用生成模型合成临床试验中的时间序列数据,提升隐私保护下的数据可用性。
TrialSynth: Generation of Synthetic Sequential Clinical Trial Data
- 基于霍克斯过程的变分自编码器,捕捉事件类型与时间间隔的动态关系。
- 在小样本真实数据集上生成高保真事件序列,性能优于现有方法。
- 兼顾数据实用性和隐私保护,适合医疗研究与试验设计优化。
分析过往临床试验数据是优化新试验设计、实施与执行,加速救命疗法上市的关键环节。尽管静态临床数据生成已有进展,但受限于患者数量不足及隐私保护要求,细粒度的时间序列临床试验数据生成仍具挑战。由于患者在整个试验中的轨迹对优化试验设计和预防有害不良事件至关重要,亟需生成高保真时间序列数据。本文提出TrialSynth,一种基于变分自编码器(VAE)的方法,创新性地引入霍克斯过程(Hawkes Processes, HP),擅长建模事件类型与时间间隔,以捕捉序列数据结构。实验表明,TrialSynth在多种真实世界时间序列数据集上,即使在小患者源群体下,也能生成高精度事件序列,性能优于其他可生成序列数据的方法。实证结果还显示,该方法不仅超越现有临床序列生成技术,且生成数据具有更高实用性,同时有效保护患者隐私。
原文摘要 · Abstract (English)
Analyzing data from past clinical trials is part of the ongoing effort to optimize the design, implementation, and execution of new clinical trials and more efficiently bring life-saving interventions to market. While there have been recent advances in the generation of static context synthetic clinical trial data, due to both limited patient availability and constraints imposed by patient privacy needs, the generation of fine-grained synthetic time-sequential clinical trial data has been challenging. Given that patient trajectories over an entire clinical trial are of high importance for optimizing trial design and efforts to prevent harmful adverse events, there is a significant need for the generation of high-fidelity time-sequence clinical trial data. Here we introduce TrialSynth, a Variational Autoencoder (VAE) designed to address the specific challenges of generating synthetic time-sequence clinical trial data. Distinct from related clinical data VAE methods, the core of our method leverages Hawkes Processes (HP), which are particularly well-suited for modeling event-type and time gap prediction needed to capture the structure of sequential clinical trial data. Our experiments demonstrate that TrialSynth surpasses the performance of other comparable methods that can generate sequential clinical trial data at varying levels of fidelity / privacy tradeoff, enabling the generation of highly accurate event sequences across multiple real-world sequential event datasets with small patient source populations. Notably, our empirical findings highlight that TrialSynth not only outperforms existing clinical sequence-generating methods but also produces data with superior utility while empirically preserving patient privacy.
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