STANDARD OPERATING PROCEDURE

Transcription

1 STANDARD OPERATING PROCEDURE Title Reference Number End of Study Notification and Premature Discontinuation of a Study SOP-RES-025 Version Number 2 Issue Date 29 th Sep 2016 Effective Date 10 th Nov 2016 Review Date 10 th Nov 2018 Author(s) Reviewer(s) Teresa O Leary, Head of Regulatory Compliance Melanie Boulter, QA Auditor 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 9 1. Document History Version Issue Date Reason for Change Number 1 3 rd March 2014 Original SOP. It replaces SOP th Sep 2016 Biennial review.

3 Page 3 of 9 2. Introduction At the end of a research study the relevant review bodies must be notified that the study has ended. This also applies if the study has halted temporarily or ended early. This standard operating procedure (SOP) describes the procedure for suspending or terminating a study, including premature discontinuation of a study. 3. Purpose and Scope This SOP applies to the procedures for performing suspension or termination activities for all clinical trials of investigational medicinal products (CTIMPs), non-ctimps or clinical investigations of medical devices (CMDs) where Nottingham University Hospitals NHS Trust (NUH) is acting as the Sponsor. It describes the steps to be followed by all staff at NUH and/or Third Party Service Providers (SP). This SOP does not apply to studies for which NUH is not the Sponsor. 4. Responsibilities CI/Study Team To inform Research and Innovation (R&I) of any closure, premature discontinuation or temporary suspension of a research study. To complete the relevant declaration form to provide R&I with adequate information to be able to report to the Research Ethics Committee (REC) and the Medicines and Healthcare products Regulatory Agency (MHRA) where appropriate. If stated in the protocol, the study team should prepare information to send out to participants to let them know that their participation in the study is now complete. Sponsor (R&I will fulfil Sponsor responsibilities on behalf of NUH) To inform the REC and MHRA of any closure, premature discontinuation or temporary suspension of a research study, this will be carried out by a Research Project Manager (RPM) or delegated member of the R&I team.

4 Page 4 of 9 5. Definitions CA CE CI CMD CTIMP Documas GCP HRA IMP MHRA NUH QA R&I REC RPM SOP SP TMF TSC Competent Authority (in the United Kingdom this is the MHRA) "Conformité Européene" which literally means "European Conformity". The CE mark is required for all new products which are subject to one or more of the European product safety Directives. It is a visible sign that the manufacturer of the product is declaring conformity with all of the Directives relating to that product Chief Investigator Clinical Investigation of a Medical Device Clinical Trial 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 Investigational Medicinal Product Medicines and Healthcare products Regulatory Agency Nottingham University Hospitals NHS Trust Quality Assurance Research and Innovation Research Ethics Committee (in this SOP it refers to the committee providing the favourable opinion for the study) Research Project Manager Standard Operating Procedure Service Provider Trial Master File Trial Steering Committee 6. Procedure The definition of the end of study should be provided and justified in the protocol and any changes to this definition should be notified as a substantial amendment. In most cases the end of study will be the date of the last visit of the last participant or the completion of any follow-up monitoring and data collection described in the protocol. Final analysis of the data (following database lock) and report writing may occur after formal declaration of the end of the study.

5 Page 5 of 9 All end of study notifications will be stored in the study file; electronically, in the hard copy file and referenced in Documas. R&I will track end of study activities by completing the End of Study Notification Checklist (TAFR02501). Within one year from the end of the study the sponsor is required to produce the end of study report (for paediatric clinical trials please refer to the timelines set out in the European Commission Communication 2009/C28/01). It is the CI s responsibility to complete this (refer to SOP-RES-027 End of Study Report). 6.1 End of Study Notification for a CTIMP or a CMD The study team should inform R&I in writing (ResearchSponsor@nuh.nhs.uk) within three days of the end of the study. R&I will then be responsible for notifying the relevant bodies within the appropriate timelines that the study has ended. The CI should support R&I in completing the relevant documentation to be submitted Submitting the End of Study Notification for a CTIMP The R&I RPM will notify the REC and the MHRA when the trial has ended. This information will be sent when: i. The trial ends in the United Kingdom (UK) and/or ii. The complete trial has ended in all participating centres, in all countries within and outside the European Union (EU). The RPM must notify the REC and the CAs of the EU Member States concerned within 90 days of the end of trial as defined in the protocol. This notification will be sent using the EudraCT Declaration of the End of Trial Form. The RPM should inform the CI when the notification has been submitted. The CI should inform the funding body, TSC and any other relevant partners of the end of the trial. The RPM will contact the study team and CI to arrange a close out monitoring visit (refer to SOP-RES-026 Site Close Out) once the trial has ended.

6 Page 6 of Submitting the End of Study Notification for a CMD If the clinical investigation is of a non-ce marked device, or a CE marked device used outside of its intended purpose, the R&I RPM will notify the manufacturer immediately who should notify the MHRA that the clinical investigation has ended. The RPM will complete the Declaration of the End of a Study form (the HRA form used for all non- CTIMP studies) and submit it to the REC within 90 days of the end of the clinical investigation. If the clinical investigation uses a CE marked device within its intended purpose, and therefore does not fall under the scope of the MHRA, the RPM will complete the Declaration of the End of a Study form (the HRA form used for all non-ctimp studies) and submit it to the REC within 90 days of the end of the clinical investigation and inform the manufacturer (if appropriate) and the CI. The CI should inform the funding body, TSC and other partners as appropriate. 6.2 End of Study Notification for non-ctimp and non-cmd The CI must complete the Declaration of the End of a Study form and submit it to the REC within 90 days of the end of the study and provide a copy to the Sponsor (ResearchSponsor@nuh.nhs.uk). The CI should also notify the funding body, TSC and other partners as appropriate. 6.3 End of Study Notification for non NHS REC approved studies Where a project has HRA Approval and was not reviewed by an NHS REC, the HRA must be informed of when the study has ended. The RPM will notify the HRA by sending an to hra.approval@nhs.net with the IRAS ID and contact information (phone and ). 6.4 Early Termination of a Study The CI, R&I RPM or Head of Regulatory Compliance should discuss if the study requires early termination. Reasons for the early termination should be clearly explained and any follow up measures to be taken, if any (i.e. for safety reasons), should be described. R&I will be responsible for notifying the relevant bodies within the appropriate timelines that the study has ended. The CI should support R&I in completing the relevant documentation to be submitted.

7 Page 7 of Submitting the Early Termination Notification for a CTIMP Within 15 days of the termination the R&I RPM will notify the REC and the MHRA using the EudraCT Declaration of the End of Trial Form. The RPM should inform the CI when the notification has been submitted. The CI should inform the funding body, TSC and other partners as appropriate Submitting the Early Termination Notification for a CMD If the clinical investigation is of a non-ce marked device, or a CE marked device used outside of its intended purpose, the R&I RPM will notify the manufacturer immediately who should notify the MHRA that the clinical investigation has terminated early. The RPM will complete the Declaration of the End of a Study form and submit it to the REC within 15 days of the termination of the clinical investigation. If the clinical investigation uses a CE marked device within its intended purpose, and therefore does not fall under the scope of the MHRA, the RPM will complete the Declaration of the End of a Study form and submit it to the REC within 15 days of the end of the clinical investigation and inform the manufacturer (if appropriate). The CI should inform the funding body, TSC and other partners as appropriate. If the reason for early termination relates to significant non-compliance (e.g. by a SP or CI) the RPM will be instructed by the R&I Senior Research Manager or Head of Compliance to collect as much study information from the site(s) as possible. NUH QA may also be required to conduct and/or co-ordinate performance of a for cause audit to establish the extent of the problem and to provide support for NUH decisions. Studies which terminate early due to full recruitment being achieved do not need to be reported as terminating early. Early termination can be due to sponsor difficulties, amongst those could be issues of safety or slow recruitment. In all cases both the REC and CA must be notified Submitting the Early Termination Notification for non-ctimp and non-cmd Research

8 Page 8 of 9 The CI must complete the Declaration of the End of a Study form and submit it to the REC within 15 days of the termination of the study and provide a copy to the Sponsor (ResearchSponsor@nuh.nhs.uk). The CI should also notify the funding body, TSC and other partners as appropriate. 6.5 Temporary Suspension of a Study When any NUH-sponsored study is temporarily suspended, the R&I RPM will notify the MHRA (if a CTIMP or CMD) and the REC within 15 days of the temporary suspension taking effect. This includes unexpected difficulties not in keeping with the approved protocol. All sites taking part in the study should be informed of the temporary suspension and instructed that no further participants should be recruited to the study. The funding body, TSC and any other relevant partners should also be informed of the temporary suspension. This does not include studies where recruitment is suspended due to logistical reasons such as unavailability of the research team. The suspension notification should be made as a substantial amendment (refer to SOP- RES-024 Amendments) with the reasons for the temporary suspension clearly explained. Should a suspension of a site be determined to have been due to correctable errors following a QA audit and issuance of a Corrective Action Preventative Action request, it may be possible to remove the suspension after corrective actions have been applied by the affected site. To restart a trial that has been temporarily suspended, another substantial amendment should be submitted providing evidence that it is safe to restart the trial (refer to SOP-RES- 024 Amendments). If the Sponsor decides not to recommence the suspended study (i.e. to terminate the study), then the R&I RPM will ensure the REC and the CA are notified within 15 days of the decision to terminate the study (see 6.3). The information to be supplied on the end of trial notification form must include: i. Justification for premature termination of the trial; ii. Number of subjects involved; iii. Number of patients receiving any treatments; iv. Proposed management if patient treatments are involved;

9 Page 9 of 9 v. The consequences on the study data integrity and evaluation of results. 6.5 Trial Does not Commence For all NUH-sponsored studies if the CI or Sponsor decides not to commence the study, the CI should notify the MHRA (if a CTIMP or CMD) and REC clearly explaining the reasons for not starting the trial. 7. References and Associated Documents The Medicines for Human Use (Clinical Trials) Regulations 2004 The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 The Medical Devices Regulations 2002 The Medical Devices (Amendment) Regulations 2003 Medical Devices (Amendment) Regulations 2007 Medical Devices (Amendment) Regulations 2008 Research Governance Framework for Health and Social Care: Second edition, 2005 International Conference on Harmonisation Guidelines for Good Clinical Practice E6 (R1) ISO 14155:2011 Clinical investigation of medical devices for human subjects - Good clinical practice Good Clinical Practice Guide Compiled by the Medicines and Healthcare products Regulatory Agency, published 2012 SOP-RES-024 SOP-RES-026 SOP-RES-027 TAFR02501 Available from the HRA Website Amendments Site Close Out End of Study Report End of Study Notification Checklist Declaration of the End of Trial Form for CTIMP studies Declaration of the End of Study Form for non-ctimp studies