{"doi":"10.1002/psp4.70114","title":"A Dose‐Aware Model for Revealing Dose‐Risk Relationship of Drug–Drug Interaction","abstract":"Drug-drug interaction (DDI) is a common cause of adverse drug events (ADEs). Despite real-world data-based studies have developed knowledge on DDI, the precise relationships between doses of two-drug combinations exposure and the risks of ADEs remain largely unknown. The estimation of the dose-risk relationship (DRR) under commonly used regression models could be subject to model misspecification or overspecification. We developed a dose-aware model (DAM) for revealing DRR. DAM could improve the DRR estimation by identifying the optimal model from a large number of meaningful models of doses of two-drug combinations exposure and risks of ADE. We compared DAM with commonly used models (e.g., exposed-versus-unexposed model, dose-response model, and saturated model), in which DAM had higher performance metrics on model fitting in real-world data analyses and DRR estimation in a simulation study. In conclusion, DAM is a powerful tool for estimating DRR for potential adverse two-drug combinations, which could be used to mitigate DDI-induced harm.","journal":"CPT Pharmacometrics & Systems Pharmacology","year":2025,"id":575252,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":678154,"name":"Anna Sun","orcid":"0000-0002-4772-4271","position":1,"is_corresponding":false},{"id":1150921,"name":"Yuedi Yang","orcid":"0000-0003-3355-4723","position":2,"is_corresponding":false},{"id":326907,"name":"Hongmei Nan","orcid":"0000-0002-9957-616X","position":3,"is_corresponding":false},{"id":1390817,"name":"Jing Xu","orcid":"0000-0003-3673-7592","position":4,"is_corresponding":false},{"id":928123,"name":"Mu Shan","orcid":null,"position":5,"is_corresponding":false},{"id":307583,"name":"Michael T. Eadon","orcid":"0000-0003-3066-2876","position":6,"is_corresponding":false},{"id":1287599,"name":"Jing Su","orcid":"0000-0001-9845-8084","position":7,"is_corresponding":false},{"id":1150922,"name":"Pengyue Zhang","orcid":"0000-0002-9148-5589","position":8,"is_corresponding":false},{"id":1390818,"name":"Yi Shi","orcid":"0000-0003-0145-2968","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T02:57:48.486077Z","pmid":"40965243","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}