{"doi":"10.1016/j.breast.2020.05.012","title":"Estimation of historical control rate for a single arm de-escalation study – Application to the POSITIVE trial","abstract":"BACKGROUND: Although randomized controlled clinical trials are optimal to evaluate the effect of an experimental therapy, single-arm trials are required whenever randomization is unethical or not feasible, such as de-escalation studies. We propose using prospectively identified historical controls to place results of single-arm, de-escalation trials into context. METHODS: POSITIVE is a prospective, single-arm study in young women with hormone-receptor-positive early breast cancer to determine if temporarily interrupting adjuvant endocrine therapy in order to become pregnant increases the risk of a breast cancer event. After 272 women enrolled in POSITIVE, we identified a cohort of 1499 SOFT/TEXT patients potentially eligible to enroll in POSITIVE who did not interrupt endocrine therapy. Method I used the SOFT/TEXT cohort to calculate annualized hazard rates by a piecewise exponential model. Method II used the SOFT/TEXT cohort to group-match SOFT/TEXT patients to POSITIVE patients; sample sets of SOFT/TEXT patients were randomly drawn 5000 times to obtain sets having patient, disease, and treatment characteristics more balanced with POSITIVE participants. RESULTS: Compared with SOFT/TEXT, POSITIVE participants were younger, less likely to be overweight/obese, had fewer positive nodes, and fewer received aromatase inhibitor or chemotherapy. The estimated 3-year breast cancer free interval event rates were 9.5% (95% CI: 7.9%,11.1%) for Method I and 9.4% (95% CI: 7.8%,10.9%) for Method II, compared with 5.8% initially assumed when POSITIVE was designed. CONCLUSION: External control datasets should be identified before launching single-arm, de-escalation trials and methods applied during their conduct to provide context for interim monitoring and interpretation of the final analysis.","journal":"The Breast","year":2020,"id":78016,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8822,"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":407905,"name":"Samuel M. Niman","orcid":null,"position":1,"is_corresponding":false},{"id":406328,"name":"Olivia Pagani","orcid":"0000-0001-9739-6299","position":2,"is_corresponding":false},{"id":292886,"name":"Ann H. Partridge","orcid":"0000-0002-4722-4824","position":3,"is_corresponding":false},{"id":287597,"name":"Hatem A. Azim","orcid":"0000-0003-4865-3193","position":4,"is_corresponding":false},{"id":406329,"name":"Fedro A. Peccatori","orcid":"0000-0001-8227-8740","position":5,"is_corresponding":false},{"id":406330,"name":"Monica Ruggeri","orcid":"0000-0002-9025-0745","position":6,"is_corresponding":false},{"id":406331,"name":"Angelo Di Leo","orcid":"0000-0002-3665-9056","position":7,"is_corresponding":false},{"id":406332,"name":"Marco Colleoni","orcid":"0000-0002-5743-3013","position":8,"is_corresponding":false},{"id":406333,"name":"Richard D. Gelber","orcid":"0000-0001-8270-8712","position":9,"is_corresponding":false},{"id":406334,"name":"Meredith M. Regan","orcid":"0000-0002-2428-6109","position":10,"is_corresponding":false},{"id":406327,"name":"Zhuoxin Sun","orcid":"0009-0004-5367-6028","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:49:40.769098Z","pmid":"32535486","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":[]}