Defining operational safety in clinical artificial intelligence systems

Abstract The clinical adoption of artificial intelligence (AI) has focused on enabling automation, but conventional accuracy metrics fail to answer a key question: when is it safe to trust an AI system? We introduce the Safety-Aware Receiver Operating Characteristic (SA-ROC) framework, which defines operational safety as an ability to meet pre-specified reliability levels. The SA-ROC curve delineates a Rule-in and a Rule-out Safe Zone, where autonomous action is permitted, and a Gray Zone, where human review is mandated. To quantify this non-automated workload, we introduce the Gray Zone Area (Γ Area ), a metric measuring the operational cost of indecision. Our framework reveals a key reversal: in a case study of two FDA-cleared algorithms for cancer screening, the model with a statistically superior AUC was found to be operationally less safe for high-confidence screening. SA-ROC enables active governance, translating clinical policy into optimized workflows that inform operational safety and complement regulatory safety evaluation.