arXiv:2605.04071cs.LGcs.AI2026-05被引 1

FlatASCEND能生成患者特异性临床轨迹,验证药物作用机制。

FlatASCEND: Autoregressive Clinical Sequence Generation with Continuous Time Prediction and Association-Based Pharmacological Testing

论文配图:FlatASCEND: Autoregressive Clinical Sequence Generation with Continuous Time Prediction and Association-Based Pharmacological Testing
图 1 · 摘自论文原文
  • 用扁平复合令牌和零膨胀对数正态时间头建模临床序列
  • 在MIMIC-IV上4/10正确恢复药物作用方向,9/10显著(p<0.05)
  • 适合评估生成模型是否捕捉真实药理机制,不适用于长程或跨站点预测

自回归模型可预测临床事件,但针对患者条件的多步轨迹生成及干预后反应是否保留已知药理关联的研究仍有限。我们提出FlatASCEND,一个1450万参数的自回归临床序列模型,采用扁平复合令牌与零膨胀对数正态时间头。标准分布指标(雅各比相似度0.889–0.954)无法区分该模型与基线;其价值在于患者特异性前缀下的条件生成。提示打乱消融实验显示,患者条件使类固醇→血糖、利尿剂→钾的机制效应增强2.0–2.2倍,而胰岛素→血糖等混杂关联不变(0.9倍)。基于事件用户的框架在MIMIC-IV上评估方向一致性(每组N=500):4/10恢复正确机制方向,2/10再现治疗上下文关联,4/10错误(9/10显著,Wilcoxon p<0.05)。该模式——残余混杂下部分恢复——符合学习到的观察关联而非因果区分。直接偏好优化使用代理奖励会破坏所有正确关联(3/3降至0/3),揭示奖励与评估共享结果域时的奖励滥用问题。生成证据最强于短时程重症数据;门诊时间保真度较弱(中位10天对比INSPECT的154天),零样本跨站点迁移需适应才能维持性能。

原文摘要 · Abstract (English)

Autoregressive models can predict clinical events, but generating patient-conditioned multi-step trajectories that respond to intervention tokens and testing whether those responses preserve known pharmacological associations has received limited attention. We present FlatASCEND, a 14.5M-parameter autoregressive clinical sequence model using flat composite tokens and a zero-inflated log-normal time head. Standard distributional metrics (Jaccard 0.889-0.954) do not distinguish FlatASCEND from trivial baselines; the model's value lies in conditional generation from patient-specific prefixes. A prompt-shuffle ablation shows patient-specific conditioning amplifies mechanistic pharmacological effects (2.0-2.2x for steroid to glucose, diuretic to potassium) while leaving confounding-driven associations unchanged (0.9x for insulin to glucose). An incident-user framework assesses directional consistency against prior pharmacological knowledge on MIMIC-IV (N=500 per comparison): 4/10 recover correct mechanistic directions, 2 reproduce treatment-context associations, 4 are incorrect (9/10 significant, Wilcoxon p<0.05). This pattern - partial recovery under residual confounding - is consistent with learned observational associations without causal distinction. Direct preference optimisation with surrogate reward destroys all correct associations (3/3 to 0/3), illustrating reward exploitation when reward and evaluation share an outcome domain. Generative evidence is strongest for short-horizon ICU data; outpatient temporal fidelity is weaker (median 10 vs 154 days on INSPECT), and zero-shot cross-site transfer degrades without adaptation.

临床生成药理验证条件生成

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