You Need to De-Risk Your Clinical Trials with Independent Experts

The FDA Data Monitoring Committee guidance refers to the interaction between two different expert committees: endpoint adjudication committees (EACs) and data monitoring committees (DMCs). DMCs monitor unmasked trial data in an unbiased way, while EACs focus on evaluating individual medical events to verify that they meet the clinical trial design’s defined endpoints or adverse event criteria. Adjudication determinations regarding individual events are incorporated into the overall trial data, which ultimately impacts the DMC’s analysis. Thus, proper EAC committee selection is essential.

Challenges of Non-Outsourced Models

Adjudication is a process to ensure that safety and efficacy assessments are objective and without bias. “The goal of an EAC is to provide a consistent, repeatable process to evaluate how events will be classified,” states Shaena Kauffman, executive director of EAC Operations at WCG. “EACs act as independent bodies to classify events, efficacy outcomes, and safety outcomes. For an EAC to function properly, it must be an independent body.” This means that members are not involved in treatment of the study’s patients or participating as investigators at the site. This separation can often be tricky if sponsors or contract research organizations (CROs) attempt to create and manage these committees in-house, where conflicts of interest may be prevalent.

Both large and small sponsors and CROs have encountered difficulties with committee management, but particularly with EAC management. What typically happens for companies using a non-outsourced model for their EAC is that they add more members to the team who traditionally work in clinical trial management. While these members understand clinical trial management, they frequently do not have EAC process knowledge and experience that an outsourcing provider would have. Only with experience and guidance are EACs able to recognize potential issues that need more attention quickly and avoid wasting precious time on those that do not.

Outside Expertise

“When we think about adjudication and subjectiveness of normal and abnormal interpretations, there is of course an increased likelihood that there'll be discrepant readings of endpoint data,” notes Kauffman. “Sponsors must have a consistent process in how adjudication occurs, so it's viewed favorably by regulatory agencies.”

While the decision to outsource or not to an expert provider is a common question, sponsors and CROs must be careful in the provider they choose. It is essential that the independent expert committee be properly managed and supported to set them up for success. An effective EAC provider can handle any committee interpersonal issues or guide inexperienced members. As Kauffman explains, “Because they have knowledge, that is critical. The provider and sponsor collaborate to verify that there is not an overlapping conflict, and to verify that the members understand their role on the committee.” But EAC management does not stop here.

Since critical workflows and documents are developed simultaneously as the committee is formed, Kauffman highlights key areas that CROs and sponsors should focus on when evaluating an expert provider. “Proper planning templates, knowledge of the industry, best practices, as well as having access to experts to sit on your committee is essential. So the charter, which is really the first deliverable about forming a committee, must be inclusive of all of that, and it should be available upon request.” When evaluating expert committee providers, sponsors and CROs must select one that has the expertise, tools, and infrastructure needed to create the documentation simultaneously.

Rescue Committees

While the optimal approach is to work with an experienced EAC provider from the start, there are times when problems arise, and sponsors need their adjudication committee rescued. Often, when sponsors face issues with their adjudication committees, they are unable to immediately recognize or fully address the problem. This is the time that extensive adjudication experience and regulatory knowledge are needed. When selecting a rescue committee, sponsors and CROs should look for EAC providers who have a well-designed approach, beginning with a thorough assessment.

From this point, they create a transition plan and make recommendations to both the sponsor and adjudication committee. By incorporating adjudication and sponsor input, the EAC committee management provider can create a customized adjudication system to address analysis needs and previous pain points. After a complete assessment, charter amendments are created and finalized and the EAC provider is then able to resume work for the trial.

Given the importance of adjudication, both the FDA and EMA recommend that committee members and management be separate from sponsors or CROs. As illustrated above, rescuing a committee is not a simple or quick task. Sponsors must, however, be selective when partnering with an outside EAC provider at any stage. Not only must they be experienced and familiar with adjudication nuances, but EAC providers must also have the same focus as the sponsor, which revolves around keeping the end goal in mind.