Lessons Learned from a Recent Industry Roundtable: Technology is Enhancing the Efficiency of Clinical Trial Endpoint Adjudication Management
It’s well known that even the most experienced investigators can interpret everyday clinical events—whether for safety or efficacy—very differently. This is especially true in large multi-center and multi-country studies when clinical endpoints are subjective, image-based, or complex to assess, such as cardiovascular events, pain, fatigue, depression, neurological scans, and genetic information.
Incorrect or late identification of outcomes results in more variable clinical data. This can cause lengthy and expensive delays that negatively impact budgets and development timelines for new drugs and devices. This is why the industry has widely embraced Clinical Endpoint Committees (CECs) over the past few decades.
CECs provide independent, blinded evaluation of suspected clinical events. However, managing CECs is costly and resource intensive. Many research groups are now using clinical trial technology to streamline their endpoint adjudication processes, but many continue to rely on outdated and laborious methods.
Recently, Medidata held a roundtable that brought together industry leaders to discuss best practices in endpoint adjudication in clinical trials. Below is a summary of the discussion and key takeaways, focused on the following theme: Best practices, lessons learned, and trends for implementing, managing, and harmonizing endpoint adjudication processes and CECs.
Summary of Key Takeaways
CECs Are Strongly Recommended for Subjective Endpoints and Should Be Established Early.
Despite no definitive industry requirement for implementing a CEC, the experts strongly recommended doing so when endpoints are subjective and require unbiased medical judgment. The participants accepted that a ~20% discordance exists among site and central assessments. The general consensus was that the earlier implementation begins, the better the study outcome will be.
A CEC Charter Should Clearly Articulate the Criteria for CEC Membership, and Junior Members Should Not Be Overlooked.
Participants stressed the importance of establishing a CEC charter—ideally via an independent vendor—that clearly states the membership requirements. A major criterion must be that members are free of any conflicts of interest. Participants also discussed a recent trend in which more junior members are recruited, with oversight from an experienced chair, because junior members tend to have more time available. The majority of participants also agreed that it’s best to have an odd number of members to help break ties in clinical trial endpoint adjudication and that a geographically-diverse membership is beneficial.
Determining Standards and Definitions for the CEC Is a Shared Responsibility.
Participants agreed that definitions must be clearly defined within the charter. CRO/ARO standards typically incorporate sponsor requirements, which should be reviewed and approved by the CEC chair and/or members.
Identified Events for Adjudication Should Come Directly from Trial Sites and in Real Time.
Participants agreed that identified/triggered events should ideally come directly from clinical trial sites. But the CEC or automated technologies (using MedDRA terms) may flag them. Identification should also occur in real time, but this is uncommon. Best practices include having events available automatically in the adjudication system as soon as they are submitted within the electronic data capture (EDC) system and that outputs should be frequent to limit bottlenecks/delays at database lock.
Patient Narratives Are Trending Down.
The overall dossier should be free of bias. While many physicians and trial sites add narratives, this is becoming less common because it can introduce bias and needs to be managed as part of the clinical trial dataset. Participants agreed that a best practice is to collect key information directly in the EDC case report forms.
Narrow Down the Number of Source Documents. Ideally, Obtain Source Information Directly from the EDC.
A best practice for determining what is needed for each event is to create a checklist of specific source documents required per event type. This is a multidisciplinary team effort. Consider narrowing down the number of documents required, if possible. To reduce potential obstacles to document collection, it was agreed that obtaining source information directly from the EDC is strongly preferred when inadequate source information is provided.
Manual Protected Health Information Redaction Is Inefficient. Data Management Technologies Can Help.
Source document redaction is difficult, tedious, and not 100% effective. Participants agreed that data management technology-enabled tools reduce the error issues seen with manual redactions.
Clinical Trial Adjudication Processes Are Continually Evolving. Technology Is Making the Process More Efficient.
Participants agreed that a typical adjudication workflow follows a 2–3-step CEC review process, beginning with an independent review of the same event. For a disagreement, the event moves to a third adjudicator for final decision or is escalated to a full CEC consensus. Participants also noted that almost all adjudication is currently performed remotely. A CRO representative said that 95% of its adjudication activities are done independently, without meeting as a committee. It uses technology to move events with disagreement outcomes seamlessly to the CEC for final review. That technology allows for both single and parallel workflows and accommodates voting. Participants stated that technologies need to be able to securely import data, documents, and sometimes DICOM (Digital Imaging and Communications in Medicine) images to support the CEC and dossier development.
Training and Retraining are Key to Successful Sites.
Sites must be trained on the checklist of documents and the source documents’ content. Providing the training manual in a Just-in-Time manual is paramount to receiving comprehensive source documents from the site.
Manual Adjudication Management Has Many Challenges. Adjudication Technologies Can Overcome Them.
Using spreadsheets or disparate systems adds great complexity and frequent reconciliation to the manual process, which is already cumbersome, lengthy, and error-prone. Participants noted the many challenges associated with manually tracking data. Participants concurred that a technology-enabled endpoint adjudication system could help get events adjudicated faster and with less effort.
Medidata Adjudicate – An Efficient Clinical Trial Adjudication Solution
Modern cloud-based solutions are rapidly transforming the adjudication process and help alleviate many of the challenges raised at the industry roundtable. These solutions integrate directly with EDC systems, allowing for instant access and real-time data management by CEC members worldwide, enhanced quality controls, comparison of adjudicators to peer groups, and enhanced uniformity and security of all documents within a patient dossier. For instance, Medidata Adjudicate offers comprehensive capabilities to support clinical trial event management, including integration with Medidata Rave EDC, customized workflows per event type, event status visibility and reporting, self-service configuration, web-based dossier creation and editing tools, and flexible communication options (e.g., additional data requests and queries with configurable query templates). Let Medidata Adjudicate transform the quality and cost-effectiveness of your next clinical trial.
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