Truth, Ltd., 3311 Blue Ridge Court, Westlake Village, CA 91362, USA.
Stat Med. 2010 Jan 30;29(2):210-8. doi: 10.1002/sim.3757.
I consider the underlying structure for a test of qualitative interaction of a treatment when assessing heterogeneity between stages in an adaptive trial. Since decisions about the clinical utility of a drug are based on the balance of risks and benefits, a quantitative interaction in treatment efficacy across different groups could lead to qualitatively different decisions. Thus, the difference between quantitative and qualitative interactions is not a true dichotomy. I show that the standard tests for qualitative interactions (Gail and Simon,Biometrics 1985; 41:361-372; Piantadosi and Gail, Statist. Med. 1993; 12:1239-1248) are very conservative in this application. Theoretical calculations in a simpler situation confirm that the published criteria are very conservative, which may help explain why the tests are known to have very low power to detect interaction. I introduce the concept of 'minimum detectable effect', which is the smallest effect that a study could identify as statistically significant. I propose that important heterogeneity between stages in an adaptive trial be identified when two criteria are met. First, at least one individual stage must be below the overall study mean by at least the minimum detectable effect. Second, using an appropriate critical value based on simulations, there must be statistically significant heterogeneity between the stages.
当评估适应性试验中各阶段之间的异质性时，我考虑了用于检验定性治疗相互作用的基本结构。由于药物临床应用价值的决策是基于风险和效益的平衡，因此不同组之间治疗效果的定量相互作用可能会导致定性不同的决策。因此，定量相互作用和定性相互作用之间的差异并不是真正的二分法。我表明，用于检验定性相互作用(Gail 和 Simon，Biometrics 1985；41：361-372；Piantadosi 和 Gail，Statist. Med. 1993；12：1239-1248)的标准检验在这种应用中非常保守。在更简单的情况下的理论计算证实，已发表的标准非常保守，这可能有助于解释为什么这些检验已知的检测相互作用的功效非常低。我引入了“最小可检测效应”的概念，这是研究可以确定为具有统计学意义的最小效应。我建议，当满足两个标准时，应识别适应性试验中各阶段之间的重要异质性。首先，至少一个个体阶段必须至少比整个研究平均值低最小可检测效应。其次，根据模拟使用适当的临界值，阶段之间必须存在统计学上显著的异质性。
