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临床 GAN:利用患者数字孪生为临床试验中的患者监测提供动力。

ClinicalGAN: powering patient monitoring in clinical trials with patient digital twins.

机构信息

ZS, 2nd Floor, MFAR Manyta Tech park, Phase IV, Manayata Tech Park, Nagavara, Bengaluru, Karnataka, India.

ZS, 1560 Sherman Ave, Evanston, IL, 60201, USA.

出版信息

Sci Rep. 2024 May 28;14(1):12236. doi: 10.1038/s41598-024-62567-1.

Abstract

Conducting clinical trials is becoming increasingly challenging lately due to spiraling costs, increased time to market, and high failure rates. Patient recruitment and retention is one of the key challenges that impact 90% of the trials directly. While a lot of attention has been given to optimizing patient recruitment, limited progress has been made towards developing comprehensive clinical trial monitoring systems to determine patients at risk and potentially improve patient retention through the right intervention at the right time. Earlier research in patient retention primarily focused on using deterministic frameworks to model the inherently stochastic patient journey process. Existing generative approaches to model temporal data such as TimeGAN or CRBM , face challenges and fail to address key requirements such as personalized generation, variable patient journey, and multi-variate time-series needed to model patient digital twin. In response to these challenges, current research proposes ClinicalGAN to enable patient level generation, effectively creating a patient's digital twin. ClinicalGAN provides capabilities for: (a) patient-level personalized generation by utilizing patient meta-data for conditional generation; (b) dynamic termination prediction to enable pro-active patient monitoring for improved patient retention; (c) multi-variate time-series training to incorporate relationship and dependencies among different tests measures captured during patient journey. The proposed solution is validated on two Alzheimer's clinical trial datasets and the results are benchmarked across multiple dimensions of generation quality. Empirical results demonstrate that the proposed ClinicalGAN outperforms the SOTA approach by 3-4 on average across all the generation quality metrics. Furthermore, the proposed architecture is shown to outperform predictive methods at the task of drop-off prediction significantly (5-10% MAPE scores).

摘要

最近,由于成本不断攀升、推向市场的时间延长以及高失败率,临床试验的开展变得越来越具有挑战性。患者招募和保留是直接影响 90%临床试验的关键挑战之一。尽管人们已经非常关注优化患者招募,但在开发全面的临床试验监测系统以确定有风险的患者并通过在正确的时间进行正确的干预来提高患者保留率方面,进展有限。早期关于患者保留的研究主要集中在使用确定性框架来对患者旅程过程的固有随机性进行建模。现有的用于对时间数据建模的生成式方法,如 TimeGAN 或 CRBM,都面临着挑战,并且无法解决关键要求,例如个性化生成、可变的患者旅程以及对建模患者数字孪生所需的多变量时间序列。为了应对这些挑战,当前的研究提出了 ClinicalGAN,以实现患者级别的生成,有效地创建患者的数字孪生。ClinicalGAN 提供了以下功能:(a) 通过利用患者元数据进行条件生成来实现患者级别的个性化生成;(b) 动态终止预测,以便能够主动进行患者监测,从而提高患者保留率;(c) 多变量时间序列训练,以纳入患者旅程中不同测试措施之间的关系和依赖关系。该解决方案在两个阿尔茨海默病临床试验数据集上进行了验证,并在多个生成质量维度上进行了基准测试。实验结果表明,所提出的 ClinicalGAN 在所有生成质量指标上的平均表现均优于 SOTA 方法 3-4 个百分点。此外,所提出的架构在下降预测任务上的表现明显优于预测方法(MAPE 得分高出 5-10%)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/627c/11133486/28928e8e6250/41598_2024_62567_Fig1_HTML.jpg

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