SPOT: Sequential Predictive Modeling of Clinical Trial Outcome with Meta-Learning

TL;DR

SPOT is a novel meta-learning framework that models clinical trial sequences to improve outcome prediction accuracy, interpretability, and adaptability across different trial phases.

Contribution

It introduces a topic-based clustering and sequence modeling approach combined with meta-learning to enhance trial outcome predictions.

Findings

21.5% PR-AUC lift on phase I trials

8.9% PR-AUC lift on phase II trials

5.5% PR-AUC lift on phase III trials

Abstract

Clinical trials are essential to drug development but time-consuming, costly, and prone to failure. Accurate trial outcome prediction based on historical trial data promises better trial investment decisions and more trial success. Existing trial outcome prediction models were not designed to model the relations among similar trials, capture the progression of features and designs of similar trials, or address the skewness of trial data which causes inferior performance for less common trials. To fill the gap and provide accurate trial outcome prediction, we propose Sequential Predictive mOdeling of clinical Trial outcome (SPOT) that first identifies trial topics to cluster the multi-sourced trial data into relevant trial topics. It then generates trial embeddings and organizes them by topic and time to create clinical trial sequences. With the consideration of each trial sequence as a task, it uses a meta-learning strategy to achieve a point where the model can rapidly adapt to new tasks with minimal updates. In particular, the topic discovery module enables a deeper understanding of the underlying structure of the data, while sequential learning captures the evolution of trial designs and outcomes. This results in predictions that are not only more accurate but also more interpretable, taking into account the temporal patterns and unique characteristics of each trial topic. We demonstrate that SPOT wins over the prior methods by a significant margin on trial outcome benchmark data: with a 21.5\% lift on phase I, an 8.9\% lift on phase II, and a 5.5\% lift on phase III trials in the metric of the area under precision-recall curve (PR-AUC).