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

Authors Xiaojin Li, Yan Huang, Rashmie Abeysinghe, Zenan Sun, Hongyu Chen, Pengze Li, Xing He, Shiqiang Tao, Cui Tao, Jiang Bian, Licong Cui, Guo-Qiang Zhang

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ACM Subject Classification
  • Theory of computation → Theory and algorithms for application domains
Keywords
  • Temporal ensemble logic
  • Clinical trials
  • Logic-based modeling

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Abstract

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.

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Xiaojin Li, Yan Huang, Rashmie Abeysinghe, Zenan Sun, Hongyu Chen, Pengze Li, Xing He, Shiqiang Tao, Cui Tao, Jiang Bian, Licong Cui, and Guo-Qiang Zhang. Temporal Ensemble Logic for Integrative Representation of the Entirety of Clinical Trials. In 32nd International Symposium on Temporal Representation and Reasoning (TIME 2025). Leibniz International Proceedings in Informatics (LIPIcs), Volume 355, pp. 13:1-13:16, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025) https://doi.org/10.4230/LIPIcs.TIME.2025.13

Author Details

Xiaojin Li
  • The University of Texas Health Science Center , at Houston, TX, USA
Yan Huang
  • The University of Texas Health Science Center , at Houston, TX, USA
Rashmie Abeysinghe
  • The University of Texas Health Science Center , at Houston, TX, USA
Zenan Sun
  • The University of Texas Health Science Center , at Houston, TX, USA
Hongyu Chen
  • University of Florida, Gainesville, FL, USA
Pengze Li
  • Mayo Clinic in Florida, Jacksonville, FL, USA
Xing He
  • Indiana University Bloomington, Bloomington, IN, USA
Shiqiang Tao
  • The University of Texas Health Science Center , at Houston, TX, USA
Cui Tao
  • Mayo Clinic in Florida, Jacksonville, FL, USA
Jiang Bian
  • Indiana University Bloomington, Bloomington, IN, USA
Licong Cui
  • The University of Texas Health Science Center , at Houston, TX, USA
Guo-Qiang Zhang
  • The University of Texas Health Science Center , at Houston, TX, USA

Funding

This work was supported in part by the National Science Foundation Award IIS2500624 and the National Institutes of Health grants R01AG084236, of the United States. The views of the paper are those of the authors and do not reflect those of the funding agencies.

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