ETHICS COMMITTEE. TITLE: Safety Reporting STANDARD OPERATING PROCEDURE SOP006

Transcription

1 1 PURPOSE The purpose of this SOP is to describe the Peter MacCallum Cancer Centre (Peter Mac) Ethics Committee process for submission and handling of safety reports arising out of research reviewed by the Peter Mac Ethics Committee as the reviewing Human Research Ethics Committee (HREC). For safety reporting requirements for research conducted at Peter Mac that was reviewed by an Ethics Committee other than Peter Mac, refer to Guideline 009 Site Specific Assessment Process. 2 SCOPE This document applies to the handling of AEs. SAEs, SUSARs, USADEs, SUSAR/USADE Line Listings/Summary Reports, Annual Safety Reports, Investigator Brochures/Product Information updates, Investigator Alerts and all other forms of safety reporting. This SOP applies equally to single centre and multi centre ethical review processes. In the multicentre ethical review process (Interstate Mutual Acceptance) the Coordinating Principal Investigator is responsible for submitting all safety reports to the reviewing HREC on behalf of all participating sites included in the reviewing HREC approval. To maintain prompt reporting of individual AE/SAEs and individual SUSAR/USADEs occurring at participating sites included in the reviewing HREC approval, the site Principal Investigator can submit the report directly to the reviewing HREC. 3 RESPONSIBILITY It is the responsibility of Coordinating Principal Investigators, Principal Investigators, or delegates, conducting clinical trials involving medical therapeutic interventions and all Ethics Committee Secretariat staff members to follow and adhere to the procedures set out in this SOP. This SOP is consistent with the NHMRC Australian Health Ethics Committee (AHEC) Position Statement on Monitoring and Reporting of Safety for Clinical Trials Involving Therapeutic Products (May 2009). In addition to the Position Statement, all requirements outlined in the National Statement on Ethical Conduct in Human Research (2007, (updated May 2013)) and VMIA Guidelines for Clinical Trials (2012) must also be met. Prepared by Ethics Coordinator Approved by Chair, Clinical Research Governance Committee Page 1 of 10

2 4 DEFINITIONS Reviewing HREC The Human Research Ethics Committee (HREC) that issued the Ethical Approval for the project. Under the multisite review system coordinated by the Consultative Council for Clinical Trial Research (CCCTR) a NHMRC certified HREC or CCCTR accredited HREC can review and issue ethical approval for a project at multiple sites. These multiple sites will be named in the initial Ethical Approval or be added as an amendment to the initial Ethical Approval. This reviewing HREC is then responsible for the ongoing monitoring of the project at those sites. Coordinating Principal Investigator (CPI) A CPI must be nominated for each multisite ethical review project. The CPI is responsible for coordinating the initial submission to the reviewing HREC of all required documents for ethical review on behalf of all sites included in the review. The CPI is also responsible for submitting all documents requiring ethical review during the life of trial to the reviewing HREC i.e. protocol and PICF amendments, annual updates of IBs or Product Information, SAEs, SUSARs and all other required safety reports, protocol violations/deviations, complaints, progress reports, final reports - from all sites. The CPI is also the Principal Investigator (PI) for their own site. Principal Investigator (PI) The PI is responsible for submitting initial governance documents to their site Research Governance Officer (RGO). The PI is responsible for submitting site SAEs, SUSARs, protocol violations / deviations, complaints, progress reports, and final reports relating to their study site to the CPI for submission to the reviewing HREC. The PI is responsible for submitting HREC approved amendments to the site RGO and other reports as required by their site RGO. Adverse Event (AE) Serious Adverse Event (SAE) Adverse Event is defined as any untoward medical occurrence in a clinical trial or other clinical research project. Serious Adverse Event is defined as any untoward medical occurrence in a clinical trial or other clinical research project that: results in death is life-threatening requires in-patient hospitalisation or prolongation of existing Page 2 of 10

3 hospitalisation results in a persistent or significant disability/incapacity is a congenital abnormality/birth defect; or Project-specific definitions of SAEs are provided in Clinical Trial Protocols SUSAR USADE SUSAR/USADE LINE LISTING / SUMMARY REPORT ANNUAL SAFETY REPORT INVESTIGATOR ALERT INVESTIGATOR S BROCHURE / PRODUCT INFORMATION SINGLE SITE REVIEW ONLY MULTI-SITE REVIEW ONLY EVENT OCCURRED AT PETER MAC EVENT OCCURRED AT EXTERNAL SITE CCCTR Suspected Unexpected Serious Adverse Reaction Unanticipated Serious Adverse Device Effect Summary of SUSARs or USADEs, for a given project, occurring over a specified period Summary of all new available safety information relevant to a trial that is received over a 12 month period Notification of safety related information relevant to a given project. A compilation of the clinical and nonclinical data on the investigational product(s) that is relevant to the study of the product(s) in humans. Instructions for SINGLE SITE ONLY apply to projects that have been ethically reviewed by the Peter Mac Ethics Committee as a single site project for the Peter MacCallum Cancer Centre. The Peter Mac Ethics Committee is only responsible for monitoring the project at the Peter MacCallum Cancer Centre. Instructions for MULTI-SITE REVIEW ONLY apply to projects that have been ethically reviewed by the Peter Mac Ethics Committee for multiple sites. The Peter Mac Ethics Committee is responsible for monitoring the project at all sites listed on the ethical approval. Event occurred at Peter Mac site. Site is required to report to Peter Mac Ethics Committee as the reviewing HREC Event occurred at external site that is required to report to Peter Mac Ethics Committee as the reviewing HREC under multi-site review Consultative Council for Clinical Trial Research (formerly CCHRE), Department of Health, Victoria, Page 3 of 10

4 5 PROCEDURE MULTI-SITE REVIEW ONLY: Submitted safety documents must be reviewed by a Coordinating Principal Investigator, Principal Investigator or delegate. FOR SINGLE SITE REVIEW ONLY: Submitted safety documents must be reviewed by the Principal Investigator or delegate. 5.1 Submission and Processing of individual AE or SAE and individual SUSAR or USADE events occurring at sites required to report to the Peter Mac Ethics Committee as the reviewing HREC Events that have occurred at a site that is required to report to the Peter Mac Ethics Committee as the reviewing HREC must be processed as per below: The site Principal Investigator or treating clinician must determine the likely causation of the event, if the information materially impacts the continued ethical acceptability of the trial and whether or not action is required to be taken. If the information materially impacts on the continued ethical acceptability of the trial or requires or indicates the need for a change to the trial protocol, including changed safety monitoring in the view of the investigator or sponsor it must be submitted promptly to the Ethics Committee as follows: 1. Event occurred at Peter Mac: Following Investigator review, the event must be entered into the Peter Mac Serious Adverse Events Database. The database-generated cover sheet should then be attached to any event documentation and signed by the Principal Investigator. Event occurred at external site required to report to Peter Mac Ethics Committee as the reviewing HREC: All AE or SAE submissions require an AE and SAE Report form to be filled out. The form can be found on the CCCTR website at the following location: 2. If the event is identified at the time of initial submission as a SUSAR or USADE then instead a SUSAR/USADE Site Report form is required to be filled out. The form can be found on the CCCTR website at the following location: USADE-Site-Report. This report form MUST be completed and attached to the safety report documentation. 3. Multi-site review only projects: An AE and SAE Report or SUSAR/USADE Site Report should be submitted only once, either by the Coordinating Principal Investigator or by the Principal Investigator of the site where the event occurred. Page 4 of 10

5 4. All the documentation must be promptly submitted to the Ethics Committee Secretariat. (Within 24 hours of the researcher becoming aware of the event). 5. The submission will then undergo review on behalf of the Ethics Committee by an appropriately qualified representative. 6. Any queries or actions required to be taken will be communicated to the Coordinating Principal Investigator and/or site Principal Investigator, as applicable. 7. Submitted reports will be acknowledged on behalf of the Ethics Committee and returned to the Coordinating Principal Investigator, Principal Investigator or delegate, as applicable. 8. Event occurred at Peter Mac: A record of any actions required to be taken will be maintained in the Peter Mac Serious Adverse Events Database. 5.2 Submission and Processing of Investigator Alerts and Other Forms of Safety Reporting for sites required to report to the Peter Mac Ethics Committee as the reviewing HREC All Investigator Alerts and all other forms of safety reporting must be submitted and processed as per below: 1. Other than the safety reporting described in sections 5.1 and 5.3, ONLY alerts and reports that are deemed to require urgent action or materially impact on the continued ethical acceptability of the trial must be promptly submitted to the Ethics Committee Secretariat. There is no form or set format for these alerts or reports. 2. A Sponsor Statement must be included with the report regarding the implications for participants and the conduct of the study. If the Sponsor did not provide a statement, then a reason must be provided. 3. The investigator must state in the submission what action is recommended to be taken. 4. Submitted reports will be acknowledged on behalf of the Ethics Committee. 5. The cover page of the report will be copied and filed in the Ethics Committee Secretariat project file, and the original report documentation will be returned by the Ethics Committee Secretariat to the Principal Investigator, Coordinating Principal Investigator or delegate as applicable. 6. Multi-site review only projects: Report should be submitted by the Coordinating Principal Investigator only once on behalf of all sites listed on the ethical approval from the Peter Mac Ethics Committee. Page 5 of 10

6 5.3 Submission and Processing of SUSAR/USADE Line Listings/Summary Reports (Australian and International) and Annual Safety Reports or Investigator Brochures (IB) / Product Information for sites required to report to the Peter Mac Ethics Committee as the reviewing HREC These documents must be submitted and processed as per below: 1. The following MUST be submitted to the Ethics Committee Secretariat: At least six monthly: SUSAR/USADE Line Listing/Summary Report. At least annually: Annual Safety Report, or Investigator Brochure or Product Information update. 2. All submissions require a SUSAR/USADE Line Listing Report to be filled out. This form MUST be completed and attached to the documentation. The form can be found on the CCCTR website at the following location: 3. A Sponsor Statement must be included with the report regarding the implications for participants and the conduct of the study. If the Sponsor did not provide a statement, then a reason must be provided. 4. The investigator must record on the submission whether or not action is recommended to be taken. 5. Submitted reports will be acknowledged on behalf of the Ethics Committee and returned to the Coordinating Principal Investigator, Principal Investigator or delegate, as applicable. 6. The cover page of the report will be copied and filed in the Ethics Committee Secretariat project file, and the original report documentation will be returned by the Ethics Committee Secretariat to the Coordinating Principal Investigator, Principal Investigator or delegate, as applicable. 7. Multi-site review only projects: Reports should be submitted by the Coordinating Principal Investigator only once on behalf of all sites listed on the ethical approval from the Peter Mac Ethics Committee. Page 6 of 10

7 Table 1: Submission Requirements for sites required to report to the Peter Mac Ethics Committee as the reviewing HREC SAFETY REPORT Per Section 5.1 above: Individual AE or SAE and individual SUSAR or USADE events SUBMIT: ONLY IF the information materially impacts on the continued ethical acceptability of the trial or requires or indicates the need for a change to the trial protocol, including changed safety monitoring in the view of the investigator or sponsor Per Section 5.2 above: Investigator Alerts and Other Forms of Safety Reporting SUBMIT: ONLY alerts and reports that are deemed to require urgent action or materially impact on the continued ethical acceptability of the trial Event occurred at Peter Mac site and Peter Mac required to report to Peter Mac Ethics Committee as the reviewing HREC Review by PI or delegate. Enter into Peter Mac Serious Adverse Events Database. Submit database generated coversheet. WHAT TO DO Event occurred at non-peter Mac site and site required to report to Peter Mac Ethics Committee as the reviewing HREC Submit using a AE and SAE Report form. If identified at time of initial submission as SUSAR or USADE submit using a SUSAR/USADE Site Report. Submit promptly (within 24 hours of becoming aware of the event). Review by CPI (multi-site review only), PI (single site review only) or delegate. There is no form or set format for reporting. Sponsor statement must be included regarding implications for participants and conduct of the study. If no statement, include reason why. Investigator must state in the submission what action is recommended to be taken. Submit promptly. Review by CPI (multi-site review only), PI (single site review only) or delegate. Per Section 5.3 above: SUSAR/USADE Line Submit using a SUSAR/USADE Line Listing Report. Listings/Summary Reports (Australian Sponsor statement must be included regarding implications for participants and conduct of and International) and Annual Safety the study. If no statement, include reason why. Reports or Investigator Brochures Investigator must state in the submission what action is recommended to be taken. (IB)/Product Information Submit six monthly: SUSAR/USADE Line Listing/Summary Report. Submit annually: Annual Safety Report, or Investigator Brochure or Product Information update. Submitted reports will be reviewed and acknowledged on behalf of the Peter Mac Ethics Committee. Multi-site review only: Reviewed by Peter Mac Ethics Committee for multiple sites NOTE: Report should only be submitted to the Ethics Committee once by either the CPI or by the PI of the site where the event occurred. NOTE: Report should only be submitted to the Ethics Committee once by the CPI or delegate on behalf of all sites. Page 7 of 10

8 Table 2: PI and CPI Submission Requirements for sites required to report to the Peter Mac Ethics Committee as the reviewing HREC SINGLE SITE REVIEW MULTI- SITE REVIEW Peter Mac PI or delegate CPI or delegate and PI or delegate Per Section 5.1 above: Individual AE or SAE and individual SUSAR or USADE events Event occurred at Peter Mac and Peter Mac Ethics Committee is the reviewing HREC Submit to reviewing HREC (Peter Mac Ethics Committee) Submit to reviewing HREC (if Peter Mac Ethics Committee use this SOP) Submit only once from either the CPI or the Peter Mac PI. Event occurred at external site required to report to Peter Mac Ethics Committee as the reviewing HREC Submit to reviewing HREC (if Peter Mac Ethics Committee use this SOP) Submit only once from either the CPI or the PI of the site where the event occurred. SAFETY REPORT Per Section 5.2 above: Investigator Alerts and Other Forms of Safety Reporting Submit to reviewing HREC (Peter Mac Ethics Committee) CPI or delegate: Submit to reviewing HREC (if Peter Mac Ethics Committee use this SOP) PI or delegate: DO NOT SUBMIT Per Section 5.3 above: SUSAR/USADE Line Listings / Summary Reports (Australian and International) and Annual Safety Reports or Investigator Brochures (IB) / Product Information Submit to reviewing HREC (Peter Mac Ethics Committee) CPI or delegate: Submit to reviewing HREC (if Peter Mac Ethics Committee use this SOP) PI or delegate: DO NOT SUBMIT Page 8 of 10

9 6 RELEVANT DOCUMENTS INTERNAL DOCUMENTS POLICY Responsible Conduct of Research SOP 004 Monitoring of Ongoing Research EXTERNAL DOCUMENTS National Statement on Ethical Conduct in Human Research (2007, updated May 2013) NHMRC Australian Health Ethics Committee Position Statement (2009) TGA - Note for guidance on clinical safety data management: definitions and standards for expedited reporting (CPMP/ICH/377/95) Annotated with TGA comments (2000) TGA - Guidelines on the reporting of adverse drug reactions by drug sponsors (2010) TGA - Access to Unapproved Therapeutic Goods (2004) TGA - Australian Clinical Trial Handbook (2006) VMIA Guidelines for CTN Clinical Trials (2012). Page 9 of 10

10 Safety Reporting Appendix 1 - Safety Reporting Procedures As per Section 5.1 above: Individual AE/SAE or individual SUSAR/USADE events occurring at a site required to report to the Peter Mac Ethics Committee as the reviewing HREC As per Section 5.2 above: Investigator Alerts and other forms of Safety Reports for projects required to report to the Peter Mac Ethics Committee as the reviewing HREC As per Section 5.3 above: SUSAR/USADE Line Listing/Summary Report (Australian and International) or Annual Safety Report (Australian and International) or Investigator Brochures (IB) or Product Information for projects required to report to the Peter Mac Ethics Committee as the reviewing HREC Site PI or delegate Review CPI, PI or delegate Review Record in the Peter Mac Safety Record Database Submit to the Ethics Committee Secretariat if the information materially impacts on the continued ethical acceptability of the trial or requires or indicates the need for a change to the trial protocol, including changed safety monitoring in the view of the investigator or sponsor Submit to the Ethics Committee Secretariat Review by Ethics Committee representative Acknowledged on behalf of Ethics Committee Submitted documents returned to CPI/PI or delegate Investigator Brochure s forwarded to Clinical Trials Pharmacist by Ethics Committee Secretariat All other submitted documents returned to CPI/PI or delegate END OF DOCUMENT Page 10 of 10