Marie-Claire Rickard, RG and GCP Manager Jimena Lovos, Quality Assurance Manager Elizabeth Clough, R&D Governance Operations Manager

Transcription

1 Standard Operating Procedures (SOP) for: Pharmacovigilance processing for the JRMO SOP Number: 26c Version Number: V1 Effective Date: 5/8/16 Review Date: 5/8/17 Author: Reviewer: Reviewer: Authorisation: Name / Position Signature Marie-Claire Rickard, RG and GCP Manager Jimena Lovos, Quality Assurance Manager Elizabeth Clough, R&D Governance Operations Manager Sally Burtles, Director of Research Services & Business Development Date 21/7/16 Background Under the Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 2004/1031) and all subsequent amendments, sponsors of clinical trials of medicinal products have legal requirements for recording and reporting serious adverse events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs). Of particular importance is the assessment of any event for causality and expectedness. Under the Research Governance Framework 2005, researchers have a responsibility to record any adverse drug reaction or other adverse events (AEs). It is vital that this SOP is followed as failure to record and report SAEs/SUSARs or deal with them adequately can have the potential to jeopardise the safety and well-being of trial subjects. Purpose and Objective: To identify and standardise the process for receiving, logging and acknowledging Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs) and Suspected Unexpected Serious Adverse Reactions (SUSARs) Adverse Events of Special Interest (AESI) and Pregnancies. To outline JRMO actions and responsibilities related to Safety reporting. Scope: This SOP covers procedures followed by JRMO to process the Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs) and Suspected Unexpected Serious Adverse Reactions (SUSARs) Adverse Events of Special Interest (AESI) and Pregnancies for projects sponsored by BH or QMUL. This SOP is relevant to the JRMO staff and associated staff names within this SOP only. Please note : The JRMO ReDA Database collects and records Pharmacovigilance for Sponsor oversight purposes only. Medical assessment, trends, safety signals and Data collection of events for statistical analysis are the responsibility of the Chief investigator. Due to this the PV management with JRMO is during working hours only. Abbreviations: BH Barts Health NHS Trust JRMO Joint Research Management Office QMUL Queen Mary University of London Definitions (if needed) See Appendix A for Study definitions. Relevant SOP s SOP 26a Pharmacovigilance and Safety Reporting for Sponsored CTIMPs/ATMP - for researchers SOP 26b Safety reporting for non-ctimps SOP 10 Filing SOP 26c Pharmacovigilance processing at the JRMO V1.0 Page 1 of 7

2 SOP Text Responsibility Activity Pharmacovigilance event management 1. R&D and Governance Operations Manager 2. GCP Manager 3. Clinical Trial Monitor (CTM) Ensure a suitable database is available to log and manage safety events on behalf of QMUL and BH sponsored studies. Assign a Clinical Trial Monitor (CTM) to be responsible of managing the Pharmacovigilance desk (currently on a 4 monthly basis). Ensure CTM is appropriately trained prior to and adequately supported throughout PV assignment. Ensure the PV desks is appropriately supported, managed and covered at all times. 1. Check the Pharmacovigilance desk ( /FAX) for new correspondence at least every working day. All new events must assessed for type and validity within 2 working days. All new event should be assessed: To establish if JRMO procedures require these to be logged. o The JRMO will only log AESI, SAES, SUSAR s and pregnancies for CTIMP/ATIMPS and clinical investigations. o For Non CTIMPS only Related and Unexpected events reportable to REC will be logged. For type of event (Pregnancy/SAE/SUSAR) For completeness/validity of submission Validity of submission If the event received has not been signed by the PI or delegated medical representative or there is no evidence of PI or delegated medical representative assessment the report is considered invalid, and therefore will not be logged. The SAE report should be returned to the sender explaining the reason for not logging the event and the possible GCP deviation in case of not receiving the valid report within the 24hr reporting period. (SOP 26a for researchers: Pharmacovigilance and Safety Reporting for Sponsored CTIMPs/ATMP). 2. For valid SUSARs immediately notify one of the two GCP managers (or if both GCP managers are absent the QA manager) of potential SUSAR. 3. Log event within ReDA SUSAR tab using above principles. (See Associated Document 1). All events must be logged within 5 working days. All valid reported events should be logged in ReDA. 4. All submitted forms must be saved into Indemnity using the same format name used in ReDA: Sub Study patient number/id, SAE Event name, JRMO date SAE received by JRMO/dd-mm-yy Example: Sub R055, SAE Portal Vein Thrombosis, JRMO Upload all submitted forms into the ReDA: Upload all submitted forms into the ReDA in the Documents tab under the safety section. Ensure SAE paper work is label correctly (See Associated Document 1). 6. Issue formal acknowledgement of events on day of logging. Acknowledgement should be sent to sender and Trial Coordinator stating the name of the SAE that has been logged and whether there is any missing information or signature that is still to be received. SOP 26c Pharmacovigilance processing at the JRMO V1.0 Page 2 of 7

3 4. GCP manager 7. Follow up events. Follow up details will be logged in the existing ReDA entry when the Initial Report was logged. 8. Save all submitted forms into Indemnity using the same format name used in ReDA and adding f-u (for follow-up): Sub Study patient number/id, SAE Event name, JRMO date SAE received by JRMO/dd-mm-yy Example: Sub R055, SAE Portal Vein Thrombosis, JRMO f-u 9. To upload all submitted forms into the ReDA: Documents tab/safety When notified of a pending end of trial, ensure all events are closed/completed. 10. Ensure all safety events correspondence is filed within indemnity as per SOP 10 (Filing). 11. Twice a year compare team SAE log to ReDA event log to ensure constancy. Process and log SUSARS as per UK regulatory guidance. Review all valid SUSARs as notified by Clinical Trial Monitor (CTM). Establish Day 0 and notify all involved. Ensure PI and CI assessment correspond. If not discuss with CI and if needed seek independent advice as per sections 6 and 7. Log SUSAR within QMUL and BH e-susar (see MHRA main website for web address) account as per current MHRA guidance and within UK regulatory and HRA time lines. A SUSAR occurring in the UK which is fatal or life-threatening should be logged as soon as possible and in any event within 7 days after the sponsor becomes aware of the event. Any additional information should be submitted within 8 days of sending the first report. Non-fatal or life-threatening events should be logged as soon as possible and in any event within 15 days after the sponsor became aware of the event. Reports of SUSARs in double-blind trials should be unblinded prior to submission. Procedures related to un-blinding for SUSAR report purposes can be found in study specific SOPs. Any interpretation of wording on SUSAR reports should be checked with CI prior to esusar submission. Once logged download the PDF and send it CI, Trial Coordinator and local JRMO CTM for logging at local level. Medical assessment of SAEs 5. Sponsor oversight group Ensure CI fulfills their role as CI and medical assessor. Escalating problems as necessary. The CI must ensure sites are aware of the requirement to report Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs) and Suspected Unexpected Serious Adverse Reactions (SUSARs) Adverse Events of Special Interest (AESI) and Pregnancies to the JRMO. On the rare occasion that the CI fails to comply with pharmacovigilance reporting timelines or provide adequate CI oversight as outlined in SOP 26a (For researchers: Pharmacovigilance and Safety Reporting for Sponsored CTIMPs/ATMP), the sponsor will escalate this in accordance with their escalation policy, commencing with the Sponsor Oversight Group. Unless otherwise formally agreed by the sponsor and delegated, the sponsor is responsible for ensuring that all relevant information about a SUSAR which occurs SOP 26c Pharmacovigilance processing at the JRMO V1.0 Page 3 of 7

4 during the course of a clinical trial in the United Kingdom, or that are UK-relevant are reported to the Competent Authority (MHRA). The CI is delegated by the sponsor to be the pharmacovigilance medical assessor. 6. GCP team To seek independent review in case of dispute between CI and PI when assessing an SAE. Should a dispute arise between CI and PI when assessing an SAE, the GCP team will contact the Clinical Director for Research and Development for clinical expertise. 7. Clinical Director for Research and Development To provide or arrange independent review to the GCP team in case of dispute between CI and PI when assessing an SAE. Clinical Director is ultimately responsible for making a final decision on behalf of the sponsor. Medical assessment and review of pregnancies within a CTIMP/ATMP. 8. GCP team Obtain independent medical advice for any pregnancy reports received. When receiving a pregnancy report, the GCP team will request medical review and advice on length of follow up needed from a Professor of Women s Health and Clinical Epidemiology. 9. CTM To log any pregnancy in ReDD as per instruction on Associated Document The Professor of Women s Health and Clinical Epidemiology Arrange for a member of the obstetric department to review any reports of pregnancies that are received by the JRMO. To provide independent medical expertise to the GCP team. Expertise may include but is not limited to - classifying normal or abnormal birth, length of follow up needed and if needed if the participant can remain on the study. 11. GCP team Ensure CI and Study team is aware of advice and that the event is followed up as advised. Log all information and documentation within ReDA and study files. Annual reporting 12. GCP Manager Review BH and QMUL Sponsored CTIMPS Annual Progress reports and Development Safety Update Reports. Review should include ensuring current templates are use, all section are complete and information correct (to Sponsors knowledge) e.g. are all SUSAR listed. Inform QA manager if submissions are late (see section 12). 13. QA manager To log all late CTIMP submissions on the Non-Conformance log. Work with Clinical Trial Facilitator to compile quarterly figures for SOG meeting (as per section 14) including any lateness that needs to be escalated to the SOG. 14. Assigned Clinical Trial Monitor Ensure reminders are set up and actioned (this includes appropriate escalation) within ReDA and per Associated Document 2. Individual event reminders must not be switched off until final version and submission evidenced is received. Ensure draft copies of Annual Reports, GCP manager s approval, final version and evidence of submission are saved as per SOP 10 (Filing). Sponsor Oversight Group 15. Clinical Trial Ensure all events are logged when notified of the quarterly reporting period. Monitor 16. QA Manager Once notified that all events are logged, proceed to run two reports: 1) Number of SAE, SAR and SUSAR for all sponsored CTIMPS within reporting period. 2) To identify on time and late reported SAEs and SUSARs. Assist CTF in collating Annual Reports due, completed and overdue. Provide figures to Clinical Trial Facilitator to compile meeting papers. 17. Sponsor Oversight Group members Review Safety information as per Group remit. Action as necessary. SOP 26c Pharmacovigilance processing at the JRMO V1.0 Page 4 of 7

5 Change Control This is a new SOP List of appendices Appendix A Appendix name Definitions List of Associated Documents Associated Document 1 Associated Document 2 Document name ReDA instructions to log safety events Annual Reports reminders template Appendix A Definitions: Investigational Medicinal Product (IMP): An IMP is a pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial including products already with a marketing authorisation. Non-Investigational Medicinal Product (NIMP): Products that are not the object of investigation (i.e. other than the tested product, placebo or active comparator) that may be supplied to subjects participating in a trial and used in accordance with the protocol. For instance, some clinical trial protocols require the use of medicinal products such as support or rescue/escape medication for preventative, diagnostic or therapeutic reasons and/or to ensure that adequate medical care is provided for the subject. They may also be used in accordance with the protocol to induce a physiological response. These medicinal products do not fall within the definition of an IMP and are called NIMPs. Adverse Event (AE): Any untoward medical occurrence in a subject to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product. Adverse Reaction (AR): Any untoward and unintended response in a subject to an investigational medicinal product which is related to any dose administered to that subject. Adverse event of special interest (AESI): An adverse event of special interest (serious or non-serious) is one of scientific and medical concern specific to the sponsor s product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it. Depending on the nature of the event, rapid communication by the trial sponsor to other parties (e.g., regulators) might also be warranted. (Based on CIOMS VI) Serious Adverse Event (SAE): Any adverse event or adverse reaction that Results in death Is life threatening Requires hospitalization or prolongation of existing hospitalisation Results in persistent or significant disability or incapacity Consists of a congenital anomaly or birth defect. Note - Some medical events may jeopardize the subject or may require an intervention to prevent one of the above characteristics or consequences. These should also be considered as serious in accordance with the definition. Serious Adverse Reaction (SAR): Any adverse reaction that is classed as serious in nature and where there is evidence to suggest a causal relationship between the drug and the adverse event. Suspected Unexpected Serious Adverse Reaction (SUSAR): Any adverse reaction that is classed as serious in nature and which is not consistent with the information about the medicinal product in question a. In the case of a licensed product, the summary of product characteristics (SmPC) for that product b. In the case of any other SOP 26c Pharmacovigilance processing at the JRMO V1.0 Page 5 of 7

6 investigational medicinal product, the Investigator s Brochure (IB) relating to the trial in question. Note to fulfill the definition of SUSAR, there must be suspicion of a causal relationship between the event and the IMP. UK relevant SUSARS: The MHRA s definition of UK-relevant includes: SUSARs originating in the UK SUSARs originating outside the UK where the sponsor has an ongoing trial in the UK involving the same medicinal product Day 0 : The day the Chief Investigator first receives a written SAE report (by fax or ), which has been medically assessed by the site. Urgent Safety Measures: An urgent safety measure is a procedure not defined by the protocol that is put in place prior to authorisation by the sponsor, MHRA, REC and sponsor in order to protect clinical trial subjects from any immediate hazard to their health and safety. During the course of a Clinical Trial involving an IMP, new safety information in the form of a Serious Adverse Event or information received from an external source may necessitate an immediate change in the study procedures or a temporary halt to the study in order to protect clinical trial subjects from any immediate hazard to their health and safety. If time does not allow for an amendment to be authorised by the Sponsor, MHRA, and Research Ethics Committee (REC), this change in procedure can be implemented as an urgent safety measure, by the Investigator, in accordance with the process put in place by the MHRA, and as detailed in this SOP. Code break: Code break involves unblinding a participant so that the treatment allocation is made known, this can be single (just to research team or double to research team and participant. SOP 26c Pharmacovigilance processing at the JRMO V1.0 Page 6 of 7

7 SAFETY PI/Site Submit a Safety event to JRMO PV desk CTM Twice a year compare team SAE log to ReDA event log to ensure consistency. Check the PV desk every working day. Assess for type and validity within 2 working days. For Non CTIMPS only Related and Unexpected events reportable to REC will be logged. For valid SUSARs immediately notify allocated GCP manager of potential SUSAR. GCP Manager To process and log SUSARS as per UK regulatory guidance. Invalid submissions Valid submissions Events not signed by PI or delegated medical representative or no evidence of PI or delegated medical representative assessment. The report is considered invalid, and therefore will not be logged. CTM Should be logged in ReDA within 5 working days. Save all submitted forms into Indemnity using the same format name used in ReDA. Upload the all submitted forms into the ReDA Follow up details will be logged in the existing ReDa entry when the Initial Report was logged. To return the SAE report to the sender explaining the reason for not logging the event and the possible GCP deviation in case of not receiving the valid report within the 24hr reporting period. To issue formal acknowledge of events on day of logging. GCP Manager To seek independent review in case of dispute between CI and PI when assessing an SAE. Obtain independent medical advice for any pregnancies reports received. SOP 26c Pharmacovigilance processing at the JRMO V1.0 Page 7 of 7