Also called Endpoint Adjudication Committees, Clinical Endpoint Committees (CECs) are an increasingly common component of drug development and medical device evaluation. A CEC is a centralized decision-making body for safety and efficacy endpoints. The goal of a CEC is to standardize outcomes and optimize data quality, ultimately driving study success. A CEC addresses the challenge of defining efficacy and safety endpoints that are scientifically measurable, objective, and valid.
What do CECs do?
Clinical trials are often driven by clinical events, which may lack standard definitions and are subject to interpretations. Sponsors need a method to reduce the impact of this potential variability on conclusions drawn from outcomes data.
A CEC is an independent group of clinical and/or diagnostic experts who:
- Centrally review and classify possible safety and/or efficacy endpoints in a blinded, unbiased, confidential, and consensus-based manner
- Determine whether potential endpoints meet protocol definitions and endpoint criteria
- Provide standardized endpoint outcomes for statistical analysis
- Classify events as related to a study device or procedure
In addition to endpoint-specific data, CECs also review overall subject data. This review includes serious adverse events, reports of death, and adverse events that have the potential to become clinical study endpoints. In the case of medical devices, a CEC review also includes serious adverse device effects, unanticipated adverse device effects, and device deficiencies.
When does a trial need a CEC?
The classification of study endpoints is partly a subjective process, applying a set of medical endpoint criteria to an often complex clinical event. Investigator classifications are subject to variability due to individual differences in medical training, clinical judgment, and regional norms. CECs are recommended when there is a high degree of variability between study sites. CECs help to mitigate these differences by:
- Limiting the number of individuals tasked with classifying study endpoints
- Providing greater assurance of the systematic application of the protocol definitions of suspected endpoints
- Employing experts to assign these classifications, ensuring greater precision and standardization
Centralized adjudication is also helpful when:
- Endpoints are complex and/or subjective
- Studies cannot be blinded
- Studies are expected to have a high enrollment or long duration
- Significant cultural differences are expected across study sites, a common issue for international trials
- Endpoints of interest fall outside an investigator’s therapeutic specialty
- Data is needed to support Data Monitoring Committee or Data Safety Monitoring Board functions, interim analyses, or adaptive study designs
How are CEC-adjudicated outcomes used?
CEC-adjudicated outcomes typically validate, negate, or otherwise modify initial classifications of possible endpoints, such as those assigned by sponsors or investigators. CECs sometimes identify new, previously unreported suspected endpoints for investigation and follow-up. CEC-adjudicated outcomes are not provided to study investigators because knowing the results may bias investigator reporting of future suspected endpoint.
However, CEC-adjudicated endpoints may be incorporated into a number of important decisions, such as power estimations, periodic safety reviews, sample size re-estimation, and overall safety and efficacy analyses. Consequently, CEC-adjudicated outcomes must be finalized and made available to appropriate parties on an ongoing basis throughout the entire lifespan of a trial.
CECs enable early identification of safety risks and efficacy signals, facilitating go/no-go decisions that have the potential to reduce overall study costs. As such, CECs play a particularly integral role in adaptive design trials.
Are CECs necessary for regulatory approval?
CECs may not be officially required, but they are recommended for sponsors looking for a smooth market approval process. Having the right CEC in place inspires greater confidence from regulatory authorities, such as the FDA. Additionally, the regulatory environment in both the U.S. and Europe is placing increased emphasis on benefit-risk balance, putting sponsors under greater pressure to minimize variability in endpoint outcomes. For these reasons, the use of CECs have been included in guidances from both the FDA and the European Medicines Agency.
What else is there to know about CECs?
Of course, this overview just scratches the surface. To find out more, be sure to read our recent white paper, Clinical Endpoint Committees: Ensuring the Quality, Validity, and Integrity of Clinical Trial Results, for the full story. And don’t forget to register for our next medical device webinar on the role of CECs in device trials.