Optimizing Remote Monitoring Visits Logistics for Clinical Trials

Remote Monitoring Visits Logistics for Sites What You Need to Know Bariatu Smith-OCSO, DAIDS Karen Hufham -PPD

Regulatory Background: COVID-19 Pandemic FDA Guidance Background Monitoring Considerations Objective: assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity during the COVID- 19 pandemic. If planned on-site monitoring visits are no longer possible, sponsors should consider optimizing use of central and remote monitoring programs to maintain oversight of clinical sites and ensure oversight of safety of trial participants, maintaining compliance with good clinical practice (GCP), and data integrity. Reference: FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic. Guidance for Industry, Investigators, and Institutional Review Boards. March 2020, updated April 16, 2020 2

Contingency Plan Monitoring Operations Branch Engage PPD In discussion Remote Monitoring Survey sites for EMRs and availability for remote visits PPD PPD considers monitoring of clinical trials essential to Support safety and well-being of participants Support data integrity General Monitoring Plan revised Appendices added to indicate sections affected by inability to perform onsite visits Develop Tools and Checklists to assist in remote reviews Train Monitors Self-guided training module developed and tracked in PPD s LMS Multiple live Q&A sessions 3

Remote Monitoring -SCOPE Review Protocol Registration Ensure no IRB approval gaps Review temperature logs Pharmacies Labs Review EDC Data Identify protocol deviations, SAEs, Discrepant data Entry errors Interview Designated Site Staff Review outstanding issues Assess current staffing/staff changes Fill gaps in remote document reviews Review Various Logs Delegation logs Training logs Screening/Enrollment logs ICF logs 4

Remote Monitoring Pre-Visit Process Monitor will contact site to schedule call(s) Previsit Letter will be sent to the site via NCRMS Monitor will send site an email with a document checklist and dial-in details Monitor completes pre-visit data review

Monitor Will Contact Site +Monitors will schedule call(s) with designated site representatives may include + Study Coordinator or designee + Regulatory Coordinator or designee + Pharmacist of Record or designee - recommend separate call to avoid unblinding + CRS Leader for debriefing call +Depending on the site schedule and preference, there may be a joint call with all attendees or separate calls +Available call options: Microsoft Teams, Skype, VoiceNet 6

Monitor Will Contact Site Optional Calls Optional Calls Logistics of the remote visit, follow-up issues to be addressed answer questions about the remote visit process Opening Call Review findings from individual assessments prior to the debriefing with the CRS Leader. Review Call 7

Pre-Visit Letter Will be Sent +A Pre-Visit Letter (PVL) will be sent once the call dates have been confirmed +DAIDS has waived the 3-week timeline notice for visits which have already been cancelled due to COVID-19 +A list of requested documents will be included in the PVL 8

Monitor will Send a List of What to Provide Before The Call At least 5 days prior to the call + Delegation of Duties Log(s) + Training Log(s) + ICF log (if used) + Screening / Enrollment log(s) + Monitoring Visit Log (current page) + Any new Form FDA 1572s, IoRs, Financial Disclosures, Protocol Signature Pages that have not been submitted to Protocol Registration + Any regulatory documents that would resolve outstanding follow-up issues + Staffing change information start/end dates, CVs, Licenses, training certificates for new employees (HSP / GCP certificates) + Date of last Emergency Cart review by site (if applicable to country) + Specimen storage temperature logs + Pharmacy temperature log(s), primary (continuous) and secondary (manual) Provide requested documents via email Ensure all data queries have been answered Ensure Protocol Registration is current with updated documents No participant Source documentation is to be requested or submitted. All participant identifiers must be redacted from any documents sent. 9

Pre-Visit Data Review the Monitors Process Once the calls have been scheduled, the monitor will begin Essential document reviews Protocol Registration reviews Study Product reviews eCRF data reviews New staff delegations, trainings, CVs, licenses, etc Logs Delegation Training ICF/Screening/Enroll ment ICF and enrollment data checks Logic checks on all eCRFs Protocol deviations Submission/approval of protocol documents to IRBs Storage requirements/ conditions 10

The Remote Monitoring Call Site participants Dial in at designated time to number provided Attendance may vary by topic Duration of Call 1 - 2 hours Vary Number of changes Protocol Registration documents Findings during pre-data review Additional Questions Based on findings from pre-visit data review Discussion of Study Product with Pharmacist of Record should be scheduled separately with consideration of potential for unblinding 11

The Report The same report templates will be used, indicating which assessments could or could not be completed remotely and why Findings will be included in the Site Monitoring Report (SMR) per the usual process and timelines Monitoring report will be submitted within 15 business days as per usual process 12

Post COVID-19 +On-site Monitoring Suspension will be lifted +Gradually ease into on-site monitoring +Multiple on-site visits within a quarter +Monitoring will initially focus on priority protocols ( High risk and registrational Protocols +Monitors will review Source Documents for data reviewed in the EDC during remote Monitoring 13

QUESTIONS +If a site has electronic regulatory and EMR systems, will monitors be requesting access to them? This may require changes to site SOPs regarding system access? + Can you clarify how sites should proceed in communicating about remote monitoring to their IRBs and relevant stakeholders 14