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 CRN Website for the latest version. Version: 6.0 Status: Consultation in Use Effective: November 2014

2 NIHR CSP Operating Manual Table of Contents 1 Introduction Purpose Updates to the NIHR CSP Operating Manual Additional Documentation General Requirements Overview of NIHR CSP Eligibility Roles Standard Correspondence CSP Module NIHR CSP Study Wide Process Study Wide Application Study-wide Review Eligibility Decision Suspending Studies in NIHR CSP Principles of Suspension Suspend Status Criteria for Submitting a Suspend Status Assessing a Suspend Review Suspension of Studies Unsuspending a Review Delays to the Review Use of Single SSI Forms Overview Process Criteria for Secondary Care Musketeer s Memorandum Criteria for Subsidiary or Continuing Care sites Criteria for Primary Care NIHR CSP Local Process Submission of the SSI Applications for a Research Site Local Review Granting NHS Permission for Research NHS Assurance Primary Care Version 6.0

3 NIHR CSP Operating Manual 6.5 PIC Approval Amendments To NIHR CSP Studies Overview of Amendments Impact of Amendments on NHS Organisations Amendment Categories Amendments Process Abandoning Studies in NIHR CSP Not Eligible for the NIHR Clinical Research Network (CRN) Portfolio Chief Investigator Does Not Proceed with the Study Abandoning Studies or Sites During a Review Key Features of NIHR CSP Study Wide Application Flow diagram of Single SSI process Local Application Study Amendments Handling of Revised R&D Submissions CSP Module Document Repository Management Responsibility for Uploading Documents File Format Standard Correspondence Portfolio Application Form Correspondence R&D Submission Correspondence Site Specific Information (SSI) Submission Correspondence CSP Review Correspondence Suspending Studies Correspondence Single SSI process correspondence Study Amendments Correspondence Abandoning Studies Correspondence Correspondence for Studies Involving Devolved Administrations Correspondence Relating to Handling of Revised R&D Forms Performance Management CSP Metrics Calculation Validation Targets CSP Process Improvement Targets Legal Responsibilities Version 6.0

4 NIHR CSP Operating Manual Appendix 1 Appendix 2 Appendix 3 Appendix 4 Devolved Administration Contacts Study Wide Criteria by Study Type Study Wide Review Criteria UK Study-wide governance report Appendix 5 Costs and Contracts Review Procedure Section 1 CSP integrated costs and contract review process flow chart Section 2 CSP integrated costs and contract review process flow chart step instructions Section 3 CSP integrated protocol amendment costs and contract review process flow chart 166 Section 4 CSP integrated protocol amendment costs and contract review process flow chart step instructions Section 5 CSP integrated cost and contract review process: study-wide cost completion checklist Section 6 CSP integrated cost and contract review process: study-wide contract modification checklist Section 7 CSP integrated cost and contract review process: review delegation process Appendix 6 Appendix 7 Appendix 8 Appendix 9 Appendix 10 Appendix 11 Appendix 12 Common Examples of Criteria for Study Status of Suspend Reasons for Delay in Completion of Review Guide to Authorisations Required for a Single SSI Form Single SSI Form Summary Review Local Criteria by Study Type Local and PIC Review Criteria Amendment Categorisation Examples of the how amendments are categorised into the three different categories Glossary Document Control Version 6.0

5 NIHR CSP Operating Manual Introduction 1 INTRODUCTION The National Institute for Health Research Coordinated System for gaining NHS permission (NIHR CSP) is a process for gaining: Permission for NHS organisations to perform clinical research studies in England Approval for NHS organisations to act as participant identification centres (PICs) for clinical research studies in England Permission to continue research after an amendment is made to a study which has been processed through NIHR CSP NIHR CSP standardises and streamlines R&D approval for commercial and noncommercial studies. NIHR CSP has been in operation since November It is funded by the Department of Health via the NIHR Clinical Research Networks (NIHR CRN). It operates as a partnership between: The NIHR CRN Coordinating Centre The Local Clinical Research Networks The NHS Partner Organisations NIHR CSP is supported by other linked systems within the NIHR CRN National Coordinating Centre (NIHR CRN CC) such as Portfolio eligibility. The CSP Module is the supporting IT system which manages the NIHR CSP process. NIHR CSP has arrangements to coordinate with the NHS permission systems in the Devolved Administrations. This includes Northern Ireland, Scotland and Wales, and will fulfil a commitment to UK wide working. 1.1 PURPOSE This is the Operating Manual for NIHR CSP. Its purpose is to define: The standard business process for gaining NHS permission for research supported by the NIHR How the NIHR CSP process is managed in CSP Module The role of the various participants within NIHR CSP including the investigators, Portfolio Application Team (PAT), CSP Unit (CSPU) and Local Clinical Research Networks (LCRNs) The reviews for the different study types received Version 6.0 5

6 NIHR CSP Operating Manual Introduction 1.2 UPDATES TO THE NIHR CSP OPERATING MANUAL The NIHR CSP Operating Manual will undergo a periodic review. It will be updated to reflect changes in the NIHR CSP process. The main changes will be recorded, please refer to Document Control on page 232. To provide feedback on the manual, please contact the CSP Helpdesk crncc.csp@nihr.ac.uk. 1.3 ADDITIONAL DOCUMENTATION The NIHR CSP Operating Manual defines the usual business processes for NIHR CSP. This manual sits within the study set up part of the Research Delivery Pathway 1. This manual does not cover any additional processes which are issued separately by the NIHR. This includes expedited research for use in a pandemic which will result in alternative processes being followed. This manual does not describe how to use CSP Module. Please refer to the CSP Module User Manual for guidance 2. This manual does not describe how to use IRAS. Please refer to the IRAS E-Learning Module for guidance 3. This manual does not detail the full eligibility review process for commercial or noncommercial studies applying for CRN support and inclusion in the NIHR CRN Portfolio GENERAL REQUIREMENTS CSP Module users should have access to The Proportionate and Pragmatic CSP e-learning training modules. Users should also have access to any local training and support workshops, if provided by the LCRN Training on the CSP Module. This is provided by the LCRN on a one to one or group basis 1 Programme/lcrnguidancesuite/researchdelivery/Research%20Delivery/LCRN%20Guidance%20S6%20- %20Research%20Delivery%20v1.1.pdf Further information on this and access to the NIHR Clinical Research Network: Eligibility and adoption process for non-commercial studies Standard Operating Procedure v1.8 8 January 2014 can be obtained from the Portfolio Application Team portfolio.applications@nihr.ac.uk. Version 6.0 6

7 NIHR CSP Operating Manual Introduction CSP Module users should be competent to deliver NIHR CSP and use the CSP Module as their individual role requires Version 6.0 7

8 NIHR CSP Operating Manual Overview of NIHR CSP 2 OVERVIEW OF NIHR CSP NIHR CSP helps investigators by providing: An efficient process for gaining NHS permission, assurance or PIC approval. The process is available to studies that are: o NIHR Infrastructure supported o Eligible for the NIHR CRN Portfolio o Potentially eligible for the NIHR CRN Portfolio Support and advice from the LCRNs Access to NHS service support for non-commercial studies. This is provided through the eligibility process for the NIHR CRN Portfolio Access to CRN support for commercial studies. This is provided through the eligibility process for the NIHR CRN Portfolio A single point of entry is provided via the Integrated Research Application System (IRAS) for English led studies Note: The CSP Unit (CSPU) and LCRNs cannot give NHS permission or PIC approval. Their role is to facilitate and support the process in a coordinated way. 2.1 ELIGIBILITY The following studies can use NIHR CSP: Studies that are eligible for consideration for CRN support and inclusion in the NIHR CRN Portfolio. Refer to the portfolio website 5 for details. Studies applying for the NIHR CRN portfolio can use NIHR CSP whilst an eligibility decision is made. If they are deemed not eligible they cannot continue to use NIHR CSP. There will be a ten day appeal window before this is confirmed within NIHR CSP. Note: The NIHR CRN non-commercial eligibility and adoption process and the commercial eligibility and feasibility process are separate parallel processes which must be completed prior to the completion of NIHR CSP with NHS permission. Studies that are supported through NIHR Infrastructure funding and not through NIHR CRN support. Refer to the NIHR website for details on the types of awards this covers & Version 6.0 8

9 NIHR CSP Operating Manual Overview of NIHR CSP 2.2 ROLES There are several roles which play a part in the NIHR CSP process Investigator Role in NIHR CSP Chief Investigator/ Sponsor The sponsor and Chief Investigator are responsible for the overall management of the study. This may include deferring some responsibilities to a study coordinator. The Chief Investigator applies for the study wide review and eligibility (portfolio) assessment for their study. This involves: Submitting the Portfolio Application Form (PAF) Submitting the NHS R&D Application Form with supporting documents identified in the IRAS R&D Application Form Checklist Selecting the Lead LCRN (England led studies) or confirming they wish to use NIHR CSP (Devolved Administration led studies) The Chief Investigator will work with RM&G staff in the Lead LCRN for study set up and delivery support. This includes resolving any issues with the PAF and R&D application forms. The Chief Investigator is also responsible for submitting amendments to NIHR CSP studies. Amendments are submitted via IRAS. Amendment documentation is attached to the IRAS R&D Form Checklist and resubmitted from the R&D esubmission tab. Note: Previous documentation should be removed from the IRAS checklist by the Chief Investigator when submitting a further amendment as any attached documents will be resubmitted and form part of the subsequent amendment submission. Principal Investigator Principal Investigators are responsible for the management of the study at NHS organisations. They apply for NHS permission for a study at a specific NHS organisation. This involves: Submitting the SSI Application Forms with supporting documents identified in the IRAS SSI Application Form Checklist Principal Investigators will work with RM&G staff in the participating LCRN for study set up and delivery support. This includes resolving any issues with the SSI application forms. Version 6.0 9

10 NIHR CSP Operating Manual Overview of NIHR CSP Relationship between the RM&G Team and Investigators Research management and governance (RM&G) staff are available within the CRN to help investigators obtain NHS permission for their studies. The role of each RM&G team is to: Advise and assist investigators on the applications and approvals required for their studies Help investigators obtain authorisations within NHS organisations that feed into the NHS permission process Undertake reviews required for the studies and: o Work with the investigators and NHS organisations to resolve any difficulties o Provide evidence of the outcome of the review o Work with NHS organisations to issue NHS permission NHS Organisation Roles in NIHR CSP Each NHS organisation is a separate legal entity. NHS permission or PIC approval must be granted at every NHS organisation involved. NHS organisations participating in a study are either research sites or a participant identification centres (PICs). A research site: Receives the local and study wide governance reports and decides if NHS permission to perform research is granted at the site Receives details of amendments to studies which have already been granted NHS permission and decides if permission continues A PIC: Receives the local and study wide governance reports and decides if PIC approval is granted to support the participant identification process for a study The NHS permission signatory for the NHS organisation is responsible for signing NHS permission letters, PIC approval letters, Notification of Continued NHS Permission letters (research site), agreements and contracts. All NHS partner organisations in England work within their LCRNs to provide research infrastructure to support NIHR CRN Portfolio studies. Version

11 NIHR CSP Operating Manual Overview of NIHR CSP Relationship between the RM&G Team and NHS Organisations RM&G staff work with Principal Investigators and all departments in an NHS organisation. This helps to facilitate the timely set up and delivery of studies to indicated timelines. This may include working with clinical departments, laboratories, pharmacies, data protection officers, trust finance, NIHR CRN staff, and more. NHS organisations work with RM&G staff to provide clarity regarding: What internal authorisations are required for studies. Note: There are best practice examples available where some NHS organisations do not require signatures or reviews for involvement. They have adopted a risk based approach to providing authorisation through service improvement development. This is consistent with the principles of the Research Support Service (RSS) 7 to ensure proportionate and pragmatic procedures Where service support resources are placed Who in the NHS organisation is the NHS permission signatory. This includes details of any delegation Local Clinical Research Network Roles in NIHR CSP LCRNs facilitate partnerships within their geography to set up and deliver clinical research within the NHS. There are several NHS organisations within one LCRN. LCRNs work closely with their NHS organisations to provide RM&G services to investigators, see NHS Organisation Roles in NIHR CSP on page 10 for details. There are two main roles for LCRNs: Participating LCRN Lead LCRN Participating CRNs Any LCRN with NHS organisations or PICs participating in a study is a Participating CRN. They ensure that all issues relating to a specific study site are addressed. The key tasks undertaken by the RM&G team in the Participating LCRN are: Contacting Principal Investigators and helping with study set up. Principal Investigators are identified from the R&D submission Helping Principal Investigators with the SSI submission where necessary. 7 Version

12 NIHR CSP Operating Manual Overview of NIHR CSP Note: It is the Principal Investigator s responsibility to discuss an application with an R&D representative within the NHS organisation in accordance with Q23 of the SSI form Performing the local review for the study Working proactively with the Principal Investigator and internal departments to resolve any governance, costing or contracting issues. This may be supported by the LCRN Industry Operations Manager for commercial studies Working with the Lead CRN to resolve any issues not relevant to a specific site. The CSPU can be used for support and escalation. This ensures that the Chief Investigator has to deal only with one main contact point They may undertake quality control reviews after the local review is complete. This should take into account the complexity of the study and the experience of the local reviewer Uploading issued NHS permission letters to the CSP Module. This marks the end of the NHS permissions process at this research site, unless an amendment is submitted Ensuring participating NHS organisations are aware of any amendments Ensuring any sites that have withdrawn permission are recorded using the Objection Review task if NHS Permission has been previously granted In rare cases, ensuring the sponsor is informed about any sites that are not able to implement an optional amendment but are able to continue in the study Lead LCRN The Lead LCRN is identified by the Chief Investigator/ sponsor in the IRAS submission pages. It is usually the LCRN covering the geographic area where the Chief Investigator is employed and the Lead NHS R&D Office is based. Note: Some LCRNs will lead on more studies than others. This is due to the research portfolios of the academic and clinical organisations within their area. If a LCRN has reached capacity, it is possible to appoint a Lead LCRN in a different geographic area to the Chief Investigator. Note: Discussions can be enhanced by the submission of a draft R&D form from IRAS. This may occur without any previous contact between the Lead LCRN and the Chief Investigator. A draft R&D form will contain the contact details for the Chief Investigator. The Lead LCRN can use this to establish contact and offer support. This would form part of the pre-application study support service. A staff member of the Lead LCRN RM&G team is nominated as the key point of contact for the study. For commercial studies this may be an LCRN Industry Operations Manager. This contact works with the Chief Investigator. The key tasks undertaken by the Lead LCRN within NIHR CSP are: Contacting Chief Investigators and helping with study set up. This may include liaising with Principle Investigators and CSPU Version

13 NIHR CSP Operating Manual Overview of NIHR CSP Helping Chief Investigators with the R&D submission where necessary Undertaking the study-wide review Undertaking the cost and contract review procedure for a commercial study Working proactively with the Chief Investigator to resolve any identified issues that are not relevant to a specific site Assessing whether a revised R&D submission is required Validating a revised R&D submission if a previous submission was deemed valid Communicating with the Portfolio Application Team (PAT) where issues with the application are identified Undertaking quality control reviews after all the study-wide reviews are complete. This ensures that local reviewers have confidence in the study-wide review Support for the progress of the study through NIHR CSP Discussing issues related to an R&D submission from a Devolved Administration with the relevant permissions centre or unit. This may include liaising with CSPU Validate and classify any amendments as notifiable to participating sites, or nonnotifiable Reviewing all study-wide amendment documentation that has been submitted via IRAS and assessing the impact of the amendment Entering amendment details in the Amendment Classification task window The Lead LCRN can call on the support of CSPU for assistance with queries relating to other Participating LCRNs or process clarifications and as an escalation route if necessary NIHR CRN National Coordinating Centre Roles in NIHR CSP Staff in the NIHR CRN CC play a key role in the management of studies in the NIHR CSP process. CSP Management Group The CSP Management Group is responsible for: The management oversight of NIHR CSP and associated processes Ensuring NIHR CSP delivers benefits for investigators and NHS organisations The development and improvement of business processes The CSP Management Group also assesses requests to use a single SSI application form for research sites or a sub group of research sites on a study. Participating LCRNs are notified of their involvement by . Version

14 NIHR CSP Operating Manual Overview of NIHR CSP Portfolio Application Team (PAT) The PAT is responsible for: Accepting studies into NIHR CSP Note: exceptions to this would be NIHR Infrastructure supported and Devolved Administration studies which do not receive a PAF. Assessing whether or not studies are eligible for CRN support and inclusion in the NIHR CRN Portfolio The PAT provides the link between NIHR CSP and the NIHR CRN Portfolio Team and NIHR CRN Industry team. It coordinates the process for reviewing the eligibility of studies to receive CRN support and be included in the NIHR CRN Portfolio. These teams will liaise with the Chief Investigator or study coordinator regarding the eligibility decision process. These teams work closely together and with the CSP Unit within the NIHR CRN CC Research Delivery Directorate. CSP Unit (CSPU) The CSPU has an overview of a study across all sites. It provides a central information hub for sharing study information across all NHS sites and the NIHR CRN. The CSPU provides support to LCRN-funded RM&G staff working on the study. The main functions of CSPU are: Validating the first final R&D submission. A RM&G Coordinator will perform the validation. They will liaise with the Chief Investigator or study coordinator during this part of the process. The name of the RM&G Coordinator will be recorded in the study record Providing support to the Lead LCRN for communications and queries relating to Participating CRNs if required Providing an oversight of the NIHR CSP process from a national perspective Confirming study wide suspension requests Acting as an escalation route when necessary Identify and confirm Lead LCRN for studies led by a Devolved Administration Discussing issues related to a R&D submission from a Devolved Administration with the Lead LCRN. The CSPU will raise issues with the lead Devolved Administration if required CSP Helpdesk The CSP Helpdesk: Version

15 NIHR CSP Operating Manual Overview of NIHR CSP Provides advice on the purpose and use of NIHR CSP Identifies areas for improvement in NIHR CSP. These are discussed within the CSP Management Group Collates suggestions and feedback for the development of CSP processes and supporting documentation Receives complaints about NIHR CSP Note: Correspondence and progress reports about a particular study are not handled by the CSP Helpdesk. These should be sent directly to the CSP Unit. 2.3 STANDARD CORRESPONDENCE The NIHR CSP process involves communication via . Some of this correspondence is automatically generated within the CSP Module. Some will be created by the user. There are defined communication points for the NIHR CSP Process. Communication to Chief Investigators, Study Coordinators and Principal Investigators must be correct and consistent. Standardised correspondence ensures this requirement is met. These s must be uploaded to the document repository in a.pdf format. See 11 Standard Correspondence on page 64 for details about standard s. 2.4 CSP MODULE NIHR CSP is supported by bespoke CSP Module software. The software: Integrates the work of PAT, CSPU, Lead LCRN and Participating LCRNs by providing access to study data and the ability to edit study records as criteria are completed 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 through the CSP Reporting Module A separate user manual providing detailed information regarding the use of CSP Module is available Version

16 NIHR CSP Operating Manual NIHR CSP Study Wide Process 3 NIHR CSP STUDY WIDE PROCESS Study wide applications for NIHR CSP are applied for via IRAS as an e-submission to the CSP Module in England led studies. The Chief Investigator/ sponsor will select the Lead CRN when submitting the PAF and R&D applications. This will be a manual submission where the study is led by a Devolved Administration. The Chief Investigator/ sponsor will confirm that they wish the study to use NIHR CSP and the CSPU will allocate a Lead CRN. IRAS holds the standard dataset to apply for a range of regulatory approvals including Ethics and NHS permission. Investigators can generate application forms from the completed IRAS dataset. The questions in the IRAS Project Filter are used to route to the relevant forms and submission process to apply for NHS permission through NIHR CSP 9. Note: The investigator must answer the appropriate questions in the IRAS Project Filter to generate an application form for NIHR CSP. Question 3a allows the investigator to indicate that the lead research site is in England. Question 5a and 5b allow the investigator to indicate if they want to use NIHR CSP. Note: Industry investigators using NIHR CSP are expected to use unmodified model agreements. These can be found on the NIHR website 10. Delays may occur for legal reviews if an alternative agreement is used. Please refer to Appendix 5 Costs and Contracts Review Procedure on page STUDY WIDE APPLICATION There are two study wide submissions. 1. Portfolio Application Form (PAF) 2. NHS R&D Application Form with supporting documents Note: A Portfolio Application Form will not be generated if the study is funded entirely by an NIHR Infrastructure award. These studies have access to NHS infrastructure for research such as service support costs through this funding. Note: A Portfolio Application Form will not be generated if the study is led by a Devolved Administration See suite of model agreements on the NIHR website Version

17 NIHR CSP Operating Manual NIHR CSP Study Wide Process Submission of the Portfolio Application Form Note: A PAF can be submitted whilst an application for funding is in progress. Following receipt of an R&D submission, a final decision cannot be made without secured funding for the full research costs of the study. The target for validating the PAF and assessing whether the application is potentially eligible for CRN support and inclusion in the NIHR CRN Portfolio is two working days. The Lead LCRN is alerted when a PAF of a potential study in their area has been validated and the study is deemed potentially eligible. Note: If the study is commercially sponsored, the company or Contract Research Organisation (CRO) is encouraged to contact the NIHR CRN Industry Team before submission of the PAF to discuss eligibility for the NIHR CRN Portfolio through the Industry Application Gateway (IAG) 11. Note: If the study is led by a Devolved Administration, there will be no PAF and the eligibility process will start on the receipt of the R&D submission Validation and Potential Eligibility Review Process for the Portfolio Application Form The PAF is validated and reviewed by the Portfolio Application Team (PAT) to decide if the study is potentially eligible for NIHR for CRN support and inclusion on the CRN Portfolio. The validation and review ensures the PAF 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 The PAF is assessed as being either: Invalid. Details of issues/ omissions will be supplied Study is potentially eligible for inclusion on the NIHR CRN Portfolio Study is ineligible for inclusion on the NIHR CRN Portfolio confirmation is sent by PAT. See 11.1 Portfolio Application Form Correspondence on page Version

18 NIHR CSP Operating Manual NIHR CSP Study Wide Process Submission of the NHS R&D Application The second stage of the study-wide application process is the submission of the NHS R&D application. An R&D application e-submission cannot be made until the PAF is validated. Note: If the study is led by a Devolved Administration, the R&D application is validated and reviewed by the Devolved Administration. The application then is sent to CSPU to manually input it into NIHR CSP. CSPU will liaise with the Chief Investigator regarding the use of NIHR CSP. Please refer to Appendix 1 Devolved Administration Contacts on page 102 for details. The Chief Investigator can discuss the R&D submission with the Lead LCRN. This is part of the pre-application support offered within the study support service 12. This discussion will ensure all information is included before it is submitted. A draft R&D form can be submitted to facilitate discussion before the final submission. R&D Applications can be submitted before regulatory approvals have been received. The application can be assessed, but the study wide review cannot be completed until all necessary regulatory approvals have been received. For commercial studies, the optimum time to start the application process is when the regulatory packages are prepared and ready for submission. The optimum time to start the R&D application process for a non-commercial study.is after a grant has been awarded An R&D application cannot be validated until funding has been secured and evidence of the source has been provided. This must be at least one of the funding elements in the case of multiple funders. A final decision on an application cannot be made until sufficient funding has been secured to cover the full research costs of the study. The R&D submission should include the supporting documents detailed in the IRAS R&D Form checklist except those not included in the agreed UK wide Checklist (see paragraphs below). Any supporting documents which are not available when submitting the form must be submitted to the Lead LCRN when they are available. This must be limited to those not required in the original submission for example, regulatory approvals. There is an agreed UK wide checklist which differs slightly from that provided within the IRAS R&D form Checklist generated for NIHR CSP applications. The R&D validator will not request any documents not contained within the UK wide Checklist to ensure alignment Programme/lcrnguidancesuite/researchdelivery/Research%20Delivery/LCRN%20Guidance%20S6%20- %20Research%20Delivery%20v1.1.pdf Version

19 NIHR CSP Operating Manual NIHR CSP Study Wide Process CSP UK wide Principle (for removal R, for addition A) Interview Schedules or topic guides for participants Validated Questionnaire Summary CV for CI R covered in the Sample diary card/ patient card and protocol R no governance issues R assessed as PI at site Pharmacy Manual Laboratory Manual A to highlight this is required prior to site initiation visit to prevent delays A to highlight this is required prior to site initiation visit to prevent delays Checklist items moved Item CSP UK wide Instructions for use of medical device Project Information Documents required prior to site initiation visit Note: Supporting documents not received through the IRAS Interface can be manually uploaded to the CSP Module document repository Validation Process for the First Final R&D Submission The target for validating the R&D application, to ensure it is complete and that funding for the study is secured, is three working days. The CSPU validates the first final R&D submission for a study. This will include all R&D submissions which have been resubmitted after an initial submission has been assessed as invalid. Revised R&D submissions requested during the study wide review are validated by the Lead LCRN. The validation will ensure that: 1. The application is written in English, comprehensible and contains sufficient information. 2. All relevant sections of the R&D Form have been completed and contain the relevant electronic authorisations. The IRAS R&D Form Checklist contains details on the documents submitted with the R&D submission. The checklist should have a list of version numbers of the submitted documents. The list will be cross checked with the documents to confirm that the version numbers and names are consistent. Version

20 NIHR CSP Operating Manual NIHR CSP Study Wide Process 3. The IRAS R&D Form Checklist contains valid reasons any document are not included with the R&D submission if necessary. A query should be raised if a reason has not been provided. Note: Some documents, such as approvals from regulatory bodies, may not be available when the R&D Form is submitted. These documents 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. 4. An R&D Submission with minor issues can be queried and left pending a response from the Chief Investigator or Sponsor. An stating the required action will be sent. See CSPU Notification that the R&D Submission requires further documents/clarification on page 72. The validation task is marked pending response until the issue is resolved. A R&D submission pending response will be invalidated after 14 calendar days if the issue is not rectified. 5. A full description of the first final R&D validation process can be found in the document Validation of First Final R&D Submission v The RM&G Coordinator will confirm if the submission is valid or invalid. A confirmation will be sent to the Chief Investigator, sponsor s representative, and Study Coordinator. See 11.2 R&D Submission Correspondence on page 69 for details of the standard s.a confirmation message will be sent from the CSP Module to the esubmission tab in the R&D Form page of the IRAS study record within the History section. 7. The RM&G Coordinator will export a valid R&D submission (form in pdf and xml and documents) to any Devolved Administration identified within the Project filter question 3 where the study is led by England Note: Electronic authorisations are invalidated when an invalid R&D Form is rejected in CSP Module and the resubmitted form has been updated. Electronic authorisations must be reapplied to the revised form. A validated R&D form and all associated documents are made available to the Lead LCRN and Participating LCRNs and NHS organisations named on the form through the CSP Module. This: Enables the LCRNs to support the investigator with the R&D application Gives advance warning of the study to the NHS organisations involved prior to the local application. This enables them to support the investigator in the study set up 13 AL.pdf Version

21 NIHR CSP Operating Manual NIHR CSP Study Wide Process Devolved Administration Led Studies Note: The location of the Lead NHS R&D contact determines which country leads the study. If the study is led by a Devolved Administration, the study wide application process requires interaction with the system for gaining NHS permission in that Devolved Administration. Please refer to Appendix 1 Devolved Administration Contacts on page 102 for details. In these cases, the CSPU will allocate a Lead LCRN for the study once agreed with the LCRN concerned. Northern Ireland Primary Care does not have an NHS Permissions coordinating function. If the study is led by a Devolved Administration, the R&D submission is validated by the Devolved Administration. These studies cannot be electronically submitted through IRAS to the CSP Module and documents cannot be attached to the IRAS Checklists. These submissions will be ed in the first instance to the CSPU by the NHS Permission coordinating function of the Devolved Administration for the manual creation of the study record. An will be sent by CSPU to confirm to the CI the Lead LCRN in England who will be coordinating with the lead devolved administration. See CSPU Confirmation of Receipt of R&D Submission from a Devolved Administration and Lead LCRN for England on page 96. Subsequent documentation and the governance report will be supplied by the devolved administration directly to the Lead LCRN. Note: If the study is set up originally as a single site study in Scotland and then additional sites are added in England, NRS PCC will forward the study wide documentation. The study will then become English led for the purposes of CSP. 3.2 STUDY-WIDE REVIEW A validated R&D application undergoes a study-wide review. The Lead LCRN undertakes the study wide review based on information provided within the R&D submission. This is viewable by all Participating LCRNs in the CSP Module. Note: When performing a study-wide review, it is important to read through the R&D Application Form and associated documents, especially the Participant Information Sheet. This will give a sense of the study as a whole and help to highlight any potential issues early in the process. Version

22 NIHR CSP Operating Manual NIHR CSP Study Wide Process Study-wide Review Criteria Study-wide reviews are based on criteria which apply to studies as a whole. The criteria are used to: Support the R&D application review undertaken on behalf of all NHS organisations participating in the study 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) The set of criteria undertaken for each study is determined by the study type (e.g. Clinical Trial of an Investigational Medicinal Product). Reviewers are expected to review only the criteria that apply to the research study they are reviewing. See Appendix 2 Study Wide Criteria by Study Type on page 103 for details. Guidelines are provided for the criteria to: Ensure a standard and consistency of lead review across the NHS in the UK Allow for judgement to be used to manage specific situations Identify the information and communication required to support the review Each criterion has a category and a unique number. The category is represented by a letter. The study matrix in Appendix 2 Study Wide Criteria by Study Type on page 103 shows which criteria are relevant to the different study types. Each criterion describes: Introduction: introduces the criterion to be considered Study-wide considerations: identifies the areas of the criterion the lead reviewer should consider when conducting the review Notes/ Resources: the notes provide further information about the criterion under consideration that may assist the reviewer in completing the review. The resources provide further sources of information that the reviewer may wish to refer to in conducting the review, e.g. reference material, web addresses. 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 review. The outcome of the review of each criterion should be described. Additional information to support the assessment should be recorded. Version

23 NIHR CSP Operating Manual NIHR CSP Study Wide Process Note: Comments entered for study-wide criteria provide assurance to the RM&G staff working on the local review. Extra care should be taken to ensure a clear and professional standard of commenting is used. The comments also appear in the Governance Report that is issued to the NHS permission signatory. See Appendix 3 Study Wide Review Criteria on page 107 Study Wide Criteria by Study Type for details of the criteria Study-wide Review Process 1. Use the study matrix to determine the relevant study-wide criteria for the study type in Appendix 2 Study Wide Criteria by Study Type on page 103. This will be automatically generated as a list for IRAS study types in the CSP Module 2. Conduct a rapid initial assessment 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 required to support the study. This will assist NHS research sites and NHS PICs in their local reviews. Identify any issues that are likely to have a major impact on the ability of NHS organisations to issue NHS permission, NHS assurance or PIC approval for the study 3. Discuss any issues or required clarifications with the sponsor or Chief Investigator. Allow them the opportunity to respond to a query prior to placing a study-wide review in suspension. See 4 Suspending Studies in NIHR CSP on page 26 for guidance on suspending a study. 4. A revised R&D submission will be required if a substantive change is required. For example, if an issue is identified in the project filter to ensure there is access to the necessary information 5. The Chief Investigator may request a change which would require a revised R&D form. The reason for the revision must be provided in writing to the Lead LCRN when the revised R&D submission is made 6. If the Chief Investigator submits a revised R&D form without informing the Lead LCRN of the changes, the Lead LCRN will contact the Chief Investigator for clarification. After clarification is received, the information should be circulated to the Participating LCRNs by and then uploaded to the study record. The information should be uploaded as a study wide document with the filename Revised R&D form update [insert date]. If there is no response within 14 calendar days, the submission will be rejected 7. Subsequent documents submitted during the review are to be downloaded and sent to any devolved administrations by the Lead LCRN as soon as possible after receipt 8. Where a study is submitted from industry, ensure that the costings and contracts processes are followed. See Appendix 5 Costs and Contracts Review Procedure on page 156 for details 9. Review and identify issues that only need to be looked at once for the study in a proportionately risk-based manner. This includes risks to patients, staff, or study delivery and potential problems 10. 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 local reviewers 11. Highlight information to support the local review. Provide additional clarity on the study. Provide information for reviewers to work from. Clarify whether any local criteria are not relevant. Describe if there are arrangements that need to be managed locally Version

24 NIHR CSP Operating Manual NIHR CSP Study Wide Process 12. Highlight where different issues or risks may exist for the different types of research site. This includes subsidiary sites, continuing care sites, data collection centres, principal treatment centres etc 13. Highlight where different issues or risks may exist for PICs 14. Highlight any country specific issues that need to be addressed in each participating nation 15. Within the Study-Wide Governance Report there is no requirement to set out the criteria that are satisfied by the information provided in the application. Where information or clarification has been obtained following further questioning of the Sponsor or applicant this must be clearly set out in the Study-Wide Governance Report as it is important that participating organisations do not raise duplicate queries. Record information within the criteria comments boxes in the CSP Module. Comments can be supported by documentation in the document repository if necessary 16. Where a lead reviewer is uncertain of the requirements of the governance criterion being considered, they should seek advice from another member of staff with relevant research governance knowledge 17. If the study has research sites in a Devolved Administration, the Lead LCRN will send the study-wide review in the study-wide governance report to the Devolved Administration. See Appendix 4 UK Study-wide governance report on page 151. Please refer to Appendix 1 Devolved Administration Contacts on page 102 for contact details. Criteria can be marked with the following outcomes from the drop down list: Not Started In Progress Completed Minor Issue (i.e. review completed but a minor issue to note that does not prevent NHS permission insert comment) Completed Proceed (i.e. all OK) Suspend (i.e. review is suspended due to study wide suspension) 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] Devolved Administration Led Studies If the study is led by a Devolved Administration, the study-wide review is performed by the Devolved Administration. They will provide a study wide governance report to the Lead LCRN. The Lead LCRN will review for any aspects of English law where this differs from the legislation within a devolved administration Study-wide Quality Control Study-wide QC is carried out by the Lead LCRN when all criteria have been completed in a study-wide review. Version

25 NIHR CSP Operating Manual NIHR CSP Study Wide Process Study-wide QC gives assurance that: A study-wide review has been performed correctly The comments associated with each criterion comply with the guidance specified in Appendix 3 Study Wide Review Criteria on page 107. If the study-wide review has not been performed correctly, the QC reviewer will indicate in the Perform Governance QC task those criteria that require further review. They should work with the person performing 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 stop the Study-wide CSP Governance Quality Control being confirmed, but will need to be rectified immediately so that other LCRNs are not affected. Information in the criteria comments and the document repository will be printed on the Governance Report Study Wide Governance Report The study-wide governance report will be exported to the necessary Devolved Administrations where the study is led by England. This can be downloaded as an excel document from the CSP Module for export. These must be sent on a per study basis to ensure clarity. The governance report can be used by the NHS organisations to decide whether to grant permission for research or approval to act as a PIC. 3.3 ELIGIBILITY DECISION The process for conducting the eligibility assessment is described elsewhere 14. The study must be eligible for the NIHR CRN Portfolio to complete CSP. If the study is ineligible, it will exit CSP at this point. See 8.3 Abandoning Studies or Sites During a Review on page Further information on this and access to the NIHR Clinical Research Network: Eligibility and adoption process for non-commercial studies Standard Operating Procedure v1.8 8 January 2014 can be obtained from the Portfolio Application Team portfolio.applications@nihr.ac.uk. The NIHR CRN website contains further information on eligibility processes: & Version

26 NIHR CSP Operating Manual Suspending Studies in NIHR CSP 4 SUSPENDING STUDIES IN NIHR CSP A study wide review may be suspended in NIHR CSP. This occurs if no further activity, discussion or negotiation can proceed due to circumstances outside the control of the NHS or Clinical Research Network. 4.1 PRINCIPLES OF SUSPENSION Suspension requests will be rejected if negotiations are on-going, or other activity may still proceed A suspended status should only be granted where delays have occurred due to factors outside of NHS or CRN control A suspended status should not be used to try to control metrics regarding recruiting the first participant 4.2 SUSPEND STATUS If a reviewer wants to suspend the study wide review, they will set the outcome of one of the study wide review criteria to Suspend. 4.3 CRITERIA FOR SUBMITTING A SUSPEND STATUS In order to assign a suspend status; the study must fulfil all of the following criteria: The review is still on-going All other criteria have been completed as far as is possible and no further review can be undertaken. As soon as this stage is reached the study may be suspended Where the request to suspend a study 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. Please specify these requests within the comments or provide in a supporting . Sufficient information about the delay has been recorded in the criteria comments box (not the task comments box) A clear explanation of the reason for the suspension request must be provided in relevant the criteria comment field. This must include any details of information requests made or reference appropriately where delays have been communicated by the sponsor. This can be supported by an additional sent to crncc.cspunit@nihr.ac.uk if this information is held in an chain. See Lead LCRN Request for Suspension on page 86. Version