{"doi":"10.17615/0kb4-bt23","title":"Selection of the initial design for the two-stage continual reassessment method","abstract":"The continual reassessment method (CRM) was proposed in a Bayesian framework whereby the first patient is assigned to the prior guess of the maximum tolerated dose which is usually not the lowest dose level. This assignment may lead to safety concerns in practice because physicians usually prefer not to skip lower dose levels before escalating to the higher dose levels. The two-stage CRM was proposed to address such concern whereby model based dose escalation is preceded by a pre-specified escalating sequence starting from the lowest dose level. While a theoretical framework to build the two-stage CRM has been proposed, the selection of the initial dose escalating sequence, generally referred to as the initial design, remains arbitrary, either by specifing cohorts of three patients or by trial and error through extensive simulations. Motivated by a currently ongoing oncology dose finding study for which physicians stated their desire to start from the lowest dose even though the maximum tolerated dose was thought to be one of the higher dose levels, we proposed a systematic approach for selecting the initial design for the two-stage CRM. The initial design obtained using the proposed algorithm yields better operating characteristics compared to using a cohort of three initial design with a calibrated CRM. The proposed algorithm simplifies and provides a systematic approach for the selection of initial design for the two-stage CRM. Moreover, initial designs to be used as reference for planning a two-stage CRM are provided.","journal":"UNC Libraries","year":2020,"id":142713,"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":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":599781,"name":"Shing M. Lee","orcid":"0000-0001-8413-6869","position":1,"is_corresponding":false},{"id":378763,"name":"Anastasia Ivanova","orcid":"0000-0003-4321-2073","position":2,"is_corresponding":false},{"id":609850,"name":"Xiaoyu Jia","orcid":"0000-0002-8611-7220","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:34.768426Z","pmid":null,"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":[]}