Scaling Up Formal Representation of Clinical Trial Protocols in Ensemble Logic Using LLMs: A Preliminary Study

The reliance on unstructured free text for documenting clinical trial protocols creates a significant barrier to automated reasoning, cohort discovery, and trial simulation.

The lack of formal structure obscures critical temporal phenotypes, such as dynamic eligibility criteria and event timing constraints.

Although Temporal Ensemble Logic (TEL) offers an expressive framework for modeling these elements, manual encoding remains a prohibitive bottleneck.

We introduce the CT-TEL workflow: a scalable pipeline leveraging Large Language Models (LLMs) to translate narrative clinical protocols into TEL formulas.

We applied CT-TEL to generate logical models for 23 real-world trials from this http URL.

We evaluated translation fidelity via a back-translation approach, using LLMs to convert TEL formulas back into natural language and measuring semantic similarity against source texts.

The resulting semantic retention suggests that LLMs may offer a pathway for mapping informal protocols to computable logic, providing preliminary evidence toward scalable clinical trial emulation within the emerging "Symbolic Biomedicine" paradigm championed by the corresponding author.