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This task is challenging because the optimal treatment pathway for each patient needs to be personalized due to the significant heterogeneity among individuals. Therefore, it is naturally promising to investigate how to use the abundant electronic health records to recommend effective and safe prescriptions. However, prescription recommendation needs to consider multiple aspects of life-critical evidence, such as the information relevance in terms of medical concepts, the health condition in terms of diagnosis history, and the further constraint in terms of side information (e.g., patient demographics and drug side effects). To this end, in this article, we propose a novel prescription recommendation framework named OntoPath to predict the next drug in disease treatment pathways, by building an ontology-aware hierarchical-attention model that integrates multiple medical evidence from domain knowledge guidance, medical history profiling, and side information utilization. Specifically, our method can be characterized from three aspects: (1) by incorporating the longitudinal diagnosis history, we enrich the profiling of patients in terms of comprehensive health conditions, which can largely influence a drug\u2019s outcome on individual patients; (2) using the hierarchical disease and drug ontology structures, we are able to model the domain-specific relevance between patients and drugs at multiple levels of granularity and achieve in-depth collaborative filtering; (3) we introduce a pre-training stage to enhance the discriminativeness of network representations, which helps us obtain a premium model initialization to further boost the final recommendation training. We perform extensive experiments on a large-scale depression cohort with over 37,000 patients from a real-world medical claims database. The quantitative and qualitative results demonstrate the effectiveness of OntoPath through the consistent outperformance over state-of-the-art prescription recommendation baselines and the interpretation of model mechanism in case studies.<\/jats:p>","DOI":"10.1145\/3579994","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T15:46:25Z","timestamp":1673538385000},"page":"1-29","update-policy":"https:\/\/doi.org\/10.1145\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Ontology-aware Prescription Recommendation in Treatment Pathways Using Multi-evidence Healthcare Data"],"prefix":"10.1145","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3647-8770","authenticated-orcid":false,"given":"Zijun","family":"Yao","sequence":"first","affiliation":[{"name":"The University of Kansas, Lawrence, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-5334","authenticated-orcid":false,"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"West Virginia University, Morgantown, WV, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9459-9461","authenticated-orcid":false,"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2227-5243","authenticated-orcid":false,"given":"Daby","family":"Sow","sequence":"additional","affiliation":[{"name":"IBM Research, Yorktown Heights, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2813-9480","authenticated-orcid":false,"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Regeneron, Tarrytown, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"320","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1145\/3219819.3219904"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-51455-6_20"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.18653\/v1\/2020.acl-main.282"},{"key":"e_1_3_2_5_2","first-page":"6775","volume-title":"Advances in Neural Information Processing Systems","author":"Cao Wei","year":"2018","unstructured":"Wei Cao, Dong Wang, Jian Li, Hao Zhou, Lei Li, and Yitan Li. 2018. 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