csp@nihr.ac.uk) provides a consistent source of advice for matters relating to the purpose and use of NIHR CSP, identifying areas for improvement which are discussed within the CSP Management Group. The CSP Helpdesk collates suggestions and feedback for use in the continual development of CSP processes and supporting documentation. Any complaints about CSP should be directed to the CSP Helpdesk. Correspondence and progress reports about a particular study are not handled by the CSP Helpdesk and should be sent directly to the CSP Unit (crncc.cspunit@nihr.ac.uk). The CSP Helpdesk also handles technical issues relating to IRAS and the CSP Module, and these should be directed to crncc.csp@nihr.ac.uk in the first instance. In the initial stages of implementation of CSP Module, certain functions can only be undertaken through a request to the CSP Helpdesk, including but not limited to: Version

14 Change of Lead CLRN Change of RAF Change of Governance or QC reviewer Abandoning a study outside a governance process NIHR CSP from the Lead CLRN Perspective The Lead CLRN plays a fundamental role in NIHR CSP. The Lead CLRN role in supporting study set up is described elsewhere and encompasses facilitating access to NHS service support resources and finding sites. 6 These discussions are enhanced by the introduction of the ability to submit Draft R&D Forms from IRAS once the study has been flagged as 'potentially eligible' within the Potential Portfolio Eligibility Review Process task or has indicated that all its funding has been provided through an NIHR Infrastructure grant. For commercial studies, the NIHR CRN Industry Team does the same, working in collaboration with the Industry Managers based in all CLRNs with participating sites for that particular study. In the context of NIHR CSP, a Lead CLRN-funded member of the RM&G staff is nominated as the point of contact for the study and works with the Chief Investigator, providing advice on the regulatory approvals and research governance standards required for the study and supports applications for NHS Permission through NIHR CSP. The Lead CLRN is the key contact point for the Chief Investigator/Study Coordinator about the progress of the study through NIHR CSP. Similarly all study-wide research governance queries are raised with the Chief Investigator/Study Coordinator via the Lead CLRN even if they have been identified in a Participating CLRN. The Lead CLRN can call on the support of CSPU for assistance with queries relating to other CLRNs or process clarifications. The key tasks undertaken by the Lead CLRN within NIHR CSP are: 1. Allocating a CLRN-funded member of staff working within or on behalf of an NHS organisation to be the key contact for the study with the Chief Investigator/Study Coordinator 2. For a non-commercial study, working with the Chief Investigator/Study Coordinator to confirm when funding for the study has been secured and supporting them to make a high quality application 3. Undertaking the study-wide governance review for the study and ensuring that issues, risks, risk mitigation and information regarding costs or contracts are recorded within the comments box of the relevant governance criterion for the Perform Study Wide Governance Review Process task. 4. Working with the CSPU RAF to ensure good communication with Participating CLRNs concerning key information and issues identified by the Participating CLRNs 5. Working proactively with the Chief Investigator/Study Coordinator to resolve any research governance issues that may arise 6 See the paper Facilitating the Set-Up for Multi-Centre Clinical Research Studies: The proposal for Lead Network by Jonathan Gower 21 st July ed to CLRN Clinical Directors and Senior Managers and P/TCRN Directors and Assistant Directors on 23 July Version

15 6. When all the study-wide governance review is complete, a quality control review of the criteria is undertaken to ensure that local reviewers can have confidence in the study-wide review 7. Working with CSPU, to keep the Chief Investigator/Study Coordinator up to date with how the study as a whole is progressing through NIHR CSP. Due to the research portfolios of the academic and clinical organisations within their area, some CLRNs will lead on more studies than others. This should be recognised in resource allocation for RM&G staff. If a Lead CLRN has reached capacity, it is possible for a CLRN not geographically co-located with the Chief Investigator/Study Coordinator to undertake the same role NIHR CSP from the Participating CLRN Perspective NHS organisations which are either study sites or PICs are within what are termed Participating CLRNs. They play a key role within NIHR CSP as they ensure that all research governance issues relating to the specific study site(s) have been addressed. Often there are several NHS sites within one CLRN. The Lead CLRN is usually also a Participating CLRN. Participating CLRNs are staffed by CLRN-funded RM&G staff, many of whom are based in the NHS organisation that has been designated as a study site. The key tasks undertaken by the NHS organisation (Participating CLRN) are: 1. Contacting Principal Investigators and helping with study set up arrangements and assisting with preparation of the SSI submission 2. On receipt of the SSI submission, facilitating and ensuring that all appropriate internal authorisations are obtained. Where possible or other internal mechanism can be used to improve efficiency. Principal Investigators should not have to collect wet signatures before the submission of the SSI application. If a Trust requires wet signature internal authorisations, CLRN-funded RM&G staff can obtain them. Principal Investigators remain responsible for appropriate liaison with relevant staff at the study site and for managing the set-up of the study at that site 3. Undertaking the local governance review ensuring that any issues, risks, risk mitigation and information regarding costs or contracts are recorded in the Comments section of the relevant governance criterion within the Perform Local Governance Review Process task 4. Working proactively with the Principal Investigator and internal departments to resolve any governance, costing or contracting issues. This may be supported by the CLRN Industry Manager for commercial studies 5. Working with the CSPU RAF to ensure good communication with the Lead CLRN concerning key information and issues identified by the NHS organisations (Participating CLRN). NHS organisation (Participating CLRN) queries to each study team should be communicated to CSPU which will pass the query to the Lead CLRN. This ensures that the Chief Investigator has to deal only with one main contact point 6. When both the local study site governance review and study-wide governance review are complete, an appropriate level of quality control check of the local review may be undertaken, taking into account the complexity of the study and the experience of the local reviewer Version

16 7. A Governance Report may be issued to the NHS Permission signatory in order that an NHS Permission Letter can be issued. Local arrangements should be in place to facilitate this part of the process to ensure the NHS Permission signatory understands any risks and their mitigation identified for that study 8. Once the NHS Permission Letter is issued, the NHS organisation (Participating CLRN) uploads a copy to CSP Module. This marks the end of the NHS Permissions process at this site, unless an amendment is submitted NIHR CSP from the NHS Organisation Perspective All NHS organisations in England are members of a CLRN and work closely with those CLRNs to provide a high quality research infrastructure to support NIHR CRN Portfolio studies. CLRNs either provide a centralised RM&G service to NHS organisations for NIHR CRN Portfolio studies or fund RM&G working within those NHS organisations to provide the NIHR CSP service. In devolved management models, RM&G staff often work on NIHR CRN Portfolio and non-portfolio studies in parallel; in those areas these local staff work on behalf of the CLRN. Some CLRNs operate a mixed model. Regardless of where RM&G staff are based, it is vital that they work very closely with all departments within an NHS organisation, for example, clinical departments, laboratories, pharmacy, data protection officers, Trust finance, other RM&G staff, and so on, to facilitate studies and obtain relevant internal approvals. There should be clarity regarding what internal authorisations are required for studies, where service support resources are placed and who within the NHS organisation is authorised to sign NHS Permission Letters, agreements and contracts. CLRNs are encouraged to work with local NHS staff to put in place arrangements for delegation of internal authorisation to CLRN-funded RM&G staff in appropriate circumstances. This is consistent with the principles of the Research Support Service (RSS) 7 to ensure proportionate and pragmatic procedures. The NHS organisation signs and issues the NHS Permission Letter based on the evidence provided in the Governance Report that is issued at the end of the CSP process. In doing so, it acknowledges responsibility for delivery of that study. It is essential that the NHS organisation should have confidence that any identified risks and mitigations have been made known to them within the Governance Report. The Lead RM&G Manager in each CLRN is responsible for ensuring clarity between NHS organisations and CLRN-funded RM&G staff exists. To the investigator, the system should be seamless the NHS organisation and the CLRN are partners in delivering research within an NHS organisation CSP Module NIHR CSP is supported by bespoke CSP Module software. The software: integrates the work of PAT, CSPU, Lead CLRN and Participating CLRNs by providing access to study data and the ability to edit study records as governance criteria are completed 7 Version

17 receives some study information directly from IRAS provides an electronic document repository for all study documentation generates the Governance Report after CSP Sign-off (Local) is complete generates reports of NIHR CSP activity and performance. A separate user manual providing detailed information regarding the use of CSP Module is available at Version

18 3. KEY CSP PROCESS DETAILS 3.1. Receipt and Validation of Submissions Details of new studies entering NIHR CSP are received through the Integrated Research Application System (IRAS) via a series of electronic forms: Portfolio Application Form (PAF) (where relevant) R&D Form and associated documents Site-Specific Information (SSI) Form and associated documents. Key data from these forms are transferred automatically from IRAS to the CSP Module, where they can then be viewed by the CSP Unit (CSPU), Lead Comprehensive Local Research Network (CLRN) and NHS organisations (Participating CLRNs). Notes: The R&D application cannot be submitted until the PAF has been validated, where the PAF is required The SSI application cannot be submitted until the R&D application has been validated. Please note that manual submissions can be created out of this sequence as there is no electronic link to the IRAS system where these rules are in place Supporting Documentation Documents associated with the main R&D submission will be submitted along with the IRAS R&D Form Checklist via IRAS. Any documents not received through the IRAS Interface can be manually uploaded to the CSP Module document repository. The documents required will be listed within the IRAS R&D Form Checklist. It is important that communication to Chief Investigators, Study Coordinators and Principal Investigators is correct and consistent. A set of standard correspondence is supplied in Section 11. Please ensure that standard s that are sent generated by a CSP Module task are stored in the document repository in a.pdf format Validation Validation is the process of ensuring that information submitted to CSP is adequate for the process of conducting governance review in NIHR CSP to begin. Validation of the PAF should be completed within 2 working days and is undertaken by the Portfolio Application Team (PAT). Validation of the R&D submission should be completed within 3 working days. This is undertaken by CSPU, along with any subsequent submission due to this being assessed as invalid. Once the R&D submission has been validated by CSPU, any subsequent Version

19 submissions of the R&D application will be validated by the Lead CLRN. Validation of the SSI submission should be completed within 3 working days. This is undertaken by the appropriate NHS organisation (Participating CLRN). Validation of the submissions will include the form and associated documents stated within the IRAS R&D or SSI Form Checklist. This will include opening the documents to ensure that the version and naming within the document is consistent with that in the document title and IRAS Checklist. Some documents, such as approvals from regulatory bodies, may not be available at the time of submitting the R&D Form and need to be provided through IRAS as soon as they are available. These are indicated in the IRAS R&D Form Checklist 'Documents required for NHS Permission' section Validation of the Portfolio Application Form An initial assessment is made of the PAF to ensure the study meets the following criteria: All relevant fields of the IRAS project filter and PAF have been completed Chief Investigator is based in England Study is funded by an eligible or potentially eligible funder Validation of the R&D Submission CSPU is responsible for validating the first R&D submission for all studies. Subsequent submissions, when this is not due to an initial invalid assessment, will be validated by the Lead CLRN. An assessment of the validity of the R&D submission will ensure that: 1. All relevant sections of the R&D Form have been completed (in English) such that the application is comprehensible and contains sufficient information a. The IRAS Project Filter questions, particularly question 2, have been completed and are consistent with information supplied elsewhere in the form Note: This will be a cursory assessment as this will be reviewed in detail within governance criterion A1 IRAS Project Filter completed correctly. b. A lead Sponsor has been named (including contact details) c. Question A65 indicates that research funding from at least one funder has been secured for the study d. For CTIMPs, there is a EudraCT number (A5-1) and, if the Sponsor is outside the European Economic Area (EEA), a legal representative within the EEA has been named (A64-4) e. In the case of Sponsors and Chief Investigators outside the NHS, arrangements have been made (for both the Sponsor and the Chief Investigator) to have insurance or indemnity to cover any liability arising from the research f. The form has been authorised/signed through IRAS by the Chief Investigator and Version

20 Sponsor in Part D Declarations 2. The associated IRAS R&D Form Checklist will contain details on the documents submitted as part of the submission with version numbers listed. The documents will be opened to confirm that the version and name on the Checklist is consistent with that in the document title and version 3. The associated IRAS R&D Form Checklist will contain details of the documents that are not included in the submission and the reason. Where a reason is not given for a document not being included, this will be queried. Some documents, such as approvals from regulatory bodies, may not be available at the time of submitting the R&D Form and need to be provided through IRAS as soon as they are available. These are indicated in the IRAS R&D Form Checklist section headed 'Documents required for NHS Permission'. The R&D Applications Facilitator (RAF) will confirm if the submission is valid and send a confirmation to the Chief Investigator, copying the Study Coordinator if applicable. A confirmation message will appear on the esubmission tab in the R&D Form area within IRAS. The study is then able to progress to the next stage of submitting SSI applications. If the submission has minor issues and is an electronic submission, it will not be invalidated and the validation task will be left pending whilst the issue is clarified. If the issue is not clarified within 14 calendar days the submission will be invalidated. It should be noted that from April 2012 any time spent in validation will be included in metrics. If the submission is invalid, the Chief Investigator and Study Coordinator, if applicable, will be informed. See Section 11.2 for details of the standard s. Note: If electronic authorisations have been used within IRAS, these are also invalidated when an invalid R&D Form is rejected in CSP Module. The form must be corrected and resubmitted to CSP, and if using electronic authorisations, these must be reapplied to the revised form Validation of the SSI Submission The Participating CLRN is responsible for validating the SSI Submission when it appears in the CLRN Task list. An assessment of the validity of an SSI Submission will ensure that: 1. All relevant sections have been completed (in English) such that the application is comprehensible and contains sufficient information. a. The form has been authorised/signed through IRAS by the Principal Investigator. b. There is no requirement for the internal authorisations in Question 23 to be completed or signed for the submission to be valid. Participating CLRN-funded research management and governance (RM&G) staff working within or on behalf of NHS organisations can assist in identifying which internal authorisations are required, and obtaining those authorisations in the form of wet signature, or other internally acceptable form of authorisation once the submission has been validated. Note: Where possible, or other internal mechanisms can be used to improve efficiency. Principal Investigators should not have to collect wet signatures before submission of the SSI Form. If a Trust requires wet signature internal authorisations, CLRN-funded RM&G staff can obtain them. Authorisations should be made on the evidence of the submitted validated SSI Form. Additional forms should not be generated. Over time, when technology allows we will move towards electronic internal Version

21 authorisation. 2. The associated IRAS SSI Form Checklist will contain details on the documents submitted as part of the submission with version numbers listed. The documents will be opened to confirm that the version and name on the Checklist is consistent with that in the document title and version. Please note that the site specific agreement/contract is not required as part of the initial SSI submission. The Participating CLRN will confirm if the submission is valid. A confirmation message will appear on the esubmission tab in the SSI Form area in IRAS and an will be sent to the Principal Investigator, Chief Investigator and Study Coordinator, if applicable. If the submission is invalid, the Principal Investigator, Chief Investigator and Study Coordinator, if applicable, will be informed. See Section 11.3 for details of the standard s used Use of a Single SSI Form In certain situations, a single SSI Form may be used for all sites or a sub-set of sites. These circumstances are set out in APPENDIX 1. USE OF A SINGLE SITE SPECIFIC INFORMATION (SSI) FORM. In these cases, only study-wide documents are required Governance Criteria Central to NIHR CSP is the notion of governance criteria. These provide assurance that studies are compliant with applicable regulations and with the key domains of the Research Governance Framework (Ethics, Science, Health & Safety, Information and Finance & Intellectual Property). Governance criteria within NIHR CSP are either study-wide (undertaken once on behalf of all NHS organisations participating in the study) or local (criteria specific to an individual NHS organisation, which must therefore be undertaken once for each NHS organisation participating in the study). Some governance criteria can have study-wide and local elements. The set of governance criteria undertaken for each study is determined by the study type (eg Clinical Trial of an Investigational Medicinal Product). The Lead CLRN undertakes the study-wide review. This is viewable by all Participating CLRNs in the CSP Module. Using information on the SSI Form, associated documents and discussions with key staff in the NHS organisation, the Participating CLRN-funded RM&G staff working within or on behalf of the NHS organisation identified on the SSI Form, complete the local governance review for each NHS organisation CSP Governance Quality Assurance CSP Governance Quality Assurance is designed to give assurance that a study has been appropriately reviewed before the Governance Report is presented to the NHS Permission signatory at each site. Version

22 While the responsibility for NHS Permission remains with NHS organisation granting that permission, the Lead RM&G Manager in each CLRN has a responsibility to ensure that there are robust systems in place to provide assurance of the quality of the review. Governance QC (Study-wide) is carried out by the Lead CLRN when all the study-wide criteria have been completed. The default position is that this will be performed on all studies. Governance QC (Local) is carried out by the Participating CLRNs. The default is that this will not be performed but can be used when selected at a study location. Once Governance QC (Study-wide) and Governance QC (Local) (if selected) has been completed, and the study is eligible for the Portfolio (where applicable), a Grant NHS Permission task is generated for the NHS organisation CSP Governance Quality Control (Study-wide) CSP Governance Quality Control (Study-wide) relates to the study-wide review for the study carried out by the Lead CLRN and gives assurance that the study-wide governance review has been appropriately undertaken. It is an essential part of the CSP process as other CLRNs (and therefore host NHS organisations) will rely on the study-wide governance review undertaken by the Lead CLRN. CSP Governance Quality Control (Study-wide) is undertaken by the Lead RM&G Manager (or delegated deputy) after the Perform Study-wide Governance Review task has been completed and provides assurance that: The necessary review for the study has been undertaken. The comments associated with each governance criterion comply with the guidance specified in APPENDIX 3. GOVERNANCE CRITERIA REVIEW PROCEDURE. If the review has not been performed correctly, the Lead RM&G Manager (or delegated deputy) will be able to indicate in the Perform Governance QC task those governance criteria that require further review, and should work constructively with the person undertaking the review to reach the required standard. Note: A proportionate risk-based approach is recommended. Small discrepancies, such as a wrongly assigned category in the document repository may not prevent CSP Governance Quality Control (Study-wide) being confirmed, but will need to be rectified immediately so that other CLRNs are not affected. Please remember that the information in the governance criteria comments and the document repository will be printed on the Governance Report CSP Governance Quality Control (Local) CSP Governance Quality Control (Local) relates to the local review for the study carried out by the CLRN-funded RM&G staff within or on behalf of NHS organisations and gives assurance to the NHS Permission signatory that all local issues for the study have been addressed. The CSP Governance Quality Control (Local) is turned off by default but if it is conducted, it provides assurance that: The necessary local review for the study has been undertaken Version

23 The comments associated with each local governance criterion comply with the guidance specified in APPENDIX 3. If the review has not been performed correctly, the Lead RM&G Manager (or delegated deputy) will be able to indicate in the Perform Governance QC for Study xxxx task those governance criteria that require further review and should work constructively with the person undertaking the review to reach the required standard. Note: A proportionate risk based approach is recommended but must be in line with what the local NHS Permission signatory will expect to see in the Governance Report Governance Reports and Liaison with NHS Organisations Governance Report The Governance Report is a record of the governance review completed for a study at a particular participating NHS organisation (or Consortia acting on behalf of NHS organisations). Along with associated study documentation, the Governance Report is provided as evidence to NHS organisations, to support them in granting NHS Permission, and should be uploaded to the document repository as part of the evidence of the study governance review. The Governance Report is produced automatically by CSP Module and summarises: Basic study details (Study ID, Study Type, Full Title, Short Title, Chief Investigator, Sponsor(s), CLRN, NHS organisation, Principal Investigator) Governance reviews undertaken and the comments related to each criterion (as entered in the Comments field when the criterion was completed) Supporting documentation (stating the filename, document category, document type and version number of the documents provided) The contact details of the NHS organisation (Participating CLRN) contact (to be added manually). Note: As the comments appear exactly as entered in the Comments box, care should be taken to ensure that the wording is professional and appropriate to appear in the Governance Report Liaison with NHS Organisations Once a Governance Report for a particular NHS organisation has been generated, the Participating CLRN-funded RM&G staff working within or on behalf of the NHS organisation liaises with the NHS organisation (or Consortia acting on behalf of NHS organisations) in order to secure NHS Permission NHS Permission Granted When the signed letter of NHS Permission is received, the NHS organisation (Participating CLRN) must upload it to the CSP Module document repository as a local document, recording the date of the letter. Version

24 The date when NHS Permission is granted for the NHS organisation marks the point at which a study can begin at that site Authorised Signatories Prior to NHS Permission, each study must have appropriate internal authorisations in place at the local site, there should be clarity over who will sign agreements and contracts and the NHS Permission Letter Internal Authorisations Internal authorisations ensure that clinical and service departments within an NHS organisation know about and are able to work with the study. CLRN-funded RM&G staff working within or on behalf of NHS organisations should know who can give local authorisations for different departments. See Section for more details on internal authorisations NHS Permission Signatories CLRN-funded RM&G staff working within or on behalf of NHS organisations should know who is authorised to sign NHS Permission Letters on behalf of a member NHS organisation. It is advised that NHS Permission signatories have at least one deputy Authorised Signatories A recognised signatory for an NHS organisation will sign legal contracts or agreements unless this responsibility has been delegated (eg within the context of a consortium). Neither CSPU staff nor CLRN core staff have the authority to sign any legal agreement. There should also be clarity concerning which types of contracts/agreements are sent for legal review prior to signature. It is not expected that unmodified model agreements will require additional legal review at the local level Standard Correspondence It is important that communication to Chief Investigators, Study Coordinators and Principal Investigators is correct and consistent. A set of standard correspondence is supplied in Section 11. These standard s will be an output of their associated CSP Module tasks and will be sent to the account of the user completing the task to be forwarded appropriately CSP Module Document Repository CSP Module provides a study-wide and local electronic facility for storing documents. Documents or correspondence connected with the set-up of a study processed through NIHR CSP should be stored in the document repository, unless they contain confidential information (see Section 3.8.4) Responsibility for Uploading Documents Version

25 The responsibility for uploading documents relating to study-wide review rests with the Lead CLRN. Documents relating to local criteria should be uploaded by the NHS organisation (Participating CLRN) for each participating NHS organisation Access to Uploaded Documents Access to uploaded documents within the CSP Module document repository is limited to users depending on their user account and document level. When uploading documents in the capacity of a Lead CLRN, these must be uploaded to the study-wide view allowing users in all CLRNs associated with the study to view the document. NHS organisations (Participating CLRN) should upload documents to the local view Documents Supplied as Hard Copy Documents received as hard copy should be scanned and stored electronically in the document repository, unless they contain confidential information Confidential Documents Documents containing commercially sensitive or confidential information, such as salary details, National Insurance numbers or commercial contracted costs, should not be stored in the document repository. These should be stored outside CSP Module, and details of their location in the local filing system should be logged within the document repository in CSP Module (using the same method as for uploading a document, but specifying the Document Location instead of browsing to select the file to be uploaded) File Format To ensure that all CSP Module users are able to view the documents stored in the document repository, Adobe Portable Document Format (.pdf) should be used, and investigators are requested to submit documents as.pdfs wherever possible. If documents are received in other file formats, such as Microsoft Word, these should be converted to.pdf before being uploaded. This will not apply to those that are received from IRAS to the CSP Module as there is no limitation to the document type submitted through IRAS. Exceptions apply for template documents that are placed in the repository as a resource Document File Names Where possible, the document should be uploaded to the document repository using the original file name provided by the Chief Investigator or Principal Investigator. Where the original file name is unsuitable, the document should be renamed, and the new filename should identify the document s context (eg Ethics, ARSAC, MHRA) and purpose (eg Application, Request for further information, Conditional approval). If required, the file name should be changed in the local folder before upload, as files cannot be renamed within the document repository. Where a document has been renamed, the original file name must be recorded when the file is uploaded. Version

26 Recording Date and Version The document version number and/or date must be recorded in the appropriate boxes when a document is uploaded. For documents submitted to the CSP Module through IRAS, the document version and/or date will be recorded in the associated IRAS Form Checklist. Where a version number has not been assigned to the document, the date recorded within the relevant document should be entered in the Version field. Where a document does not have either a version number or a date within the document, the date of receipt should be entered in the Version field Document Category and Document Type Documents must be assigned a Document Category and Document Type at upload, using the options provided in CSP Module (Refer to the NIHR CSP Module User Guide) Site-specific Assessment Site-Specific Assessment (SSA) involves an assessment of the suitability of the Principal Investigator and the participating site using information contained within the SSI Form and the Curriculum Vitae. The completion of SSA through CSP provides assurance to the research ethics system that, where appropriate, local aspects that may affect the ethical opinion are managed. SSA, where it is relevant, is intrinsic to the local governance review and is therefore not indicated separately in the governance criteria Communications Flow within CSP A key aim of NIHR CSP is to provide a smooth and efficient service to investigators seeking NHS Permission for their research. The CSP Module will provide a much greater degree of visibility than previous IT systems CSP Unit Point of Contact When the PAF has been validated or Final R&D submission received, a RAF is assigned to be responsible for the study. The RAF will be the main point of contact for the study in CSPU. The RAF will liaise directly with the Chief Investigator or Study Coordinator over any issues in connection with the Final R&D submission validation, but subsequently will not contact them directly. All communications between the Lead CLRN and Participating CLRNs should include the CSPU central address (crncc.cspunit@nihr.ac.uk) Lead CLRN Point of Contact After CSPU has validated the R&D submission, the Lead CLRN will assign a team member as the main point of contact for the study. This person will be the main link between CSP and the Chief Investigator or Study Coordinator, updating them about the study s progress through NIHR CSP and liaising with them about any issues during the governance review process. This person will act as a channel for any information requests originating from other CLRNs and CSPU relating to any issues other than those that are only relevant to a specific site, so that the Chief Investigator or Study Coordinator is not contacted repeatedly by Version

27 different CLRNs with requests for the same information Participating CLRN Point of Contact When the organisation (Participating CLRN) receives notification of the valid R&D submission, they will assign a team member as the main point of contact for the study at that site. This person will be the main link between CSP and the Principal Investigator, updating them about the study s progress through NIHR CSP and liaising with them about any issues during the governance review process. If the Participating CLRN has an enquiry that relates to study-wide information or study-wide governance review, this should be referred to the Lead CLRN point of contact Industry Studies The NIHR CRN Coordinating Centre Industry Team has significant involvement with companies using CSP to gain NHS Permission. However, communication about any issues relating to CSP should still be raised via the Lead CLRN to the company. The NIHR CRN Coordinating Centre Industry Team or TCRN/PCRN Industry Liaison Managers will liaise with the assigned RAF who will communicate with the Lead CLRN point of contact for the study. Industry studies not using CSP will be referred back to the NIHR CRN Coordinating Centre Industry team. Version

28 4. GOVERNANCE REVIEW The research governance review of each study passing through NIHR CSP should be undertaken in a holistic and proportionately risk-based manner. The governance criteria, and procedures to undertake the governance review, see APPENDIX 3. GOVERNANCE CRITERIA REVIEW PROCEDURE, support the research governance review, and provide evidence to the NHS Permission signatory that the necessary review has been carried out Governance Review The review should not be viewed as simply a tick-box exercise. It is important, when reviewing a study, to briefly read through the R&D submission (Form and associated documents (especially the Participant Information Sheet)) to get a sense of the study as a whole and to highlight any potential issues early in the process. For study-wide governance reviews, a rapid initial assessment by an appropriately experienced and senior member of Comprehensive Local Research Network (CLRN)-funded research management and governance (RM&G) staff should be used to identify studies with complex arrangements or unclear information. This will highlight at an early stage if additional information is required or particular expertise is needed to support the review. For local governance reviews, the NIHR Research Support Services study planning tool should be used by an appropriately experienced and senior member of CLRN-funded RM&G staff to identify local issues that may impact on the ability to issue permission for the study in a timely way. The CLRN-funded RM&G staff working within or on behalf of NHS organisations should not act alone identifying these issues but in partnership with those giving internal authorisation from clinical and service departments. The aim is to ensure that the NHS organisation is aware of what the study involves and to work effectively and speedily with those setting up the study (the Principal Investigator, members of the research team, CLRN, Primary Care Research Network or Topic-specific Clinical Research Network staff). The Governance Criteria comments boxes should be used to highlight any issues to the NHS Permission signatory and should be supported by a report in the document repository if necessary (see Section 4.2). Risks and mitigations should be clearly identified but should rarely prevent a NIHR Clinical Research Network (CRN) Portfolio study taking place. A risk-averse culture is to be avoided and a culture where risks are proportionately addressed encouraged Internal Authorisations Internal authorisations should be used, where required, to provide assurance from relevant experts and professionals that a study can be delivered in an NHS organisation. Delegation of internal authorisations to R&D staff may be used, where appropriate, as part of a proportionate and streamlined process. Lead RM&G Managers should support local staff in working with NHS staff to provide a proportionate and streamlined process for ensuring local delivery of a study. The requirement for internal authorisation should be tailored to the nature of the study and therefore, in general, signatures should not be requested in advance of the Site Specific Information (SSI) submission. Version

29 It is important that those providing internal authorisations have the authority to do so and understand what that authorisation means. There should be systems in place locally to ensure that CLRN-funded RM&G staff know who is the appropriate person to give internal authorisation for each department and that there is a collaborative way of working together on study set up to ensure that risks are identified and mitigated. Those giving internal authorisations should have cover arrangements in place for sick and annual leave. Internal authorisations can be given by , in writing or by wet signature on the SSI Form Clarifications and Corrections During the process of undertaking the governance review, there may be the need to work with the Chief Investigator to clarify or correct parts of the application so that the governance review can be completed. It is not necessary to require the Chief Investigator to resubmit the R&D Form to reflect the correction; rather the clarification should be recorded within the governance criterion Comment box within CSP Module. Where Participating CLRNs identify a query which impacts on the study as a whole, the CLRN-funded RM&G staff working within or on behalf of NHS organisations should contact the Lead CLRN who can in turn communicates with the Chief Investigator/Study Coordinator. The Chief Investigator/Study Coordinator should have one point of contact for such queries this is one of the benefits of a networked system to the investigator Undertaking Governance Review APPENDIX 2. Governance CRITERIA by STUDY TYPE lists the governance criteria for different study types. APPENDIX 3. GOVERNANCE CRITERIA REVIEW PROCEDURE describes the way in which governance review should be undertaken, indicating which criteria are study-wide or local and the judgements that should be made by those undertaking the review. The comments box should be used to describe the findings from the assessment and the decision made. All comments should provide a risk-based, proportionate assessment. Governance criteria can be marked with the following outcomes from the drop down list: Not Started In Progress Completed - Proceed (ie all OK) Completed - Minor Issue (ie review completed but a minor issue to note that does not prevent NHS permission insert comment) Completed - Major Issue (review completed but there is a serious problem to note that will prevent NHS permission a comment should be inserted). Governance criteria that are not applicable to the study should be marked as Completed Proceed, and a note should be entered into the associated Comments box for each of these criteria saying Not Applicable because [insert reason] Recording Comments for Governance Criteria Purpose of Comments The comments entered by the Lead CLRN and NHS organisations (Participating CLRNs) for Version

30 each governance criterion appear in the Governance Report that is issued to the NHS Permission Signatory. The comments entered by the Lead CLRN for study-wide criteria provide assurance to the NHS organisation (Participating CLRNs) who are working on the local review. Therefore extra care should be taken to ensure a clear and professional standard of commenting is used. The local review provides the NHS Permission Signatory with information to assess whether the study can be delivered locally to all applicable standards and requirements Content of Comments The format and content of local governance comments is for local discretion. The information below is provided as a starting point for local agreement. To provide assurance to local reviewers of the quality of the study-wide review,a standard format should be followed when entering comments. 1. Write a brief comment. This should be concise, but sufficiently detailed to indicate that the procedure outlined in APPENDIX 3. GOVERNANCE CRITERIA REVIEW PROCEDURE for that criterion was followed, and to provide enough information to give assurance to the NHS Permission Signatory that the review has been performed adequately. The focus of the review and the comments should be on identifying unusual features or issues, and the assurances or resolution obtained. Note: The level of detail provided is at the discretion of the person performing the review this requires an element of judgement and common sense. A pragmatic approach is recommended, with the emphasis on what the reader will need to know. Standard comments may be used for training purposes in undertaking the review, but cutting and pasting comments is generally discouraged as this risks a lack of engagement in the thought processes and judgement required to perform the review. 2. Include the filename/description of the document (as given in the document repository) used as evidence of the review, if appropriate. It is not necessary to quote question numbers in the application form unless information is unusually presented in the application. 3. Version numbers (or identifying names in the case of documents such as SSI Forms) associated with documents in the document store must be completed. These details are particularly important when revised documents have been submitted in response to issues raised during review. Version

31 5. ABANDONING OR SUSPENDING STUDIES IN CSP 5.1. Abandoning Studies in CSP Prior/Post Governance Review A study or research site may be abandoned or withdrawn at any point during CSP. A study that is submitted to CSP may be withdrawn from, or fail to complete, the NIHR CSP process for a number of reasons, leading to a change in study status. This study, or particular site within a study, will become Abandoned and this will be recorded within the CSP Module. Described below are the different scenarios that may occur and the corresponding exit procedures Not Eligible for the NIHR Clinical Research Network (CRN) Portfolio There is currently a 10 working day grace period between the original notification of the study being ineligible or not adopted and the study being abandoned in CSP, to allow for any appeals to be received Ineligible Studies Some studies will be identified as ineligible for the NIHR CRN Portfolio on the basis of the information in the Portfolio Application Form (PAF). The Portfolio Application Team (PAT) will notify the Chief Investigator by that the study is not eligible for the NIHR CRN Portfolio (Section 11.1). Where a study is deemed to be ineligible, the study will be abandoned within the CSP Module. This occurs automatically on the completion of the Confirm Portfolio Eligibility Task as Not Eligible. Potentially Eligible Studies not Included in the NIHR CRN Portfolio The process of determining whether a potentially eligible study can be included in the NIHR CRN Portfolio happens in parallel with the CSP process. If a potentially eligible study starts to be processed through CSP, but does not pass the adoption process, it cannot be included in the NIHR CRN Portfolio. Whilst such studies cannot continue to be processed by NIHR CSP, Comprehensive Local Research Networks (CLRNs) should assist the Chief Investigator to access other routes to gaining NHS Permission. The CSP Unit (CSPU) will alert the Lead and Participating CLRNs, and a partial Governance Report showing progress to date should be forwarded, along with any supporting documentation, to the participating NHS organisations. This information may be retrieved from the CSP Module in order to provide it to the relevant staff. When a study is not included in the NIHR CRN Portfolio, the study will be abandoned within the CSP Module. This occurs automatically on the completion of the Confirm Portfolio Eligibility Task as Not Eligible. PAT will notify the Chief Investigator by that the study is not eligible for the NIHR CRN Portfolio (Section 11.1) Chief Investigator does not Proceed with the Study The standard messages notify the Chief Investigator at various key steps in CSP that, in the event that the Chief Investigator decides not to proceed with the study, he/she must inform the Lead CLRN as soon as possible. If the study-wide governance review is still in progress when the Lead CLRN receives this information the process described below within Version

32 section 5.2 is followed. If the study is prior or post the governance review, the Lead CLRN should make an request to the CSP Helpdesk for the study to be abandoned Abandoning Studies in CSP during the Governance Review Where the study or research site has been identified as needing to be abandoned during the governance review, the appropriate governance review task will be used to generate the Abandon Review task. When it is established that the study-wide or local governance review has not provided satisfactory assurance, the Lead CLRN or NHS organisation (participating CLRN) will send a notification to the Chief Investigator to confirm that study-wide or to the Participating Investigator to confirm that local governance reviews within CSP have not been satisfied and the reason(s) why (Section 11.4). If a study-wide governance review fails, the study will be unable to proceed at any participating NHS organisation. If a local governance review fails, the study will be unable to proceed at a particular NHS organisation. Study Wide When the study wide governance reviewer wishes to abandon the study wide governance he/she will set the outcome of the most appropriate study wide governance criteria to Completed - Major Issue. A clear comment requesting that the study be abandoned, along with a brief explanation for the request, must be made in the comment field for the study wide governance review. This can be optionally supported by an additional sent to crncc.cspunit@nihr.ac.uk (section ). Where a clear comment has not been made, CSPU will request further confirmation from the Lead CLRN that the study requires abandoning and there is no likelihood of it restarting. An Abandon Review task will then be completed by CSPU. This will abandon the study at a study-wide level and will close any remaining tasks at research sites or Participant Identification Centres (PICs). Once the task has been completed, an (section 11.5) will be sent by CSPU confirming that the study has been abandoned. Local When the local governance reviewer wishes to abandon the study at a research site or PIC they will set the outcome of the most appropriate local governance criteria to Completed - Major Issue. A clear comment requesting that the site be abandoned, along with a brief explanation for the request, must be made in the comment field for the local governance review. This can be optionally supported by an additional sent to crncc.cspunit@nihr.ac.uk (section ). Where a clear comment has not been made, CSPU will request further confirmation from the Participating CLRN that the research site requires abandoning and there is no likelihood of it restarting. An Abandon Review task will then be generated for CSPU which can then be completed as Abandon. This will abandon the study at this research site or PIC. Once the task has been completed, an (section 11.5) will be sent by CSPU confirming that the study has been abandoned. Version

33 5.3. Suspending Studies in CSP A study or research site may be suspended where no further activity, discussion or negotiation can proceed due to circumstances outside the control of the NHS or CRN. PICs are not currently measured through performance management reports and should not be placed in a suspend state. All time spent suspended is not counted in metrics to measure study-wide or local review times or overall NHS Permission times. See APPENDIX 4. COMMON EXAMPLES OF CRITERIA FOR STUDY OR SITE STATUS OF SUSPEND Suspend Status Study Wide When the study wide governance reviewer wishes to suspend the study wide governance they will set the outcome of one of the study wide governance criteria to Completed - Major Issue. A clear comment requesting that the study wide governance review be suspended and why must be made in the comment field. This can be supported by an additional sent to crncc.cspunit@nihr.ac.uk (section 11.5). A task will then be generated for CSPU to either agree with the suspension or resume the study wide governance. This decision will be made in consultation with the Lead CLRN in line with the principles below. Notification will be sent to the Lead CLRN by to their central CSP address (section ). The suspended time starts at the point of initial request and continues if confirmed. If the suspension is not confirmed, and the governance review is resumed, the time in suspension finishes. Please note that a study wide suspension will not create local suspensions. Local When the local governance reviewer wishes to suspend the local governance they will set the outcome of one of the local governance criteria to Completed - Major Issue. A clear comment requesting that local governance review be suspended and why must be made in the comment field. This can be supported by an additional sent to crncc.cspunit@nihr.ac.uk. Notification will be sent to both the Participating CLRN and Governance Reviewer by (section ). This will be copied to the Lead CLRN where this appears to be a study wide issue or requires their input. A task will then be generated for CSPU to either agree with the suspension or resume the local governance. This decision will be made in consultation with the NHS research site, copying in the Participating CLRN if by , in line with the principles below. The suspended time starts at the point of initial request and continues if confirmed. If the suspension is not confirmed, and the governance review is resumed, the time in suspension finishes. If a study wide suspension is for an issue that impacts the local governance review the local suspensions will need to be requested separately. Version

34 Principles 1. Any requests for suspended status where active negotiations are on-going, or other activity may still proceed will be rejected. There may be exceptions to this where there are significant changes due to an amendment or delays to issuing site specific contracts to sites. 2. A local suspended status cannot be granted for the reason of study-wide review still ongoing. Where the issues appear to be study-wide, the NHS organisation (participating CLRN) should liaise with the Lead CLRN to submit the suspended request. Suspension requests that are suspected to be a study-wide issue will be highlighted to the Lead CLRN. 3. A suspended status should only be granted where delays have occurred due to factors outside of NHS or CRN control. 4. A suspended status should not be used to try to control metrics regarding recruiting the first participant. 5. It can be possible to satisfy the local governance prior to ethics approval as confirmation of approval is a study wide check. Changes implemented by Research Ethics Committees would not normally affect local governance criteria and permission is not issued until the study wide review is complete. If the suspension is due to another delaying factor or an amendment this would be a reason for sites to also go into suspension Assigning a Suspend Status to a Study In order to assign a suspend status, the study must fulfil all of the following criteria: The governance review is still on-going All other criteria have been completed as far as is possible and no further governance review can be undertaken. As soon as this stage is reached the study or research site may be suspended Where the request to suspend a study or research site relates to awaiting a response from another party, there must have been at least two requests for the information over a period of several days or communication regarding a specific delay Sufficient information about the delay has been recorded in the governance criteria comments box (not the governance task comments box) and submitted to CSPU using the selection of 'Completed - Major Issue' outcome for a governance criteria during the Perform Governance Review for Study xxxx task. As soon as the review can proceed again, the Lead CLRN (for study wide) or NHS organisation (Participating CLRN) must notify CSPU to ask them to resume the governance review task. This takes the study out of the suspended status. This decision to resume is made by the CLRN/NHS organisation, since they will receive the information. Notification will be sent to the CLRN by (section ) by CSPU on the resumption of the governance review task Delays to the Governance Review Version

35 Delays due to factors outside the direct control of R&D offices or CRN, but incurred as part of the NHS review or CSP process may not be used to suspend a study or research site. Such delays can be noted within the governance review comments but will continue to be included in metrics. Delays incurred due to negotiation between NHS organisations and sponsors or waiting for an internal department may not be used to suspend a study or research site. Metrics are intended to measure the whole of the NHS Permissions process, not the direct activity of R&D staff. See REASONS FOR DELAY IN COMPLETION OF REVIEW. Version

36 6. ARRANGEMENTS FOR INDUSTRY STUDIES Provided they meet certain adoption criteria, Industry sponsored/industry funded (contract) studies are eligible for inclusion in the NIHR Clinical Research Network (CRN) Portfolio and are therefore able to use NIHR CSP to gain NHS Permission Support for Industry from the Clinical Research Networks The NIHR CRN provides investigators undertaking adopted Industry clinical trials with additional support and access to the Network s research infrastructure, to help ensure timely site set up and delivery of patient recruitment targets. Industry sponsored/industry funded studies must be conducted within the NHS at full cost recovery from the Industry funder. NIHR CSP provides a single point to apply to gain NHS Permission. Industry studies that are eligible for the NIHR CRN Portfolio, gain NHS Permission via NIHR CSP. Industry expects the following outcomes from the NIHR CRN: To facilitate and expedite the NHS Permission process for Industry Sponsored studies through NIHR CSP. To ensure effective communication between involved parties (company, Chief Investigator/Principal Investigators, Comprehensive Local Research Network (CLRN) core team, CSP Unit (CSPU) R&D Applications Facilitators (RAFs), NIHR CRN Industry Liaison Managers). To ensure visibility of progress of study-wide governance review and CSP Governance Quality Control (Study-wide) and, at the site level, local governance review and CSP Governance Quality Control (Local) Role of the CLRN Industry Manager The CLRN Industry Manager is a CLRN core team member who, amongst other responsibilities, has a key role in the NIHR CSP process. CLRN Industry Managers work with their Lead Research Management and Governance (RM&G) Managers and CLRN-funded RM&G staff working in or on behalf of NHS organisations, to facilitate the necessary NHS approval process for all Industry sponsored studies adopted to the CRN (including Topicspecific Clinical Research Networks (TCRNs), Primary Care Research Network (PCRN) and Comprehensive Clinical Research Network (CCRN)). Specifically the CLRN Industry Managers are expected to: Link with the NHS site CLRN-funded RM&G staff working in or on behalf of NHS organisations to ensure that local and study-wide governance reviews are initiated and progressed in a timely manner for adopted Industry studies being undertaken within their CLRN. Maintain an overview of the progress of all adopted Industry studies through NIHR CSP with sites within their CLRN. Ensure effective feasibility is carried out for CCRN Industry studies, including capability and capacity of appropriate support services. Version

37 Facilitate costing and contract negotiation for all Industry studies adopted to the CRN (TCRNs, PCRN and CCRN) in a timely manner to support NIHR CSP governance review and sign off of the model Clinical Trial Agreement (mcta). Liaise with the Principal Investigator and Study Coordinator to ensure that the Site Specific Information (SSI) Submission is made through IRAS after the R&D Submission has been validated and as soon as the site is ready to proceed. Liaise with TCRN/PCRN Local Research Network Managers as necessary, to ensure that local requirements for NIHR CSP are being completed. Liaise regularly with the Lead RM&G Manager and CLRN-funded RM&G staff working in or on behalf of NHS organisations, to raise and resolve issues affecting progress of Industry studies within NIHR CSP. Ensure a faxed copy of the mcta signature page is available to the company at the same time as the issue of the site approval letter, to ensure the site activation is expedited Communication Channels R&D Applications Facilitator The CSPU RAF for a study maintains an overview of the study-wide and local review progress and status of Industry studies in NIHR CSP. In order to perform this role, the RAF may liaise with the following parties: Lead RM&G Managers, CLRN-funded RM&G staff working in or on behalf of NHS organisations, and CLRN Industry Managers from Participating CLRNs Company Study Coordinator NIHR CRN Industry Liaison Managers (TCRNs/PCRN/CCRN) CLRN and CLRN-funded RM&G Staff The CLRN-funded RM&G staff working in or on behalf of NHS organisations responsible for performing the NIHR CSP review should communicate with the following parties at key stages to ensure visibility of progress and timely completion of review: Company Study Coordinator RAF Lead RM&G Manager and CLRN Industry Manager CLRN Industry Managers The CLRN Industry Managers should work closely with the Lead RM&G Managers to regularly review progress of locally occurring Industry studies in order to identify and resolve any issues. CLRN Industry Managers will communicate with the relevant NIHR CRN Industry Liaison Manager (TCRNs/PCRN/CCRN) in case of any issues/delays with NIHR CSP sign off at any particular site. Version

38 NIHR CRN Industry Liaison Managers The relevant NIHR CRN Industry Liaison Managers from the network coordinating centres are in regular contact with the company at the pre-adoption stage, in order to coordinate the Industry feasibility and adoption process. This adoption process may occur before or in parallel with the NIHR CSP submission. The relevant NIHR CRN Industry Liaison Manager will ensure the Portfolio Application Team (PAT) is informed of any adoption decision, so PAT can update the CSP Module. Post-adoption, the NIHR CRN Industry Liaison Manager continues to liaise with the Study Coordinator on a regular basis to facilitate study/site set up and performance manage delivery of the study Industry Funded/Non-Industry Sponsored Studies Industry funded, non-industry sponsored studies (often referred to as Investigator-initiated, industry collaborative studies) are eligible for inclusion in the NIHR CRN Portfolio but require formal consideration through an adoption process. Industry funded, non-industry sponsored studies adopted on to the NIHR CRN Portfolio have access to infrastructure support and to NHS service support costs. The only way that an Industry funded, non-industry sponsored study can apply for NIHR CRN Portfolio adoption is via the completion of the NIHR Portfolio Application Form (PAF) through IRAS; such studies must use NIHR CSP in order to gain NHS Permission. As Industry funded, non-industry sponsored studies potentially have access to NHS support costs, they are treated in the same way as non-commercial studies, unlike Industry sponsored studies. For example; Industry funded, non-industry sponsored studies should not be costed using the Industry Costing Template or other commercial costing methods. The Portfolio team at the NIHR CRN Coordinating Centre manages the adoption process for Industry funded, non-industry sponsored studies. The Portfolio team will ensure PAT is informed of any adoption decision so that the CSP Module Confirm Portfolio Eligibility task can be completed. Version

39 7. ARRANGEMENTS FOR DEVOLVED ADMINISTRATION STUDIES CSP is available for all NIHR Clinical Research Network (CRN) Portfolio studies where the lead NHS R&D contact and/or all participating NHS organisations are located in England. Arrangements for handling studies led from Scotland, Wales or Northern Ireland with participating sites in England, or led from England with participating sites in Scotland, Wales or Northern Ireland are provided in this section. In many instances, the Chief Investigator and lead NHS R&D contact will be in the same location. However, there are occasions when the two roles are in different countries, in which case the location of the lead NHS R&D contact will determine which country leads the study. For example, if the Chief Investigator is based in Scotland but the lead NHS R&D contact is in England, it will be led from England. With the exception of Primary Care studies led from Northern Ireland, the lead country will ensure all study-wide forms and supporting documentation is shared with the other participating countries, and will also undertake and share the study-wide governance review. For studies that are not led from England, Comprehensive Local Research Networks (CLRNs) will accept the study-wide governance report provided by the lead country and will support review of a study at a local level, recording the governance reviews on the CSP Module. For studies led from Scotland, Wales or Northern Ireland, the Lead CLRN will be allocated by the CSP Unit (CSPU) on a case-by-case basis, taking into account available resources and factors such as the level of research activity within the CLRN. Please note that arrangements for handling studies involved the devolved administrations will be revised as changes within IRAS, the CSP Module, or the UKwide Compatibility Group devolved administrations processes, are implemented. Version

40 7.1. UK Wide Coordination The table below provides information on the coordination of studies within each devolved administration. Please also refer to the contact information in DEVOLVED ADMINISTRATION CONTACTS. Devolved Administration Scotland Coordination NRS Permissions Coordinating Centre [NRS Permissions CC]. NB The study-wide Governance Report is referred to as the Certificate of Compliance. Wales National Institute for Social Care and Health Research (NISCHR) Permissions Coordinating Unit (PCU). NB - The NISCHR Permissions Coordinating Process is applicable to Primary Care studies and all NEW Secondary Care studies from 4 July This will include studies that are 'old' to England but which have added a Welsh secondary site post 4 July If you are unsure whether or not NISCHR PCU will handle a study with Secondary Care sites in Wales, please contact the PCU directly. Contact details can be found in DEVOLVED ADMINISTRATION CONTACTS.. Northern Ireland Primary Care Northern Ireland Secondary Care None. No coordinating centre but one person will act as a central point of contact for studies led from England. Responsibility for Validating the R&D Submission: The lead country will validate an R&D submission in accordance with its own procedures. It will not be revalidated by the participating countries. However, for studies led from Scotland, Wales or Northern Ireland Secondary Care, if the Lead CLRN is concerned about any issue (other than missing documentation) with the R&D submission, this should first be discussed with CSPU, who will then raise the matter with the lead country if required. Any discrepancies with the identification of devolved administrations and sites (the answers to Project Filter question 3, question A72 and/or Part C of the R&D Form) will not prevent an R&D submission being validated. A. for studies led from England where the R&D Form indicates that sites in Scotland and Wales will be involved, CSPU will accept the R&D submission as it is. NRS Permissions CC and NISCHR PCU will contact the Chief Investigator to clarify which sites in their devolved administration are taking part in the study B. for studies led from England, where it is noted that Northern Ireland Primary Care is taking part, CSPU will advise the Chief Investigator to contact the NHS primary care Version

41 organisations in Northern Ireland directly C. for studies led from England, where it is noted that Northern Ireland Secondary Care is taking part but there are no sites listed in Part C of the R&D Form, CSPU will advise the Chief Investigator that the R&D submission and study-wide Governance Report cannot be exported to the Northern Ireland Secondary Care Coordinator until Part C has been corrected and the form resubmitted through IRAS D. for studies led from Scotland, Wales or Northern Ireland Secondary Care, the devolved administrations will forward all study details to CSPU. CSPU will liaise with the Chief Investigator to discuss applying for inclusion in the NIHR CRN Portfolio and the use of CSP. On those occasions when the Chief Investigator does not wish his/her study to be included in the NIHR CRN Portfolio, CSPU will advise the devolved administrations that no further correspondence is required for that study. E. for studies led from Northern Ireland Primary Care, there is no agreed process for handling UK-wide studies. One of the other participating administrations may take the lead nation role, following discussion amongst the participating nations Lead NHS R&D Contact in England with Additional NHS Research Sites or NHS Participant Identification Centres (PICs) in Scotland, Wales or Northern Ireland Secondary Care. The CSP Unit: identifies from Project Filter question 3, question A72 and/or Part C of the R&D Form that the study includes sites in Scotland, Wales or Northern Ireland Secondary Care during the R&D submission validation process. using standard correspondence , s the validated R&D Form in.pdf and.xml formats (.pdf only for Scotland) together with supporting documentation, the Research Ethics Committee (REC) reference number and study short title to NRS Permissions CC, NISCHR PCU and/or the Northern Ireland Secondary Care Coordinator advising which CLRN will lead on the study in England and providing the appropriate contact details. The Lead CLRN should be copied into this . s the standard R&D validation to the Chief Investigator, copying in the Lead CLRN, revising the text to advise that: o the R&D Submission has been ed to NRS Permissions CC, NISCHR PCU and/or the Northern Ireland Secondary Care Coordinator. o the Lead CLRN will forward the study-wide governance report and final versions of documents to NRS Permissions CC, NISCHR PCU and/or the Northern Ireland Secondary Care Coordinator when the study-wide governance review is complete. The Lead Comprehensive Local Research Network (CLRN): s any additional documentation to NRS Permissions CC, NISCHR PCU and/or the Northern Ireland Coordinator, using standard correspondence , as and when it is provided. s the study-wide Governance Report to NRS Permissions CC, NISCHR PCU and/or the Northern Ireland Secondary Care Coordinator, using standard correspondence , once the Lead CLRN study-wide governance review is complete. Final versions of supporting documentation should be ed with the study-wide Governance Report. Version

42 7.3. Lead NHS R&D Contact in England with Additional NHS Research Sites or NHS PICs in Northern Ireland Primary Care There are no current plans for a coordinating centre for Northern Ireland Primary Care, so all communication will be directly with the Chief Investigator. The CSP Unit identifies that the study includes sites in Northern Ireland Primary Care during the R&D submission validation process and amends the R&D validation to advise the Chief Investigator that he/she should contact Health Boards or sites in Northern Ireland directly. The Lead CLRN s the study-wide Governance Report to the Chief Investigator for information, once the Lead CLRN study-wide review is complete Lead NHS R&D Contact in Scotland (NRS Permissions CC), Wales (NISCHR PCU) or Northern Ireland Secondary Care with Additional NHS Research Sites or NHS PICs in England NHS Permissions CC/NISCHR PCU/NI Lead Health & Social Care Trust identifies that a study includes sites in England and s the validated R&D Form in.pdf and.xml formats (where possible) to CSPU, along with all supporting documentation supplied with the R&D application. NRS Permissions CC/NISCHR PCU/NI Lead Health & Social Care Trust will any additional supporting documentation to CSPU as soon as it is received, and the study wide governance report when the study-wide governance review has been completed. The CSP Unit discusses and confirms the role of Lead CLRN, following discussion with an appropriate Lead RM&G Manager s NHS Permissions CC/NISHCR PCU/NI Lead Health & Social Care Trust, using standard correspondence , to acknowledge receipt of the R&D submission, documentation and/or study wide governance report, and advise who the Lead CLRN is. requesting the R&D form xml if necessary, creates a manual R&D submission in the CSP Module to start both the study-wide governance and the Portfolio Eligibility processes. uploads the initial receipt of study-wide documentation to the CSP Module. copying in the Lead CLRN, s the standard R&D validation to the Chief Investigator revising the text to advise: o that the R&D Submission has been received from NRS Permissions CC/NISCHR PCU/Northern Ireland Secondary Care Coordinator o which CLRN will lead on the study in England, providing the appropriate contact details o that NRS Permissions CC/NISCHR PCU/Northern Ireland Secondary Care Coordinator will forward the study-wide governance report and final versions of documents to CSPU when complete o contact details of the participating CLRNs. Version

43 forwards any additional documentation and the study-wide governance report to the Lead CLRN upon receipt. The Lead CLRN Upon receipt from NRS Permissions CC/NISCHR PCU/NI Health & Social Care Trust, the Lead CLRN: uploads any additional documentation to the CSP Module upon receipt uploads the study-wide governance report and final versions of documents to the document view reviews the study-wide governance report and applies any England-specific legislation completes the study-wide governance tasks, adding a comment referring to the governance report in the document view Lead NHS R&D Contact in Northern Ireland Primary Care with Additional NHS Research Sites or NHS PICs in England When the Lead R&D contact is in Northern Ireland Primary Care, the Chief Investigator can be advised to select England as the Lead Nation in IRAS. The English sites will be processed through CSP as normal Handling of Amendments/Revised R&D Forms There is currently no agreed UK-wide process for handling of amendments. The following interim procedures will apply: for studies with the Lead NHS R&D contact in England, in the situations where the Lead CLRN provides the study-wide documents to the devolved administrations, the Lead CLRN should also pass any documents accompanying an amendment to the devolved administrations. This will ensure that study-wide documents are handled in a consistent fashion. for studies where the Lead NHS R&D contact is in Scotland, Wales or Northern Ireland Secondary Care, amendment documents will be forwarded by that devolved administration to the Lead CLRN. Version

44 8. PARTICIPANT IDENTIFICATION CENTRES (PICs) 8.1. Background and Principles What is a Participant Identification Centre? A Participant Identification Centre (PIC) is any organisation responsible for identifying and informing potential participants about a study taking place in another organisation. The other organisation is responsible for the subsequent assessment of potential participants and their possible recruitment and informed consent into the study. As a PIC is not responsible for the delivery of research procedures, it is not a research site. Where an NHS organisation is acting as a PIC, the study is not required to undergo the same scrutiny as those where an NHS organisation is acting as a research site and hosting the research. However the NHS organisation should still review the study to confirm its agreement to act as a PIC and identify potential participants (see below). A PIC within the NHS would typically be a NHS Trust/Health Board, a GP practice or a NHS dental practice. A PIC is not responsible for the conduct of research procedures specified in the research protocol. Research procedures include informed consent of participants, and any eligibility assessment or screening intervention(s) (eg blood test or X-ray) to determine if a participant is eligible for randomisation When is an NHS Organisation Acting as a Participant Identification Centre? An NHS organisation is acting as a PIC when clinicians or clinical units: inform patients or services users about potential opportunities to participate in research which is managed by a research team based in another organisation and is not a clinical referral provide information to patients or service users either directly or through public display, about a specific study, for example through leaflets or posters When is an NHS Organisation not Acting as a Participant Identification Centre? An NHS organisation is not acting as a PIC when: the organisation itself is responsible for conducting research procedures specified in the research protocol (even if the procedures are follow-up procedures) it s activity in relation to research is its normal clinical activity. Examples of when an NHS organisation is not acting as a PIC are: Where it provides research data (including existing data in medical records held by it) to external researchers for a specific project (ie not to a register or database). This is a research site. Version

45 Where it provides tissue/samples (including existing samples held in a diagnostic repository) to external researchers for a specific project (ie not to a research tissue bank). This is a research site. Where its employees participate in research during the course of their employment. The NHS employer retains responsibility for its employees where they take part in research during the course of their employment, and must therefore give permission for such activity, and be managed as a research site. In certain situations, patients may be referred to take part in a clinical trial for clinical reasons, eg where other treatment options are not clinically appropriate and a clinical trial offers access to a treatment not otherwise available. In these cases, the activity is managed through normal clinical arrangements and the organisation is not a PIC or a research site. There is no requirement for any additional review by the NHS organisation. Where generic leaflets or posters about research (eg on behalf of a network or department) are to be displayed, these should be assessed through the organisation s normal public communication routes, and NHS organisations are expected to consider displaying such materials as part of their normal public engagement in research. Requests to display generic leaflets or posters should not be reviewed as research sites or PICs. Organisations or units developing such generic materials are encouraged to consider seeking Research Ethics Committee (REC) review through voluntary arrangement with the REC (see NRES Standard Operating Procedures (SOPs) 4.55) Mixed NHS and Non-NHS Research Sites and Participant Identification Centres Research studies could have: NHS research sites only; non-nhs research sites only; mixed NHS /non-nhs research sites, and NHS organisations acting as PICs. In most cases a non-nhs research site will be an academic site, but other examples are identified in the NRES REC SOPs Application for Agreement to Act as a Participant Identification Centre The application for agreement to act as a PIC consists solely of the study-wide documents. A Site-Specific Information (SSI) Form or local versions of documents are not required. Agreement to act as a PIC may take place before or in parallel with NHS Permission from research sites. 8 Version

46 Except where the PIC activity is limited to displaying leaflets or posters only, all PICs should be named in Part C of the R&D Form. However, in the event that a large number of PICs are identified over a period of time, an alternative format of listing the PICs, for example a spreadsheet, may be used at the discretion of the Lead Comprehensive Local Research Network (CLRN). This format should include the name of the research site associated with each PIC and should clearly identify the dates when new PICs are added. Updates should be notified to the Participating CLRNs, via the CSP Unit (CSPU), at regular intervals NHS Organisation Agreement to Act as a Participant Identification Centre The review undertaken by an NHS organisation in agreeing to identify and inform potential participants (ie for that organisation to act as a PIC) should be limited to any issues relating solely to identifying and informing patients and service users as potential participants. Where no issues arise, the NHS organisation should agree to act as a PIC. The site undertaking the research procedures specified in the research protocol is responsible for maintaining the safety of the participants and for providing indemnity or insurance for the research procedures specified in the protocol. This is not a responsibility of the NHS organisation responsible for the PIC. The term referral is commonly used to describe the process whereby a healthcare professional provides information about a research study to a potential participant, and either invites the patient to contact the research team, or obtains appropriate agreement to pass on the relevant details of the patient to the research team. The use of the term referral in this context is therefore not the same as the definition used in a clinical context, and the responsibilities of clinical referral do not apply to PICs. Where information is given about research in other NHS sites, the wider governance review will be undertaken by the NHS organisation responsible for the research site as part of the NHS permissions process and other regulatory reviews. Where information is given about research in non-nhs sites, the wider review is undertaken through the ethical review process, including a Site Specific Assessment conducted by the REC, where required. Where identification and provision of information to potential participants takes place as part of a health care professional s private practice, the NHS organisation has no responsibility to agree the activity Proportionate Approaches to Reviewing a Request to Act as a Participant Identification Centre The PIC s responsibility for an overall duty of care in relation to delivery of healthcare and provision of information is met through assessing issues relating to confidentiality, resource use and the appropriateness of the contact arrangements between the patient or service user and the research team. Version

47 When the activity at the PIC is limited to leaving study-specific leaflets or displaying a studyspecific poster in public areas, only study-wide review is required. In these cases, PICs do not need to be named in the R&D Form (Part C Overview of Research Sites). Local NHS organisations only need to register the study as potentially involving its patients, but no other local review or assessment should be necessary. Sponsors should not request display of such materials at the PIC until confirmation of the acceptability of the documents has been given following the study-wide review. When the activity at the PIC is to identify and inform potential participants, the NHS organisation, in agreeing to do so, needs to be satisfied that: the process is in line with the NHS duty to ensure a safe system of care for its patients relevant regulatory approvals or authorisations are in place for the research the process meets data protection and confidentiality standards arrangements for compensation for clinical negligence are clearly described to potential participants the process will not give patients the impression that a referral is being made for the purposes of their treatment by that NHS organisation or that the research is done by or on behalf of that NHS organisation or by people acting in a capacity relating to that NHS organisation any resource implications for staff in identifying and informing potential participants have been addressed. The NHS organisation providing agreement for the activity at the PIC should not consider the treatment costs of the research or any future implications of the research as part of the assessment as these should not affect the decision to act as a PIC Addition of New Participant Identification Centres Since PICs are not research sites, the addition of new PICs does not follow the study amendments process. There is no need for PICs to review amendments except in exceptional circumstances where an amendment may impact on the willingness of the PIC to continue to identify and inform patients Governance Review for a Participant Identification Centre When a PIC is identified on the R&D Form, study-wide Governance Reviewers will be assigned a task to undertake a study-wide review for PICs when there are no NHS research sites taking part in the study. For studies which have NHS research sites, the study-wide review undertaken by the Lead CLRN will encompass study-wide review for the PICs. PIC review at a local level is assigned and undertaken in the same way as for local site governance. Some of the assigned governance criteria may not be applicable in which case they should be marked as Complete - Proceed and a comment of Not Applicable should be added to the comment box. Version

48 CLRN users should review the R&D Form (Part C Overview of Research Sites) to confirm whether their location is listed as a PIC or as a research site. The criteria below satisfy the NHS organisation responsibilities around PICs as described in Section 8.1. The NHS organisation providing agreement for the activity at the PIC should not consider the treatment costs of the research or any future implications of the research as part of the agreement to the activity at the PIC. These are the responsibility of the research site Study-wide Review The Lead CLRN will perform the study-wide review for a PIC for studies in which there are no NHS sites. It should be noted that the review is limited to the criteria set out in APPENDIX 2 and does not extend to the elements that apply to research sites Local Review The NHS organisation (Participating CLRN) will perform the local review for a PIC. It should be noted that the review is described in the criteria set out in APPENDIX NHS Agreement to Act as a Participant Identification Centre PIC Authorisation is undertaken in the same way as NHS Permission for research sites Correcting a Study Record when Participant Identification Centres have not been Identified Correctly at R&D Submission Validation The Chief Investigator or Study Coordinator should include the PIC information at question A73-1 in IRAS and Part C Overview of Research Sites of the R&D Form. The following procedure is used to correct the study record when PICs have not been identified correctly: Lead CLRN should request that the Chief Investigator/Study Coordinator updates the R&D Form within IRAS in Part C 'Overview of Research Sites'. If the study does not already include NHS PICs, the Chief Investigator/Study Coordinator will be required to select: o Yes to IRAS Project Filter Question 5, Will any research sites in this study be NHS organisations o Yes to Question A73-1, Will potential participants be identified through any organisations other than the research sites listed above? o Yes to Question A73-2, If yes, will any of these organisations be NHS organisations? o List PICs (if known) in Part C of the R&D Form If PIC sites are declared at the start of the study as unknown, and will be identified as part of the study, the Chief Investigator or Study Coordinator should not be asked to resubmit an R&D Form each time a new PIC is identified. This information should be communicated directly to the Lead CLRN for cascading to the Participating CLRNs via CSPU. Version

49 9. HANDLING OF REVISED R&D SUBMISSIONS 9.1. Introduction This section provides guidance on when revised R&D Submissions may be submitted and when revised forms require signing or authorising. It should be read in conjunction with guidance on processing amendments to studies Principles Where a Lead Comprehensive Local Research Network (CLRN) is advising applicants about the requirement for resubmission, the decision tree in Figure 1 below should be used. Where a revised R&D Submission is submitted without being requested, the decision tree in Figure 2 below should be used. Researchers should be encouraged to discuss the R&D Form with the Lead CLRN research management and governance (RM&G) staff at an early stage, so that all necessary information is included within the R&D Form before the initial submission. A Draft R&D Submission facility is provided to facilite discussion before final submission. Where the need for a revised submission is identified, in accordance with the guidance in this document, researchers should also be encouraged to discuss revisions to the R&D Form so that they can be processed as quickly as possible. A revised R&D Submission without a notification of amendment may only be submitted prior to regulatory approvals. After regulatory approvals have been obtained, the amendment process should be followed. Applicants may choose to submit revised R&D Submissions along with a notice of amendment, but a revised form is not required except for the addition of new sites and new Participant Identification Centres (PICs). A revised R&D Submission may be requested if the submission is invalid or if the changes required involve the addition of new sites or new PICs into Part C. A revised R&D Submission may also be requested for changes or corrections to the application that are sufficiently substantial to require resubmission. In particular, a revised form should be requested where the change or correction in IRAS would result in new questions being generated. The reason for the revision to the R&D Form must be provided by the Chief Investigator/Sponsor in writing to the Lead CLRN. Any clarifications or corrections that do not warrant a revised submission of an R&D Form will be handled in correspondence between the Chief Investigator/Sponsor and the Lead CLRN. The correspondence will be made available to Participating CLRNs through the document repository and, where appropriate, explanations should be provided in the comments for the governance criteria. Except for CTIMPs, revisions to add new sites or new PICs to Part C prior to Research Ethics Committee (REC) approval do not require any signature or authorisation on the R&D Form. For CTIMPs, revisions to add new sites or new PICs to Part C prior to REC/MHRA approval require new signatures/authorisations on the R&D Form. For addition of new sites or new PICs after regulatory approval please see the amendments process. Version

50 Other revisions to the R&D Form are only warranted where the revision is substantial and the form must be signed/authorised again Responsibilities The Lead CLRN is responsible for: Providing a contact for the CSP process for the Chief Investigator/Study Coordinator Assessing whether a revised R&D Submission is required Communicating with the researcher for information on revisions within a submitted revised R&D Form Validating a revised R&D Submission. Each Participating CLRN is responsible for: Ensuring all issues regarding a R&D Submission are communicated to the Lead CLRN so that they can liaise with the Chief Investigator/Study Coordinator according to these principles. The CSP Unit (CSPU) is responsible for: Validating a revised R&D submission if received due to the original form being rejected as invalid Processing of Revised R&D Submissions Validation of a Revised R&D Submission Where a Lead CLRN is advising applicants about the requirement for resubmission, the decision tree in Figure 1 below should be used. Where a revised R&D Submission is submitted without being requested, the decision tree in Figure 2 below should be used. If the revised R&D Form has been submitted due to the original application being determined to be invalid by CSPU it will be processed by CSPU Where the submission is not due to an invalid original R&D Submission, the Lead CLRN will receive the Validate R&D Submission task The Lead CLRN checks whether there is correspondence from the Chief Investigator/Sponsor/Study Coordinator regarding the revisions. If no correspondence has been received the process in Section should be followed. When the information on changes has been communicated and the changes are seen within the submission, the submission is validated by the Lead CLRN within the 3 day validation period. If there has been no communication received please go to section Version

51 The Lead CLRN will notify the Chief Investigator/Study Coordinator of the validation of the revised R&D Submission by using standard correspondence Verification of Reasons for Receipt of Revised R&D Form If the Chief Investigator has provided no details of the reason for resubmission, the Lead CLRN will send an enquiry by using standard correspondence in section Lead CLRN Request for information on the submitted revised R&D Form. This is to determine whether the change has come from a: REC substantial amendment non substantial amendment change requested by a regulatory body during review new sites or new PICs other reason. The Lead CLRN will not validate the revised submission until the required information has been received. Where the form has been accidentally submitted and there are no changes, no action will be taken and no changes are made in the CSP Module. Where the reason for the submission of a revised submission is due to a substantial or nonsubstantial amendment, the amendment process should be followed. Any effects of the change on study-wide review and Governance QC will be captured during this process as this will not occur prior to regulatory approval.. Once the information has been received the revised R&D Submission will be validated by following steps 4 and 5 inclusive in section Version

52 9.3. Figure 1 Decision Tree for Submitting Revised Forms (Researcher Contact) Researcher contacts Lead CLRN RM&G staff to discuss study Lead CLRN RM&G staff need to ascertain: Change requested by regulatory body to their submission impacts on integrated dataset Change to Part C with the addition of new research sites or new PICs Change during parallel regulatory submission Change post regulatory approval Revised R&D Form Submission requested & submitted through IRAS by Chief Investigator Clarification that can be noted using correspondence Substantial or nonsubstantial amendment required Place in Document Repository and notify Participating CLRNs (via CSPU) Amendments process Version

53 9.4. Figure 2 Decision Tree for Revised R&D Form Received without being Requested Revised R&D Submission received YES Has Lead CLRN received notification from Chief Investigator? NO Has the study received regulatory approvals? Chief Investigator corresponds with Lead CLRN Lead CLRN s Chief Investigator for clarification (section 9.2.2) NO YES No response received after 1 month Revised R&D Submission validated (section 9.2.1) Amendment Process Submission rejected with explanation Version

54 10. STUDY AMENDMENTS This section defines the process for the handling of amendments. The process should replace any existing arrangements used by Comprehensive Local Research Networks (CLRNs) or NHS organisations for studies that gained NHS Permission for research via NIHR CSP (or that are currently being processed through NIHR CSP) Impact of Amendments on NHS Organisations Amendments may affect the whole study and all participating research sites, for example a revision to the inclusion/exclusion criteria in the protocol, or just one research site, for example where the Principal Investigator is changing. Amendments could affect the NHS organisation in a number of ways, such as: 1. the resources/staff required to support the amended study 2. the role of support departments (such as pharmacy, radiology, laboratories, pathology, etc) 3. the subjects eligible for study inclusion 4. the study end-point. NHS organisations need to be aware of all amendments to understand their implications and to implement them in a timely manner (assuming that there is no objection to continuation of NHS Permission). NHS organisations must instigate change control processes (eg change to the existing agreement with the study Sponsor) to ensure that amendments are managed appropriately Principles for Handling Amendments The process for handling amendments via NIHR CSP operates according to the following principles: An amendment is a change to research already given a favourable opinion by the Research Ethics Committee (REC). For a change to research prior to or during review by the REC, please see NRES SOP section 1.77 to These changes should be handled as revisions to the REC submission. All correspondence with the REC should be submitted as part of the R&D application, either as part of the initial application or as additional information. The facility to process amendments through NIHR CSP is only available to: o studies which gained NHS Permission via NIHR CSP in the first instance o studies currently progressing through NIHR CSP. Substantial and non-substantial amendments are handled in the same way. However, many amendments will have minimal or no impact on the NHS organisation. Version

55 Signed-off study-wide criteria affected by the amendment are not modified retrospectively in the CSP Module. The NHS organisation reviews the amendment and if they have an objection to the amendments indicates this is in the Review Amendment task. This is a governance process and does not replace the Chief Investigator s/sponsor's responsibility to notify Principal Investigators and other local staff. The notice of amendment should be provided to the Lead CLRN in parallel to the regulatory bodies, where applicable, to allow NHS organisations sufficient time to confirm continuation of NHS Permission. As Participant Identification Centres (PICs) are not research sites, if the use of PICs as a method of identifying potential participants is covered by the existing REC approval, the addition of a PIC is not an amendment. However, the introduction of PICs to a study as a new method of identifying potential participants does constitute an amendment. The amendment will be implemented 35 calendar days after receipt of the complete amendment application. The start date is the date on which the complete amendment application is received by CSP. It is recommended that the NHS organisation issues a formal letter confirming continued permission and that the amendment may be implemented within this 35 day period. No amendment, other than a safety amendment, may be implemented until the relevant regulatory approvals are in place. A letter confirming continued permission may not be issued until the relevant regulatory approvals have been received. Safety amendments that the Chief Investigator/Sponsor identifies as requiring immediate implementation should be implemented immediately and a formal letter of confirmation sent Responsibilities The Chief Investigator is responsible for submitting amendments via IRAS, by attaching the documentation to the IRAS R&D Form Checklist and resubmitting from the R&D esubmission tab. The Lead CLRN study-wide Governance Reviewer is responsible for: Validating the amendment submission Reviewing all study-wide amendment documentation that has been submitted via IRAS and assessing the impact of the amendment Completing the Amendment Summary Form and saving it to the document repository. Once the amendment has been validated, the local Governance Reviewers at the NHS organisations (Participating CLRNs) are responsible for ensuring that: The participating NHS organisations are aware of the amendment Any sites that have withdrawn permission are recorded using the Amendment Review task. Version

56 10.4. Processing of Amendments Handling of Amendments within NIHR CSP The Chief Investigator/Sponsor should contact the Lead CLRN as soon as possible for advice on preparing the amendment and the associated documentation. The contact details for the Lead CLRN will be provided in the initial correspondence during the permissions process. The Chief Investigator/Sponsor submits the appropriate amendment form and supporting documents through IRAS to the REC and/or MHRA (and other regulatory bodies as required), and to the Lead CLRN. It is recommended that the Chief Investigator/Sponsor submit the amendment to the Lead CLRN in parallel to submission to the relevant regulatory bodies. The Lead CLRN Amendment Validator receives a task to validate the amendment application. If the submitted amendment application is not complete, the Lead CLRN will work with the Chief Investigator/Sponsor to correct the problem and resubmit the amendment application for further review. Amendment Reviewers at the NHS organisations (Participating CLRNs) receive a task to ensure the NHS organisations are made aware of the amendment. Once the amendment has been validated, a task is sent to the Amendment Reviewer at the Lead CLRN to review the amendment and complete the Amendment Summary Form. There is no requirement to undertake a study-wide review or initiate a change control process in order to complete the Amendment Summary Form. Once the Amendment Reviewer at the Lead CLRN has completed the Amendment Summary Form, a notification is sent to the Amendment Reviewers at the NHS organisations (Participating CLRNs). The 35 day period allowed for the review of an amendment does not stop while regulatory bodies are awaiting any further information in respect of the application. If any documents are revised as a result of the REC or MHRA review of the proposed amendment, these revised documents and relevant REC/MHRA correspondence should be submitted through IRAS to the CSP Module. When the MHRA/REC Letter is received, the Chief Investigator/Sponsor submits a copy to the Lead CLRN using IRAS. The participating NHS organisations may issue a Notification of Continued NHS Permission to the Principal Investigator (standard correspondence section ), copied to the Chief Investigator and Sponsor. The NHS organisations (Participating CLRNs) upload the Notification of Continued NHS Permission to the document repository in CSP Module as a study-wide document in the permission category. Where the initial amendment submission is rejected by a regulatory body, a revised amendment may be submitted. As outlined in NRES procedures, this should be processed within 14 days, unless the site advises that they require additional review time or withdraws NHS Permission. Note: When an amendment is received (in its entirety) before NIHR CSP Governance Version

57 Quality Control (Study-wide) is completed, the Lead CLRN will incorporate review of the amendment in the study-wide review Notification of Research Sites where the Amendment cannot be Implemented In the event that it is not locally feasible for a participating NHS organisation to work to the amendment, the following process should be followed: The participating NHS organisation sends the letter of objection to the Principal Investigator, copying it to the Chief Investigator, the Participating CLRN and the Sponsor The Participating CLRN informs the Lead CLRN that the amendment is not locally feasible, The Lead CLRN ensures that the Chief Investigator/Sponsor has been informed The Lead CLRN liaises with the NHS organisation (Participating CLRN) to assess any study-wide implications and then takes appropriate action if required. Note: Where an NHS organisation is unable to accommodate the requirements of a REC and/or MHRA approved amendment, the research will normally have to be terminated at that site Submitting Amendments to Regulatory Bodies and CLRNs Please also refer to Section 10.5 for the minimum documentation requirements. Clinical Trials of Investigational Medicinal Products (CTIMPs) To distinguish whether an amendment is substantial or non-substantial please refer to the European Commission guidance: 1. Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial, and 2. 'Detailed guidance on the application format and documentation to be submitted in an application for an Ethics Committee opinion on the clinical trial of medicinal products for human use'. For substantial amendments, the Chief Investigator submits the European Commission Notification of Substantial Amendment Form and other relevant documents through IRAS to the main REC or the MHRA, of both organisations (as appropriate), and to the Lead CLRN. For CTIMPs, addition of a new site or change of Principal Investigator (not previously listed in Part C of IRAS) constitutes a substantial amendment. Please refer to Section for further details. For non-substantial amendments, the Chief Investigator submits notification of the amendment through IRAS to the Lead CLRN, with any supporting documentation. Clinical Investigations of Medical Devices To distinguish whether an amendment is substantial or non-substantial, please refer to Version

58 section 5 of the NRES SOPs. MHRA (Devices) does not distinguish between the handling of substantial and non-substantial amendments. For substantial amendments, the Chief Investigator submits the Notice of Substantial Amendment form and other relevant documentation through IRAS to the MHRA, REC and Lead CLRN. The addition of a new site or change to Principal Investigator (not previously listed in Part C of IRAS) does not require submission to the REC as a notification of substantial amendment; this type of local amendment is covered by the original favourable opinion and conditional on NHS Permission. The Chief Investigator submits notification of this type of amendment through IRAS to the MHRA and the Lead CLRN, along with any supporting documents. Refer to Section for further details. For non-substantial amendments, the Chief Investigator submits notification of the amendment through IRAS to the MHRA and the Lead CLRN, along with any supporting documentation. Other research To distinguish whether an amendment is substantial or non-substantial please refer to the NRES SOPs section 5. For substantial amendments, the Chief Investigator submits the Notice of Substantial Amendment form and other relevant documents through IRAS to the main REC and to the Lead CLRN. The addition of a new site or change to Principal Investigator (not previously listed in Part C of IRAS) does not require submission to the REC as a notification of substantial amendment; this type of amendment is covered by the original favourable opinion and conditional on NHS Permission. The Chief Investigator submits notification of this type of amendment through IRAS to the Lead CLRN, along with any supporting documents. Refer to Section for further details. For non-substantial amendments, the Chief Investigator submits notification of the amendment ythrough IRAS to the Lead CLRN, along with any supporting documentation Amendments Consisting of the Addition of New Research Sites or Change of Principal Investigator Only For amendments comprising addition of new sites only, the Chief Investigator/Sponsor adds the site details to Part C in IRAS 'Overview of Research Sites' and submits the amended R&D Form to the Lead CLRN with the other amendment documentation, including the amendment form/letter. The amended R&D Form does not require new signatures or authorisations. There is no requirement for the Lead CLRN to review the rest of the R&D Form for any other changes. Only amendments that are specified in the amendment form or letter are accepted. For a new site, the Chief Investigator/Sponsor also creates a Site Specific Information (SSI) Form for the new site and sends this to the Principal Investigator for completion; the governance review is undertaken as usual. Version

59 For a change in Principal Investigator, where the original SSI Form required a electronic authorisation/signature, a new SSI Form should be created and submitted through IRAS along with the CV and the amendment form/letter (this can be done by duplicating the original SSI Form and revising the details of the Principal Investigator). The suitability of the Principal Investigator will be assessed as usual. When no electronic authorisation/signature from a Principal Investigator on an SSI Form is required, details of the change can simply be provided in the amendment form/letter Revisions to the R&D Form Amendments may require changes to some of the study arrangements. There is no need for Investigators to update the IRAS data set for every change. If amendments are supplied to NIHR CSP as described above, it is not necessary for the Chief Investigator/Sponsor to resubmit an amended R&D Form unless there are additional research sites Amendment Submission Documentation Non-substantial Amendments Minimum documentation requirements for NHS sites for a non-substantial amendment Study Type Approval Minimum documentation Clinical Trial of a Medicinal Product R&D review for relevant research site Notify by letter or Revisions to original submission documentation, where applicable REC No notification required Clinical Investigation of a Medical Device Other Research Study MHRA (Medicines) R&D review for relevant research site REC MHRA (Devices) R&D review for relevant research site REC No notification required Copy of MHRA letter Revisions to original submission documentation, where applicable No notification required Notify by letter Notify by letter or Revisions to original submission documentation, where applicable No notification required Substantial Amendments Addition of new site or change of Principal Investigator Addition of a new site or Principal Investigator meets the definition of a substantial amendment to the information assessed by the REC (if not listed in the original application). However, the process for handling such an amendment depends on the type of study. Other substantial amendments Version

60 For clinical trials of medicinal products, refer to the European Commission Detailed guidance on the request to the competent authorities for authorisation of a clinical trial on a medicinal product for human use, the notification of substantial amendments and the declaration of the end of the trial (revision 3Mar10) on whether to submit to the MHRA or NRES. Version

61 Minimum documentation requirements for NHS sites for addition of a new site or change of Principal Investigator Study Type Approval New research site Change of PI at research site Clinical Trial of a Medicinal Product R&D review for relevant research site Clinical Investigation of a Medical Device Other Research Study Copy of NRES cover letter Notification of Substantial Amendment 1 (signed or authorised) SSI Form (signed or authorised) Relevant local documents including CV of PI R&D Form with updated Part C (no signature required) Copy of NRES cover letter Notification of Substantial Amendment 1 (signed or authorised) CV of PI Where the original SSI Form required a signature, a new SSI should be created and submitted REC Cover letter Notification of Substantial Amendment 2 (signed or authorised) REC form with updated Part C Cover letter Notification of Substantial Amendment 2 (signed or authorised) REC form with updated Part C MHRA No notification required No notification required R&D review for relevant research site Copy of MHRA letter SSI Form (signed or authorised) Relevant local documents including CV of PI R&D Form with updated Part C (no signature required) Copy of MHRA letter CV of PI REC No notification required 3 No notification required 3 MHRA (Devices) Notify by letter Notify by letter R&D Notify by letter Notify by letter review for SSI Form (signature or CV of PI may be required relevant authorisation may be research required) site Relevant local documents R&D Form with updated Part C (no signature required) REC No notification required 3 No notification required 3 1 European Commission form (available from IRAS) 2 European Commission form (available from IRAS) 3 covered by original favourable opinion Version

62 11. STANDARD CORRESPONDENCE This section defines the standard set of s to be used by the Portfolio Application Team (PAT), CSP Unit (CSPU) and Comprehensive Local Research Network (CLRN) to facilitate the NIHR CSP process. Many of these standard s will be generated from the CSP Module after the completion of a task and will be sent to the user's account for modification. The fields within the ##xxxx## will be auto-populated by the CSP Module. Others will not be generated by the system and will be indicated by the absence of the flag 'CSP Module'. The yellow highlighted text instructions should be removed before sending the message. Notes: Where details of a Study Coordinator have been provided in the Portfolio Application Form (PAF) and R&D Form, all correspondence should be copied to them. This is particularly important for industry sponsored studies. All correspondence should be uploaded to the document repository as a.pdf document Portfolio Application Form Correspondence Upon receiving a PAF, PAT will view the details and make an assessment based on the information provided in the form. PAT will then the Chief Investigator within 2 working days to confirm the outcome of the PAF review CSP Module PAT Notification that the Portfolio Application Form is Invalid This is to be sent by PAT to the Chief Investigator if the submitted PAF is incomplete. Subject: To: NIHR CSP Ref. ##Study ID## ( of user who completed Validate PAF task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator Name## Re: ##Study ID## - ##Study Short Title## Thank you for submitting your Portfolio Application Form through IRAS. Unfortunately some of the information we need is missing from the form or requires further clarification. To allow us to process your application, please return to IRAS, complete the following fields in the Portfolio Application Form and resubmit it: [PAT to add any fields that require completion before sending] We look forward to receiving your amended form so we can continue to progress this study. Version

63 Kind regards NIHR Portfolio Application Team NIHR Clinical Research Network Coordinating Centre CSP Module PAT Notification that the Portfolio Application Form is Potentially Eligible for Inclusion in the NIHR Clinical Research Network Portfolio This is to be sent by PAT to the Chief Investigator when the study has been identified as potentially eligible for the NIHR CRN Portfolio. Subject: To: NIHR CSP Ref. ##Study ID## ( of user who completed Potential Portfolio Eligibility task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator Name## Re:##Study ID## - ##Study Short Title## Thank you for submitting your Portfolio Application Form. Your study has been registered on NIHR CSP and you are now able to send your completed R&D Submission via IRAS. Your R&D Form and the accompanying documents as set out in IRAS will be reviewed and, if the required information is present, your study will begin processing through NIHR CSP. If your study is to be considered for the NIHR Clinical Research Network (CRN) Portfolio in order to receive service support funding or research infrastructure support through the Comprehensive Clinical Research Network, we will you within 30 working days of receiving your R&D Form to confirm whether your study is eligible. If your study is not funded by an NIHR Partner, you will be contacted first by the appropriate Research Network, who will arrange for your study to be assessed for inclusion in the NIHR CRN Portfolio. [The following text is to be included in the only where a new funder has been identified Please be aware that the Department of Health has determined that studies funded by NIHR, other areas of Government and NIHR non-commercial partners are automatically eligible to be included in the NIHR CRN Portfolio. The funder for your study, [FUNDER NAME], will need to provide a self-declaration that they meet the criteria to become an NIHR Partner organisation before we are able to make a final decision on the eligibility of your project.] We look forward to receiving your R&D Submission so we can continue to progress this study. The Lead CLRN will contact you in a few days to offer assistance in compiling the documentation to support your R&D application. Further information on NIHR CRN Portfolio and NIHR CSP can be found by clicking on the links provided. Kind regards Version

64 NIHR Portfolio Application Team NIHR Clinical Research Network Coordinating Centre CSP Module PAT Notification that the Portfolio Application Form is Not Eligible for Inclusion in the NIHR Clinical Research Network Portfolio This is to be sent by PAT to the Chief Investigator when the PAF has been identified as not eligible for NIHR CRN Portfolio. Subject: To: NIHR CSP Ref. ##Study ID## ( of user who completed Portfolio Eligibility Review Task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator Name## Re:##Study ID## - ##Study Short Title## Thank you for submitting your Portfolio Application Form to NIHR CSP. Unfortunately your study is not eligible to use NIHR CSP for gaining NHS Permissions as it is funded by an organisation which does not meet the criteria specified by the Department of Health for studies to be included in the NIHR Clinical Research Network (CRN) Portfolio. Further information about Eligibility for Inclusion of Studies in the NIHR CRN Portfolio, is available on our web site at: To continue with your application through your local R&D Office, please return to IRAS and select the Project Filter link (at the top of the left-hand menu). Scroll down to Question 5b and click No, and then click the Navigate button at the bottom of the page; the Portfolio Application Form is removed from the Project Forms list. For instructions on how to proceed, please refer to the notes on the Submission tab in the NHS/HSC R&D Form area. Contact details for your local R&D office can be found on the R&D Forum website Kind regards NIHR Portfolio Application Team NIHR Clinical Research Network Coordinating Centre portfolio.applications@nihr.ac.uk Lead CLRN Confirmation of Lead CLRN This is to be sent by the Lead CLRN once they have been notified of a study record to Version

65 make initial contact with the Chief Investigator. This may be at the Draft R&D Form stage. Subject: To: NIHR CSP Ref IRAS project ID Confirmation of Lead CLRN Chief Investigator; Study Coordinator (if applicable) Dear Chief Investigator name Re: Study title (IRAS project ID) Confirmation of Lead CLRN Thank you for your recent submission to NIHR CSP. We can confirm that name of Lead CLRN will support you through the CSP process and we look forward to working with you on this study Please notify us as soon as possible in the event of any amendments to the study. If you have any questions or require assistance please contact name of the Lead CLRN main study contact at address and/or telephone number. Should you decide not to proceed with this study, please inform us as soon as possible. Further information on NIHR CRN Portfolio and NIHR CSP can be found on Kind regards Your name Research Management and Governance Manager Lead CLRN name CLRN Contact Details R&D Submission Correspondence First submission The CSPU R&D Applications Facilitator will validate the R&D Form and associated documents to determine whether the information it contains is valid. A confirmation message appears in the Submission tab in the IRAS R&D Form area, but an must also be sent by CSPU to advise the Chief Investigator within 3 working days. Subsequent submissions: The Lead CLRN will the form and associated documents to determine whether the information it contains is valid. A confirmation message appears in the Submission tab in the IRAS R&D Form area, but an must also be sent by the Lead CLRN to advise the Chief Investigator within 3 working days CSP Module Confirmation that the Submitted R&D Submission is Valid Subject: NIHR CSP Ref. ##Study ID## - R&D Submission Confirmation To: ( of user who completed Validate R&D task ) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator Name## Version

66 Re:##Study ID## - ##Study Short Title## Thank you for your R&D Submission. We are pleased to confirm that your study is proceeding through NIHR CSP. Any other CLRNs participating in your study will contact the Principal Investigators listed in the R&D Form, in order to provide assistance with the SSI Submissions for the other study sites. [Delete as appropriate retain when validation performed by CSPU] Please contact the Lead CLRN, ##Lead CLRN Name##, for this study if you require any further information. If new research sites or Participant Identification Centres (PICs) are added to the study, you should amend the list of sites in Part C of the R&D Form and resubmit via IRAS. Please inform the Lead CLRN at this time. Further information on NIHR CRN Portfolio and NIHR CSP can be found by clicking on the links provided. Should you decide not to proceed with this study, please inform the Lead CLRN as soon as possible. Kind regards ##RAF Name## R&D Applications Facilitator, CSP Unit NIHR Clinical Research Network Coordinating Centre ##CSPU Central Address## [Delete as appropriate retain when validation performed by Lead CLRN] If new research sites or PICs are added to the study, you should amend the list of sites in Part C of the R&D Form and resubmit via IRAS. Please inform the Lead CLRN at this time. Further information on NIHR CRN Portfolio and NIHR CSP can be found by clicking on the links provided. As your Lead CLRN please contact us if you require any further information or if you decide not to proceed with this study. Kind regards Research Management and Governance Manager ##Lead CLRN Name## ##Lead CLRN Central Address## CSP Module Notification that the Submitted R&D Submission is Invalid Subject: To: NIHR CSP Ref. ##Study ID## - R&D Submission Amendment Required ( of user who completed Validate R&D task) Version

67 To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator Name## Re:##Study ID## - ##Study Short Title## Thank you for your R&D Submission. Unfortunately some of the information we need is missing, or requires further clarification. To allow us to progress your application, please return to your R&D Form in IRAS, update the following items, and then submit the revised form (and documents as required): [insert missing fields or information needing to be clarified] [Delete as appropriate retain when validation performed by CSPU] Please do not hesitate to contact the Lead CLRN (##Lead CLRN Name##) for this study if you require any further information or assistance. This is copied to ##Lead CLRN Name## at ##Lead CLRN Central Address## for information. Kind regards ##RAF Name## R&D Applications Facilitator, CSP Unit NIHR Clinical Research Network Coordinating Centre crncc.cspunit@nihr.ac.uk [Delete as appropriate retain when validation performed by Lead CLRN] As your Lead CLRN please contact us if you require any further information or assistance. Kind regards Research Management and Governance Manager ##Lead CLRN Name## ##Lead CLRN Central Address## CSP Module PAT Study is Eligible for the NIHR CRN Portfolio (R&D Form) This is to be sent by PAT to the Chief Investigator, when the study has been reviewed and assessed as eligible for the NIHR CRN Portfolio, based on the information provided in the R&D Submission. Subject: To: NIHR CSP Ref. ##Study ID## ( of user who completed Final Portfolio Eligibility Review task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator Name## Re: ##Study ID## - ##Study Short Title## Version

68 We are pleased to inform you that your study is eligible to be included in the NIHR Clinical Research Network Portfolio. Further information about Eligibility for Inclusion of Studies in the NIHR CRN Portfolio, is available on our web site at: Your study will continue through NIHR CSP and you will receive further communications as your study moves through the process of gaining NHS Permission. Kind regards NIHR Portfolio Application Team NIHR Clinical Research Network Coordinating Centre CSP Module PAT Study is Not Eligible for the NIHR CRN Portfolio (R&D Form) This is to be sent by PAT to the Chief Investigator, when the study has been reviewed and assessed as not eligible for the NIHR CRN Portfolio, based on the information provided in the R&D Submission. Subject: To: NIHR CSP Ref. ##Study ID## ( of user who completed Final Portfolio Eligibility Review task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator Name## Re: ##Study ID## - ##Study Short Title## Following a review of the study details you have provided, we are writing to inform you that unfortunately your study is not eligible for inclusion in the NIHR Clinical Research Network Portfolio. This decision was based on the following information: [Delete as appropriate] Your funder has made a self-declaration that they do not meet the criteria required to be an NIHR Partner, namely: Awarding research funds as a result of open competition across England with high quality peer review Funding research that is of clear value to the NHS Having strategic direction for the research that they fund. [Delete as appropriate]your study has not been identified as a structured research project, which is defined as a structured activity, with a defined research question intended to provide new knowledge which is generalisable. [Delete as appropriate]your study has been identified as relating to the establishment or operation of a [delete as appropriate] tissue bank /disease registry /data bank /cohort or other resource which underpins a number of research studies, but which is not a research Version

69 project in its own right (i.e. there is no research question ). NIHR CSP Operating Manual This decision means that your study is not eligible to be processed for NHS Permissions through NIHR CSP. You will receive a further shortly from the Lead CLRN advising you how to proceed. Kind regards NIHR Portfolio Application Team NIHR Clinical Research Network Coordinating Centre portfolio.applications@nihr.ac.uk CSP Module PAT Study is Not Eligible for the NIHR CRN Portfolio (R&D Form) due to Change of Funding This is to be sent by PAT to the Chief Investigator, when the study has been reviewed and assessed as not eligible for the NIHR CRN Portfolio, based on the information provided in the R&D Submission. Subject: To: NIHR CSP Ref. ##Study ID## ( of user who completed Final Portfolio Eligibility Review task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator Name## Re: ##Study ID## - ##Study Short Title## Following a review of the change to study details you have provided, we are writing to inform you that unfortunately your study is not eligible for inclusion in the NIHR Clinical Research Network Portfolio. This decision was based on the following information: [Delete as applicable] [Unfortunately your study is not eligible to use NIHR CSP for seeking NHS Permissions as it is funded by an organisation which does not meet the criteria specified by the Department of Health for studies to be included in the NIHR CRN Portfolio. Further information about Eligibility for Inclusion of Studies in the NIHR CRN Portfolio, is available on our web site at: [Your funder has made a self-declaration that they do not meet the criteria required to be an NIHR Partner, namely: Awarding research funds as a result of open competition across England with high quality peer review Funding research that is of clear value to the NHS Having strategic direction for the research that they fund.] [Add further comments on funder changes as necessary] This decision means that your study is not eligible to be processed for NHS Permissions Version

70 through NIHR CSP. You will receive a further shortly from the Lead CLRN advising you how to proceed. Kind regards NIHR Portfolio Application Team NIHR Clinical Research Network Coordinating Centre portfolio.applications@nihr.ac.uk CLRN Confirmation of NHS Organisation (Participating CLRN) This is to be sent by a NHS organisation (Participating CLRN) to make initial contact with the Principal Investigator when the R&D Submission has been validated. Subject: To: NIHR CSP Ref IRAS project ID Confirmation of Participating CLRN Principal Investigator, Study Coordinator (if applicable) Dear Principal Investigator name Re: Study title (IRAS project ID) Confirmation of Participating CLRN We have been notified that you may be participating in the above study. If the Chief Investigator or Study Coordinator confirms this, name of Participating CLRN will support you locally through the NIHR CSP process and we look forward to working with you on this project. Further information on NIHR CRN Portfolio and NIHR CSP can be found at If you have any questions or need further assistance, please contact name of Participating CLRN main study contact on telephone number and/or . Kind regards Your name Research Management and Governance Manager Participating CLRN name CLRN contact details Site Specific Information (SSI) Submission Correspondence On receiving an SSI Submission, the CLRN-funded RM&G staff will determine whether the information it contains is valid. A confirmation message appears in the Submission tab in the IRAS SSI Form area, but an must also be sent by the CLRN to advise the Principal Investigator within 3 working days CSP Module Participating CLRN Confirmation the Submitted SSI Submission is Valid Version

71 This is to be sent by the CLRN to the Principal Investigator when the submitted SSI Submission has been validated. Subject: To: NIHR CSP Ref. ##Study ID## - SSI Submission Confirmation ##Study Site Name## (user who completed the Validate SSI task) To: ##PI address##, ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Principal Investigator Name## Re:##Study ID## - ##Study Short Title## Thank you for SSI submission for ##Study Site Name##. We are pleased to confirm that your study is proceeding through NIHR CSP. Further information on NIHR CRN Portfolio and NIHR CSP can be found by clicking on the links provided. If you have any questions or need further assistance, please contact us using the contact details below. Should you decide not to proceed with this study, please inform us as soon as possible. Kind regards [Your name] Research Management and Governance Manager ##Participating CLRN Name## ##Participating CLRN Central Address## [may wish to add personal contact details] CSP Module NHS Organisation (Participating CLRN ) Notification the Submitted SSI Submission is Invalid This is sent by the CLRN when the submitted SSI Submission is invalid as some of the information is missing or requires further clarification. Subject: To: NIHR CSP Ref. ##Study ID## - SSI Submission Requires Amendment ##Study Site Name## (user who completed the Validate SSI task) To: ##PI address##, ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Principal Investigator Name## Re:##Study ID## - ##Study Short Title## Thank you for SSI submission for ##Study Site Name##. Version

72 Unfortunately some of the information needed is missing or requires further clarification To allow us to progress your application, please return to your R&D Form in IRAS, update the following items, and then submit the revised form (and documents as required): [insert missing fields or information needing to be clarified] We look forward to receiving your amended form in the near future. Please contact us using the contact details below if you require any further information. Kind regards [Your name] Research Management and Governance Manager ##Participating CLRN Name## ##Participating CLRN Central Address## [may wish to add personal contact details] CSP Governance Review Correspondence CSP Module CLRN Confirmation of Study-wide governance review completion This is to be sent to the Chief Investigator when the Study-wide governance review has been completed for the study by the Lead CLRN. Subject: To: NIHR CSP- Ref ##Study ID## - Governance Reviews Complete ( of user who completed Governance task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator Name## Re: ##Study ID## - ##Study Short Title## We are writing to inform you that all study-wide governance criteria have been undertaken for your study. When the local governance criteria have been completed for each participating NHS organisation, each R&D office will be provided with a Governance Report which includes all the necessary information to grant NHS Permission. Please note that you cannot commence the study at a particular site until you have received a letter of NHS Permission for that site. For further information regarding how to notify us of any amendments to the study please refer to the Amendments Guidance for Researchers. Please contact us if you require any further information. Kind regards [Your name] Research Management and Governance Manager Version

73 ## Lead CLRN Name## ##Lead CLRN Central Address## CSP Module NHS Organisation (Participating CLRN) Local governance review completion Subject: To: NIHR CSP- Ref ##Study ID## - Governance Reviews Complete at ##Study Site Name## (user who completed Governance) To: ##PI address##, ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Principal Investigator Full Name## Re: ##Study ID## - ##Study Short Title## We are writing to inform you that all local governance criteria have been undertaken for your study at ##Study Site Name##. Please note that you cannot commence the study at ##Study Site Name## until you have received a letter of NHS Permission. For further information regarding how to notify us of any amendments to the study please refer to the Amendments Guidance for Researchers. Please contact us if you require any further information. Kind regards [Your name] Research Management and Governance Manager ##Participating CLRN Name## ##Participating CLRN Central Address## CSP Module Lead CLRN Notification that CSP Study-wide Governance Review has Failed This is to be sent by the Lead CLRN if the study-wide review has a governance criteria with a 'Completed- Major Issue'. Subject: To: NIHR CSP- Ref ##StudyID## -Study-Wide Governance Review Failed (user who completed Governance) To: ##PI address##, ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator Name## Version

74 Re: ##Study ID## - ##Study Short Title## Unfortunately during the research governance review of your study the following problem(s) with the study arrangements were identified: [Major issues identified] This means that your study can no longer proceed through NIHR CSP. If you have any further questions please contact us and we will be able to answer your queries and advise you on how to proceed. Kind Regards [Your name] Research Management and Governance Manager ## Lead CLRN Name## ##Lead CLRN Central Address## CSP Module CLRN Notification that CSP Local Governance Review has failed This is to be sent by the NHS organisation (Participating CLRN) if the local review has a governance criterion recorded as 'Completed-Major Issue'. Subject: To: NIHR CSP- Ref ##StudyID## - Local Governance Review Failed at ##Study Site Name## (user who completed Governance) To: ##PI address##, ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Principal Investigator Full Name## Re: ##Study ID## - ##Study Short Title## Unfortunately during the research governance review of your study at ##Study Site Name## the following problem(s) with the study arrangements were identified: [Major issues identified] This means that your study can no longer proceed through NIHR CSP at this site. If you have any further questions please contact us and we will be able to answer your queries and advise you on how to proceed. Kind Regards Your name Research Management and Governance Manager ##Participating CLRN Name## ##Participating CLRN Central Address## Version

75 CSP Module NHS Organisation (Participating CLRN) Notification of NHS Permission/PIC Authorisation Subject: To: NIHR CSP Ref. ##Study ID## - NHS Permission Granted for ##Study Site Name## (user who completed the Grant Permission task) To: ##PI address##, ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Principal Investigator## Re:##Study ID## - ##Study Short Title## NHS permission/pic Authorisation for the above research study was granted at the following site(s): ##Study Site Name## [Insert Date] Reminder: to attach NHS Permission letter For further information regarding how to notify us of any amendments to the study please refer to the Amendments Guidance for Researchers. Kind regards #NHS Signatory Facilitator Name# #StudySite Name# Abandoning and Suspending Studies Correspondence CSP Unit Confirmation of Abandon at (Study Wide/Local NHS Organisation) This is to be sent to the Lead CLRN for a study wide suspension and the Governance Reviewer and Participating CLRN for a local NHS organisation suspension. Subject: From: To: Cc: NIHR CSP Ref IRAS project ID Confirmation of Abandon at (Study Wide/Local NHS organisation). CSP Unit Lead CLRN generic CSP Mailbox (Study-wide), Participating CLRN generic CSP Mailbox and NHS organisation Governance Reviewer (Local) Participating CLRNs generic CSP Mailbox (Study-wide) Dear CLRN name Re: IRAS Project ID Study Short Title Version

76 We are writing to confirm that we have abandoned this study/site. Kind regards Your Name CSP Unit Insert personal contact numbers. NIHR CSP Operating Manual CSP Unit Confirmation of Suspend Review This is to be sent to the Lead CLRN for a study wide suspension and the Governance Reviewer and Participating CLRN for a local NHS organisation suspension. Subject: From: To: NIHR CSP Ref IRAS project ID Confirmation of (Valid/Invalid) Suspend Review at (Study Wide/Local NHS organisation). CSP Unit Lead CLRN generic CSP Mailbox (Study-wide), Participating CLRN generic CSP Mailbox and NHS organisation Governance Reviewer (Local) Dear CLRN name Re: IRAS Project ID Study Short Title We are writing to confirm that we have reviewed your request for this suspension. This has been judged to be Valid/Invalid If Valid: Once you are ready for the governance review to resume, please contact crncc.cspunit@nihr.ac.uk or phone one of the numbers listed in the address footer below. If Invalid: [State reason]. Kind regards Your Name CSP Unit crncc.cspunit@nihr.ac.uk Insert personal contact numbers CSP Unit Confirmation of Governance Review Task Resumption This is to be sent to the Lead CLRN for a study wide suspension and the Governance Reviewer and Participating CLRN for a local NHS organisation when removed from suspension. Subject: From: NIHR CSP Ref IRAS project ID Confirmation of Suspend Task Completion at (Study Wide/Local NHS organisation). CSP Unit Version

77 To: Lead CLRN generic CSP Mailbox (Study-wide), Participating CLRN generic CSP Mailbox and NHS organisation Governance Reviewer (Local) Dear CLRN name Re: IRAS Project ID Study Short Title We are writing to confirm that we have completed the Suspend Review task resumed your governance review task. This should be with the allocated governance reviewers shortly. Kind regards [Your Name] CSP Unit Insert personal contact numbers CLRN Request for Suspension This is to be sent from the Lead CLRN for a study wide suspension and the Participating CLRN for a local NHS organisation suspension if required to supplement the information in the governance review comments. Subject: From: To: NIHR CSP Ref IRAS project ID Request for Suspension at (Study Wide/Local NHS organisation). Lead (Study-wide) or Participating (Local) CLRN CSP Unit Dear CSP Unit Re: IRAS Project ID Study Short Title We are writing to confirm that we wish to suspend this study at Study Wide/[Name of NHS organisation] and have completed a governance criteria as Completed- Major Issue. This is because [insert description of reason to support governance review comments].. Kind regards [Your Name] Research Management and Governance Manager ## CLRN Name## ## CLRN Central Address## CLRN Request for Abandon This is to be sent from the Lead CLRN to abandon the study and the Participating CLRN to abandon the study at a local NHS organisation if required to supplement the information in the governance review comments. Version

78 Subject: From: To: NIHR CSP Ref IRAS project ID Request for Abandon at (Study Wide/Local NHS organisation). Lead (Study-wide) or Participating (Local) CLRN CSP Unit Dear CSP Unit Re: IRAS Project ID Study Short Title We are writing to confirm that we wish to abandon this study at Study Wide/[Name of NHS organisation] and have completed a governance criteria as Completed- Major Issue. This is because [insert description of reason to support governance review comments]. Kind regards [Your Name] Research Management and Governance Manager ## CLRN Name## ## CLRN Central Address## Study Amendments Correspondence CSP Module Lead CLRN Notification that the amendment submission is valid Subject: To: NIHR CSP Ref. ##Study ID## - Receipt of an Amendment (user who completed the Validate Amendment task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## [please add any Devolved Administration contacts as required] Dear ##Chief Investigator## Re: ##Study ID## - ##Study Short Title## - Amendment ##Amendment ID## Date of Submission to REC date Thank you for submitting the above amendment. As your Lead CLRN, we have made this amendment available to each participating NHS Trust. As such, local governance review is now under way at each site that has issued NHS Permission. Sites that have not yet issued NHS Permission (if applicable) have also been notified of the amendment and will consider it as part of their overall governance review. If applicable, please ensure you send copies of your regulatory approval(s) (REC, MHRA and other supporting documents) to this address or through the IRAS document submission. We will make these available to all participating sites. Trusts have 35 calendar days to undertake their local governance review. Accordingly, subject to the three conditions below, you will be able to implement the amendment on dd/mmm/yy, at all sites already in receipt of NHS Permission: Version

79 - You may not implement this amendment until and unless you receive, and forward to us, all required regulatory approvals (where applicable) - You many not implement this amendment at any site which informs you that they require additional review time, until they notify you that this review has been satisfactorily completed. - You may not implement this amendment at any site that withdraws its NHS Permission. NB: you may only implement changes that were described in the amendment notice or letter. If you receive your regulatory approvals after this date, and submit the document(s) to us, you may then immediately implement at all sites that have NHS Permission in place and that have not requested addition review time, or withdrawn NHS Permission. As it is the responsibility of each individual NHS Trust to notify you if you may not locally implement the amendment, you are not required to wait for receipt of the Notification of Continued NHS Permission from the NHS Trust in relation to the amendment before you may implement on the above date. Please note that as Chief Investigator/Sponsor, it remains your responsibility to ensure the PIs at each of your sites (if applicable) are informed of this amendment. Please contact name if you require any further assistance. Kind regards [Your name] Research Management and Governance Manager ##Lead CLRN Name## ##Lead CLRN Central Address## CSP Module Lead CLRN- Notification that Amendment Submission is Invalid Subject: To: NIHR CSP Ref. ##Study ID## - Receipt of an Incomplete Amendment (user who completed the Validate Amendment task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator## Re: ##Study ID## - ##Study Short Title## - Amendment ##Amendment ID## Thank you for submitting the above amendment. Unfortunately some of the information we need is missing or requires further information. To allow us to progress your submission, please return to IRAS and resubmit providing the following information [insert information required here] Please do not hesitate to contact us if you require any further information or assistance. Kind regards [Your name] Research Management and Governance Manager ##Lead CLRN Name## Version

80 ##Lead CLRN Central Address## CSP Module Notification of Amendment Withdrawn due to Not Receiving Regulatory Approval Subject: To: NIHR CSP Ref. ##Study ID## - Amendment did not receive regulatory approval (user who completed Confirm REC and/or NHRA Review task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator## Re: ##Study ID## - ##Study Short Title## - Amendment ##Amendment ID## We have been notified that regulatory approval has not been granted for the above amendment. This will mean that the amendment has been withdrawn and will not be implemented. Kind regards [Your name] Research Management and Governance Manager ##Lead CLRN Name## ##Lead CLRN Central Address## CSP Module Notification of Amendment for new sites only Subject: To: NIHR CSP Ref. ##Study ID## - New Sites Only Amendment (user who completed the Validate Amendment task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator## Re:##Study ID## - ##Study Short Title## - Amendment ##Amendment ID## The amendment that you have submitted has been identified as only including new sites. The new sites participating in your study will contact the principal investigators for the new sites listed in the R&D Form, in order to provide assistance with the SSI Form submissions for the other study sites. Kind regards [Your name] Research Management and Governance Manager ##Lead CLRN Name## Version

81 ##Lead CLRN Central Address## CSP Module Notification of No Objection to Amendment Subject: To: NIHR CSP Ref. ##Study ID## - No Objection to Amendment (user who completed the Amendment Review task) To: ##PI address##, ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Principal Investigator## Re: ##Study ID## - ##Study Short Title## - Amendment ##Amendment ID## This amendment has been reviewed at ##Study Site Name## and can be implemented. [Attach letter of continuing permission if applicable] Please contact us using the contact details below if you require any further information. Kind regards [Your name] Research Management and Governance Manager #Study Site Name# ##Participating CLRN Name## ##Participating CLRN Central Address## [may wish to add personal contact details] CSP Module Notification of Objection to Amendment Subject: To: NIHR CSP Ref. ##Study ID## - Objection to Amendment (user who completed the Amendment Review task) To: ##PI address##, ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Principal Investigator## Re: ##Study ID## - ##Study Short Title## - Amendment ##Amendment ID## This amendment has been reviewed at ##Study Site Name## and unfortunately cannot be implemented. Please find attached our letter of objection. Please contact us using the contact details below if you require any further information. Kind regards [Your name] Research Management and Governance Manager Version

82 #Study Site Name# ##Participating CLRN Name## ##Participating CLRN Central Address## [may wish to add personal contact details] CSP Module Notification that Amendment can be implemented Subject: To: NIHR CSP Ref. ##Study ID## - Amendment can be implemented (user who completed Confirm REC and/or MHRA Review task) To: ##CI address##, ##Study Coordinator address##, ##Sponsor Representative address## Dear ##Chief Investigator## Re: ##Study ID## - ##Study Short Title## - Amendment ##Amendment ID## This amendment has received the necessary regulatory approvals and been reviewed by all participating study sites. It can now be implemented at all sites unless a site has objected and withdrawn NHS Permission. Please contact us using the contact details below if you require any further information. Kind regards [Your name] Research Management and Governance Manager ##Lead CLRN Name## ##Lead CLRN Central Address## Correspondence for Studies Involving Devolved Administrations CSPU Notification to Devolved Administrations of Valid R&D Submissions For studies led from England. This is to be sent by CSPU with the valid R&D Submission Subject: To: Cc: NIHR CSP Ref IRAS project ID R&D Submission NRS Permissions CC /NISCHR PCU /Northern Ireland Secondary Care Coordinator Lead CLRN Dear NRS Permissions CC /NISCHR PCU /Northern Ireland Secondary Care Coordinator REC Reference number: XXXXXXXX Short Title: XXXXXXXXXXXXXXX Please find the attached validated R&D Submission in respect of the above mentioned study. Version

83 Name of Lead CLRN will be the Lead CLRN on this English-led study. The staff at the CLRN can be contacted on:- Telephone: Core team central phone number central CSP address Should you have any questions regarding this study, please contact the Lead CLRN in the first instance. Kind regards Name CSP Unit Lead CLRN Notification to Devolved Administrations of Additional/Final Versions of Supporting Documentation and/or Study-wide Governance Report For studies led from England. This is to be sent by the Lead CLRN with the R&D Form additional or final versions of supporting documentation and/or study-wide Governance Report. Subject: To: NIHR CSP Ref IRAS project ID [select as appropriate] R&D Form Supporting Documentation /Study-wide Governance Report NRS Permissions CC /SPARC /NI Lead Health & Social Care Trust Dear Devolved Administration contact With reference to the above study, please find the attached [select as appropriate] additional/final versions of Supporting Documentation and/or Study-wide Governance Report for study IRAS project ID and REC ref number. Kind regards Name Job Title Name of CLRN Lead CLRN Confirmation of Lead CLRN Role For studies led from England. This is to be sent by the Lead CLRN once they have accepted a study record and to make initial contact with the Chief Investigator. Subject: From: To: Cc: NIHR CSP Ref IRAS project ID R&D Form Validation Lead CLRN Chief Investigator Study Coordinator Dear Chief Investigator Name Version

84 Thank you for your recent submission to NIHR CSP. We can confirm that name of CLRN will be the Lead CLRN, which means we will be your main contact in England and will undertake the study-wide governance checks. Once the study-wide governance checks are complete, we will send a copy of the report to country/ies where it will be reviewed to identify any issues specific to that country. So that the local governance checks can be undertaken in England, please ensure the Principal Investigators submit the SSI Forms and supporting documentation through IRAS selecting the corresponding CLRN as indicated in the table below. The CLRN will contact the Principal Investigator to provide support to the local research team. NHS organisation CLRN CLRN central address XXXXX XXXXX XXXXX If you have any questions or require any advice on this study, please do not hesitate to contact us by or telephone contact details. Kind regards Name Job Title Name of CLRN Correspondence relating to handling of revised R&D Forms Lead CLRN Request for information on the submitted revised R&D Form This is sent by the Lead CLRN when no information has been provided on the reason for any changes and/or the nature of the changes are not clear for the submitted revised R&D Submission. Subject: Status: From: To: Cc: NIHR CSP Ref IRAS project ID R&D Form Revision Information required Should be set as High Lead CLRN Chief Investigator CSP Unit, Lead CLRN generic CSP Mailbox (if not sent from here), Sponsor, and Study Coordinator (if applicable) Dear Chief Investigator Name, Re: Study title (IRAS project ID) Thank you for submitting your revised R&D Form through IRAS. To allow us to progress your application, please could you provide information on whether the revision is due to: - REC substantial amendment Version

85 - non substantial amendment - change requested by a regulatory body during review - new sites or new PICs - other reason (please provide details) Please do not hesitate to contact me if you require any further information or assistance. Please note that if no information is received on the nature of the revision by one month post receipt, the received R&D Form will be rejected. If the revised R&D Form was submitted in error, please return to your IRAS account and 'Recall' the form from the submission tab. Kind regards Lead CLRN Staff Contact Name Name of CLRN address Version

86 12. PERFORMANCE MANAGEMENT CSP metrics calculation Calculation method from 1 April 2012 Study-wide (Global) Time to complete study-wide review = Review Number of calendar days between the date of receipt of first valid Final R&D submission and the date study-wide review was completed (Study Wide Governance Review and QC satisfied and date Eligibility Confirmed). Local (Site) Review Time to complete local review = Number of calendar days between the date of receipt of the first valid Site Specific Information (SSI) submission and the date the NHS Permission letter was signed. Version

87 13. LEGAL RESPONSIBILITIES The legal responsibilities of NHS organisations are unaffected by NIHR CSP (including compliance with the Research Governance Framework and other applicable regulations). NIHR CSP generates a standard set of evidence, including the Governance Report which is viewable in the CSP Module. This pack of evidence is intended to inform the decision of the person authorised to give permission on behalf of each host organisation (or Consortia acting on behalf of NHS organisations). The host organisation retains legal responsibility for granting permission. NIHR CSP helps by assembling the evidence. It does not change the position in relation to potential liability. The CSP Unit and Comprehensive Local Research Networks are not legal bodies and cannot, therefore, assume any of the legal responsibilities of NHS organisations or sign documents, agreements or contracts on behalf of NHS organisations. This notwithstanding, NIHR CSP will, by introducing standardised best practice approaches, help NHS organisations meet their own legal responsibilities. Version

88 14. ON-GOING STUDY MANAGEMENT (XML FILES) Some trusts have requested an XML version of the R&D Form and Site Specific Information (SSI) Forms, for use in on-going study management databases such as ReDA II and EPS. An XML version of the R&D and SSI Forms is available from the CSP Module document repository. Version

89 APPENDIX 1. USE OF A SINGLE SITE SPECIFIC INFORMATION (SSI) FORM The use of a single SSI Form for all sites or a sub-set of sites is currently being piloted. All requests to use a single SSI Form should be made to the CSP Management Team via the CSP Helpdesk. Version 5.2 Appendix 1-1

90 APPENDIX 2. GOVERNANCE CRITERIA BY STUDY TYPE NIHR CSP Operating Manual Reference Governance Review Criteria Study-wide Local single SSI Clinical trial of an investigational medicinal product Clinical investigation or other study of a medical device Combined trial of an investigational medicinal product and an investigational medical device Other clinical trial or clinical investigation (changed to Other clinical trial to study a novel intervention or randomised clinical trial to compare interventions in clinical practice) Basic science study involving procedures with human participants Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology - ANONYMISED DATA ONLY Study administering questionnaires/interviews TO NHS STAFF for quantitative analysis, or using mixed quantitative/qualitative methodology Study involving qualitative methods only Study limited to working with data and/or human tissue samples or other human biological samples (specific project only) (changed to Study limited to working with human tissue samples (or other human biological samples) and data (specific project Study limited to working with data and/or human tissue samples or other human biological samples (specific project only) - ANONYMISED ONLY Study limited to working with data (specific project only) Other research Participant Identification Centres A A1 B B1 B2 C Initial Assessment IRAS Project filter completed correctly Risk assessment (risks to participants). Participant information and consent documents and process Emergency /Backup /Support arrangements assessed Risk assessment (risk to study) S S L S only L S only () Version 5.2 Appendix 2-1

91 Reference Governance Review Criteria Study-wide Local single SSI Clinical trial of an investigational medicinal product Clinical investigation or other study of a medical device Combined trial of an investigational medicinal product and an investigational medical device Other clinical trial or clinical investigation (changed to Other clinical trial to study a novel intervention or randomised clinical trial to compare interventions in clinical practice) Basic science study involving procedures with human participants Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology - ANONYMISED DATA ONLY Study administering questionnaires/interviews TO NHS STAFF for quantitative analysis, or using mixed quantitative/qualitative methodology Study involving qualitative methods only Study limited to working with data and/or human tissue samples or other human biological samples (specific project only) (changed to Study limited to working with human tissue samples (or other human biological samples) and data (specific project Study limited to working with data and/or human tissue samples or other human biological samples (specific project only) - ANONYMISED ONLY Study limited to working with data (specific project only) Other research Participant Identification Centres C1 D D1 D2 D3 D4 D5 Principal Investigator (PI)/research team suitability assessed. Risk assessment (risks to organisation) Risks to NHS organisations assessed Allocation of responsibilites and rights is agreed and documented Insurance/indemnity arrangements assessed Financial management arrangements assessed Implications for internal departments assessed S S S S L L L L L L S only Version 5.2 Appendix 2-2

92 Reference Governance Review Criteria Study-wide Local single SSI Clinical trial of an investigational medicinal product Clinical investigation or other study of a medical device Combined trial of an investigational medicinal product and an investigational medical device Other clinical trial or clinical investigation (changed to Other clinical trial to study a novel intervention or randomised clinical trial to compare interventions in clinical practice) Basic science study involving procedures with human participants Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology - ANONYMISED DATA ONLY Study administering questionnaires/interviews TO NHS STAFF for quantitative analysis, or using mixed quantitative/qualitative methodology Study involving qualitative methods only Study limited to working with data and/or human tissue samples or other human biological samples (specific project only) (changed to Study limited to working with human tissue samples (or other human biological samples) and data (specific project Study limited to working with data and/or human tissue samples or other human biological samples (specific project only) - ANONYMISED ONLY Study limited to working with data (specific project only) Other research Participant Identification Centres D6 E E1 F F1 F2 F3 Adequacy of facilities assessed Risk assessment (risks to researcher) Risks to researcher assessed. Legal compliance Data Protection Act and data security issues assessed S L Arrangements for compliance S L with the Clinical Trial Regulations assessed Arrangements for compliance L with the Mental Capacity Act assessed L L S only Version 5.2 Appendix 2-3

93 Reference Governance Review Criteria Study-wide Local single SSI Clinical trial of an investigational medicinal product Clinical investigation or other study of a medical device Combined trial of an investigational medicinal product and an investigational medical device Other clinical trial or clinical investigation (changed to Other clinical trial to study a novel intervention or randomised clinical trial to compare interventions in clinical practice) Basic science study involving procedures with human participants Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology - ANONYMISED DATA ONLY Study administering questionnaires/interviews TO NHS STAFF for quantitative analysis, or using mixed quantitative/qualitative methodology Study involving qualitative methods only Study limited to working with data and/or human tissue samples or other human biological samples (specific project only) (changed to Study limited to working with human tissue samples (or other human biological samples) and data (specific project Study limited to working with data and/or human tissue samples or other human biological samples (specific project only) - ANONYMISED ONLY Study limited to working with data (specific project only) Other research Participant Identification Centres F4 F5 F6 G G1 G2 Principal Investigator(PI)/research team Human Resources arrangements in place. Radiation - Arrangements for compliance with IRMER assessed Compliance with any other applicable laws and regulations Approvals and authorisations Research Ethics Committee favourable opinion received CTIMPs - Clinical Trial Authorisation (CTA) letter received S S S L L L may be CI Version 5.2 Appendix 2-4

94 Reference Governance Review Criteria Study-wide Local single SSI Clinical trial of an investigational medicinal product Clinical investigation or other study of a medical device Combined trial of an investigational medicinal product and an investigational medical device Other clinical trial or clinical investigation (changed to Other clinical trial to study a novel intervention or randomised clinical trial to compare interventions in clinical practice) Basic science study involving procedures with human participants Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology Study administering questionnaires/interviews for quantitative analysis, or using mixed quantitative/qualitative methodology - ANONYMISED DATA ONLY Study administering questionnaires/interviews TO NHS STAFF for quantitative analysis, or using mixed quantitative/qualitative methodology Study involving qualitative methods only Study limited to working with data and/or human tissue samples or other human biological samples (specific project only) (changed to Study limited to working with human tissue samples (or other human biological samples) and data (specific project Study limited to working with data and/or human tissue samples or other human biological samples (specific project only) - ANONYMISED ONLY Study limited to working with data (specific project only) Other research Participant Identification Centres G3 G4 G5 RSS Plan ning Tool Devices - MHRA notice no objection received Radiation - ARSAC approval received Other regulatory approvals and authorisations Administrative Check to be shown with governance criteria Have you used the RSS Planning Tool for this study at your site? Yes /No S S L L Version 5.2 Appendix 2-5

95 APPENDIX 3. GOVERNANCE CRITERIA REVIEW PROCEDURE Aims The aims of the guidelines for the criteria are to: Set the standard for undertaking the NHS research governance review Ensure consistency of review across the NHS Allow for judgement to be used to manage specific situations Identify the information and communication required to support the review. Description Each criterion has a category (indicated by a letter) and a specific number. Some criteria have a study-wide and a local element details are given within the guidance for each criterion. The study matrix in Appendix 2 shows which criteria are relevant to the different study types. Each criterion has general introductory guidance, including wider contextual information. The guidance sets out the remit of other parties, including research ethics committees and sponsors, which should not be duplicated by the NHS research governance review. The issues for consideration are described for the study-wide and local aspects, as relevant. Relevant resources providing background guidance are included, where appropriate. Reviewers are expected to be familiar with all the resources. The Research Governance Framework is not included in the resources as this is relevant to all aspects of the governance review. The outcome of the review of each criterion should be described. The criteria for each study may be recorded as satisfied, not satisfied or not applicable. Additional information to support the assessment should be recorded. UK-wide studies Arrangements are in place to ensure a smooth permissions process for studies taking place across the UK. There is on-going work to align the governance reviews across the UK. It should be noted that studies using NIHR CSP do not require peer review, assessment of the protocol, or review of the arrangements for dissemination of results as part of CSP. The criteria for eligibility for adoption to the NIHR CRN Portfolio are based on quality criteria that replace the requirement to assess the protocol, peer review, or dissemination of results. Elsewhere in the UK, these criteria may be assessed separately. The criteria for determining if a study is eligible for consideration for Clinical Research Network support are given at NIHR-funded studies in Biomedical Research Centres (BRCs), Biomedical Research Units (BRUs) or Collaborations for Leadership in Applied Health Research and Care (CLAHRCs) are able to use NIHR CSP, although they are not included on the NIHR CRN Portfolio as they do not require clinical infrastructure service support. Version 5.2 Appendix 3-1

96 Process for conducting the study-wide review 1. Use the study matrix: Determine the relevant study-wide criteria for the study type. 2. Conduct a rapid initial assessment: Identify any issues that are likely to have a major impact on the ability of NHS organisations to issue permission for the study. Discuss the issues with the sponsor/ci. 3. Review issues that only need to be looked at once for the study: Confirm details of study-wide arrangements such as regulatory approvals. 4. Identify issues that need to be resolved once for the study: Identify risks (to patients, staff, or study delivery) and potential problems, to resolve them once. Identify mitigation strategies that can be assessed locally. Where information is unclear or inadequate, request the information once for the study and make it available to local reviewers. Where there are hazards or problems with the study arrangements, obtain clarification once for the study or highlight the implications to the applicant and/or local reviewers. 5. Highlight information to support the local review: Provide additional clarity on the study, and guide the local review by providing information for reviewers to work from or clarifying whether any local criteria are not relevant. Describe for the local reviewers if there are arrangements that need to be managed locally. Process for undertaking the local review 1. Use the study matrix: Determine the relevant local criteria for the study type. 2. Look at the study-wide review: Review any issues and resolution or mitigation described in the study-wide review. Where the study-wide and local reviews are being undertaken in parallel, the study-wide criteria should be reviewed regularly during the local review. 3. Complete the NIHR Research Support Services (RSS) planning assessment: Identify any showstopper criteria that will prevent permission being issued by the site. Identify any rate-limiting criteria that will affect the organisation s ability to issue permission swiftly. Review the rate-limiting criteria first and put in place arrangements to minimise any delaying factors. 4. Rely on local quality assurance: Following RSS principles, take account of local systems and processes within the organisation or the research team that can be relied on as assurances that the criteria have been addressed. Local quality assurance (QA) systems such as SOPs/policies, monitoring systems and audits within the host organisation allow the organisation to minimise the need for up-front detailed review by relying on effective systems for identifying and addressing issues as they arise. 5. Take a proportionate and pragmatic approach: Different studies and situations require different approaches. Consider any hazards, consequences, mitigation and opportunity cost. Version 5.2 Appendix 3-2

97 Section 1 Review criteria for research sites F. INITIAL ASSESSMENT A1. IRAS project filter completed correctly The Integrated Research Application System (IRAS) project filter is important to each study application. The answers given to the questions in the project filter will determine: The forms the system will generate; The information the applicant will be asked to provide in the Full Set of Project Data ; and The declarations that need to be signed/electronically authorised and submitted. The study types (IRAS Project Filter Q2) are particularly important for ensuring the appropriate governance review is conducted A1.1. Study-wide Considering the study as a whole, have the project filter questions been completed correctly in IRAS? Areas that may require particular attention are studies that involve: Ionising radiation, and specifically research exposures Human tissue samples Participants who are children Participants who are adults lacking capacity Students undertaking research as part of an educational qualification A1.2. Local No review required A1.3. Resources: IRAS Filter Guidance Approval for Medical Devices Research MHRA algorithm nicaltrialauthorisationrequired/index.htm Version 5.2 Appendix 3-3

98 G. RISK ASSESSMENT (RISK TO PARTICIPANTS) B1. Participant information & consent documents and process Potential participants in any study need information upon which to base their choice to take part. Information sheets and consent forms are only one part of the process of seeking informed consent. The National Research Ethics Service (NRES) provides guidance on information sheets and consent forms. It advises that the length and level of detail in any information sheet should take account of the complexity and risk of the research. Where appropriate the information sheet could be divided into two parts. The Research Ethics Committee (REC) will consider whether the information given to potential participants: Provides brief clear information on the essential elements of the study Provides information of the condition or treatment under study Describes the voluntary nature of taking part Describes what will happen during and after the study Describes the participant s responsibilities Describes the potential risks, inconveniences and benefits. Additional information on aspects such as confidentiality and data protection, access to medical records by researchers, regulators and auditing staff, indemnity and compensation, publication, treatment available after the study (where applicable) and if applicable communication with the GP may be included if appropriate. The REC will only consider the ethical implications of the information provided to potential participants, and of the consent process. NHS organisations have a duty to ensure participants receive accurate information on the research that may affect their care, and for ensuring any legislation relating to that research is followed. It may be more appropriate for certain legal aspects and important issues to be included as separate consent statements or forms, especially if these elements are optional for participants. The REC will consider whether such arrangements are necessary. Examples might include: Participant identifiable information the collection of participant identifiable information, eg initials, date of birth, normally requires explicit consent; Genetic testing; Additional invasive tests or samples required for study purposes; The use of audio/video recording, with possible use of verbatim quotes or photographs; Transfer of data/samples to countries with differing laws and regulations for data protection; Agreement to receive individual feedback from any study results; and Studies involving children or adults lacking capacity. Where tissues samples are taken as part of the research, the REC will consider whether: Tissue is to be stored in a participant identifiable format Tissue will be used for human application in research such as transplantation Version 5.2 Appendix 3-4

99 Tissue may produce information from the analysis of genetic material Where necessary, it should be flagged as to what happens to the tissue samples at the end of the study B1.1. Study-wide Consider the proposed consent process to ensure that any legal implications presented by the study are highlighted. Highlight any specific requirements within the participant information sheet and consent process that may have local implications. Consider the accuracy of the information describing which organisation is responsible for providing care to the participant. Consider the accuracy of the information relating to insurance/indemnity and compensation. Consider the accuracy of any information relating to study medication and a participant s treatment after their participation in the study. The information given to potential participants regarding the treatment available after participation must be accurate. If the REC decides that provision of treatment after the study is an ethical precondition, the sponsor must ensure that: arrangements are in place for the funding of the treatment, and that agreement has been reached on end-of-study arrangements if the treatment will be unlicensed at the end of the study B1.2. Local Participants should normally receive information that is local to the site where they are participating in the study. Ensure local information given to potential participants provides: o Information about the site eg name of site, address and telephone number (usually included in the letterhead of the site) o Contact details of the local investigator(s), and if applicable, other members of the research team, eg research nurses o Emergency contact information, if appropriate o Contact information for complaints and, where appropriate, independent advisors. Assess whether the arrangements for seeking consent at the site (including the staff involved) can be conducted in accordance with the REC approved arrangements. Where it is planned to include participants who may not adequately understand verbal explanations or information written in English, assess the practical arrangements to be Version 5.2 Appendix 3-5

100 made at a site for the provision of information to participants in a format that meets their needs. Primary Care: For primary care studies with independent contractors such as GP practices and NHS dental practices, it is the responsibility of the independent contractor to ensure that the local information is provided and is in place before the research is started B1.3. Resources: Consent guidance and forms Version 5.2 Appendix 3-6

101 B2. Emergency/Backup/Support arrangements assessed NHS organisations need to ensure that the safety of study participants and of the research staff, and other staff is given priority at all times. Therefore NHS organisations must ensure that adequate safeguards have been put in place to minimise risk and to provide protection. This will include processes/procedures to provide emergency care in the event of harm but also to provide backup and support to study participants, research staff and other staff. It is also important that all those involved in the study are aware of the arrangements for emergency/backup/support and can implement them appropriately should the need arise. The extent and type of arrangements will vary according to the nature of the study B2.1. Study-wide No review required B2.2. Local Assess whether the potential risks have been clearly described and where there are areas of concern, whether suitable risk management plans and safeguards can be implemented to minimise potential risks (eg the effects of additional treatments or changes in treatment; the effects of additional invasive procedures or exposures). Assess whether any emergency procedures that may be necessary have been clearly described and can be conducted at the site in accordance with the REC approved arrangements (eg to protect the participant in the event of a life-threatening incident or adverse event). Assess whether any other backup/support arrangements that may be necessary have been clearly described and can be conducted at the site in accordance with the REC approved arrangements (eg to support a participant or research staff when discussing upsetting/embarrassing topics or news; sensitivity to a participant s confidentiality/data security; notification of other health or social care staff with an interest in the participant s care). Consider whether appropriate mechanisms for identifying and reporting safety concerns/incidents can be implemented locally (including out of hours, if relevant). Consider any arrangements that might need to be put in place to ensure that other healthcare professionals are aware of the participant s involvement in the study, and are able to report any safety concerns/incidents. Primary Care: For primary care studies conducted by an independent contractor it is the responsibility of the independent contractor to ensure that appropriate emergency/backup/support arrangements are implemented and are in place before the study is initiated. However, the independent contractor should be following any policies implemented by the NHS organisation to which they provide services under NHS contract. For primary care studies with NHS staff it is the responsibility of the NHS organisation to ensure that appropriate emergency/backup/support arrangements are implemented and are in place before the study is initiated. Version 5.2 Appendix 3-7

102 H. RISK ASSESSMENT (RISK TO STUDY) C1. Principal Investigator (PI)/research team suitability assessed Each individual involved in carrying out research activities in a study should be qualified by education, training, and experience to perform their task(s). The Medicines for Human Use (Clinical Trials) Regulations 2004, as amended, (Regulation 28) states that no person shall conduct a trial other than in accordance with the conditions and principles of Good Clinical Practice; it therefore follows that each person involved in a clinical trial should receive training in Good Clinical Practice at an appropriate level and frequency commensurate with their roles and responsibilities. The frequency of training is not defined in the regulations. However, in accordance with Regulation 28, all staff must conduct the trial in accordance with the conditions and principles of GCP defined in the legislation. Hence the training should be given at intervals appropriate to ensure staff members maintain current awareness of UK regulations and applicable European guidelines. There is no legal requirement for training in the conditions and principles of Good Clinical Practice for research studies outside the scope of the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended. However, the principles of good clinical practice are relevant to research outside with scope of the regulations, and appropriate training should be undertaken where relevant, including training for specific aspects of the research (eg in ISO for device studies or in arrangements for adults lacking capacity) C1.1. Study-wide No review required C1.2. Local Are there any concerns about whether the Principal Investigator is appropriately qualified and trained to undertake their task(s) in the study and assume responsibility for the conduct of the study at the site? Are there any concerns about whether the other members of the research team are appropriately qualified and trained to undertake their task(s) in the study at the site? Are there any concerns about whether the management of the study within the NHS organisation can be appropriately conducted by the PI and the research team? Consider whether any possible conflict of interest from personal involvement with the sponsor or funder has been declared by the PI or research team member, and ensure their employer is aware of this. Ensure any necessary local clinical or management supervision is arranged C1.3. Resources: IRAS CV Template Version 5.2 Appendix 3-8

103 (log in and go to My Account) NIHR CSP Operating Manual The Medicines for Human Use (Clinical Trials) Regulations 2004 SI 2004/ The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 SI 2006/1928, Schedule 1, Part 2, (2) Version 5.2 Appendix 3-9

104 I. RISK ASSESSMENT (RISK TO ORGANISATION) D1. Risk to NHS organisation assessed When an NHS organisation is considering hosting a study any potential risks to the organisation need to be taken into consideration. Risks to an NHS organisation can arise from harm to patients or wider population, inadequate communications and failure to comply with legal and governance frameworks. This can potentially lead to a decline in research through an inability to obtain funding, to obtain acceptance as a sponsor for research, or to lose the status of being an acceptable research site. The following areas are examples of areas that may present risk to an NHS organisation and should be considered during the review: Reputation eg impact on services provision and resources; reputation of funding source; undesirable publicity from poor compliance with legal and governance frameworks; possible fraud and misconduct; undertaking research of poor quality. Ethics eg consent processes; confidentiality and data protection; sensitive participant populations or research area. Feasibility eg time for recruitment and the process; recruitment criteria; Financial risk eg inappropriate cost identification and attribution; financial implications of continued treatment beyond the study. Service delivery eg impact of changing patient care pathways, or of implementing new clinical procedures Intellectual property opportunity eg overlooked opportunities; lost opportunities through inappropriate disclosure. Liability eg liability arrangements with collaborators; complaints. Collaborations/partnerships eg whether the conduct of a study with a collaborator/partner organisation could impact on the relationships with other collaborators/partner organisations. For each risk identified, the consequences should be considered. Arrangements for mitigation of the risk should be identified, whether through existing systems and monitoring or through study-specific arrangements D1.1. Study-wide Review any potential hazards to any of the NHS organisations, and if there are any areas of concern these should be highlighted D1.2. Local Review any potential hazards to the NHS organisation, consider the consequences, and Version 5.2 Appendix 3-10

105 where there are areas of concern ensure suitable risk management plans and safeguards are introduced to minimise and control the probability and/or impact of potential risks. Primary Care: For primary care studies, the considerations of risk and implementation of suitable risk management plans and safeguards is the responsibility of the independent contractor. However the independent contractor should be following any policies implemented by the NHS organisation to which they provide services under NHS contract D1.3. Resources: A risk matrix for managers Version 5.2 Appendix 3-11

106 D2. Allocation of responsibilities and rights is agreed and documented A complex array of organisations and individuals may be involved in a study. There should be appropriate clear agreement of the allocation of responsibilities and rights. Examples of agreements include, but are not limited to: the protocol; contracts; service level agreements; technical agreements; or delegation of responsibility logs. Where the NHS organisation obtains services in support of the study (eg X-rays; CT or MRI scans; echocardiograms) from another organisation, the supporting organisation should not undertake a full review of the study. The supporting organisation should only be determining if they can provide the requested service for the duration of the study. For primary care studies with independent contractors, it is unlikely but not impossible that there will be implications for support departments of the NHS organisations. Where a department is to provide support to study with independent contractors, separate agreements between the sponsor and the support department of the NHS organisation will be required. The agreement for the provision of support to the study must be in place before the study is initiated D2.1. Study-wide Review the agreement template (or other relevant documents) to confirm the appropriate elements for agreement are present. An agreement would normally specify: The sponsor organisation for the study, as specified in IRAS question A64. Details of research sponsor(s) and IRAS section D2. Declaration by the sponsor s representative of the R&D Form The distribution of the key responsibilities. And, where appropriate: The arrangements for financial management The arrangements for monitoring of the study, pharmacovigilance or safety reporting The level of compensation for negligent and non-negligent (for commercial studies or if specified by the REC) harm Any services contracted out to a sub-contractor (eg central laboratory services; centralised ECG interpretation; study monitoring and data collection). Some of the information may be contained in another document, such as the protocol. Where possible, model agreements should be used. These agreements should be used as set out in their accompanying guidance. Where the model agreements have been altered this should be highlighted and the impact of the alteration considered D2.2. Local Assess whether the allocation of responsibilities between the parties is appropriate to the study without creating unnecessary burden. Version 5.2 Appendix 3-12

107 Assess whether the delivery of the allocated responsibilities can be sustained for the duration of the study. Ensure that appropriate agreements are in place before the study is initiated. For studies where the NHS organisation obtains services in support of the study (eg X-rays; CT or MRI scans; echocardiograms) from another organisation, who in essence is acting as a sub-contractor, then the NHS organisation should ensure that appropriate agreements (eg sub-contracts; service level agreements) are in place before the study is initiated. Primary Care: For primary care studies with independent contractors such as GP practices and NHS dental practices, the agreement will normally be between the sponsor and the independent contractor. It will therefore be the independent contractor s responsibility to ensure that fully signed and appropriate agreements are in place before the study is initiated. For primary care studies with employees of the NHS organisation, it is the responsibility of the NHS organisation to ensure that fully signed and appropriate agreements are in place before the study is initiated because of their responsibilities as an employer. In some instances, the allocation of responsibilities and rights may be described in another document such as a GP agreement or GP information sheet D2.3. Resources: Model commercial and collaborative agreements Model agreements Version 5.2 Appendix 3-13

108 D3. Insurance/indemnity arrangements assessed NIHR CSP Operating Manual It is a sponsor s responsibility to ensure there is provision for indemnity or compensation in the event of injury or death attributable to a study, and any insurance or indemnity to cover the liability of the investigator and sponsor(s). A copy of the relevant policy must be provided, or if not available then a copy of the insurance certificate and a statement from the Sponsor that there are no applicable exclusions that would affect the insurance cover available for study participants. Where two or more non-commercial organisations are co-sponsors, the relevant information about insurance/indemnity for each partner should be assessed. Negligent harm indemnity The policy/insurance certificate shall usually specify Public & Products liability including Clinical Trials Liability, and Professional/Employers liability. Management of the study: The sponsor will normally hold insurance or provide indemnity to cover their liabilities as sponsor which would cover the overall management of the study. For commercial studies where a company is sponsor then insurance will be provided through an insurance scheme. A copy of the relevant policy/certificate must be provided. For non-commercial studies where a university or higher education institution is sponsor then insurance will be provided through an insurance scheme. A copy of the relevant policy/certificate must be provided. Where an NHS organisation is a sponsor, then indemnity is provided through NHS schemes. No proof of indemnity is required for NHS sponsored research. Design of the study: The design of the research is the responsibility of the protocol author and normally the employer of the author will hold insurance or provide indemnity to cover their liabilities. For commercial studies the insurance will be provided through an insurance scheme. A copy of the relevant policy/certificate must be provided. For non-commercial studies where the protocol author is employed by a university or higher education institution, or the design of the research has been undertaken in the course of an honorary arrangement with a university or higher education institution then insurance will be provided through an insurance scheme. A copy of the relevant policy/certificate must be provided. This situation applies to researchers employed by a university, regardless of whether or not they hold any honorary contract with an NHS organisation. For non-commercial studies where the protocol author is the substantive employee of an NHS organisation, then indemnity is provided for harm arising from the design of the study through NHS schemes. No proof of indemnity is required. Conduct of the study: The conduct of the research refers to the study procedures, as described in the protocol or proposal, which are conducted by the research team with participants, data or tissues. Employers of the research team are normally responsible for the actions of their staff who conduct research procedures as part of their employment. Version 5.2 Appendix 3-14

109 Where the research involves NHS patients under the care of NHS organisations, indemnity for harm to participants resulting from clinical negligence is provided through NHS indemnity schemes. Formal permission from the NHS organisation (R&D approval) must be obtained in writing before the start of the research. No proof of indemnity is required. Primary Care: Independent contractors (eg GP practices, NHS dental practices) or the staff members they employ are not normally covered by NHS indemnity. Where the research involved NHS patients under the care of independent contractors, indemnity for harm to participants resulting from clinical negligence is provided through professional indemnity. Independent contractors are usually covered for clinical negligence through Medical Defence organisations or similar bodies. The cover provided is normally for the services they are providing to the NHS under contract. Independent contractors should ensure that they are covered to undertake research activity through this cover or through separate arrangements. Non-negligent harm indemnity (also known as No Fault compensation) For commercial studies, arrangements for no fault compensation will normally be provided in accordance with the Association of British Pharmaceutical Industry (ABPI) or Association of British Healthcare Industry (ABHI) schemes. A copy of the form of indemnity (unsigned) to be used should be included in the model agreement. For non-commercial studies, arrangements for no fault compensation cannot be made in advance by the NHS or other public bodies (eg MRC). Such organisations, although not accepting liability, may consider making an ex gratia payment on a voluntary basis in the event of a claim. It is the role of RECs to decide whether or not a study can go ahead without a scheme of compensation for harm caused where there is no negligence. For non-commercial studies, some universities or higher education institutions may choose to provide no fault compensation for research involving their employees. If this is the case a copy of the policy should be provided. Equipment indemnity Occasionally a research site might not have access to a necessary piece of equipment to undertake the study, eg an ECG machine that transmits data directly to a central reading facility. In this case the Sponsor might make arrangements for the piece of equipment to be loaned or gifted to the research site. The equipment might be provided to all sites or to individual sites. Although it might be arranged by the Sponsor, the supplier of the equipment is not usually the Sponsor. Where equipment is loaned or gifted to a research site there should be confirmation that the supplier(s) of the equipment has registered with the Master Indemnity Agreement scheme(s) in the UK countries in which the study is to be conducted. If the supplier has not registered with the appropriate scheme(s) the Chief Investigator and/or the Sponsor should be informed that the equipment supplier(s) will need to complete one of the following forms and provide evidence of Public and Product Liability Insurance of at least 5 million for each. Form of Indemnity A if the equipment is to be returned at the end of the study Form of Indemnity B if ownership of the equipment is to be transferred to the NHS organisation Registration occurs once only in each UK country and only one Form of Indemnity need be completed for each country. Version 5.2 Appendix 3-15

110 The NHS Delivery Note is completed each time goods or equipment are delivered to a NHS organisation D3.1. Study wide Before a study is initiated an agreement about compensation in the event of harm to participants should have been reached. If any organisation, or the sponsor themselves, offers compensation without proof of negligence, they should have made the necessary arrangements. Review the following aspects of the insurance/indemnity arrangements: o The level of insurance/indemnity and if it is appropriate to the study type and purpose o Any specific exclusions to the cover provided o If the study is being conducted by independent contractors (eg GP practices, NHS dental practices). For studies where equipment is to be loaned or gifted to a research site confirm that the supplier(s) of the equipment have registered with the Master Indemnity Agreement scheme(s) in the UK countries in which the study is to be conducted. There is no requirement for NHS organisations to request renewals of insurance certificates since it is the sponsor s responsibility to maintain insurance as set out to the REC. Any change to the insurance arrangements would constitute a substantial amendment D3.2. Local No review required D3.3. Resources: The Medicines for Human Use (Clinical Trials) Regulations 2004 SI 2004/ The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 SI 2006/1928, Schedule 1, Part 2, (14) Responsibilities, liabilities and risk management in clinical trials of medicines Arrangements for Clinical Negligence Claims in the NHS B8161/0/NHSIndemnity.rtf Association of the British Pharmaceutical Industry (ABPI) Indemnity Form (England and Wales) (Scotland) Version 5.2 Appendix 3-16

111 Association of British Healthcare Industries (ABHI) Indemnity Form Equipment Indemnity England: Scotland: Wales: Version 5.2 Appendix 3-17

112 D4. Financial management arrangements assessed The way in which a study is financed is important to NHS organisations as they are legally accountable for use of public funds in compliance with the law and the rules set out by HM Treasury. It is important that NHS organisations are aware of the activity involved in supporting a study and what it costs. NHS organisations need to be aware of the planned expenditure and attribution of costs to ensure financial probity, compliance with the law and with the rules set out by HM Treasury regarding the use of public funds. Where the study is funded through one or more programme grant(s), the R&D Form should reflect the amount or percentage of funding that is to be used for the study. This will give a clearer indication of the study funding than the value of the total programme grant. Some studies may have standard costing templates available and these should be reviewed to ensure that all potential costs have been identified and appropriately attributed. Alternatively, confirm that a sense-check or validation of the template has been undertaken D4.1. Study-wide Consider whether the financial management arrangements have been appropriately described. Assess the appropriateness of the cost identification and the attribution of costs for the study and the study procedures. Assess whether the arrangements to cover the following are appropriate and in line with any guidance applicable to the attribution of cost: o Research costs o NHS service support costs o (Excess) treatment costs o HEI costs where members of the research team are employed by a HEI Consider the appropriateness of arrangements to reimburse other parties D4.2. Local Assess whether all the study costs have been appropriately identified and attributed. Consider whether the NHS organisation would be willing to support the study within the financial arrangements described. The PI/research team at the study site should discuss the study costs with the NHS organisation R&D office to ensure that costs have been appropriately attributed and the study can be adequately supported. Primary Care: For primary care studies with independent contractors, the negotiations regarding financial management and costs will normally be between the sponsor and the Version 5.2 Appendix 3-18

113 independent contractor, particularly for commercial studies. It would be the independent contractor s responsibility to ensure that financial management arrangements and costs are appropriate, and have been documented before signing an agreement with the sponsor. For non-commercial studies, review of financial arrangements may be undertaken on behalf of GPs by the NHS research governance review. For primary care studies with NHS staff and/or which use NHS facilities eg laboratories or x- ray, the NHS organisation should ensure that financial management arrangements and costs are appropriate, and have been documented before signing an agreement with the sponsor D4.3. Resources: Attributing revenue costs of externally funded non-commercial research in the NHS (ARCO) ce/dh_ NIHR Industry Costing Templates Version 5.2 Appendix 3-19

114 D5. Implications for internal departments assessed When an NHS organisation agrees to undertake a study it is important that any additional work to be undertaken by the organisation has been assessed and agreed. This includes assessment and agreement from the relevant clinical divisions/departments as well as support departments of the organisation (eg pharmacy, pathology, X-ray), where relevant. The agreement to undertake any additional work should be supported by appropriate internal management authorisation/agreement. Arrangements for internal authorisations vary, but it is recommended that, where possible, this is coordinated through R&D staff and that streamlined and efficient systems for review and authorisation (including delegation of authorisation) are put in place in the NHS organisation D5.1. Study-wide No review required D5.2. Local If any division/department is to undertake additional work to support a study, then they need to ensure that it is able to support the study for the duration of their required support, and that the impact of any additional work on their routine work has been assessed. Account should be taken of activities required during the planning, conduct and archiving phases of the study. Assess the additional workload required to support the study for the duration of the required support. Assess the impact of the additional workload on the division s/department s ability to deliver their services to non-research activities required by the organisation. Consider the implementation of any additional processes or procedures to support the research activity. Consider any additional resources, equipment or facilities required to support the activity. Consider any long term retention/archiving requirements eg imaging, study records, pharmacy worksheets, etc. It is important that the division/department and the principal investigator/research team at the study site have discussed the implications of the study and the support being requested before the authorisation signatory signs off their agreement. Certain departments may require additional information/documents to support study set-up. These are not part of the R&D application package as their purpose relates to the conduct of the study. These discussions and agreement should be completed before the study is initiated. Where a study involves treatment that is not included in NICE guidelines or a local prescribing policy, this should not influence the decision to undertake the study locally, since the purpose of research is to obtain evidence to inform future guidelines and policy. Version 5.2 Appendix 3-20

115 The REC will have considered the arrangements for post-study treatment. If any specific arrangements are agreed, the sponsor is required to make any necessary financial and practical arrangements for post-study treatment. Local prescribing policies should, therefore, not influence these arrangements. Primary Care: For primary care studies with independent contractors it is the responsibility of the independent contractor to ensure the relevant internal management authorisations are in place before the study is initiated (eg senior practice partner; Caldicott Guardian of the practice). Version 5.2 Appendix 3-21

116 D6. Adequacy of facilities assessed It is important that any NHS organisation agreeing to undertake a study has adequate resources, equipment and facilities to conduct the research activities in a safe manner. Where the NHS organisation obtains services in support of the study (eg X-rays; CT or MRI scans; echocardiograms) from another organisation, the supporting organisation (or subsidiary site) must also be able to support the conduct of the obtained service for the duration of the whole study. The supporting organisation should not undertake a full review of the study as they should only be determining if they can provide the requested service for the duration of the study. Where the provision of such a service forms part of an existing clinical arrangement, additional documentation of the arrangement may not be necessary, although the supporting organisation should give permission for the research activity they are providing. Where care during a study is shared across sites, the shared care sites must give permission for their involvement in the study D6.1. Study-wide No review required D6.2. Local If an NHS organisation is to agree to undertake a study, the organisation needs to be able to support the conduct of the study for the duration of the whole study. Assess the adequacy of facilities for any novel procedures or for procedures not part of existing clinical activity. Assess the ability of the local facility to meet any quality requirements of the sponsor. Assess the availability of resources required and any additional resources needed. Assess the availability of equipment needed and any additional equipment and storage requirements. Assess the availability and use of facilities and any additional facilities required. Consider the impact of undertaking a study on current resources, equipment and facilities. Version 5.2 Appendix 3-22

117 J. RISK ASSESSMENT (RISK TO RESEARCHER) E1. Risks to researcher assessed The employer of the researcher carries primary responsibility for the safety and well-being of the researcher E1.1. Study-wide No review required E1.2. Local Where the NHS organisation is the employer of the researcher: o Take account of the following risks to the researcher s career and reputation: service pressures on time available for research, inadequate patient recruitment, noncompletion of research, and damage to reputation arising from misconduct. o Obtain the relevant clinical or management internal authorisation to confirm that the research activities will be managed within that department/unit/practice, and that the employer is aware of the risks to the employee. Where the NHS organisation is not the employer of the researcher: o Use the pre-engagement checks assessment and the Research Passport or NHS-to- NHS arrangements to ensure that the employer is aware of the employee s activities. 9 Where students or junior staff are involved in conducting research: o Ensure that adequate clinical/management supervision arrangements are in place. Ensure that occupational health and health and safety requirements are addressed through the above arrangements. Assess any risks to the researcher arising from the location of the research procedures and identify any specific arrangements required (eg where lone worker arrangements need to be put in place). Assess any risks to the researcher arising from the participant population and identify any specific arrangements required, and whether the researchers have the relevant experience to be able to assess and to deal with possible risks (eg prison research) E1.3. Resources: Research in the NHS: HR Good Practice Resource Pack 9 See F4. Principal Investigator (PI)/research team Human Resources arrangements in place Version 5.2 Appendix 3-23

118 K. LEGAL COMPLIANCE F1. Data Protection Act and data security issues assessed There are a range of complex legal and professional obligations that limit, prohibit or set conditions in respect of the management, use and disclosure of information and, similarly, a range of statutes that permit or require information to be used or disclosed. NHS organisations must protect the way identifiable information is handled in accordance with the Data Protection Act 1998, ensure privacy is maintained in accordance with the Human Rights Act 1998 and satisfy the common-law duty of confidentiality. Those who work within or under contract to NHS organisations are expected to comply with NHS-specific codes of practice and to demonstrate high standards of information governance. The 'Confidentiality: NHS Code of Practice' sets out the required standards of practice concerning confidentiality and patients' consent to use their health records. It is based on legal requirements and best practice. The 'Information Security Management: NHS Code of Practice' is a guide to the methods and required standards of practice in the management of information security. It is based on current legal requirements, relevant standards and professional best practice. The 'Records Management: NHS Code of Practice' sets out the required standards of practice in the management of records, based on current legal requirements and professional best practice. NHS Information Governance - Guidance on Legal and Professional Obligations, is best practice guidance, which outlines the likely impact of these provisions to NHS information F1.1. Study-wide The sponsor is responsible for ensuring that the protocol and study-wide arrangements comply with the law. Sponsors may, however, not be familiar with NHS-specific standards and codes. Ensure the arrangements for confidentiality and data security comply with the law, and with NHS-specific standards and codes. Obtain clarification from the sponsor/chief Investigator if there is uncertainty about the compliance of any aspects of the study. Identify whether the research only involves processing of data that have already been anonymised or pseudonymised. Identify who will have access to personal identifiable information in the course of identifying potential participants, undertaking research procedures or analysing research data. Where personal identifiable information will be anonymised or pseudonymised during the course of the research, assess whether the arrangements are clearly described. Identify any aspects of the arrangements for processing or storing data that local sites will need to consider. Version 5.2 Appendix 3-24

119 Assess the security of any arrangements for storing or transferring data on computers or through other electronic means. Assess whether the arrangements for transfer of data to other organisations are clearly described. Identify whether a Data Transfer Agreement is provided. Identify if data will be transferred outside the UK. Assess whether the information for participants accurately describes the handling of personal identifiable information and associated access permissions F1.2. Local If the research only involves processing of data that have already been anonymised or pseudonymised, further review is not required. For other studies, the review required will depend on the nature of activities relating to the use of personal identifiable information. Review by a Data Protection Officer or Caldicott Guardian may be delegated to suitably experienced RM&G staff when this would provide a proportionate approach. Where relevant, assess whether the individuals who will have access to personal identifiable information, for which the NHS organisation is responsible, are in accordance with the organisation s policies. Ensure arrangements are in place for secure access to, and processing of, personal identifiable information in accordance with the organisation s policies. Ensure that the arrangements for anonymisation or pseudonymisation of personal identifiable information set out in the protocol can be undertaken locally, if relevant. Assess whether the arrangements for transfer of data to other organisations are in accordance with the organisation s policies. Ensure that the arrangements are agreed between the relevant parties, eg in a Data Transfer Agreement. Assess the compliance of any archiving arrangements with NHS policies. Ensure that the arrangements for storage of data at the site during and after the study can be undertaken locally. Primary Care: Where research is being undertaken through independent contractors, it is the independent contractor s responsibility to ensure that arrangements meet local policies and standards. Independent contractors may seek advice to meet their responsibilities. The RSS planning assessment should have identified any unusual features of the project that may require additional or different systems or resources to be put in place during the permission process. Note that where internal forms are used to collect information for internal monitoring and reporting as part of normal healthcare delivery, these should not be presented to sponsors as additional local application forms. It is expected that CLRN-funded staff will support the provision of relevant local information. Version 5.2 Appendix 3-25

120 F1.3. Resources: Data Protection Act Confidentiality: NHS Code of Practice nce/dh_ Information Security Management: NHS Code of Practice Records Management: NHS Code of Practice nce/dh_ NHS Information Governance - Guidance on Legal and Professional Obligations NHS Care Record Guarantee for England - version 5 The Caldicott Guardian Manual ndcaldicottguardians/dh_ MRC: Personal Information in Medical Research Research involving the NHS retention of records pdf The Medicines for Human Use (Clinical Trials) Regulations 2004 SI 2004/ The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 SI 2006/1928, Schedule 1, Part 2, (9) Version 5.2 Appendix 3-26

121 F2. Arrangements for compliance with the Clinical Trials Regulations assessed NHS organisations are responsible for ensuring that clinical trials of investigational medicinal products (CTIMPs) that meet the definitions set out by MHRA 10 are conducted locally in accordance with the requirements of the UK Clinical Trials Regulations, as amended. MHRA assesses the information relating to the handling of the IMP and the data relating to the safety of the IMP, in issuing a Clinical Trial Authorisation. MHRA does not review the participant information sheet or the monitoring or pharmacovigilance arrangements (although a check for safety reporting provisions is conducted). The REC will review the participant information sheet and the overall arrangements for monitoring safety during the study. However, the REC will not review the site-level monitoring or pharmacovigilance arrangements F2.1. Study-wide The sponsor has responsibilities under the regulations in relation to this specific study. The sponsor may delegate tasks within these responsibilities to the sites. Assess whether the protocol and/or template contract/agreement set out the arrangements clearly so that sites will understand what is expected of them. Obtain clarification if there is no clear description of the arrangements for the sites. Assess whether the expectations of the sponsor in delegating activities is appropriate and feasible for NHS sites. Highlight any aspects that NHS sites should consider whether they are capable of delivering. Assess whether the sponsor has provided clear information relating to consent. Where relevant, consider whether adequate and appropriate guidance is provided on the specific arrangements relating to adults lacking capacity, including on-going consent and arrangements for loss of capacity or withdrawal. Where there are different types of patient information sheets and consent forms, assess whether there is clear guidance from the sponsor for the circumstances in which the different documents are required. Consider whether there is clear information on expectations of the site in relation to the following: o monitoring o pharmacovigilance o consent o handling of IMP o security, storage and archiving of trial material, eg documents and samples nicaltrialauthorisationctarequired/index.htm Version 5.2 Appendix 3-27

122 F2.2. Local Determine whether the site has SOPs/policies and systems in place to undertake the activities expected by the sponsor. If not, ensure that study-specific arrangements are put in place. Assess whether there are local arrangements in place for identifying personal or professional legal representatives where the study involves adults unable to consent for themselves. Assess whether the research team and other relevant staff suitably resourced and trained to comply with: o the research procedures set out in the protocol and other supporting information such as study manuals or procedures o the requirements for reporting to the sponsor on progress and pharmacovigilance o the monitoring arrangements expected by the sponsor o the arrangements approved by the REC for seeking consent in particular where the study involves adults unable to consent for themselves, participants under the age of 16 or emergency research o the arrangements for handling of IMP o the arrangements for security, storage and archiving of trial material, eg documents and samples Where the sponsor is providing the IMP, ensure that it will provide evidence of Qualified Person (QP) certification for each batch of IMP once available (which will be after permission is issued). Such assurance may be a copy of the QP certification document or a letter or confirmation from the sponsor (the communication may apply to more than one batch of IMP). 11 Primary Care: Where research is being undertaken through independent contractors, the arrangements may be agreed directly between the independent contractor and the sponsor. Independent contractors may seek advice to meet their responsibilities. The site may be assured that information reviewed by the MHRA is compliant with the regulations. 12 The NHS organisation may be able to rely on clinical trials units and research teams within their organisation that regularly undertake clinical trials having systems and resources in place to undertake commercial and/or non-commercial clinical trials. Evidence of these arrangements can be assessed on a generic basis rather than always requiring studyspecific review. The RSS planning assessment should have identified any unusual features of the project that may require additional or different systems or resources to be put in place during the permission process. Examples might include IMP requiring unusual or unfamiliar handling, an early phase trial in a unit without prior experience or a trial with demanding research procedures actice/frequentlyaskedquestions/index.htm#im ngclinicaltrialsubmissionstothemhra/index.htm Version 5.2 Appendix 3-28

123 On-going host QA arrangements may allow the NHS organisation to be satisfied about the capability of the site to meet the requirements. Study-specific review may therefore be adjusted proportionately F2.3. Resources: Medicines for Human Use (Clinical Trials) Regulations 2004, as amended Annex 13, Investigational Medicinal Products, Volume 4 EU Guidelines to The Good Manufacturing Pharmacovigilance Practice Guide EudraLex - Volume 10 Clinical trials guidelines Clinical trials for medicines htm ICH Topic E 6 (R1), Guideline for Good Clinical Practice Section Monitoring pdf Consent Guidance ICH Topic E 6 (R1), Guideline for Good Clinical Practice Section Supplying and Handling Investigational Product(s) pdf Archiving of Documents Version 5.2 Appendix 3-29

124 F3. Arrangements for compliance with the Mental Capacity Act assessed NHS organisations are responsible for ensuring that all interventional research other than clinical trials of investigational medicinal products (CTIMPs) is conducted in accordance with the requirements of the Mental Capacity Act. The requirements for ethical review for studies involving adults lacking capacity dependent on the parts of the UK involved. The sponsor is responsible for ensuring that the protocol and study-wide arrangements comply with the legal requirements. The Mental Capacity Act sets out the study-wide arrangements that a REC within the NRES must review F3.1. Study-wide No review required F3.2. Local Determine whether the site has SOPs/policies and systems in place to undertake the activities approved by the REC. If not, ensure that study-specific arrangements are put in place. Assess whether there are local arrangements in place for identifying personal or nominated legal consultees separate from the research team. Assess whether the research team is suitably resourced and trained to comply with the requirements for: o Initial assessment of capacity o On-going assessment of capacity o Arrangements for adults who may become incapacitated during the course of the research o Research involving emergency treatment Primary Care: Where research is being undertaken through independent contractors, it is the independent contractor s responsibility to ensure that arrangements meet local policies and standards. Independent contractors may seek advice to meet their responsibilities. Units and teams that regularly undertake research in specific therapy areas such as dementia would be expected to have training, systems and resources in place to meet legal requirements. NHS organisations may have systems in place to ensure that staff training to meet legal requirements is kept up to date. The RSS planning assessment should have identified any unusual features of the project that may require additional or different systems or resources to be put in place during the permission process. Examples might include staff unfamiliar with assessing capacity to consent, or research involving emergency treatment. On-going host QA arrangements may allow the NHS organisation to be satisfied about the capability of the site to meet the requirements. Study-specific review may therefore be Version 5.2 Appendix 3-30

125 adjusted proportionately F3.3. Resources: Requirements for REC review for studies involving adults lacking capacity across the UK Adults lacking capacity online toolkit Guidance on nominating a consultee for research involving adults who lack capacity to consent Version 5.2 Appendix 3-31

126 F4. Principal Investigator (PI)/research team Human Resources arrangements in place NHS organisations are responsible for ensuring that appropriate management and supervision arrangements are in place for individuals undertaking research activities in or through the organisation. This includes compliance with relevant employment law. Where pre-engagement checks are not required, this criteria does not require specific review, and the letter of access may be issued as part of the letter of NHS permission. Where a single SSI Form is used across all sites or a sub-set of sites, the requirements relating to any central research team may be reviewed once by the Lead CLRN for these sites F4.1. Study-wide No review required F4.2. Local Consider whether the site has HR systems in place to ensure appropriate management and supervision of researchers. If not, ensure that study-specific arrangements are put in place. Ensure the arrangements are documented in appropriate contracts or agreements. For employees of the NHS organisation (including those with honorary clinical contracts) or employees of independent contractors providing services to the NHS: The employer is responsible for ensuring that staff only undertake activities that are appropriate to the job and competencies of the individual, and that appropriate supervision is in place. Ensure that internal authorisation from the relevant department/directorate/practice is obtained in accordance with the organisation s standard procedures. For other individuals not employed by the organisation (including students): Following the guidance in the Research in the NHS Human Resources (HR) Good Practice Resource Pack, undertake the following for all individuals performing research activities in or through the research site: Review the pre-engagement checks required for each individual, taking account of the activities to be undertaken. Where required, review the pre-engagement checks assured by the employer or place of study, using the Research Passport or relying on NHS-to-NHS assurances. Put in place arrangements for issuing Honorary Research Contracts, Letters of Access or other agreements/contracts or verify that an appropriate organisational level agreement is in place (eg students on an educational placement) Version 5.2 Appendix 3-32

127 Put in place arrangements for day-to-day management and supervision, as appropriate. For GPs, dentists, opticians and pharmacists who are independent contractors: It is the responsibility of the individual and the practice to ensure that the research activities are appropriately managed and supervised. The RSS planning assessment should have identified any unusual or unexpected features of the project or the researchers involved that may require additional or different systems or resources to be put in place during the permission process. For example an organisation with low levels of research activity involving external researchers may be unfamiliar with using Research Passports. On-going host QA arrangements may allow the NHS organisation to be satisfied about the capability of the site to meet the requirements. Study-specific review of the local aspects may therefore be adjusted proportionately. For example, an organisation with appropriate systems for identifying changes in the research team and putting necessary HR arrangements in place before research activities are commenced, may be able to issue permission prior to HR arrangements being completed F4.3. Resources: IRAS guidance on student applications Research in the NHS: HR Good Practice Resource Pack Version 5.2 Appendix 3-33

128 F5. Radiation - Arrangements for compliance with IRMER assessed NHS organisations are responsible for compliance with legislation relating to radiation. In relation to research, each NHS employer is responsible for compliance with the Ionising Radiation (Medical Exposure) Regulations 2000 in relation to the exposure of patients or other persons voluntarily participating in medical or biomedical diagnostic or therapeutic, research programmes undertaken by its staff. Procedures involving ionising radiation may include: Diagnostic X-rays, CT scans or DXA (DEXA) scans Invasive procedures conducted under radiological guidance Radiotherapy (including brachytherapy and therapy using unsealed sources) Radionuclide imaging (including diagnostic imaging and in vitro measurements). Magnetic Resonance Imaging (MRI) or ultrasound investigations do not involve ionising radiation. The additional requirements relating to Research Certificates for administration of radioactive substances, eg nuclear medicine bone scans, MUGA, PET, is reviewed separately. All research involving ionising radiation as part of the protocol (whether additional or standard care) ie research exposures must be reviewed by a Research Ethics Committee within the National Research Ethics Service, which will consider the risks and benefits of the use of radiation and the information relating to these issues that will be provided to potential participants. A research exposure is any exposure required by the protocol following initial consent by participants (including exposures which would be considered normal clinical care outside the study). The application to the REC includes a study-wide assessment by lead radiation experts, taking into account potential variation between sites. A dose/risk assessment is completed by a Lead Medical Physics Expert ( Lead MPE ), who is a clinical scientist with experience of the modality. A clinical assessment is completed by a Lead Clinical Radiation Expert ( Lead CRE ), who is a radiologist, oncologist, nuclear medicine consultant or other equivalent registered healthcare professional with relevant clinical experience F5.1. Study-wide No review required F5.2. Local The employer is responsible for reviewing all research involving radiation research exposures to ensure compliance with the Ionising Radiation (Medical Exposure) Regulations It will also be responsible for any additional requirements for compliance with any other relevant legislation such as the Ionising Radiation Regulations The individuals responsible will vary across organisations, and depend on the radiation modalities involved. Version 5.2 Appendix 3-34

129 A research exposure is defined as any exposure required by the research protocol following initial consent from the participant. It includes all exposures carried out on the participant as determined by the protocol, including those which would otherwise be part of routine clinical care for patients treated outside the research setting. It includes exposures required by the screening procedures for the protocol. Ensure that appropriate internal authorisation is obtained to confirm that the employer s responsibility relating to research exposures is met. Primary Care: Where research is being undertaken through independent contractors, it is the independent contractor s responsibility to ensure that arrangements meet local policies and standards. Independent contractors may seek advice to meet their responsibilities. Use of ionising radiation in primary care is rare, but may be relevant to research conducted by dentists. The RSS R&D Operational Capability Statement should identify the relevant individuals to review and authorise the use of research exposures in the NHS organisation. The RSS planning assessment should have identified any capacity issues that could affect the ability of the relevant staff to review compliance with IRMER during the permission process F5.3. Resources: IRAS guidance on ionising radiation NRES guidance on approval for research involving ionising radiation Section 5 - Notes for Guidance on the Clinical Administration of Radiopharmaceuticals and Use of Sealed Radioactive Sources - March The Ionising Radiation (Medical Exposure) Regulations 2000 (together with notes on good practice) nce/dh_ Version 5.2 Appendix 3-35

130 F6. Compliance with any other applicable laws and regulations NHS organisations are responsible for complying with any legislation that applies to research for which the organisation is responsible F6.1. Study-wide Assess whether the project may require review for compliance with requirements other than those set out specifically in this guidance. Examples include: o Storage, use or transfer of tissue in relation to a specific research project o Use of medical devices o Requirement for support under section 251 of the NHS Act o Use of advanced therapy medicinal products o Use of gene therapy o Use of stem cells o Research involving offenders Ensure the arrangements for the study comply with any other relevant aspects of the law, and any other NHS-specific standards and codes. Obtain clarification from the sponsor if there is uncertainty about the legal compliance of any aspects of the study. Identify any specific legal requirements that local sites will need to consider. For any study involving tissue/samples: Identify whether the study involves transferring tissue/samples for use in the specific project or to a biobank Identify whether the study involves using tissue/samples held in a biobank Identify whether at the end of the study, tissue/samples will be: o transferred to an existing biobank, for which a licence is in place, if required o stored by the research team pending Research Ethics Committee favourable opinion for use in another project o stored by the research team in a tissue/biobank for which a new licence will be/has been obtained, where required Where a tissue bank is involved, identify whether it is licensed. Assess the implications if voluntary ethical review of the biobank has not been obtained. Compliance with the legal requirements for establishing a research biobank for storage and use of tissue other than for a specific research project is not relevant. For investigations of medical devices: The following studies are likely to require applications to MHRA where commercialisation is intended: 13 See also F1 Data Protection Act and data security issues assessed Version 5.2 Appendix 3-36

131 Clinical study of a non-ce marked product Clinical study of a CE marked product that has been modified or is to be used outside its intended purpose. Confirm if the correct options have been selected in IRAS (and therefore whether the appropriate information has been provided for assessment). Where required, review the device instructions for use to confirm whether the device is being used within its intended purpose. For investigations of medical devices regulated by MHRA, ensure that ethical review was by a REC within the National Research Ethics Service only. For all studies involving medical devices, identify whether the study is likely to require review by medical engineering or other experts at each site to ensure compliance with local policies. For studies requiring support under section 251 of the NHS Act 2006 Ensure that the requirements relating to security and processing of data are clearly described F6.2. Local Assess whether the NHS organisation is able to comply with the requirements of any other relevant legislation. For studies involving tissue ensure that arrangements for any transfer and for disposal or long-term use of the tissue are agreed and documented. Ensure that any local Human Tissue Authority (HTA) licences are in place, together with arrangements for compliance with the Human Tissue Act For studies involving devices regulated by MHRA, investigators are required to comply with the standards in BS EN ISO There is no requirement for GCP under the Medical Devices Directive or Regulations. In order to meet the requirements of the Directive, ISO should be followed instead of GCP for medical device studies. Ensure that appropriate investigators are appropriately trained. Primary Care: Where research is being undertaken through independent contractors, it is the independent contractor s responsibility to ensure that arrangements meet local policies and standards. Independent contractors may seek advice to meet their responsibilities. The RSS planning assessment should have identified any studies with unfamiliar aspects, for which internal or external expert advice may need to be sought F6.3. Resources: UK Stem Cell Toolkit Experimental Medicine Toolkit Version 5.2 Appendix 3-37

132 Data and Tissues Toolkit Medtech study start-up route map MHRA devices BS EN ISO 14155: NRES guidance on studies involving medical devices entryid Offender Health Research Network Toolkit Human Tissue Authority Version 5.2 Appendix 3-38

133 L. APPROVALS AND AUTHORISATIONS G1. Research Ethics Committee favourable opinion received The current version of Governance Arrangements for Research Ethics Committees sets out the circumstances under which a research project requires a favourable opinion from a Research Ethics Committee within the National Research Ethics Service. In other circumstances, ethical review may be undertaken by a university ethics committee. The following RECs are established in accordance with GAfREC: All RECs appointed within the National Health Service and the Northern Ireland Health and Social Care Service ( NHS RECs ) All RECs appointed by the Appointing Authority for Phase 1 Ethics Committees (AAPEC) to review Phase 1 clinical trials in healthy volunteers The Gene Therapy Advisory Committee (GTAC) The Social Care Research Ethics Committee for England. All these RECs are able to review research within the NHS, but in some cases the remit is limited: AAPEC RECs only review Phase 1 trials, but this could include subjects recruited through the NHS as healthy volunteers or patient controls (but not patients with the disease the IMP is intended to treat). The Social Care REC can review social care research involving NHS patients/staff or NHS research involving social sciences methodology, provided the research does not involve any change to standard clinical care. (For social care research led from England with Welsh sites the Social Care REC review covers both England and Wales. For social care research led from Wales, the review should be conducted by a NHS REC established in Wales. Further advice should be obtained from the Research Ethics Operations Manager for Wales). GTAC only reviews gene therapy research, research into stem cell therapy derived from stem cell lines, and trials of other advanced therapy medicinal products. The Ministry of Defence (MoD) REC is not established by the Department of Health. It reviews research sponsored by MoD or its agencies, or recruiting through the UK Armed Forces. Where participants are transferred into the NHS separate review by another REC is not required. Recognised RECs are recognised by the United Kingdom Ethics Committee Authority (UKECA) for the review of clinical trials of investigational medicinal products (CTIMPs), in accordance with The Medicines for Human Use (Clinical Trials) Regulations 2004, for the class of research and geographical area indicated. Recognised RECs (apart from Type 1 Independent Ethics Committees) can also review non-ctimp research. There are two types of recognised RECs: Version 5.2 Appendix 3-39

134 Type 1 RECs. These are recognised for review of phase 1 CTIMPs in healthy volunteers only. Some Type 1 RECs are independent ethics committees (that is, they are not part of the National Health Service). Type 3 RECs. These are recognised for review of CTIMPs (other than phase 1 trials in healthy volunteers) and all other research taking place in more than one domain anywhere in the United Kingdom. They are also authorised to review other research. Authorised RECs are established under the Governance Arrangement for Research Ethics Committees (GAfREC) but not recognised by UKECA for the purposes of reviewing CTIMPs. An authorised REC may review all applications except those relating to CTIMPs. Certain types of study (medical devices, adults lacking capacity, prisoners) may be reviewed by a flagged REC with specific expertise in the relevant area. The favourable opinion may be issued with conditions. Where these changes require changes to any documents, these should be clearly set out in the letter of favourable opinion from the REC, and it will therefore be possible to confirm that the changes have been made. The National Research Ethics Service has standard requirements for letters which must be provided in hard copy with a signature (an version may be sent in advance), and those which may be sent by only. 14 The REC review may be undertaken in parallel to NHS review. It is not appropriate for NHS organisations to delay initiating review until the REC favourable opinion has been issued G1.1. Study-wide Confirm that the study has a favourable opinion from a relevant Research Ethics Committee. Identify from correspondence any clarifications made by the applicant at the Research Ethics Committee meeting or subsequently. Confirm from correspondence that any conditions of the favourable opinion have been met. Confirm that any substantial amendments requiring ethical review have a favourable opinion. Confirm the version numbers of any documents received in the R&D application: o where ethical review is still underway, the versions are the same as those listed in the acknowledgement letter or subsequent correspondence from the Research Ethics Committee o where a favourable opinion has been issued, the versions are the same as those given a favourable opinion by the Research Ethics Committee in the initial favourable opinion or subsequent substantial amendments 14 See Version 5.2 Appendix 3-40

135 o where subsequent substantial or non-substantial amendments have not required notification to the Research Ethics Committee, the versions are consistent with the above G1.2. Local No local review required G1.3. Resources: IRAS Amendment guidance NRES Governance arrangements for NHS Research Ethics Committees nce/dh_ Version 5.2 Appendix 3-41

136 G2. CTIMPs - Clinical Trial Authorisation (CTA) letter received The sponsor is responsible for determining whether a study is a clinical trial of an investigational medicinal product (CTIMP) that requires a Clinical Trial Authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA). There is no requirement for the sponsor to supply a copy of the MHRA application to the NHS organisation. Note that letters from the MHRA are not signed. The MHRA review may be undertaken in parallel to NHS review. It is not appropriate for NHS organisations to delay initiating review until the MHRA authorisation has been issued G2.1. Study-wide Confirm that the study has a Clinical Trial Authorisation. Identify from correspondence any clarifications made by the applicant to the request for the Clinical Trial Authorisation. It may not be necessary or appropriate to view all correspondence between the sponsor and MHRA, as some may be commercially confidential, or not relevant to the NHS review. Confirm that any substantial amendments requiring review by the MHRA have been accepted. Confirm that there is evidence that any conditions of the Clinical Trial Authorisation have been met G2.2. Local No local review required G2.3. Resources: Is a clinical trial authorisation required? nicaltrialauthorisationrequired/index.htm IRAS Amendment guidance Version 5.2 Appendix 3-42

137 G3. Devices - MHRA notice no objection received The sponsor is responsible for determining whether a study is an investigation that requires a notice of no objection from the Medicines and Healthcare products Regulatory Agency (MHRA). A Notice of No Objection must be obtained from MHRA Devices for a clinical investigation of a medical device undertaken by the manufacturer for CE marking purposes. This will be either an investigation of a non-ce marked product, or an investigation of a CE marked product that has been modified or is to be used outside its intended purpose. MHRA approval is not always required in the case of: Medical devices manufactured in-house in a healthcare establishment Clinician led off-label use of a medical device. The MHRA review may be undertaken in parallel to NHS review. It is not appropriate for NHS organisations to delay initiating review until the MHRA Notice of No Objection has been issued G3.1. Study-wide Confirm that the study has a Notice of No Objection. Identify from correspondence any clarifications made in the request to MHRA. It may not be necessary or appropriate to view all correspondence between the sponsor and MHRA, as some may be commercially confidential, or not relevant to the NHS review. Confirm that any amendments requiring review by the MHRA have been authorised. Confirm that there is evidence that any conditions of the Notice of No Objection have been met G3.2. Local No local review required G3.3. Resources: Guidance on whether MHRA Notice of No Objection is required IRAS guidance on medical devices IRAS Amendment guidance The Medical Devices Regulations: Implications on healthcare and other related establishments. BULLETIN No. 18 Version 5.2 Appendix 3-43

138 visionselectionmethod=latest Clinical Trials of Medical Devices Version 5.2 Appendix 3-44

139 G4. Radiation - Administration of Radioactive Substances Advisory Committee (ARSAC) approval received The sponsor is responsible for ascertaining whether a study requires a certificate at each site from ARSAC. The Medicines (Administration of Radioactive Substances) Regulations 1978 (MARS) provides a system of prior authorisation for doctors who wish to administer radioactive medicinal products to humans for diagnosis, treatment or research. ARSAC Certificates are only required for the administration of radioactive medicinal products, eg nuclear medicine bone scans, MUGA, PET etc, not for other exposures to ionising radiation. ARSAC Research Certificates are only required for a research study that involves medical exposures additional to routine practice, and are site specific. The standard of proof for whether an exposure is additional to routine practice at the site is whether there is a documented imaging pathway for the specific condition. The certificate is applied for by the relevant practitioner at the site. In some studies, alternative methods of assessment may be set out in the protocol, of which only one type requires an ARSAC Research Certificate, eg a choice between MUGA (requires ARSAC) or echocardiography (does not require ARSAC). An ARSAC Research Certificate will, therefore, only be required at those sites adopting the assessment involving administration of a radioactive substance. All research involving administration of radiation as part of the protocol (whether additional or standard care) must be reviewed by a Research Ethics Committee within the National Research Ethics Service, which will consider the risks and benefits of the use of radiation and the information relating to these issues that will be provided to potential participants. The application to the REC includes a study-wide assessment by lead radiation experts, taking into account potential variation between sites. A dose/risk assessment is completed by a Lead Medical Physics Expert ( Lead MPE ), who is a clinical scientist with experience of the modality. A clinical assessment is completed by a Lead Clinical Radiation Expert ( Lead CRE ), who is a radiologist, oncologist, nuclear medicine consultant or other equivalent registered healthcare professional with relevant clinical experience G4.1. Study-wide No study-wide review required G4.2. Local The employer is responsible for reviewing all research involving radiation. It will also be responsible for any additional requirements for compliance with any other relevant legislation such as the Ionising Radiation Regulations The individuals responsible will vary across organisations, and depend on the radiation modalities involved. Confirm that there is an ARSAC Research Certificate for the study. The relevant local practitioner can provide confirmation, which may be provided by rather than by providing a copy of the certificate. The RSS R&D Operational Capability Statement should identify the local practitioners to review and authorise the use of research exposures in the NHS organisation. Version 5.2 Appendix 3-45

140 The RSS planning assessment should have identified any capacity issues that could affect the ability of the relevant staff to apply for an ARSAC Research Certificate during the permission process G4.3. Resources: Notes for Guidance on the Clinical Administration of Radiopharmaceuticals and Use of Sealed Radioactive Sources - March The Ionising Radiation (Medical Exposure) Regulations 2000 (together with notes on good practice) nce/dh_ The Ionising Radiation (Medical Exposure)(Amendment) Regulations 2006, SI 2006/ The Medicines (Administration of Radioactive Substances) Regulations 1978, SI 1978/1006) London: HMSO (not available online) The Medicines (Administration of Radioactive Substances) Amendment Regulations 2006, SI 2006/ NRES guidance on approval for research involving ionising radiation Version 5.2 Appendix 3-46

141 G5. Other regulatory approvals and authorisations received Application to the National Information Governance Board Application to the National Information Governance Board Ethics and Confidentiality Committee (NIGB ECC) is required to access: Identifiable patient information relating to people living in, or receiving healthcare in, England and Wales without explicit consent, prior to the disclosure of confidential information or Central Register (formerly NHSCR) information (either with or without consent), or Hospital Episode Statistics/Secondary Uses Service (HES/SUS) for either identifiable or sensitive data (either with or without consent). Section 251 support from the NIGB ECC allows the NHS organisation to set aside the common law duty of confidentiality in favour of public interest. Applications for access to Hospital Episode Statistics/Secondary Uses Service (HES/SUS) data should also be sent to the NHS Information Centre. Applications for Central Register data should be submitted to the NHS Information Centre. Application to the Ministry of Justice Projects are subject to the Research Quality Assurance (RQA) process within the Ministry of Justice if taking place within the National Offender Management Service (HM Prison Service and HM Probation Service), HM Courts Service or any other agency within the responsibility of the Ministry of Justice for England and Wales and meeting any of the following criteria: National in scope Intended to be published Results to be sent to Ministers; or A study of outcomes of policy or operational changes. Application to the National Offender Management Service Research in prisons or probation services in England and Wales will require approval from the National Offender Management Service (NOMS). Research funded by the US Department of Health and Human Services (DHHS). Research funded by the US Department of Health and Human Services (DHHS) must be reviewed by a Research Ethics Committee within the National Research Ethics Service registered with the US Office for Human Research Protections (OHRP) as an Institutional Review Board (IRB)/Independent Ethics Committee (IEC). Each NHS organisation participating in the study must have Federal Wide Assurance (FWA) in place with the OHRP. Version 5.2 Appendix 3-47

142 G5.1. Study-wide Confirm that any regulatory approvals and authorisations are in place and any conditions imposed are met G5.2. Local No review required G5.3. Resources: IRAS guidance on applications to review bodies National Health Service Act 2006, s251 Research funded by the US Department of Health and Human Services (DHHS) Offender Health Research Network Toolkit National Information Governance Board for Health and Social Care - Section Version 5.2 Appendix 3-48

143 Section 2 - Review criteria for Participant Identification Centres Study-wide Review NIHR CSP Operating Manual The Lead CLRN will perform the following study-wide governance review for a PIC. It should be noted that the review is limited to the criteria set out below and do not extend to the elements that apply to research sites. A1 IRAS Project filter completed correctly Considering the study as a whole, have the project filter questions been completed correctly in IRAS? B1 Participant information and consent documents and process Consider the accuracy of the information describing which organisation is responsible for providing care to the participant. Consider the accuracy of the information relating to insurance/indemnity and compensation (in particular, where the research sites are outside the NHS, it is clear that the NHS is not responsible for the research activity). Confirm that any leaflet, poster, or letter inviting potential participants does not give patients the impression that a referral is being made for the purposes of their treatment by the PIC or that the research is done by or on behalf of the PIC or by people acting in a capacity relating to the PIC. F1 Data Protection Act and data security issues assessed Identify who will have access to personal identifiable information in the course of identifying potential participants Where personal identifiable information will be anonymised or pseudonymised during the course of identifying potential participants, assess whether the arrangements are clearly described. Assess the security of any arrangements for transferring personal identifiable information on computers or through other electronic means from the PIC to the research site. Assess how potential participants will be identified and how the details will be provided to the research team. Assess whether the information for participants accurately describes the handling of personal identifiable information and associated access permissions. F6 Compliance with any other applicable laws and regulations For studies requiring support under section 251 of the NHS Act 2006, ensure that the requirements relating to security and processing of data are clearly described. G1 Research Ethics Committee favourable opinion received Confirm that the study has a favourable opinion from a relevant Research Ethics Committee. Confirm that the relevant documents for R&D review of a PIC (protocol and participant information sheet) are the same version as that listed in the REC Favourable Opinion letter. G2 CTIMPs Clinical Trial Authorisation (CTA) received Confirm that the study has a Clinical Trial Authorisation. G3 Devices MHRA notice of no objection received Confirm that the study has a Notice of No Objection. Version 5.2 Appendix 3-49

144 G5 Other regulatory approvals and authorisations received Where applicable, confirm that the study has been granted Section 251 exemption under the NHS Act 2006 by the National Information Governance Board for Health and Social Care Local Review The CLRN will perform the following local governance review for a PIC. It should be noted that the review is limited to the criteria set out below and do not extend to the elements that apply to research sites. B1 Participant information and consent documents and process Where it is planned to include participants who may not adequately understand verbal explanations or information written in English, assess the practical arrangements to be made at a site for the provision of information to participants in a format that meets their needs. D5 Implications for departments assessed Assess the additional workload required to identify and contact potential participants. Consider whether the NHS organisation would be willing to act as a PIC within the financial arrangements described. F1 Data Protection Act and data security issues assessed Where relevant, assess whether the individuals who will have access to personal identifiable information, for which the NHS organisation is responsible, are in accordance with the organisation s policies. Ensure arrangements are in place for secure access to, and processing of, personal identifiable information in accordance with the organisation s policies. Ensure that the arrangements for anonymisation or pseudonymisation of personal identifiable information can be undertaken locally, if relevant. Assess whether the arrangements for transfer of personal identifiable information to other organisations are in accordance with the organisation s policies. F4 Principal Investigator (PI)/research team Human Resources arrangements in place For employees of the NHS organisation (including those with honorary clinical contracts) or employees of independent contractors providing services to the NHS: The employer is responsible for ensuring that staff only undertake activities that are appropriate to the job and competencies of the individual, and that appropriate supervision is in place. Ensure that internal authorisation from the relevant department/directorate/practice is obtained in accordance with the organisation s standard procedures. For other individuals not employed by the organisation (including students): Following the guidance in the Research in the NHS Human Resources (HR) Good Practice Resource Pack, undertake the following for all individuals performing research activities in or through the research site: Review the pre-engagement checks required for each individual, taking account of the activities to be undertaken. Where required, review the pre-engagement checks assured by the employer or place of Version 5.2 Appendix 3-50

145 study, using the Research Passport or relying on NHS-to-NHS assurances. Put in place arrangements for issuing Honorary Research Contracts, Letters of Access or other agreements/contracts or verify that an appropriate organisational level agreement is in place (eg students on an educational placement) Put in place arrangements for day-to-day management and supervision, as appropriate. For GPs, dentists, opticians and pharmacists who are independent contractors: It is the responsibility of the individual and the practice to ensure that the research activities are appropriately managed and supervised. Version 5.2 Appendix 3-51

146 APPENDIX 4. COMMON EXAMPLES OF CRITERIA FOR STUDY OR SITE STATUS OF SUSPEND Studywide/Local Required by Action Issue Category Description Study-wide Sponsor/CI Sponsor/CI issue CI Replacement Study-wide Sponsor/CI Amendments Amendment required (substantial or minor) Study-wide Sponsor/CI Insurance/Indemnity Insurance/Indemnity Certificates outstanding Study-wide Sponsor/CI Sponsor/CI issue CI unable to progress study temporarily Study-wide Sponsor/CI Adoption Adoption appeal by sponsor/ci Study-wide Sponsor/CI Sponsor/CI action pending Study-wide Sponsor/CI Final contract pending Awaiting information or clarification, awaiting Research Passport application, awaiting training or appointment of key staff Contract negotiation completed but revised or signed contract awaited Study-wide MHRA MHRA approval MHRA approval pending Study-wide HTA HTA Licensing HTA Licensing Pending Study-wide NIGB NIGB ECC approval NIGB ECC approval pending Study-wide REC REC favourable opinion REC favourable opinion pending Study-wide DH Adoption Adoption decision dependent on information from DH Study-wide Funder Funding pending Confirmation of funding or additional funding pending Local ARSAC ARSAC Licensing ARSAC Licensing Pending Local PI/local team PI/local team action pending Local PI/local team PI/local team action pending PI unable to progress study temporarily Awaiting information or clarification, awaiting Research Passport application, awaiting training or appointment of key staff Version 5.2 Appendix 4-1

147 APPENDIX 5. REASONS FOR DELAY IN COMPLETION OF REVIEW The following circumstances may not be assigned the status Suspend. Studywide/Local Action Issue Category Description Required by Study-wide Portfolio Adoption Pending Portfolio adoption process not completed Study-wide NHS Costing Costing agreement pending Study-wide NHS Treatment Costs Confirmation of funding of (Excess) Treatment Costs Local NHS Internal NHS organisation Local Lead CLRN Study-wide review pending Local NHS Internal NHS organisation Awaiting action or response from internal department, eg radiation (including IRMER review), pharmacy, data protection Cannot issue permission until studywide review completed Staffing or resource restrictions affecting any part of review Version 5.2 Appendix 5-1

148 APPENDIX 6. DEVOLVED ADMINISTRATION CONTACTS Scotland - NHS Research Scotland Permissions Coordinating Centre (NRS Permissions CC) Generic address nhsg.nrspcc@nhs.net Wales - National Institute for Social Care and Health Research (NISCHR) Permissions Coordinating Unit (PCU) Generic address Christopher Cotterill-Jones NISCHR PCU Manager Ann Parry NISCHR PCU Facilitator NISCHR.PCU.Allwales@wales.nhs.uk Christopher.Cotterill-Jones@wales.nhs.uk Northern Ireland Secondary Care - Initial Point of Contact For studies led from England Sally Doherty R&D Manager, Western Health & Social Care Trust Research.office@westhealth.n-i.nhs.uk For studies led from Northern Ireland Alison Murphy R&D Manager, Belfast Health & Social Care Trust Alison.Murphy@belfasttrust.hscni.net Irene Knox R&D Manager, Southern Health & Social Care Trust Paul Carlin R&D Manager, South Eastern Health & Social Care Trust Margaret Smyth R&D Manager, Northern Health & Social Care Trust Sally Doherty R&D Manager, Western Health & Social Care Trust Irene.Knox@southerntrust.hscni.net Paul.Carlin@setrust.hscni.net Margaret.Smyth@northerntrust.hscni.net Sally.Doherty@westerntrust.hscni.net Version 5.2 Appendix 6-1

149 APPENDIX 7. AMENDMENT SUMMARY FORM Version 5.2 Appendix 7-1