School of Health and Related Research, The University of Sheffield, 30 Regent Street, Sheffield, S1 4DA, UK.
Intensive Care National Audit and Research Centre (ICNARC), 24 High Holborn, London, WC1V 6AZ, UK.
Trials. 2023 Mar 22;24(1):215. doi: 10.1186/s13063-023-07202-6.
Adaptive clinical trials may use conditional power (CP) to make decisions at interim analyses, requiring assumptions about the treatment effect for remaining patients. It is critical that these assumptions are understood by those using CP in decision-making, as well as timings of these decisions.
Data for 21 outcomes from 14 published clinical trials were made available for re-analysis. CP curves for accruing outcome information were calculated using and compared with a pre-specified objective criteria for original and transformed versions of the trial data using four future treatment effect assumptions: (i) observed current trend, (ii) hypothesised effect, (iii) 80% optimistic confidence limit, (iv) 90% optimistic confidence limit.
The hypothesised effect assumption met objective criteria when the true effect was close to that planned, but not when smaller than planned. The opposite was seen using the current trend assumption. Optimistic confidence limit assumptions appeared to offer a compromise between the two, performing well against objective criteria when the end observed effect was as planned or smaller.
The current trend assumption could be the preferable assumption when there is a wish to stop early for futility. Interim analyses could be undertaken as early as 30% of patients have data available. Optimistic confidence limit assumptions should be considered when using CP to make trial decisions, although later interim timings should be considered where logistically feasible.
适应性临床试验可以使用条件功效（CP）在中期分析时做出决策，这需要对剩余患者的治疗效果做出假设。对于那些在决策中使用 CP 的人来说，了解这些假设以及这些决策的时间至关重要。
为重新分析从 14 项已发表临床试验中获得了 21 个结局的数据。使用四种未来治疗效果假设（i）观察到的当前趋势、（ii）假设效果、（iii）80%乐观置信限、（iv）90%乐观置信限，计算了累积结局信息的 CP 曲线，并与试验数据的原始和转换版本的预设目标标准进行了比较。
当真实效果接近计划效果时，假设效果假设符合目标标准，但当效果小于计划效果时则不符合。当前趋势假设则相反。乐观置信限假设在两者之间似乎提供了一种折衷，当观察到的最终效果与计划效果或更小效果时，其对目标标准的表现良好。
当有希望提前因无效而停止时，当前趋势假设可能是首选假设。可以在有 30%的患者有数据可用时进行中期分析。在使用 CP 做出试验决策时，应该考虑乐观置信限假设，但如果在后勤上可行，应该考虑更晚的中期时间。
