Departments of Medical Oncology and Hematology.
Biostatistics, Princess Margaret Hospital and University of Toronto, Toronto.
Ann Oncol. 2010 Jul;21(7):1411-1418. doi: 10.1093/annonc/mdp552. Epub 2009 Nov 30.
Phase III randomized clinical trials (RCTs) have become larger and are powered to detect small absolute benefits. Temporal changes in absolute benefits of experimental medical therapies reported in RCTs are unknown.
We identified all RCTs with sample size > or =200 evaluating experimental medical therapies for breast and colorectal cancer published from 1975 to 2007. We assessed changes over three decades in absolute differences in time-to-event end points between experimental and control arms by (i) the usual method (i.e. at one point) and (ii) as the area between time-to-event curves up to a predefined time.
We identified 236 eligible RCTs of which 57% (N = 135) evaluated adjuvant treatments. Experimental treatments became more often compared with active treatments (48% versus 59% versus 81%; P < 0.0001). Median absolute benefits of experimental adjuvant treatments decreased but outcomes in control arms improved with time. For RCTs evaluating metastatic disease, there were no changes in absolute benefit over time but incremental monthly costs of new approved treatments increased with time by 100-fold (P < 0.0001).
In RCTs of breast and colorectal cancer, new effective adjuvant treatments show decreasing absolute benefit, while new treatments of metastatic disease show unchanging levels of benefit at rapidly escalating costs.
三期随机临床试验（RCT）的规模不断扩大，旨在检测微小的绝对获益。实验性医学疗法在 RCT 中报告的绝对获益的时间变化尚不清楚。
我们确定了所有样本量大于等于 200 例的 RCT，这些 RCT 评估了 1975 年至 2007 年间用于治疗乳腺癌和结直肠癌的实验性医学疗法。我们通过（i）常规方法（即在一个点）和（ii）在预定时间之前将时间事件曲线之间的区域来评估时间事件终点的绝对差异在三个十年中发生的变化。
我们确定了 236 项符合条件的 RCT，其中 57%（N = 135）评估了辅助治疗。与活性治疗相比，实验性治疗变得越来越常见（48%比 59%比 81%；P < 0.0001）。实验性辅助治疗的中位绝对获益减少，但随着时间的推移，对照臂的结果有所改善。对于评估转移性疾病的 RCT，随着时间的推移，绝对获益没有变化，但新批准的治疗方案的每月增量成本增加了 100 倍（P < 0.0001）。
在乳腺癌和结直肠癌的 RCT 中，新的有效辅助治疗方案显示出绝对获益的减少，而转移性疾病的新治疗方案则显示出不断增加的成本和不变的获益水平。
