Department of Surgery, University of Virginia, Charlottesville, VA 22908, USA.
Clin Cancer Res. 2012 Jan 1;18(1):256-62. doi: 10.1158/1078-0432.CCR-11-1633. Epub 2011 Oct 5.
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.
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.
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.
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.
评估入组不足对试验过早关闭的影响需要一个相关的指标。我们建议根据解决主要终点（PE）的明显能力而不是达到入组目标来定义入组充足性。
评估了美国五个肿瘤临床合作组（CTCG）于 1993 年 1 月 1 日至 2002 年 12 月 31 日开放的所有三期试验的入组充足性和科学结果。充足的入组包括达到入组目标、CTCGs 文件证明足够的入组或中期分析的结论性结果；入组不足包括作为关闭原因引用的较差入组或其他原因导致试验无法解决其主要终点。基于我们的入组充足性定义的关闭率与达到入组目标和解决主要终点的比率进行了比较。确定了一个目标入组率以上的百分比，通常用于回答预期的科学问题，作为在设计中指定入组成功时达到全部目标入组的替代方法。
在 238 项合格试验中，有 158 项（66%）因入组充足而关闭。在 80 项入组不足的试验中，有 70 项（29%）因入组不足而专门关闭。仅通过达到入组目标来定义入组成功时，会过分强调入组不足的发生率。在 39%的试验中，近 75%的试验明确解决了主要终点，并且结果为阳性。达到目标入组率的 80%以上可以作为回答预期科学问题的可靠替代指标。
大约三分之一的三期试验因无法解决主要终点而入组不足而关闭，主要是由于入组不足。将入组充足性的定义定义为不仅仅是达到入组目标，更能公正地反映试验关闭情况。
