Building a robust and efficient electronic data capture system (EDC) for today’s complex clinical trials is a major undertaking. The elements of the EDC must be carefully planned, the programming must be succinct, and the risks to data integrity must be considered. Clearly, these crucial requirements demand careful thought and can be time-consuming. An option for the timely initiation of a trial may be to split the release (a.k.a., the “go-live”) of EDC elements in a controlled and considered manner. PROMETRIKA’s Data Management team has extensive experience with planning and executing successful split-release EDCs.
Planning the EDC Build
A ‘split release’ of a clinical EDC refers to creating, testing, and then releasing portions of the EDC for use before the entire EDC is complete and tested. The substance of the releases for any given trial depends on the needs of that trial. For one trial, it may be appropriate to release all Case Report Forms, followed, some time later, by all edit checks. For another trial, it may be most effective to release some forms and edit checks together (e.g., for the single ascending dose portion), followed by the remaining forms and edit checks (e.g., for the multiple ascending dose portion).
Clear communication and co-planning with all functional teams, including those of the sponsor, is crucial. PROMETRIKA’s Database Programming, Data Management, Biostatistics, Project Management, and Clinical Operations departments need to have equal input because timelines for all functional areas intersect. Each area has information needed for a successful EDC build, such as:
- the expected study workflow;
- planned SOP deviations, including a risk analysis of the impact on the EDC;
- the Core Configuration timeline, including expected study roles and workflow;
- user acceptance testing (UAT) design and timeline;
- triggers for future changes and releases.
Another factor is the integration of data from external sources, such as randomization tools and laboratories. Priority data transfer specifications and the appropriate forms for data reconciliation need to be ready before the first participants enter the study. The workflows for all of these steps also need to be agreed upon and the Data Management Plan (DMP) must be continually updated with all these processes. All of these factors affect the target date(s) of releases.
Post-production Changes
Post-production changes (PPCs) can occur at any time during the EDC build, especially over the course of multiple partial releases. The sponsor and all the involved departments must agree to the specific scope and timeline of the PPC. Data Management must perform an impact assessment, questioning what the impact may be on existing data and whether any data will be lost. Clear documentation of data that may be or will be lost is critical. The Database Programming team should be consulted about possible effects on existing custom function programming or the risk of lost data. Of major importance is whether the change will affect the statistical analyses planned for the trial. Of course, after the change is implemented within the EDC, validation, test migration of data, and UAT must be performed before the updated EDC is released.
Risks for Consideration
By its nature, a split-release plan has many ‘moving parts’; all decisions have not been made before work on the build begins. Teamwork and good communication are essential to successfully execute a split release.
Initial discussions with the sponsor must be open and frank about what can be accomplished in specific time frames. Processes that sponsors may not be familiar with need to be reviewed. For example, if edit checks are not complete for the first partial release and the sponsor wants a quick or early data report, manual checks might be needed. In this case, the sponsor will be asked to review and approve the logic of the manual checks. The risk is that this process may end up taking more time than programming the edit check.
Protocol development may be fluid when the EDC build begins. The sponsor and the PROMETRIKA team must agree on which protocol version will be the basis for the build. And, as the protocol continues to develop, it must be clear which version affects each partial release. In short, the EDC is developing ‘at risk’ of rework.
Changes in the protocol, the need for rework, and PPCs may lead to timeline and cost overruns. Timely communication with the sponsor about these risks must continue throughout the EDC build and edit.
Finally, sometimes there are human elements to consider. For example, as sponsor and site personnel enter the project, they may not be aware of the plan for split release of the EDC. This can cause confusion, frustration, and ill-feelings. The Project Management and Clinical Operations teams need to be aware of these possibilities and ensure that all personnel are kept up-to-date.