# TimeTox: An LLM-Based Pipeline for Automated Extraction of Time Toxicity from Clinical Trial Protocols

arXiv: https://arxiv.org/abs/2603.21335 · HTML: https://mlsanity.com/paper/2603.21335/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 4 of its 12 references that are in the map.
- First posted on arXiv 22 Mar 2026.

## Builds on (most cited first, 4 of 4)

- [Large Language Models Encode Clinical Knowledge](https://mlsanity.com/paper/2212.13138/) (2022)
- [Capabilities of GPT-4 on Medical Challenge Problems](https://mlsanity.com/paper/2303.13375/) (2023)
- [Large Language Models are Few-Shot Clinical Information Extractors](https://mlsanity.com/paper/2205.12689/) (2022)
- [Matching Patients to Clinical Trials with Large Language Models](https://mlsanity.com/paper/2307.15051/) (2023)

## Abstract (arXiv)

Time toxicity, the cumulative healthcare contact days from clinical trial participation, is an important but labor-intensive metric to extract from protocol documents. We developed TimeTox, an LLM-based pipeline for automated extraction of time toxicity from Schedule of Assessments tables. TimeTox uses Google's Gemini models in three stages: summary extraction from full-length protocol PDFs, time toxicity quantification at six cumulative timepoints for each treatment arm, and multi-run consensus via position-based arm matching. We validated against 20 synthetic schedules (240 comparisons) and assessed reproducibility on 644 real-world oncology protocols. Two architectures were compared: single-pass (vanilla) and two-stage (structure-then-count). The two-stage pipeline achieved 100% clinically acceptable accuracy (±3 days) on synthetic data (MAE 0.81 days) versus 41.5% for vanilla (MAE 9.0 days). However, on real-world protocols, the vanilla pipeline showed superior reproducibility: 95.3% clinically acceptable accuracy (IQR ≤ 3 days) across 3 runs on 644 protocols, with 82.0% perfect stability (IQR = 0). The production pipeline extracted time toxicity for 1,288 treatment arms across multiple disease sites. Extraction stability on real-world data, rather than accuracy on synthetic benchmarks, is the decisive factor for production LLM deployment.