Multi-Institutional Monitoring Visit

Purpose: To describe the procedure for conducting a monitoring visit at a participating site in a multi-institutional study.

STEP 1: Schedule Monitoring Visit

1. The CCR Study Coordinator/designee contacts the participating site Study Coordinator to determine date, time, and location of monitoring visit.
2. CCR Study Coordinator sends out monitoring visit confirmation letter.
   • The confirmation letter should include visit logistics and any requests for data and or meetings

STEP 2: Prepare Materials for Monitoring Visit

1. The CCR Study Coordinator/designee prepares the following materials for the visit (where applicable):
   • Previous Site Visit Reports (list of outstanding issues)
   • CTCAE (version per protocol)
   • Deviation log
   • Data Correction Form
   • Site Visit log
   • Other forms/tools as needed
   • Directions to site and phone numbers

STEP 3: Conduct Monitoring Visit

The CCR Study Coordinator/designee conducts the interim monitoring visit and reviews, but is not limited to, the following:

1. Informed consents:
   • Review informed consents for patients enrolled since last visit
   • Check that the correct version of the IRB-approved informed consent was used
   • Review for patient or patient’s LAR signature and date
   • Review for PI and witness signatures and date.
2. Check that all subjects are eligible per the protocol criteria and recorded in the source documentation.
3. Check Protocol Adherence:
   • Visit schedule and windows
   • Check that all procedures and subject visits are performed as stated in the protocol. Any deviations should be documented on the protocol deviation log and referenced in the site monitoring visit report.
4. Review CRFs (eCRFs):
   • Case Report form review and source documentation review process:
     • Start with new patients (those enrolled since last visit)
     • Review other currently enrolled subjects
     • Check all the CRF pages for each subject
     • Perform SDR (source document review) before checking the next subject’s CRF
     • Review for completeness and accuracy
     • Review each CRF in a single visit and then across visits.
   • Check each CRF for:
     • Missing, incomplete, illegible entries
     • Data recorded in the wrong field
     • Illogical, inconsistent, ambiguous data
     • Entries that demonstrate protocol violations or deviations
     • Missing signatures/dates
   • Check to ensure that changes to data on CRFs were made by authorized study site staff with a single black ink line through the original entry, initials and date, and that the initials match those on the Site Signature/Initials Form.
5. Data/CRF queries and error correction:
   • Use a correction log or form to record
   • Authorized Site personnel should make corrections to CRFs
   • Check if any changes to the CRF data alter the eligibility of subjects, safety, or key efficacy data
   • Assess if there are consistent errors in completion of CRFs
     • If so, re-instruct the study site staff on appropriate CRF correction.
6. Review Lab data:
   • Check that the Investigator or qualified designee has reviewed all clinical results, including abnormal lab results
   • Check that laboratory normal/reference ranges are valid and appropriate for the study subject population and all lab facilities in use.
7. Review all Adverse Events:
   • Verify if any SAEs have occurred and were they reported to the sponsor in the required timeframe
   • Review all data about the SAE in patient chart and supporting documentation.
8. Review of Investigational Product (IP) storage, handling, and documentation (if applicable for all steps):
   • Check that the storage conditions comply with the IP requirements specified in the protocol and local regulations
   • Check that the IP records are complete, accurate, signed and dated
   • Check expiration dates
   • Check IP usage for each specified subject against data in the CRFs and accountability records, identify discrepancies, and check for explanatory documentation
   • Assess the adequacy of IP supply for the remainder of the study
   • Check for maintenance of registration/randomization information as applicable to the protocol
   • If unblinding has occurred, verify unblinding procedures followed as per protocol
   • Check any study logs and temperature logs
   • Review any dispensing procedures.
9. Review biological specimen storage, handling, and documentation:
   • Review of laboratory results
   • Inspect storage conditions of biological specimens, if applicable
   • Check for accuracy of inventory records and shipping documents
   • Address with the study sites and/or local laboratory the handling, transportation, processing and reporting of protocol-specific laboratory procedures
   • Check that all CLIAs and reference ranges are current and appropriate, as applicable.
10. Review the Site Regulatory File:
    • Check that all relevant study documentation is complete, current, and filed appropriately using the Regulatory Documentation Checklist.
11. Visit satellite sites/other facilities:
    • If satellite sites or facilities are used, visit and perform required monitoring activities as appropriate for the procedures being performed there.
12. Meet with the participating site PI and designated team members to:
    • Review monitoring visit findings, actions, and timelines
    • Review issues with CRF completion and inadequacies in source data verification
    • Inform the Investigator of any missing regulatory documents or updates needed
    • Assess/Discuss recruitment status
    • Discuss changes or planned changes to study site staff and facilities (verify all appropriate documents are updated in regulatory binder)
    • Schedule next visit.

STEP 4: Document Activities of Monitoring Visit

1. Leave a copy of list of outstanding actions/issues to be resolved before next monitoring visit.
2. Sign the Site Visit Log in the Investigator’s Site File.
   • Note: Each day should be a separate entry/signature
3. Send participating site PI a monitoring visit follow-up letter.
4. Complete the monitoring visit report and send to PI of participating site.