Web Meeting 12./ : Study Close-out Procedures

Transcription

1 SiLVER Study A prospective, randomized, open-labeled trial comparing sirolimuscontaining versus mtor-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma Web Meeting 12./ : Study Close-out Procedures

2 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) SAE reconciliation and safety issues 2

3 AGENDA 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 Questions and discussion 3

4 Endpoint Status and Timelines 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: Monitoring visits after LPLV at individual sites to clean all ecrf data ASAP 4

5 Scheduling of Last Patient Visit 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 5

6 Safety Follow-up 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 6

7 ecrf Completion 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!) 7

8 Study Conclusion Page 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 8

9 Data Cleaning and Query Resolution 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 9

10 ecrf Signature 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 ) 10

11 SAE Reconciliation and Safety Issues 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! 11

12 PIS Addendum 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) 12

13 Drug Supply and Accountability 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) All documentation must be available in ISF 13

14 Lab Normal Ranges Project 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 14

15 Patient Insurance Insurance was prolonged until for all countries (except Australia until ) New insurance certificate will be filed in your ISF by the CRA during the next monitoring visit 15

16 ISF Completion and PI Signature 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! 16

17 End of Trial Notification 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) 17

18 Preparation for Archiving 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! 18

19 Any Other Business Prolongation of site contracts as per site request (answer received from most sites) Documents currently being prepared and will be sent soon Questions??? 19

20 Thank you!!! For all your hard work over the years and for your cooperation and efforts in the upcoming close-out phase!!!