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Involvement of clinical endpoint committees in the adjudication process can improve reliability and robustness of data.
Clinical adjudication is a standardized process to assess the safety and efficacy of new drugs, biologics, and devices during clinical trials. Through clinical adjudication, independent, blinded clinical endpoint committees (CECs) provide an unbiased review of clinical endpoints and events to ensure the validity and integrity of trial results and, more importantly, the safety of trial participants. CECs improve efficiency with real-time review of clinical endpoints that enhance transparency of study data.
However, while the benefits of CECs are clear, challenges remain that can inhibit the adjudication process. FDA supports adjudication as a best practice and has issued some guidance documents based on the trial indication but may suggest CEC involvement for specific events during a study because of a safety signal, such as for interstitial lung disease or major adverse cardiovascular events. This clinical specificity makes selecting the right adjudication partner a crucial step to the trial process, and can help guide sponsors through the complex adjudication workflow. Here’s a look at common pitfalls that sponsors must be mindful of to facilitate rigorous and effective clinical adjudication.
Effective adjudication is dependent upon knowledgeable experts in their field of practice. All members of the CEC must understand their roles and responsibilities from the onset of the trial, including important clinical event definitions and data and reporting requirements. Having a knowledgeable team who are experts in the field of the event being adjudicated, such as respiratory or cardiovascular, helps process adherence and thoughtful, timely review of clinical events. Sponsors should look for experts who are well-versed on current best-practices; are up to date on regulatory compliance; have the ability to clearly define safety events at the start of the study and collect all required data for analysis. Involving physician adjudicators in the trial planning process can help identify such things up-front and keep trials on schedule and on budget.
That experience extends to clinical nurse reviewers (CNRs) who serve in a quality control capacity during the case review workflow, making sure the “story” is in the source documents before it is shared with the CEC for analysis. This saves the committee time and provides an extra layer of clinical oversight to make sure committee members have all the information required to make an informed decision. CNRs are key to successful adjudication as they are responsible for all medical content reviews in the dossiers. They provide an additional layer of quality control to confirm the deidentification of protected health information, eliminate bias that may be introduced via source documents, and certify the study arm is not revealed.
Experienced, third-party clinical project managers are nonbiased partners who can manage the adjudication process from start to finish. Not affiliated with the sponsor or CRO, the partner will support objective charter development, provide insight to clearly defined events, and create a detailed plan and timeline to track and meet milestones and deliverables. This project manager is responsible for coordinating roles-based training, consensus meeting coordination, and serves as primary point of contact for all CEC technology customization for the study.
Technology serves a critical function of centralizing information and streamlining communication between the CEC and clinical sites. Many adjudication programs are global or become so if a trial participant experiences a clinical event while traveling, for example. When this happens, a web-based platform can enable upload of needed source material to expedite the adjudication process. Additionally, a dedicated adjudication project manager and/or support team who speaks the local language and are available 24/7 help with uploading issues or site queries by the CEC can be addressed without delay. A flexible cloud-based adjudication platform supporting the trial can help keep all tasks and support persons on schedule, and also facilitate real-time communication and regulatory compliance with all processes. A platform such as this also can alert trial sponsors and adjudicators when a consensus is not reached among the committee, so potentially costly delays can be avoided.
Choosing experienced adjudication experts should be carried out with rigor to withstand review by all study stakeholders, such as data management, clinical operations and safety and regulatory teams. The decision to incorporate CECs should be made during the trial planning process and the charter should include input from experienced adjudicators to define endpoints, reporting requirements, and the necessary source documents to support that potential clinical event.
All requirements should be clear from the onset with the expectation of full transparency and access to real-time case status reporting dashboards. Adjudication charters should include fully defined event types, the required supporting source documents, the process for data collection and the transfer of the adjudication result to provide the sponsor with the information needed for their analysis. The charter should also address who has access to the adjudication system and for what purpose. Lack of clarity around reporting requirements can result in incomplete case reviews and submissions, and ultimately, delay the trial’s progression and/or approval.
Technological advances have significantly enhanced the CEC process, previously reliant upon paper and manual spreadsheets. Therefore, it is important for study sponsors to assess the electronic adjudication system before selecting a CEC partner. Features involved in assessing systems include the following: ease-of-use and customizable platforms to meet each trial’s unique needs; 24/7 support, along with advanced security and access control; built-in e-signatures, audit trails and cloud backups to secure and protect data; audit trail transparency that is both 21 CFR Part 11 and GDPR compliant, and provides adjudicators prompt access to the necessary information on every clinical event type.
Other advances in the CEC systems include web and cloud-based systems supported by machine learning with algorithms that can drive gains in efficiency, data quality, and compliance. Also, applications and experienced support services that facilitate remote collaboration and allow committee members to review clinical events, as well as customized workflows that allow researchers to electronically manage the process around endpoints from start to finish.
Clinical adjudication must remain an independent process of the clinical trial to ensure the validity of signal detection and adjudication results. Timeliness in reporting of CEC results to safety boards allows sponsors to assess signals in the trial that may steer changes to the protocol or sometimes even halt the project due to patient safety issues. Adjudication systems should allow sponsors and other stakeholders to log in and pull reports as needed. Full access can support the planned interim analysis of study data, for example, which can lead to modifications in study size and sample size, or even early termination of the study if the data clearly indicates the trial’s success or conversely, clearly indicates the futility of continuing the study.
Clinical adjudication is an important step in the trial process, especially given the increased complexity and global scale of clinical trials. Having an independent and unbiased review of clinical events ensures the complete and accurate capture of protocol-driven endpoints. Involving CECs improves the robustness and reliability of trial data so sponsors can focus on outcomes, as well as help sponsors achieve high-quality data without clinical bias.
Judy Narisi, RN, BSN is a Senior Director of Adjudication Services and Specialty Solutions at Clario