Despite being able to make accurate predictions, most existing prognostic models lack a proper indication about the uncertainty of each prediction, that is, the risk of prediction error for individual patients. This hampers their translation to primary care settings through decision support systems. To address this problem, we studied different methods for transforming classifiers into probabilistic/confidence-based predictors (here called uncertainty methods), where predictions are complemented with probability estimates/confidence regions reflecting their uncertainty (uncertainty estimates). We tested several uncertainty methods: two well-known calibration methods (Platt Scaling and Isotonic Regression), Conformal Predictors, and Venn-ABERS predictors. We evaluated whether these methods produce valid predictions, where uncertainty estimates reflect the ground truth probabilities. Furthermore, we assessed the proportion of valid predictions made at high-certainty thresholds (predictions with uncertainty measures above a given threshold) since this impacts their usefulness in clinical decisions. Finally, we proposed an ensemble-based approach where predictions from multiple pairs of (classifier, uncertainty method) are combined to predict whether a given MCI patient will convert to AD. This ensemble should putatively provide predictions for a larger number of patients while releasing users from deciding which pair of (classifier, uncertainty method) is more appropriate for data under study. The analysis was performed with a Portuguese cohort (CCC) of around 400 patients and validated in the publicly available ADNI cohort. Despite our focus on MCI to AD prognosis, the proposed approach can be applied to other diseases and prognostic problems.

译文

尽管能够做出准确的预测,但大多数现有的预后模型都缺乏关于每个预测的不确定性的适当指示,即单个患者的预测错误风险。这妨碍了他们通过决策支持系统转化为初级保健环境。为了解决这个问题,我们研究了将分类器转换为基于概率/置信的预测变量的不同方法 (这里称为不确定性方法),其中预测与反映其不确定性 (不确定性估计) 的概率估计/置信区域互补。我们测试了几种不确定度方法: 两种著名的校准方法 (普氏定标和等渗回归),共形预测器和Venn-abeers预测器。我们评估了这些方法是否产生有效的预测,其中不确定性估计反映了地面真实概率。此外,我们评估了在高确定性阈值 (不确定性度量高于给定阈值的预测) 下做出的有效预测的比例,因为这会影响其在临床决策中的有用性。最后,我们提出了一种基于集合的方法,其中将来自多对 (分类器,不确定性方法) 的预测组合在一起,以预测给定的MCI患者是否会转换为AD。这个集合应该可以为更多的患者提供预测,同时让用户决定哪对 (分类器,不确定性方法) 更适合研究中的数据。该分析是对约400名患者的葡萄牙队列 (CCC) 进行的,并在公开可用的ADNI队列中进行了验证。尽管我们关注MCI对AD预后的影响,但所提出的方法仍可应用于其他疾病和预后问题。

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