Standard Operating Procedures (SOP) for: Pharmacovigilance and Safety Reporting for Sponsored CTIMPs/ATMP. 20/09/2013 Review Date: 20/09/2015

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1 Standard Operating Procedures (SOP) for: Pharmacovigilance and Safety Reporting for Sponsored CTIMPs/ATMP SOP 026a Version 10.0 Number: Number: Effective Date: 20/09/2013 Review Date: 20/09/2015 Author: Reviewer: Reviewer : Reviewer: Authorisation: Name / Position Signature Priscilla Aryee (Research Governance and GCP ) Marie-Claire Rickard (RG and GCP ) Julia Brown Acting Governance Operations Carol Bargery, Governance Operations Gerry Leonard, Director of Research Development Date 12/09/2013 Purpose and Objective: To identify and standardise the process for reporting Adverse Events (AEs), Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs) and Suspected Unexpected Serious Adverse Reactions (SUSARs) and Urgent Safety Measures (USM). 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 SAEs and SUSARs. Under the Research Governance Framework 2005, researchers have a responsibility to record any adverse drug reaction or other adverse events. Scope: This SOP cover procedures primarily for Barts Health NHS Trust [BH] and Queen Mary University of London (QMUL) sponsored Clinical Trials of Investigational Medicinal Products (CTIMPs). Reporting mechanisms for SAEs in CTIMPs are determined by who the sponsor is. The PI informs the sponsor of SAEs that occur in all trial participants according to the sponsor Pharmacovigilance SOP and/or the process outlined in the protocol. For all studies sponsored by an external sponsor the sponsor procedure should be followed, Please see sections 12 & 13 for reporting requirements however the principles outlined in this SOP can be applied to all studies. Definitions: For multi-site trials, the CI is responsible overall for all the sites. Each PI is delegated responsibilities for his/her site. If there is only one site in the project, the CI is responsible for the site. JRMO Pharmacovigilance Reporting for CTIMPs SOP 26a V10.0 Page 1 of 7

2 SOP Text Responsibility Activity 1. Chief An adverse event is commonly defined as an untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporarily associated with their use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. If an Adverse Event (AE) occurs during a research project follow the flowchart in Associated Document 1. The (PI) for the study assesses the AE to establish if it should be classified as a SAE. If the AE is not defined as SERIOUS, the AE is recorded in the case report form (CRF) and the participant is followed up by the research team. The AE is documented in the participant s medical notes (where appropriate). If the AE is defined as SERIOUS, proceed to Chief Details of the SAE should be recorded in the participant s medical notes (where appropriate) and the participant followed up. The CI/PI reports all SAEs to the sponsor according to the sponsor s SOP, except those that the protocol, SmPC or s Brochure identifies as not requiring reporting. Once completed the SAE form should be signed by the PI or appropriate delegated person. A scanned signed copy should be ed to: ResearchSafety@bartshealth.nhs.uk Alternatively the JRMO fax number is: Report to the JRMO within 1 working day of the CI/PI/Research Team becoming aware of the event. If the trial is NOT SPONSORED by BH/QM, please note that the sponsor s SAE form needs to be sent to the sponsor only and not the JRMO. JRMO Pharmacovigilance Reporting for CTIMPs SOP 26a V10.0 Page 2 of 7

3 For BH and QMUL Sponsored studies 3. Chief / Prior to submitting the SAE the PI makes an assessment of CAUSALITY. The treating PI makes the assessment and sends the report to the CI. PLEASE NOTE THAT THE CI CAN UPGRADE AN SAE BUT CANNOT DOWNGRADE ANY SAE. Should a difference of opinion arise the CI and PI should discuss the event, but the PI at site will make the final decision. If the SAE is assessed as not being a reaction to the medicinal product, proceed to 6.1. If the SAE is classified as being likely to be a reaction to the medicinal product, the SAE is classified as a SAR (Serious Adverse Reaction).. Proceed to Chief / The PI assesses the EXPECTEDNESS of the SAR (whether this is likely to be an expected reaction). Expected reactions should be listed in the s Brochure (IB), the Summary of Product Characteristics (SmPC) or the protocol. If the SAR is expected, proceed to 6.1 for reporting process. If the SAR is unexpected, proceed to Chief / 6.0 Chief The PI decides if the SAR should be classified as a SUSAR (Suspected Unexpected Serious Adverse Reaction). A SUSAR is a SAE which is suspected to be a reaction to the medicinal product and is UNEXPECTED i.e. it has not been seen before in the IB, SmPC or in other trials. For SUSAR reporting process, proceed to 6.2. SAE reporting process A SAE form is completed for each SAE that requires reporting. The PI s team has to complete the BH/QM reporting form. Associated Document 2 (BH/QMUL template reporting form and Guidance notes for researchers). The PI signs and submits the SAE as per point 2. The SAE should be reported to the REC if it relates to the following; a new event, related to the conduct of the trial or the development of the investigational medicinal product (IMP), that is likely to affect the safety of subjects a SAE associated with the trial procedures and which could modify the conduct of the trial; a significant hazard to the subject population such as lack of efficacy of an IMP JRMO Pharmacovigilance Reporting for CTIMPs SOP 26a V10.0 Page 3 of 7

4 6.1 Chief Expected SAR reporting A SAE form is completed for each SAR that requires reporting as per section 6 and submitted as per section 2. Expected SARs do not need be reported to the main REC apart from in the following situations; Single case reports of an expected serious adverse reaction with an unexpected outcome e.g. death An increase in the rate of occurrence of an expected serious adverse reaction which is judges to be clinically important. 6.2 Chief The SAR are also is recorded in the participant s medical notes where appropriate and the participant followed up. All SARs should be included in a line-listings format in the annual report to the REC (annual progress report) and the MHRA (Development Safety Update Report). Unexpected SARs or SUSAR reporting process SARs that are UNEXPECTED and therefore fulfil the criteria of a SUSAR require immediate reporting to the sponsor. Report to the JRMO within 1 one working day of the CI/PI/Research Team becoming aware of the event. The PI has to complete the BH/QMUL SAE template form and CIOMS form (Appendix A and B), a scanned signed copy should be ed to: ResearchSafety@bartshealth.nhs.uk Alternatively the JRMO fax number is: The sponsor has to acknowledge receipt of the SUSAR in writing to the PI, if he does not, the PI needs to contact the sponsor and request a written acknowledgment. BH/QMUL as sponsor delegates to the CI responsibility for : Informing the appropriate REC Notify all sites (PIs) Evidence that these actions have been completed should be filed in the Trial Master file by the CI/CI research team. Study Monitor/ Research/Go For a SUSAR which is fatal or life threatening, the sponsor has 7 days after becoming aware of the event to report the SUSAR to the MHRA. For a SUSAR which is not fatal or life threatening, the sponsor then has 15 days to report this event to the MHRA. The SUSAR is recorded in the participant medical notes and the participant is followed up. All SUSARs should be included in the annual safety report (the anniversary date of the annual safety report is the date on the notice of acceptance MHRA letter). The JRMO receives a SAE form. The form is checked to see that it has been completed fully. Request further information if necessary from the PI/Research team. If the event is possibly or JRMO Pharmacovigilance Reporting for CTIMPs SOP 26a V10.0 Page 4 of 7

5 vernance & GCP 7. Study Monitor/ Research/Go vernance & GCP 8. Governance & GCP likely to be a SUSAR, proceed to section 10. If the SAE is not a SUSAR, an acknowledgement receipt should be sent to the CI/research team. Follow up the SAE with the CI if necessary. Update Reda as per the Reda manual. If the SAE is classified as a SUSAR and BH/QMUL is the sponsor for the trial, the study monitor is to alert the Governance & GCP. If necessary the Governance & GCP will contact PI/CI / research team to obtain full information about the SUSAR If a life-threatening SUSAR has occurred, this is reported to the Medicines and Healthcare products Regulatory Agency (MHRA) within 7 days by the Research Governance & GCP manager via the MHRA e-susar reporting procedure. All other SUSARs are reported to the MHRA by the Research Governance & GCP within 15 days via the MHRA e- SUSAR reporting procedure The e-susar submitted data report shall be saved appropriately and sent to the CI as evidence of submission. Follow up the SUSAR with the reporting CI or trial coordinator where necessary. 9. Study Monitor/ Research Governance & GCP 10. Chief / If the event is classified as a SAE or SUSAR amend the ReDA database to record that a SAE or SUSAR has occurred. Ensure the SAE or SUSARs form is appropriately filed. File follow up information about the SAE in the project file when received. Annual reports BH/QMUL as sponsored delegates to the CI the responsibility of creating and submitting all annual reports (see below). The CI should create draft reports and submit to the sponsor via researchsafety@bartshealth.nhs.uk for review prior to submission to REC or MHRA. Once approved the reports should be finalised, signed and submitted as appropriate. Evidence of submission should be retained in the Trial Master File (and site files). A copy sent to the JRMO for their project file. Annual Progress reports to be sent to REC. Annual progress reports are submitted to the main REC twelve months after the favourable ethical opinion was granted, look up the date on that document to work out this report s due date. For Clinical Trials of Investigational Medicinal Products (CTIMPS), use national ethics template in Associated Document 3. Development Safety Update Reports to be sent to the MHRA and JRMO Pharmacovigilance Reporting for CTIMPs SOP 26a V10.0 Page 5 of 7

6 to the REC. Twelve months after the date on the MHRA Notice of acceptance letter, the annual safety report needs to be sent by the CI to the MHRA using Associated document 4: Development Safety Update Report template. 11. Chief /S ponsor/ Urgent Safety Measures The sponsor and investigator may take appropriate urgent safety measures to protect clinical trial subjects from any immediate hazard to their health and safety (Reg 30). The measures should be taken immediately. The does not need to wait for Licensing Authority approval before implementing urgent safety measures; however, they must inform the MHRA in writing within 3 days. On becoming aware of a potential hazard the CI or delegate should contact the sponsor immediately. The CI should contact the Clinical Trial Unit at the MHRA and discuss the issue with a medical assessor immediately. If the CI is unable to contact the sponsor or MHRA a USM can be implemented to protect the subject. For externally sponsored [hosted] Studies The CI must then notify (in the form of a substantial amendment) the MHRA and the REC, in writing, of the measures taken and the reason for the measures within three days. This notification should include a covering letter detailing the measures taken, the reason for them, the medical assessor contacted and any supporting documentation. The notification should be submitted to the MHRA as per their current submission guidelines on the MHRA website. Please see SOP 17a and 17b as appropriate. Site investigator Report SAE and SUSARs as per sponsor s procedures using Sponsor forms. It is important for whole site team to be aware of study specific reporting requirement. Ensure that if any SAE or SUSAR meets Trust or University Incident report systems that appropriate procedures are followed. Please see Barts Health NHS trust intranet for the Adverse incident Policy for details of events to be reported. 13. External Sponsor Forward Annual progress reports and Development Safety Update Reports to the JRMO on an annual basis. JRMO does not require SAE reports or SUSARs reports to be submitted. JRMO Pharmacovigilance Reporting for CTIMPs SOP 26a V10.0 Page 6 of 7

7 List of Associated documents Document Document name 1. Adverse event reporting flowchart. 2. BLT/QMUL SAE template SAE reporting form including CIOMS European Serious Adverse Reaction reporting form. 3. NRES annual Progress report template for clinical trials of medicines 4. Development Safety Update Report template for submission to MHRA JRMO Pharmacovigilance Reporting for CTIMPs SOP 26a V10.0 Page 7 of 7