Database Lock to DMC meeting Lisa Weissfeld Joint Statistical Meetings Denver, CO July 31, 2019

Overview DMC vs. non-DMC How clean is clean? Negotiating with the Sponsor for DBL for a DMC meeting Allow time for important data queries to be addressed Balancing “sponsor” checking vs. timelines for a DMC meeting How long is “too long” for the time lead-up time to a DMC meeting? What do you focus on fixing and what do you let go?

DMC vs. non-DMC Transfers for DMC meetings tend to be “messier” even after the initial cleaning (going to the automatic car wash) as these are “real-time” extractions. Transfers for final analyses should be clean as these are end of study extractions. (having your car detailed)

How clean is clean? Depends on the purpose for which the data are used Efficacy data (detail level) Patient status information (detail level) Key safety information (detail level) Laboratory parameters (automatic car wash) Certain listings such as medications (automatic car wash)

Negotiating with the Sponsor Typically time from DBL to report is written into the contract and should allow for time from receipt to resolution of important queries. Issues that can affect this process are: Data arrives late Answers to queries arrive late or not at all Data arrives in a different format than prior transfers

Negotiating with the Sponsor Balancing sponsor checking vs. timelines for a DMC meeting Handling situations where the sponsor wants to check the open report adds to the timeline Because the database is dynamic there are often discrepancies in analyses presented by a sponsor at open session when compared to data in the open report. Most sponsors recognize this as an issue, others want to expend more effort to reconcile any differences.

Negotiating with the Sponsor How long is “too long” for the time lead-up time to a DMC meeting? Depends on the setting (i.e., length of follow up of patients, enrollment, etc) Concern over a potential safety signal may drive the independent statistical group to attempt to shorten the interval between DBL and analysis DMC may also have opinions regarding data currency

Negotiating with the Sponsor What do you do when the Sponsor does not want to correct errors in data using methods of hard coding? What do you focus on fixing and what do you let go? Focus on the “important” data which is situation-specific Do your best to address the “important” data issues