SiLVER Study
A prospective, randomized, open-labeled trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients
undergoing liver transplantation for hepatocellular carcinoma
Web Meeting 12./13.12.2013:
Study Close-out Procedures
AGENDA
• Endpoint status and timelines
• Scheduling of last patient visit
• Safety follow-up
• eCRF completion
• Study Conclusion page
• Data cleaning and query resolution
• eCRF signature (PI or delegate)
• PIS Addendum
• Drug supply and accountability
• Lab Normal Ranges Project
• Patient insurance
• ISF completion and PI signature
• End of trial notification
• Preparation for archiving
• Any other business
• 163 endpoints reached
• Further endpoint reporting necessary until end of follow-up phase
• Immediate reporting crucial, as always, and simultaneous documentation in eCRF
• LPLV: end of February 2014
• Safety FU until latest end of March 2014
• Database lock: 15.4.2014
• Monitoring visits after LPLV at individual sites to clean all eCRF data ASAP
• November 2013 until latest end of February 2014
• "Early patients" (November visit) may return in February as per local practice
• Document visit as next visit in eCRF (no separate "final visit" in eCRF)
• Collect all remaining study medication, and all empty blisters and boxes (instruct patients in advance!)
• NO further dispensation of study medication!
• Treatment as per site-specific IS regimen
• Via phone
• At least 4 weeks after last study visit
• Must be finished by end of March
• Follow-up on ongoing (S)AEs: end date or ongoing at final contact
• Report and document new (S)AEs in eCRF
• Document phone call ("date of last contact") on Study Conclusion page in eCRF and forward phone memo to CRA for source data verification (pseudonymized
only!)
• Should also be performed for patients who could not attend their last visit
• Timely completion of eCRF vitally important (HCC recurrence, visit and AE pages, trough levels, FU letter issues, etc.)
=> ASAP after occurrence/patient visit
• Tick all completed eCRF pages (many AE pages not ticked yet!); otherwise no automated checks can be performed and no queries raised
• If patient missed last visit, enter "Not Done" for visit, perform safety FU and complete study conclusion page with date of last contact (no withdrawal!)
• To be completed after safety follow-up
• "Date of last contact with the patient" (phone call) to be entered for ALL patients (also for study
completers) on the Study Conclusion page CAVE: tick YES for all completers!
• Please enter in comment field: "date of phone contact with patient" as explanation for Data Management
• Queries will be sent for dates prior to 2014
• Should also be completed for patients who missed their last visit
• Incidence of queries will increase towards study end -> Data cleaning
-> SAE reconciliation
-> Ticking of pages (AEs, trough levels, etc.)
• Answer queries ASAP, otherwise timelines cannot be kept (re-queries)
• To avoid re-queries, answer queries as clearly as possible
• Answer all open queries BEFORE monitoring visit
• In case of doubt, please contact your CRA
• eCRF signature is the last entry in eCRF, no data entry afterwards!
• Signature by PI or delegate (entry on delegation log! Select 7 "other": eSignature)
• Check for valid account and password in advance! Good planning is essential!
• Training for eCRF signature required (instructions will be provided by your CRA)
• Can be performed only after all queries have been resolved (OK from sponsor received)
• Must be performed before database lock (scheduled for 15.4.2014)
• Safety data cleaning process: Documentation on SAE form and in eCRF have to match (diagnosis, causality, etc.)
-> Queries will be sent to clean safety data:
• Only ONE clear diagnosis per event! (Symptoms to be combinined into ONE diagnosis)
• Different episodes to be combined into ONE event
• Death is outcome, not name of event
-> Prompt answer to queries required!
• Required for all patients continuing after month 60 (per Protocol Amendment v. 9)
• If not signed, patient will be withdrawn at month 60
• If last visit for patient will be month 60, no PIS
Addendum has to be signed (original design was 5 year follow-up phase = month 60)
• Drug supply to be calculated as exactly as possible until last patient visit at your site
• Figures needed ASAP (collected by CRA)
• 1mg tablets should be ordered very carefully
• ALL study drug must be returned at last study visit (alert patients in advance!)
• No further study drug to be dispensed then
• CRA and site must perform final drug accountability: study drug for all batches received from B&C and returned by patients must be accounted for and sent back to sponsor for destruction (or locally, as agreed)
• Cleaning of normal ranges and corresponding units for every single lab used by the sites
<-> otherwise no analysis of lab results possible
• Lists sent by Dr. Kronenberg to be checked and completed ASAP (CAVE: different valid dates, age ranges, male and female) and faxed back to sponsor
• To avoid re-queries:
answer correctly and completely
• To accelerate the process: missing/corrected normal ranges or lab units will be entered in eCRF by sponsor
• Insurance was prolonged until 30.4.2014 for all countries (except Australia until 31.3.2014)
• New insurance certificate will be filed in your ISF by the CRA during the next monitoring visit
• Check of ISF/PSF for completeness by site and CRA, e.g. updated CVs (<2y), updated reference ranges, copies of temperature logs, etc.
• File all outstanding documents latest during the close-out visit (COV)
• Forms have to be signed by PI latest at COV (e.g. delegation log, temperature excursions, site close-out statement)
• Availability of PI absolutely essential for COV -> good planning important!
• Notification to Regulatory Authorities and Ethics Committees within 90 days after end of trial
• Will be performed by Sponsor
• CAVE: check if any local requirements: local
authorities, R&D (UK), internal clinic regulations, etc.? -> to be performed by site staff
(except Germany: sponsor will inform local authorities about end of trial)
• Archiving period for essential documents from clinical trials:
at least 10 years after study end
• CRA will prepare ISF/PSF for archiving
• Patient files to be archived by sites according to local regulations (but at least for 10 years)
• Completed eCRF will be provided on CD-ROM, to be archived also for 10 years
• CAVE: inspections can occur also after study end!
• Prolongation of site contracts as per site request (answer received from most sites)
• Documents currently being prepared and will be sent soon
