Liu Zihuan, Gu Yihua, Huang Xin
Data and Statistical Sciences, AbbVie Inc., North Chicago, IL, USA.
Commun Med (Lond). 2025 Jun 10;5(1):221. doi: 10.1038/s43856-025-00946-z.
The task of identifying patient subgroups with enhanced treatment responses is important for clinical drug development. However, existing deep learning-based approaches often struggle to provide clear biological insights. This study aims to develop a deep learning method that not only captures treatment effect differences among individuals but also helps uncover meaningful biological markers associated with those differences.
We introduce DeepRAB, a deep learning-based framework designed for exploring treatment effect heterogeneity by constructing individualized treatment rule (ITR). In addition, DeepRAB enables model interpretability by facilitating predictive biomarker identification. We evaluate its performance using simulated datasets that vary in complexity, treatment effect strength, and sample size. We also apply the method to the adalimumab (Humira, AbbVie) hidradenitis suppurativa (HS) clinical trial data, analyzing patient characteristics and treatment outcomes.
In analyses of simulated data under various scenarios, our findings show the effective performance of DeepRAB for subgroup exploration, and its capability to uncover predictive biomarkers when compared to existing approaches. When applied to the real clinical trial data, DeepRAB demonstrates its practical usage in identifying important predictive biomarkers and boosting model prediction performance.
Our research provides a promising approach for subgroup identification and predictive biomarker discovery by leveraging deep learning. This approach may support more targeted treatment strategies in clinical research and enhance decision-making in personalized medicine.
识别对治疗反应增强的患者亚组的任务对于临床药物开发至关重要。然而,现有的基于深度学习的方法往往难以提供清晰的生物学见解。本研究旨在开发一种深度学习方法,该方法不仅能够捕捉个体之间的治疗效果差异,还能有助于发现与这些差异相关的有意义的生物学标志物。
我们引入了DeepRAB,这是一个基于深度学习的框架,旨在通过构建个性化治疗规则(ITR)来探索治疗效果异质性。此外,DeepRAB通过促进预测性生物标志物的识别实现模型可解释性。我们使用在复杂性、治疗效果强度和样本量方面各不相同的模拟数据集评估其性能。我们还将该方法应用于阿达木单抗(修美乐,艾伯维公司)治疗化脓性汗腺炎(HS)的临床试验数据,分析患者特征和治疗结果。
在各种场景下对模拟数据的分析中,我们的研究结果表明DeepRAB在亚组探索方面具有有效性能,并且与现有方法相比,它有能力发现预测性生物标志物。当应用于真实临床试验数据时,DeepRAB展示了其在识别重要预测性生物标志物和提高模型预测性能方面的实际用途。
我们的研究通过利用深度学习为亚组识别和预测性生物标志物发现提供了一种有前景的方法。这种方法可能支持临床研究中更具针对性的治疗策略,并加强个性化医疗中的决策制定。