通过逐步想象试验变化,预测新临床试验结果。
DeepImagine: Clinical Trial Outcome Prediction via Stepwise Local Counterfactual Imaginations

- 从历史试验出发,逐项调整因素,用大模型判断每步影响。
- 多路径想象聚合后预测准确率显著高于直接预测。
- 专用于特定因素的模型可进一步提升预测性能。
预测未来临床试验结果仍是重大挑战。试验结果由药物干预、参与者特征和方案等复杂因素交互决定。本文提出DeepImagine框架,通过基于已有结果的历史试验,分步进行反事实想象来预测目标试验结果。从相关历史试验开始,每次仅修改一个差异因素,利用大语言模型(LLM)评估该单一扰动对结果的影响,将更新结果作为下一步输入,直至历史配置完全匹配目标,得到最终预测。实验证明,DeepImagine在多个现成LLM上均优于单步直接预测,且通过聚合多条不同历史起点的想象路径进一步提升性能。此外,我们构建了包含合成推理轨迹的自然反事实数据,训练了一组专用语言模型,每个模型专注于学习某一因素的局部反事实转移。将这些学习到的局部算子整合进DeepImagine,显著优于通用大模型基线。研究结果表明,分步反事实想象区别于相关性预测与显式结构因果建模,是临床试验结果预测的有前景方向。所有代码、训练脚本与评估脚本均可在https://github.com/deepimagine-counterfactual/DeepImagine获取。
原文摘要 · Abstract (English)
Predicting the outcomes of prospective clinical trials remains a major challenge. Clinical trial outcomes result from complex interactions among experimental factors such as drug interventions, participant demographics, and protocols. Here, we introduce DeepImagine, a framework that predicts target trial outcomes through stepwise counterfactual imagination anchored on historical trials with observed results. Starting from a relevant historical trial, DeepImagine sequentially modifies one differing experimental factor at a time. With each step a large language model (LLM) is posed a local counterfactual: how would the current imagined outcome change with this single perturbation? The updated result is carried forward as the input to the next step, until the historical configuration exactly matches the target, yielding the final prediction. Empirically, DeepImagine consistently outperforms direct one-step prediction across several off-the-shelf LLMs, with further gains when multiple imagination pathways, initiated from different historical anchors, are aggregated. We also construct natural counterfactuals augmented with synthetic reasoning traces and train a family of specialized language models, each dedicated to learning one factor's local counterfactual transition. Integrating these learned local operators into DeepImagine yields substantial improvements over general-purpose LLM baselines. Our findings position stepwise counterfactual imagination, distinct from both correlational prediction and explicit structural causal modeling, as a promising direction for clinical trial outcome prediction. All code, training scripts, and evaluation scripts are available at \href{https://github.com/deepimagine-counterfactual/DeepImagine}{https://github.com/deepimagine-counterfactual/DeepImagine}.
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