PDF(Pubmed)
Abstract：
In the European Union, the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) develop guidelines to guide drug development, supporting development of efficacious and safe medicines. A European Public Assessment Report (EPAR) is published for every medicine application that has been granted or refused marketing authorisation within the EU. In this work, we study the use of text embeddings and similarity metrics to investigate the semantic similarity between EPARs and EMA guidelines. All 1024 EPARs for initial marketing authorisations from 2008 to 2022 was compared to the 669 current EMA scientific guidelines. Documents were converted to plain text and split into overlapping chunks, generating 265,757 EPAR and 27,649 guideline text chunks. Using a Sentence BERT language model, the chunks were transformed into embeddings and fed into an in-house piecewise matching algorithm to estimate the full-document semantic distance. In an analysis of the document distance scores and product characteristics using a linear regression model, EPARs of anti-virals for systemic use (ATC code J05) and antihemorrhagic medicines (B02) present with statistically significant lower overall semantic distance to guidelines compared to other therapeutic areas, also when adjusting for product age and EPAR length. In conclusion, we believe our approach provides meaningful insight into the interplay between EMA scientific guidelines and the assessment made during regulatory review, and could potentially be used to answer more specific questions such as which therapeutic areas could benefit from additional regulatory guidance.
摘要：
在欧盟,欧洲药品管理局（EMA）的人用药品委员会制定了指导药物开发的指南，支持开发有效和安全的药物。欧洲公共评估报告（EPAR）是在欧盟内获得或拒绝上市许可的每个药物申请发布。在这项工作中,我们研究了使用文本嵌入和相似性度量来调查EPAR和EMA指南之间的语义相似性。从2008年到2022年，所有1024个EPAR的初始营销授权与669个当前的EMA科学指南进行了比较。文档被转换为纯文本并分成重叠的块，生成265,757EPAR和27,649指南文本块。使用句子BERT语言模型，将这些块转换为嵌入，并输入到内部分段匹配算法中，以估计全文档语义距离。在使用线性回归模型对文档距离得分和产品特性进行分析时，与其他治疗领域相比，全身使用的抗病毒药物（ATC代码J05）和抗出血药物（B02）的EPAR与指南的总体语义距离具有统计学意义，也当调整产品的年龄和EPAR长度。总之,我们相信，我们的方法为EMA科学指南与监管审查期间进行的评估之间的相互作用提供了有意义的见解，并可能用于回答更具体的问题，例如哪些治疗领域可以从额外的监管指导中受益。
