STANDARD OPERATING PROCEDURE Clinical Research Monitoring TITLE: Site Initiation Visit TITLE: Site Initiation Visit 1. PURPOSE SOP Number: Version: 1.0 MICHR CRM MON 002 Effective Date: 19Dec2013 1.1 This Standard Operating Procedure (SOP) describes the procedures, process, and responsibilities for conducting a Site Initiation Visit (SIV) for clinical trials monitored by MICHR, unless otherwise specified in the Monitoring Plan by the study team. The procedures outlined in this document are in place to ensure uniformity and consistency in monitoring procedures, regardless of the location or individual monitor, and to ensure the rights and welfare of human research participants engaged in studies monitored by MICHR are protected. 2. SCOPE 2.1 The procedures described in this document outline the process of f conducting SIVs, which are separate in scope from Interim Monitoring Visits andd Study Close Out visit are detailed throughout. 2.2 This SOP applies to all qualified colleagues or contractors of MICHR involved in managing or conducting SIV activities. Visits. The purpose, procedures, and documentation for this type of monitoring 3. POLICY This SOP supports the International Conference on Harmonization (ICH) and U.S. Food and Drug Administration (FDA) or other State, local, and institutional regulatory requirements for human subject research nvolving investigational agents and devices. 4. DEFINITIONS Blinding: A procedure in which one or more parties to the trial are kept unaware of subject treatment assignment(s). Monitoring Plan: A document that describess the study specific monitoring to be performed. It includes frequency of visits and data points to be monitored onsite and/or remotely. Clinical Trial/Study: Any investigation in human subjectss intended to discover or verify the clinical, pharmacological, and/or other pharmacodynamic effectss of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/orr to study absorption, distribution, metabolism, and excretion of an investigational product( (s) with the object of ascertaining its safety and/or efficacy. Approver Name: Cathy Radovich, Dir. CRM Next Review Date: 19Dec2015 Last Reviewed Date: N/A Page 1 of 5
STANDARD OPERATING PROCEDURE Clinical Research Monitoring TITLE: Site Initiation Visit SOP Number: Version: 1.0 MICHR CRM MON 002 Effective Date: 19Dec2013 Good Clinical Practice (GCP): A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinicall trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected. Institutional Review Board (IRB), Independent Ethics Committee (IEC), Human Subjects Review Committee (HSRC) or Ethical Review Board (ERB): a committee that has been formally designated to approve, monitor, and review biomedical and behavioral research involving humans with the aim to protect the rights and welfare of the research subjects. In the United States, the Food and Drug Administration (FDA) and Department of Health and Human Services (specifically Office for Human Research Protections) regulations have empowered IRBs to approve, require modifications in planned research prior to approval, or disapprove research. An IRB performs critical oversight functions for research conducted on human subjects thatt are scientific, ethical, and regulatory. Monitoring: Monitoring is the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures (SOPs), GCP, and the applicable regulatory requirements. Monitoring Report: A Monitoring Report is a written report from the monitor to the sponsor after each site visit and/ /or other trial related communication according to the sponsor ss SOPs. Protocol: A document that describes the objective(s), design, conduct, methodology, statistical considerations, and organization of a trial. The protocol usually also gives the scientific background and rationale for the trial, but these could be provided inn other protocol referenced documents. Throughout ICH GCP Guidelines, the term protocol referss to protocol and protocol amendments. Sponsor: An individual (Investigator), company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial. Sponsor Investigator: An individual who both initiates and conducts an investigation, and maintains the obligations of both a sponsor and an investigator. 5. RESPONSIBILITIES 5.1 Responsibilities of the The Research Monitor or qualified designeee is responsible for the arranging, conducting, and documentation of the SIV in accordance with the Monitoring Plan, this SOP (unless otherwise agreed) ), and regulatory requirements. Approver Name: Cathy Radovich, Dir. CRM Next Review Date: 19Dec2015 Last Reviewed Date: N/A Page 2 of 5
STANDARD OPERATING PROCEDURE Clinical Research Monitoring TITLE: Site Initiation Visit SOP Number: Version: 1.0 MICHR CRM MON 002 Effective Date: 19Dec2013 5.2 Responsibilities of the Monitoring Manger: The Monitoring Manager or designee is responsible for the review and approval of the SIV report. The report review and approval will be designated to another qualified colleague if the Monitoring Manager was the person that conducted the visit. 6. PROCEDURE 6.1 Process Overview 6.1.1 An SIV is arranged, conducted, and documented by the Research Monitor in order to verify regulatory compliance and readiness too begin study enrollment. The conduct of an SIV occurs in three stages: Preparing for the SIV Conducting the SIV Following up after the SIV 6.2 Preparing for the Interim Monitoring Visit 6.2.1 The monitor, or designee, will ensure that visit arrangements are made with the investigational site. The monitor should attempt to schedule the visit at a time when key staff related to the investigation are available. Potential attendees may include the PI/Co I, research nurse, study coordinator, data manager,, pharmacist (if applicable) ), and Sponsor representative(s) (if applicable). 6.2.2 The monitor, or designee, will book any needed travel in compliance with standing University of Michigan policies and procedures as well as any guidance issued by MICHR; and if needed, confirm travel plans prior to booking with the study manager, study sponsor, or other designated key personnel responsible for oversight of study budgetary expenditures. 6.2.3 The monitor, or designee, will send a confirmation communication, which may include the monitor s expected itinerary as well as a list of items necessary for the monitoring visit, to the site PI, study coordinator, study manager, and other designated study team members once a time and date for the monitoring visit has been established. 6.2.4 In some cases, the monitor, or designee, mayy create presentations or handouts to help facilitate the SIV. Possible topics for inclusionn in the presentations and/or handouts are: Good Clinical Practice overview, protocol review, study activities and schedule of events, safety reporting, and the study Monitoring Plan. 6.3 Conducting the IMV 6.3.1 Sign the Site Initiationn Visit Log. Approver Name: Cathy Radovich, Dir. CRM Next Review Date: 19Dec2015 Last Reviewed Date: N/A Page 3 of 5
STANDARD OPERATING PROCEDURE Clinical Research Monitoring TITLE: Site Initiation Visit SOP Number: Version: 1.0 MICHR CRM MON 002 Effective Date: 19Dec2013 6.3.2 Ensure that all required essential documents are present in the Investigator Regulatory file. 6.3.3 Review GCP standards and the Monitoring Plan. 6.3.4 Discuss study logisticss to ensure site preparedness for enrollment. 6.3.5 If applicable, check for the receipt, security, and proper storage of the investigational product, and review dispensing and accountability procedures. 6.3.6 Confirm that the site facilities and study personnel are adequate for the conduct of the study. 6.3.7 Document any concerns or action items. 6.4 Following up After the IMV 6.4.1 A follow up communication will be sent to the Sponsor and site as soon as possible following the final day of the visit addressing any action items identified during the visit. 6.4.2 The Research Monitor will complete an SIV Report (Appendix A) and submit the draft to the Monitoring Manager or designee for review. 6.4.3 The Monitoring Manager will review the draft report and return the draft to the Research Monitor for finalization. 6.4.4 The SIV Report should be finalized with appropriate attachments (attachments may include the confirmation communication, Essential Document Checklist, Training Log, etc.) and distributed to appropriate study personnel, including pharmacist (if applicable) within 15 business days of the last day of the SIV. 6.4.5 A copy of the SIV report should be archived perr the Monitoring Plan. 7. REFERENCES FDA 45 CFR 46 and 21 CFR 50 21 CFR 56 21 CFR 312 21 CFR 812 Protection of Human Subjects Institutional Review Boards Investigational New Drug (IND) Investigational Device Exemptions (IDE) ICH Consolidated Guideline E6 (R1) Approver Name: Cathy Radovich, Dir. CRM Next Review Date: 19Dec2015 Goodd Clinical Practice (GCP) Last Reviewed Date: N/A Page 4 of 5
STANDARD OPERATING PROCEDURE Clinical Research Monitoring TITLE: Site Initiation Visit SOP Number: Version: 1.0 MICHR CRM MON 002 Effective Date: 19Dec2013 8. APPENDICES Appendix A: Site Initiation Visit Report Template REVISION HISTORY Date Author(s) Remarks Version 09 Sep 2013 Amanda Phelps Final version. 1.0 Approver Name: Cathy Radovich, Dir. CRM Next Review Date: 19Dec2015 Last Reviewed Date: N/A Page 5 of 5
Attendees: Trial Status (at this visit) Not Started In Progress Completed Discontinued Subject Enrollment Status (Cumulative) ICF Signed Screen Baseline Enrolled Ongoing Failed (if applicable) (Randomized) (Active) Withdrawn Completed Select the appropriate response(s) for the discussion/monitoring items listed below. Provide comments as necessary. Conduct 1. Conduct trial according to the approved Protocol, Investigator s Agreement, GCP, IRB policy and Federal regulations? YES NO N/A 2. Compliance with the protocol and handling of protocol deviations? 3. Recruitment and enrollment process? 4. Instructions on study-specific procedures, windows, and timelines? 5. Randomization procedures? 6. Informed Consent procedures? 7. Progress reports to EC/IRB?
Select the appropriate response(s) for the discussion/monitoring items listed below. Provide comments as necessary. YES NO N/A 8. Procedures for subject/study discontinuation? 9. Appropriate storage of study data and supplies Investigational Product 10. Current Investigator Brochure/Instructions For Use 11. Was the study drug and storage area inspected? 12. Were ordering and control procedures discussed? 13. Were dispensing, dose modification, accountability discussed? 14. Were storage conditions discussed? 15. Was return and destruction discussed? 16. Is the expiry date compatible with the study duration? 17. Are there sufficient study drug supplies available and stored appropriately? 18. Have unblinding procedures been discussed?
Select the appropriate response(s) for the discussion/monitoring items listed below. Provide comments as necessary. YES NO N/A Adverse Events and Serious Adverse Events 19. Description of Adverse Events and Serious Adverse Events? 20. Reporting requirements? 21. Documentation of Adverse and Serious Adverse Events? 22. Reporting regular safety updates, safety alerts and (S)AEs to EC/IRB in accordance to local requirements? Case Report Forms 23. Completion of the CRFs and database entry (if applicable)? 24. Data discrepancies and query resolution? 25. Monitoring frequency as per monitoring plan? Monitoring 26. Monitoring procedures and objectives as per monitoring plan? Audit 27. The investigational site s previous audit experience and outcomes?
Select the appropriate response(s) for the discussion/monitoring items listed below. Provide comments as necessary. 28. Procedure for contacting the Sponsor in the event of notification of audit by regulatory authority? YES NO N/A Facility/Laboratory 29. Were all required lab supplies present at the site? 30. Are the central laboratory ranges current? 31. Are the central laboratory certificates current? Biological Samples 32. Has the storage area been inspected? 33. Is site staff familiar with sample taking, labeling and storage procedures? 34. Is site staff familiar with the sampling handling and shipment procedure? 35. Is freezer log or other required temperature controls available and adequate? Study File 36. Was the investigator study file reviewed?
Select the appropriate response(s) for the discussion/monitoring items listed below. Provide comments as necessary. YES NO N/A 37. Are all required documents filed in the Investigator Study File? 38. Has document storage and archiving been discussed and agreed to? Activation 1. In the opinion of the monitor, is the study site ready to begin enrollment? Yes No Additional Narrative (as needed) Item No. Action Item By Whom Status Ongoing Resolved Ongoing Resolved Ongoing Resolved Ongoing Resolved Ongoing Resolved Prepared by: Signature: Printed Name: Date: Reviewed by: Signature: Printed Name: Date: