Clinical endpoints are increasingly being adjudicated either at the express request of health authorities or simply as a method for improving clinical trial quality. But the routing through a clinical adjudication committee may contain a hidden serious compliance related risk: overlooking SAEs.
In the most common types of clinical studies where clinical adjudication is applied, the adjudicated endpoints frequently also qualify as serious adverse events (SAE). These include but are not limited to cardiac events such as angina, myocardial infarct or stroke, infectious episodes such as pneumonia and other types of events that lead to hospitalization, are life threatening or even plain deadly. Sometimes these may be excluded from expedite reporting because they are part of the main disease being investigated.
This creates special situations where these events are routed for review to the clinical adjudication committee before being formally identified and the result of the review may alter the initial qualification and classify the event as something entirely different (e.g. digestive event initially mistaken for a cardiac event). In rare cases, such a change could cause the event to be misclassified as non-serious although the seriousness criteria are still met. Is this a real risk of clinical adjudication? And how should it be mitigated?
A recent study1 by Fanaroff et al. (Trials 21, 323; 2020) investigated the question in a series of large studies involving thousands of patients and thousands of SAEs and adjudicated endpoint events. The authors followed a rigorous methodology for detecting missed SAEs among the adjudicated events and found that only 2 SUSAR (suspected unexpected serious adverse reactions) were overlooked in a cohort of 24,000 patients. They concluded that the risk is negligible and does not warrant the additional cost of putting specific measures in place.
However, even though in smaller studies the statistical risk of missing an SAE is way below 1, it may be easy enough to run a quick check at the end of the study. The use of a software adjudication platform makes such check easy and at a negligible cost.
Reference:
1. Methods for safety and endpoint ascertainment: identification of adverse events through scrutiny of negatively adjudicated events. Fanaroff, A.C., Haque, G., Thomas, B. et al. Trials 21, 323 (2020)
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