Temporal Ensemble Logic for Integrative Representation of the Entirety of Clinical Trials

Clinical trials are typically specified with protocols that define eligibility criteria, treatment regimens, follow-up schedules, and outcome assessments. Temporality is a hallmark of all clinical trials, reflected within and across trial components, with complex dependencies unfolding across multiple time points. Despite their importance, clinical trial protocols are described in free-text format, limiting their semantic precision and the ability to support automated reasoning, leverage data across studies and sites, or simulate trial execution under varying assumptions using Real-World Data. This paper introduces a formalized representation of clinical trials using Temporal Ensemble Logic (TEL). TEL incorporates metricized modal operators, such as "always until t" ( ${◻}_t$ ) and "possibly until t" ( ${♢}_t$ ), where t is a time-length parameter, to offer a logical framework for capturing phenotypes in biomedicine. TEL is more expressive in syntax than classical linear temporal logic (LTL) while maintaining the simplicity of semantic structures. The attributes of TEL are exploited in this paper to formally represent not only individual clinical trial components, but also the timing and sequential dependencies of these components as a whole. Modeling strategies and demonstration case studies are provided to show that TEL can represent the entirety of clinical trials, whereby providing a formal logical framework that can be used to represent the intricate temporal dependencies in trial structure specification. Since clinical trials are a cornerstone of evidence-based medicine, serving as the scientific basis for evaluating the safety, efficacy, and comparative effectiveness of therapeutic interventions, results reported here can serve as a stepping stone that leads to scalable, consistent, and reproducible representation and simulation of clinical trials across all disease domains.