Our process includes a set of module components that include hand picking top experts as committee members, planning the control schema for the assessment and providing fully digital evaluations.
Primary efficacy and safety endpoints are often subjective assessments made by site personnel. For international registration trials conducted over broad geographic regions and different clinical practice settings, variability in these subjective assessments can result in a loss of precision and accuracy. Centralized endpoint adjudication committees (EACs) offer a mechanism to remove treatment bias in open labeled trials and potentially increase the precision and accuracy of the assessment.
While no specific FDA guidance documents have been issued regarding the use of EACs and blinded independent central reviews (BICRs), WCC, in collaboration with Drs. Glenn Bubley, associate professor of medicine at Harvard Medical School and director of genitourinary oncology at Beth Israel Deaconess Medical Center, and Bin Yao, director of biostatistics at Amgen has published a review article which can be used as a process map for perform a central assessment of non-imaging clinical data.
We recommend that when clinical site data interpretation is variable and results of measurements are important to trial success, a BICR can provide consistent results through verifiable and uniform reader training as well as ongoing management of reader performance.
Experienced Committee Members are the Key
Each committee is sourced from board-certified experts from MGH, who have a range of experience in subspecialties, such as radiology, dermatology, oncology, cardiology, and neurology. They are able to perform blinded independent assessments and are trained by WCC to maximize the precision and accuracy of data interpretation and minimize variability.
Assessment and Control
The process starts with charter development, which includes decision algorithms for response assessment. A workload and time assessment that incorporates training and testing programs is created in conjunction with the sponsor and EAC chair.
By allocating roles and responsibilities for each member and their specialty, we ensure the highest level of validity of efficacy results. It also allows us to maintain comprehensive coverage and verify objectivity in a streamlined assessment process. We control read statistics and provide the necessary adjudication for consistent results. These statistics are fully available to the sponsor.
Fully Digital EAC Evaluation
As the size and complexity of registration trials increases, the challenges involved in managing digital EACs also increase proportionately. Electronic systems become essential to successfully collect, organize and present data for independent reviewers (IRs) in a regulatory-controlled environment. The EAC data, including clinical patient data, medical images, pathology slides, and other test results must be funnelled into a coherent central archive. A digital BICR process allows for multiple concurrent independent assessments of data followed by an adjudication triggered programmatically, if needed. Because it consists of multiple independent assessments, inter-reader variability can be analyzed and thus provide a better understanding of differences in interpretation strategies between EAC members.