This work presents the development and evaluation of an NLP-enabled probabilistic classifier designed to estimate the probability of technical and regulatory success (pTRS) for clinical trials in the field of neuroscience. While pharmaceutical R&D is plagued by high attrition rates and enormous costs, particularly within neuroscience, where success rates are below 10%, timely identification of promising programs can streamline resource allocation and reduce financial risk. Leveraging data from the ClinicalTrials.gov database and success labels from the recently developed Clinical Trial Outcome dataset, the classifier extracts text-based clinical trial features using statistical NLP techniques. These features were integrated into several non-LLM frameworks (logistic regression, gradient boosting, and random forest) to generate calibrated probability scores. Model performance was assessed on a retrospective dataset of 101,145 completed clinical trials spanning 1976-2024, achieving an overall ROC-AUC of 0.64. An LLM-based predictive model was then built using BioBERT, a domain-specific language representation encoder. The BioBERT-based model achieved an overall ROC-AUC of 0.74 and a Brier Score of 0.185, indicating its predictions had, on average, 40% less squared error than would be observed using industry benchmarks. The BioBERT-based model also made trial outcome predictions that were superior to benchmark values 70% of the time overall. By integrating NLP-driven insights into drug development decision-making, this work aims to enhance strategic planning and optimize investment allocation in neuroscience programs.
翻译:本研究提出并评估了一种基于自然语言处理的概率分类器,旨在预测神经科学领域临床试验的技术与监管成功概率。尽管医药研发领域,尤其是神经科学领域,面临着高失败率和巨大成本(成功率低于10%),但及时识别有前景的研发项目能够优化资源配置并降低财务风险。该分类器利用ClinicalTrials.gov数据库的数据以及近期开发的临床试验结果数据集中的成功标签,通过统计自然语言处理技术提取基于文本的临床试验特征。这些特征被整合到多个非大语言模型框架(逻辑回归、梯度提升和随机森林)中,以生成校准后的概率评分。模型性能在一个包含1976年至2024年期间完成的101,145项临床试验的回顾性数据集上进行了评估,总体ROC-AUC达到0.64。随后,使用领域特定的语言表示编码器BioBERT构建了一个基于大语言模型的预测模型。基于BioBERT的模型实现了0.74的总体ROC-AUC和0.185的Brier评分,表明其预测的平均平方误差比行业基准降低了40%。此外,基于BioBERT的模型在70%的情况下其试验结果预测优于基准值。通过将自然语言处理驱动的洞察整合到药物开发决策中,本研究旨在增强神经科学项目的战略规划并优化投资分配。