All phases of a trial can benefit from an EAC, from eligibility and on-study determination of safety and efficacy to overall patient status. Most of our EACs consist of sophisticated, fully digital evaluations using multiple BICRs rather than the panel review approach.
Most Common EAC
Although we offer EACs for all subjective clinical endpoints, the most common are:
Overall Patient Status in Oncology Trials
- Determination of response and/or disease progression status in cancer trials
- Safety Reviews also called clinical events committee (CEC) which focuses most often on:
- Major adverse cardiac events (MACE)
- Malignancy detection in non-oncology trials
Assessment of disease progression is often the primary endpoint of registration trials for oncolytics. These trials require collation of multiple data sets, including radiology, pathology, and clinical files. For melanoma studies, dermatology images may also be evaluated. The EAC of these trials often require multiple BICRs, one for radiology and another for pathology and then the definitive final analysis by the oncologist to determine disease status. The figure below depicts the EAC for a melanoma trial.Eac-workflow-final
WCC has developed a uniquely sophisticated digital portal that maximizes the precision and accuracy of the oncologist by allowing him/her the ability to see all prior BICR data on the patient and change assessment results. The result of these changes is provided to the reviewer in real time so that it may be incorporated into the patient's overall status assessment.Dermatology EAC
This service consists of centralized quantitative analysis of skin photographic imaging data for the pharmaceutical, biotechnology, and cosmetics industries. Our in-house staff of trained technologists perform pre-measurements, eliminating the need for a dermatologist at each clinical site to assess lesion characterization and measurements, which can result in a significant cost savings. This can be particularly compelling for large international melanoma studies, where patients are being managed clinically by the referring oncologist, making it more effective and efficient for both the sponsor and site.
A Well Designed and Conducted BICR Can Reduce Trial Costs
Simulation studies conducted in collaboration with with Dr. Fenghai Duan, assistant professor with the Department of Biostatistics and Center for Statistical Science at Brown University, demonstrate that small changes in reader precision and accuracy can result in decreased trial sample size and ultimately trial costs.
WCC believes that the results from its study can be applied to any BICR involving subjective clinical data. Our approach is the same for all BICRs - we leverage our relationship with Harvard and other leading teaching hospitals, allowing us to draw from the best subspecialty-trained, board-certified practicing physicians, who are then trained by WCC under a uniform system to maximize the precision and accuracy of data interpretation.
BICR: The FDA Weighs In
The FDA's 2011 Draft Guidance Standard for Clinical Trial Imaging Endpoints states that a blinded independent central review (BICR) is often needed in situations where clinical site image interpretation is variable and results of image measurements are important for eligibility determination, safety and/or efficacy endpoints.
"…the centralized process can better provide verifiable and uniform reader training as well as ongoing management of reader performance, ensuring that the process is accurate and that bias and variability are minimized…"
Independent Review Workflows
Whether your trial requires a single radiologist with a single modality, a double-blind read with adjudication and multiple modalities, or simply an image management platform, WorldPRO® can be configured to meet your specific needs. Complex workflows also support technical pre-measurement and EAC reviews, without requiring special hardware or in-depth training.
Clinical Event Committees
Recently the FDA and other regulatory agencies have been recommending independent reviews of safety data. We considered these clinical event committees (CEC) a type of EAC which most often focuses on specific class labeling issues. Like our other EAC, these committees use:
- Integrated teams of board certified subspecialty trained physicians
- Superior independent review assessment paradigm as compared to the consensus method of adjudication
- Pre trial and on-study training and testing
In addition we currently have multiple cost effective "On Demand" solutions for independent reviews of AEs. These rapid startup high throughput committees can provide trained expert assessment of AEs.
Since the objective of our "On Demand" safety EAC is to independently adjudicate adverse events regardless of causality, we are able to provide sponsors with a cost efficient adjudication of AEs by adding additional adverse reaction assessments to our standardized ongoing safety assessment committees. All our standard safety committee solutions have recently been reviewed by the FDA and comply with regulatory requirements.
"On demand" Cardiovascular Event Committee (CEC)
Our cardiovascular event committee, also called major adverse cardiac events (MACE), consists of leading experts from Massachusetts General Hospital. Potential events of interest are stratified by type, cerebrovascular or cardiovascular. An automated software workflow engine triages the cases to either stroke neurologist or cardiologist. Imaging data, if available, is also provided to the independent reviewers which increases their assessment confidence. Our committee uses the recent FDA recommended "Standard Definitions for End Point Events in Cardiovascular Trials". For sponsors who have ongoing cardiovascular endpoint committees, WCC has experience mapping prior dictionaries onto the new standard definitions and provides complete backward compatibility. Our board certified subspecialty experts have demonstrated excellent agreement for the assessment of major adverse cardiac events (kappa scores >0.8).
"On Demand" Malignancy EAC
Our malignancy EACs consist of research Oncologists from Harvard and certified cancer tumor registrars to capture all attributes related to tumor typing using the most current cancer dictionaries. Imaging data can also be assessed by the reviewers.
Requests for Rapid Independent Safety Review of Imaging Data
We know it is important for your safety reviews to be done fast. We have taken measures to train board-certified, practicing radiologists to be ready to complete assessments within 24 hours of receiving scans – any day of the week from around the globe. If necessary, we can deliver those reads even faster.
Efficacy assessments in imaging are often facilitated by a batch review. This causes extended delays in determining incidental safety findings. By adhering to our commitment to bring the fastest safety review turnaround in the industry, those delays can be cut to a fraction of the time.