title: Achieving sufficient accrual to address the primary endpoint in phase III clinical trials from U.S. Cooperative Oncology Groups.
abstract: OBJECTIVE
  Assessing impact of poor accrual on premature trial closure requires a relevant metric. We propose defining accrual sufficiency on apparent ability to address primary endpoints (PE) rather than attaining accrual targets.
  
  
  METHODS
  All phase III trials open January 1, 1993, to December 31, 2002, by five U.S. oncology Clinical Trials Cooperative Groups (CTCG) were evaluated for accrual sufficiency and scientific results. Sufficient accrual included meeting accrual target, CTCGs documentation attesting adequate accrual, or conclusive results at interim analysis; insufficient accrual included poor accrual as cited closure reason or other reasons rendering a trial unable to address its primary endpoints. Closure rates based on our accrual sufficiency definition are compared with rates of meeting accrual targets and addressing the primary endpoints. A percentage of target accrual above which trials commonly answer the intended scientific question was identified to serve as an alternative to meeting full target accrual in designating accrual success.
  
  
  RESULTS
  Of 238 eligible trials, 158 (66%) closed with sufficient accrual. Among 80 trials with insufficient accrual, 70 (29%) closed specifically because of poor accrual. Inadequate accrual rates are overemphasized when defining accrual success solely by meeting accrual targets. Nearly 75% of trials conclusively addressed the primary endpoints with positive results in 39% of trials. Exceeding 80% of target accrual serves as a reliable proxy for answering the intended scientific question.
  
  
  CONCLUSIONS
  Approximately one third of phase III trials closed with insufficient accrual to address the primary endpoints, primarily due to poor accrual. Defining accrual sufficiency broader than meeting accrual targets represents a fairer account of trial closures.
authors: Department of Surgery, University of Virginia, Charlottesville, VA 22908, USA. ats2x@virginia.edu
authors: Anneke T
authors: AT
authors: Schroen
authors: Gina R
authors: GR
authors: Petroni
authors: Hongkun
authors: H
authors: Wang
authors: Monika J
authors: MJ
authors: Thielen
authors: Robert
authors: R
authors: Gray
authors: Jacqueline
authors: J
authors: Benedetti
authors: Xiaofei F
authors: XF
authors: Wang
authors: Daniel J
authors: DJ
authors: Sargent
authors: Donald L
authors: DL
authors: Wickerham
authors: Walter
authors: W
authors: Cronin
authors: Benjamin
authors: B
authors: Djulbegovic
authors: Craig L
authors: CL
authors: Slingluff
mesh_terms: D000124:Achievement; D000293:Adolescent; D019985:Benchmarking; D002648:Child; D017326:Clinical Trials, Phase III as Topic / Q000379:methods* / Q000706:statistics & numerical data*; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D018579:Patient Selection; D011379:Prognosis; D012107:Research Design / Q000706:statistics & numerical data*; D014481:United States