1. 11/23/2019
Database lock to Data Safety Monitoring Board meeting – More than a click of a button
David Prince, PhD, Manager, Biostatistics
31 July 2019

2. Axio Overview Experience Services Professional
11/23/2019
Axio Overview
Providing Biostatistical and Clinical Trial Services for 40 Years
Experience
Services
Professional
Established in by University of Washington faculty as SERC
Continuing relationship with UW: faculty as “friends” and consultants, students as employees
Recently merged with Cytel
DMC support
Adaptive design interim analysis
Randomization checks
Event projection
Clinical trial design
Statistical analysis plans
Biostatistics consulting
Data Management
Statistical genetics and genomics
FDA Workshops
CDISC Advisory Council
American Statistical Association
PharmaSUG
Society for Clinical Trials
BASS
UPenn Annual Conference on Statistical Issues in Clinical Trials

3. Main aims from a report production perspective
Having sufficient time to identify and understand or resolve all issues in the data or programming.
The DMC report to accurately reflect the data at the time of the database lock.

4. Upcoming DMC meetings at Axio
For n=34 studies with upcoming meetings (as of June 2019)
Median 29 calendar days
Range from 14 to 57 days

5. What Happens between Database Lock and the Meeting
Activities before the lock
Data transfer
Production code re-run
Validation or testing code re-run
QC of the report
Sponsor review
Preparation of additional materials and final review
DMC review and meeting

6. What Happens between Database Lock and the Meeting
Activities before the lock
Review previous meeting documents
Confirmation of expected outputs (including cohorts)
Timelines (Study, Contract, Charter)
Changes to the protocol or data
Expect specific derivations, e.g. LKDA, date imputation
Data transfer
Multiple sources (and portals)
Raw vs. SDTM vs. analysis datasets
Consistency
Use of LibComp macro to identify changes

7. What Happens between Database Lock and the Meeting
Production code re-run (and updates)
Assuming Axio created
Non-standard data sources checked
Log search macro
Validation or testing code re-run (and updates)
Proc compare
Confirm agreement on analysis datasets (TLFs)
QC of the report
Min, max, outliers (e.g. exposure)
Internal consistency
Early phase or trials with substudies

8. What Happens between Database Lock and the Meeting
Sponsor review
Clarity on what the sponsor can review
Dummy randomization, different ratio
Axio cannot change the data
Preparation of additional materials and final review
Use of 23-item report production checklist
Formal interim
Validation documentation
Executive summary (include any data issues or appreciable changes)
Cover page, TOC

9. What Happens between Database Lock and the Meeting
DMC review and meeting
Generally 5 business days
Known issues communicated
DMC understands data is imperfect
Ad hoc requests common

10. Meeting the aims Planning Communication
Review reports, review documents, review specifications…