Determining Associations with Word Embedding in Heterogeneous Network for Detecting Off-Label Drug Uses

Abstract

Off-label drug use is quite common in clinical practice and inevitable to some extent. Such uses might deliver effective treatment and suggest clinical innovation sometimes, however, they have the unknown risk to cause serious outcomes due to lacking scientific support. As gaining information about off-label drug use could present a clue to the stakeholders such as healthcare professionals and medication manufacturers to further the investigation on drug efficacy and safety, it raises the need to develop a systematic way to detect off-label drug uses. Considering the increasing discussions in online health communities (OHCs) among the health consumers, we proposed to harness the large volume of timely information in OHCs to develop an automated method for detecting off-label drug uses from health consumer generated data. From the text corpus, we extracted medical entities (diseases, drugs, and adverse drug reactions) with lexicon-based approaches and measured their interactions with word embedding models, based on which, we constructed a heterogeneous healthcare network. We defined several meta-path-based indicators to describe the drug-disease associations in the heterogeneous network and used them as features to train a binary classifier built on Random Forest algorithm, to recognize the known drug-disease associations. The classification model obtained better results when incorporating word embedding features and achieved the best performance when using both association rule mining features and word embedding features, with F1-score reaching 0.939, based on which, we identified 2,125 possible off-label drug uses and checked their potential by searching evidence in PubMed and FAERS.