STANDARD OPERATING PROCEDURE

Transcription

1 STANDARD OPERATING PROCEDURE Title Reference Number Amendments to Active Research Studies SOP-RES-024 Version Number 2 Issue Date 29 th Sep 2016 Effective Date 10 th Nov 2016 Review Date 10 th Nov 2018 Author Reviewer Joanne Thornhill, Research Project manager Team Leader Teresa O Leary, Head of Regulatory Compliance Authorisation (Original signatures are retained by Research & Innovation) Dr Stephen Ryder Director of Research & Innovation Dr Stephen Fowlie Medical Director 01 st Aug nd Sep 2016 USERS OF THIS STANDARD OPERATING PROCEDURE MUST REFER TO TO ENSURE THE MOST CURRENT VERSION IS BEING USED.

2 Page 2 of Document History Version Number Issue Date Reason for Change 1 22 nd April 2014 Original SOP. It replaces SOP 51 and SOP th Sep 2016 Updated to be in line with HRA approval process for amendments

3 Page 3 of Introduction Amendments may be made to the research after it has been approved. There are two types of amendments: substantial and non-substantial, each requiring different processing. The research Sponsor is responsible for determining whether an amendment is substantial or non-substantial. Further guidance can be found on the Health Research Authority (HRA) website or, for clinical trials of investigational medicinal products (CTIMPs) specifically, Directive 2010/C 82/01. This standard operating procedure (SOP) describes the review and notification process of amendments to the protocol, other essential documents or study arrangements applicable to all studies taking place at Nottingham University Hospitals NHS Trust (NUH) where NUH is the host research site or is a participating site. This includes all studies sponsored by NUH, those included on to the NIHR (National Institute for Health Research) Portfolio, those which are not included and those studies which predate the CSP (Co-ordinated system for gaining NHS permission) system 3. Purpose and Scope This SOP applies for all substantial and non-substantial amendments that are classed as notifiable, for protocol, other essential documentation or other aspects of study arrangement. The SOP is aimed at Research and Innovation (R&I) staff, Chief Investigators (CI), Principal Investigators (PIs), research staff and all staff in concerned service departments in the Trust where research studies are hosted. 4. Responsibilities Researcher Sends the Integrated Research Application System (IRAS) Amendment Notification Form to R&I with further documentation as requested where (NUH is sponsor). CI/PI The CI/PI should not implement any deviation from- or changes to- the protocol without agreement by the Sponsor (and where required prior review and documented approval/favourable opinion from the relevant Competent Authority (CA)/Research Ethics Committee (REC)), except in circumstances to eliminate an immediate hazard(s) to study participants (i.e. urgent safety measure), or when the change(s) involve only logistical or

4 Page 4 of 10 administrative aspects of the study, e.g. change in monitor(s), change of telephone number(s). R&I Administrator Responsible for registering the amendment: I. For NUH sponsored studies on receipt of the amendment notification II. For studies where NUH is acting as a site, upon receipt of the HRA amendment notification Responsible for issuing notification of continued NHS permission/confirmation of Capacity upon the outcome of the RPM review. R&I Research Project Manager (RPM) Where the HRA has categorised the amendment as A or B, undertake the amendment review ensuring it fulfils the requirements of the Research Governance Framework for Health and Social Care: Second Edition, 2005 (RGF). Facilitates continuing NHS permission. R&I Research Project Manager Team Leader Allocated amendments to RPMs for further review. R&I Director or Deputy Director Authorise the Amendment Notification Form on the IRAS when NUH is the Sponsor of the study.

5 Page 5 of Definitions CA CSP CTA CTIMP Documas GCP HRA IB IRAS LCRN MHRA NHS NIHR NUH PI R&I REC RPM SmPC SOP Substantial Amendment Urgent Safety Measure Competent Authority (in the United Kingdom this is the MHRA) Centralised System for gaining NHS Permission Clinical Trial Authorisation Clinical Trials of an Investigational Medicinal Product A Document Management System to assist with the management, control and governance of the Research and Ethics processes covering Research and Development Projects Good Clinical Practice Health Research Authority Investigator Brochure Integrated Research Application System Local Clinical Research Network Medicines and Healthcare products Regulatory Agency National Health Service National Institute for Health Research Nottingham University Hospitals NHS Trust Principal Investigator Research and Innovation Research Ethics Committee Research Project Manager Summary of Product Characteristics Standard Operating Procedure A substantial amendment is defined as a change to the terms of the CA and/or REC application, the protocol or any other document submitted with the application, which significantly affects one of the following: - The safety or physical or mental integrity of study participants - The scientific value of the clinical study. A measure taken by the CI/PI or Sponsor to protect the health or safety of subjects from an immediate hazard.

6 Page 6 of Procedure 6.1 Amendments to Studies Sponsored by NUH If NUH is acting as study Sponsor the CI, or nominated individual, must first contact R&I (rdamend@nuh.nhs.uk) to notify the proposed changes, unless in the event of an urgent safety measure (refer to SOP-RES-022 Urgent safety Measures). Relevant documentation must be submitted in the notification. The R&I Administrator will Register the amendment, check all relevant documentation has been submitted and pass to the RPM team leader to allocate an RPM to review The RPM will review the amendment to ensure that NUH can accept the amendment as Sponsor of the study, taking into account: i. whether the amendment is such that it might affect NUH s willingness to continue sponsoring the study; ii. whether the proposed amendment will affect the insurance in place for the study; iii. financial implications; iv. contractual changes; v. internal departmental authorisations e.g. Medical Physics Expert (MPE), pathology, pharmacy, relevant clinical lead; vi. regulatory approvals including REC and MHRA; vii. whether the amendment is substantial. If any corrective action is required the RPM will communicate with the study team. The RPM will liaise with the Head of Regulatory Compliance to discuss a review of the risk assessment (as per SOP-RES-002 Risk Assessment). It may be essential to complete the risk assessment prior to the Sponsor accepting the amendment. The Head of Regulatory Compliance will communicate this with the CI. The RPM will provide confirmation to the CI, and any other nominated individual, if the amendment is considered substantial or non-substantial. Amendments considered by the Sponsor not to be substantial (non-substantial amendments) should be submitted to the HRA via hra.amendments@nhs.net. A record of these amendments should be kept by the Sponsor and details included in any subsequent notification of a substantial amendment. Only substantial amendments should be submitted to the CA/REC which originally reviewed the study. The appropriate notice of substantial amendment form with relevant authorisations and supporting documents should be included and hra.amendments@nhs.net copied into the to REC.

7 Page 7 of 10 For MHRA submissions, substantial amendments are submitted through CESP (Common European Submission Portal). For guidance on the CESP submission process refer to the MHRA website: For MHRA submissions, the following documentation should be provided (where required): covering letter outlining the substantial and any non-substantial changes signed notification of amendment form from the European Commission website updated XML and PDF versions of the clinical trial application form if it s changed since the last submission proof of payment of your fee - see guidance on making a payment for more information on the types of documents that can be submitted to avoid issues with your application - you should state your EudraCT number, which is used as a reference number reasons for the proposed changes proposed changes to the protocol or other document (eg investigational medicinal product dossier), showing previous and new wording supporting data for the change, including: summaries of data updated overall risk-benefit assessment possible consequences for subjects already in the trial possible consequences for the evaluation of results The RPM will request R&I Director or Deputy Director sign-off of the amendment form on IRAS and provide a copy to the CI, or nominated researcher to allow them to submit the amendment to the CA/REC. N.B. Sponsor amendment review and amendment form signoff does not constitute continuing NHS permission. The CI, or nominated individual, must obtain continuing NHS permission for the amendment as per Amendment Submission ALL Studies Submitting an Amendment to NUH for Continuing NHS Permission Notification of the classification of the amendment will be received by NUH from the HRA. The HRA will also issue continuing HRA approval and REC approval The sponsor/sponsor representative must submit the following documents to R&I (rdamend@nuh.nhs.uk):

8 Page 8 of 10 i. Amendment Notification Form completed in IRAS; ii. Updated study documents effected by the amendment these should be submitted in tracked changed format; iii. For CTIMPs, the Clinical Trial Application form should be updated in its entirety at the occasion of a substantial amendment. Details of any nonsubstantial amendments should be clearly noted in the documentation and differentiated from the substantial amendment(s) being made; iv. Favourable ethical opinion or acknowledgement of the amendment from the REC and HRA approval v. For CTIMPs, Notice of Acceptance of Amendment from the MHRA. On receipt of an amendment submission the R&I Administrator sets up a new amendment file and saves all applications to the R&I document and storage database, Documas. The R&I Administrator will also check the study to determine if NUH is the Sponsor or host. The R&I Administrator will check the amendment for completeness by using the HRA Approval Letter Invalid Submission If there are deficiencies in the submission the R&I Administrator will request further information from the sponsor Amendment Review and Continuing NHS Permission If all documents are present this constitutes a valid amendment submission, the date of receipt will then be entered into Documas by the R&I Administrator. The R&I Administrator will send the Valid Submission (TAFR02401) notification to the CI, or nominated individual, stating that the amendment can be implemented within 35 days if no objection to the continuation of NHS permission is raised by the R&I office. The RPM Team leader will pass the amendment on to an RPM for review. On satisfactory review the RPM: i. Updates Documas ii. After authorisation the R&I Administrator or RPM will send notification of continuing NHS permission/confirmation of capacity to study contacts

9 Page 9 of 10 N.B. From the receipt of a valid amendment submission the above process should take a maximum of 15 working days. 6.4 Addition of New Research Staff to a Study A change of CI and PI should be submitted as a substantial amendment. For other new staff the CI/PI or nominated individual should submit to rdamend@nuh.nhs.uk: i. CV (refer to HRA online guidance on researcher CVs); and ii. Up-to-date Good Clinical Practice (GCP) training certificate (where appropriate). The R&I Administrator will provide the CI/PI or nominated individual acknowledgement The R&I Administrator will enter the new staff details in to Documas (including start and GCP training certificate date), and upload them electronically to Documas.

10 Page 10 of References and Associated Documents Directive (2010/C 82/01) 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 (CT-1) Research Governance Framework for Health and Social Care: Second Edition, 2005 The Medicines for Human Use (Clinical Trials) Regulations 2004 and subsequent amendments International Conference on Harmonisation Guidelines for Good Clinical Practice E6 (R1) Good Clinical Practice Guide Compiled by the Medicines and Healthcare products Regulatory Agency, published SOP-RES-002 SOP-RES-022 TAFR02401 TAFR02403 Available from IRAS website Available from HRA website Risk Assessment Urgent Safety Measures Amendment Notifications Amendment Approval Letter Amendment Submission Checklist Amendment Notification Form EU Notification of Substantial Amendment form (for CTIMPs) NRES Notice of Substantial Amendment form (for non-ctimps)