Independent Data Monitoring Committees (DMC) safeguard both the interests of clinical trial participants and the integrity of the trial itself. In turn, an independent Statistical Data Analysis Centre, typically implemented by a CRO on behalf of a sponsor, fulfils a vital role in the process by providing robust, independent analyses based on instream data to inform the DMC’s interim decision-making. The position bears a great deal of responsibility since only the Statistical Analysis Data Centre, and the DMC have unblinded access to the interim efficacy and safety data.
While Statistical Data Analysis Centre activities may appear straightforward on the surface, they have some inherent challenges that need careful and experienced handling. In this case study, we share experiences and lessons learned from working with a sponsor on a DMC for an oncology trial. Although this project had some complexities, the success factors and learning points are generalisable and underpin Veramed’s overall approach to DMC solutions.
Phase 2 oncology trial with novel endpoint
Our client planned a pivotal phase 2 oncology trial in a rare indication using a novel, complex, derived primary endpoint. The endpoint had been described in peer-reviewed literature but was not sufficiently well specified for direct implementation without additional detail. The trial design incorporated a single interim analysis considering the futility of multiple dose choices to be overseen by a DMC, the timing of which was event-driven. The client approached our team to provide independent statistical analysis services to support the DMC.
Developing a solution and planning
Built through collaboration
With significant experience managing DMC projects, Veramed has developed a set of best practices to ensure successful outcomes. Because of the self-sufficiency that the unblinded status demands, sponsors need to place high levels of trust in their CRO partner to deliver quality, robust analyses within short timelines while assuring trial integrity.
Arguably, the planning phase of any project is where we establish the groundwork for its ultimate success, which is especially true for DMC projects. During the unblinded phase, the CRO must limit contact with the sponsor to preserve trial integrity, precluding routine day-to-day sponsor communications. Therefore, before the unblinded period, close collaboration with the sponsor is fundamental to ensure alignment regarding the analysis specifications and iron out any ambiguities or issues.
Since this trial used a novel endpoint, the planning phase was especially important, and Veramed collaborated proactively with the sponsor at the outset to build out detailed specification documents for the analysis.
With an event-driven analysis based on fast accruing data, there was little control over when the DMC would be called, so flexibility and responsiveness were critical. Bringing preparatory programming steps upfront and taking activities off the critical path improved overall efficiency and ensured adherence to demanding turnaround times. By incorporating dry runs into the schedule, we built the sponsor’s confidence in the approach and eliminated any programming glitches before the interim analysis itself.
Unblinding and supporting the DMC
Ensured through integrity
A successful statistical analysis data centre relies on a multi-disciplinary statistics and programming team to coordinate the fast-moving deliverables, liaise with the DMC members, and implement robust processes.
We drew on two core roles for this project, complemented by a wider statistical programming team to support the analysis.
An independent Statistician is the heart of the team, liaising with the DMC members and accountable for ensuring integrity of the analyses presented. For this sensitive, important role, we assigned a seasoned and self-sufficient individual with excellent judgement and the ability to communicate well with clinicians.
The lead Programmer is typically handling instream data with multiple idiosyncrasies. For this project, we allocated a lead with strong therapeutic knowledge and the technical aptitude to identify and address any data anomalies while creating outputs quickly and efficiently.
DMC members also need to remain distanced from the trial sponsor to ensure the integrity of the committee decisions. Therefore, our role also incorporated administrative support to help the members access reports and understand the analysis, as well as capture meeting minutes. In this case, the independent Statistician provided this crucial guidance and support. An alternative approach is to appoint a dedicated DMC project manager to guide this process and streamline communications and record keeping.
Delivered with Excellence
At project closeout, we ensured timely delivery of the required documentation for the trial masterfile. We completed this administrative task seamlessly thanks to the meticulous preparation and ongoing record-keeping throughout the project.
Efficiency and quality outcomes
By combining careful planning with efficient ongoing management, we successfully delivered an accurate data package to the DMC within four days from data availability to report and have achieved an even faster two day turnaround on other projects with different specifications. This outcome benchmarks extremely favourably versus an average industry timeline of closer to two weeks.
Building on success
The success factors for this project align closely with the core values of collaboration, integrity, and excellence that underpin Veramed’s overall delivery ethos. Our team of experts is committed to working with customers to navigate the challenges of DMCs and advance clinical research for the benefit of patients.
To build on our strong foundation of expertise and experience in this area, Veramed recently launched a dedicated end-to-end Data Monitoring Committee service to further develop process efficiencies and strengthen our offering for sponsors. To learn more, click below.