{"doi":"10.1093/biomtc/ujaf043","title":"Precision generalized phase I-II designs","abstract":"A new family of precision Bayesian dose optimization designs, PGen I-II, based on early efficacy, early toxicity, and long-term time to treatment failure is proposed. A PGen I-II design refines a Gen I-II design by accounting for patient heterogeneity characterized by subgroups that may be defined by prognostic levels, disease subtypes, or biomarker categories. The design makes subgroup-specific decisions, which may be to drop an unacceptably toxic or inefficacious dose, randomize patients among acceptable doses, or identify a best dose in terms of treatment success defined in terms of time to failure over long-term follow-up. A piecewise exponential distribution for failure time is assumed, including subgroup-specific effects of dose, response, and toxicity. Latent variables are used to adaptively cluster subgroups found to have similar dose-outcome distributions, with the model simplified to borrow strength between subgroups in the same cluster. Guidelines and user-friendly computer software for implementing the design are provided. A simulation study is reported that shows the PGen I-II design is superior to similarly structured designs that either assume patient homogeneity or conduct separate trials within subgroups.","journal":"Biometrics","year":2025,"id":570882,"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":0.9535,"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":104767,"name":"Peter F. Thall","orcid":"0000-0002-7293-529X","position":1,"is_corresponding":false},{"id":268557,"name":"Ying Yuan","orcid":"0000-0003-3163-480X","position":2,"is_corresponding":false},{"id":13716,"name":"Juhee Lee","orcid":"0000-0002-9787-3830","position":3,"is_corresponding":false},{"id":261714,"name":"Pavlos Msaouel","orcid":"0000-0001-6505-8308","position":4,"is_corresponding":false},{"id":454680,"name":"Yong Zang","orcid":"0000-0003-0572-4756","position":5,"is_corresponding":false},{"id":1476764,"name":"Saijun Zhao","orcid":null,"position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-19T02:57:11.713851Z","pmid":"40705487","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":[]}