title: Trends in endpoint selection in clinical trials of advanced breast cancer.
abstract: OBJECTIVE
  The selection of appropriate endpoints is crucial for the evaluation of clinical benefits and approval of novel anticancer agents. To our knowledge, this is the first study to evaluate endpoint selection and the shift in trends in phase II and phase III trials of advanced breast cancer treatment.
  
  
  METHODS
  All phase II and phase III trials of advanced breast cancer registered in the ClinicalTrials.gov registry between October 2000 and September 2012 were included in our study. Two study periods were considered for comparison: October 2000 to September 2007 (cohort A) and October 2007 to September 2012 (cohort B). Information on primary and secondary outcome measures, as well as trial characteristics, was extracted by two independent reviewers.
  
  
  RESULTS
  Of the 398 phase II and 120 phase III trials, the most frequently intended primary endpoint was progression-free survival (phase II: 28.1 %; phase III: 50.0 %). For phase II trials, a shifting trend in primary outcome was observed from cohort A to cohort B: the use of objective response rate, the most frequently intended primary outcome, significantly declined (cohort A: 60.6 %; cohort B: 39.0 %; P < 0.001), while the use of progression-free survival significantly increased (cohort A: 35.9 %; cohort B: 66.1 %; P < 0.001).
  
  
  CONCLUSIONS
  Progression-free survival is the most frequently intended primary outcome measure in phase II and phase III trials of advanced breast cancer treatment, with a shifting trend observed from objective response rate to progression-free survival in phase II trials.
authors: Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, 06974, South Korea.
authors: Seung Yeon
authors: SY
authors: Song
authors: Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, 06974, South Korea.|Department of Pharmacy, Kangbuk Samsung Hospital, Seoul, 110-746, South Korea.
authors: Heenam
authors: H
authors: Seo
authors: Department of Pharmaceutical Industry Management, Graduate School, ChungAng University, Seoul, 06974, South Korea.
authors: Gyungjin
authors: G
authors: Kim
authors: Department of Pharmaceutical Industry Management, Graduate School, ChungAng University, Seoul, 06974, South Korea.
authors: Ah Rong
authors: AR
authors: Kim
authors: Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, 06974, South Korea. eykimjcb777@cau.ac.kr.|Department of Pharmaceutical Industry Management, Graduate School, ChungAng University, Seoul, 06974, South Korea. eykimjcb777@cau.ac.kr.|Clinical Research Lab, College of Pharmacy, Chung-Ang University, Seoul, 06974, South Korea. eykimjcb777@cau.ac.kr.
authors: Eun Young
authors: EY
authors: Kim
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002648:Child; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D015331:Cohort Studies; D018572:Disease-Free Survival; D023381:Endpoint Determination / Q000379:methods* / Q000639:trends; D005260:Female; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012042:Registries
keywords: Breast cancer; ClinicalTrials.gov; Endpoint selection; Outcome measures; Phase II/phase III; Trial registration