Increasingly, regulatory authorities are placing significant focus on clinical trial processes that ensure consistent, standardized, objective and unbiased reporting of safety and efficacy results; given that the definitions for many endpoint events include subjective components, and investigator-to-investigator subjective assessments may differ. Moreover, an increasing number of trials are now conducted in multiple geographies, and clinical practices across these settings can vary substantially. The likelihood of discrepant interpretations of safety and efficacy endpoints by investigators is thus increased.
Throughout a clinical trial, therefore, it is expected by regulatory agencies that certain events that form safety or efficacy endpoints for the study undergo centralized adjudication by a clinical endpoint adjudication committee (CEC).
A CEC consists of a panel of independent experts who have the relevant therapeutic area expertise, are experienced in clinical trials and have been trained on the specific study protocol. The CEC centrally reviews subject/event data and classifies efficacy and/or safety endpoints in a blinded and unbiased manner. The centralized adjudication process should be designed to both preserve the independence of the CEC and prevent any undue bias that could impact its decision-making processes.
A CEC can be used in any therapeutic area where there is a need for an independent, accurate, consistent and standardized assessment of important study events. CECs are most commonly used in cardiovascular outcome / safety studies; however, they are also frequently used in peripheral vascular disease, neurovascular, respiratory and oncology studies.
In Cardiovascular outcomes studies, a Major Adverse Cardiac Events (MACE) composite endpoint is often used as the primary endpoint for evaluating efficacy and/ or safety. MACE is comprised of non-fatal myocardial infarction, non-fatal stroke and cardiovascular death. Once events are confirmed through centralised adjudication to meet protocol endpoint criteria, endpoint data is analysed for the number of occurrences of the composite endpoint in the respective treatment groups.
Similarly, regulatory guidance is available for the definition and adjudication of other clinical endpoints that may be complex in nature. These endpoints are often defined by a combination of signs and symptoms experienced / reported by the subject as well as biomarkers. Examples include Food Drug Administration (FDA) guidance on oncology endpoints focusing on specific cancer types (e.g. lung cancer, colon cancer) which will help support drug approval or labelling claims.
The use of CECs to adjudicate suspected endpoints has increased considerably over the past 10 years. CEC adjudicated endpoints are critical to the success or failure of many trials. CECs are vital to the objective and unbiased reporting of endpoints in complex trials running across varying clinical practice settings; trials where efficacy and safety outcomes are not clearly/easily defined and have multiple components; and outcomes trials where approvals for registration depend upon safety and efficacy outcomes.