Candel Math J J M
Department Methodology and Statistics, Maastricht University, Maastricht, The Netherlands.
Pharm Stat. 2012 Mar-Apr;11(2):97-106. doi: 10.1002/pst.502. Epub 2012 Feb 15.
When examining the effect of treatment A versus B, there may be a choice between a parallel group design, an AA/BB design, an AB/BA cross-over and Balaam's design. In case of a linear mixed effects regression, it is examined, starting from a flexible function of the costs involved and allowing for subject dropout, which design is most efficient in estimating this effect. For no carry-over, the AB/BA cross-over design is most efficient as long as the dropout rate at the second measurement does not exceed 2ρ/(1 + ρ), ρ being the intraclass correlation. For steady-state carry-over, depending on the costs involved, the dropout rate and ρ, either a parallel design or an AA/BB design is most efficient. For types of carry-over that allow for self carry-over, interest is in the direct treatment effect plus the self carry-over effect, with either an AA/BB or Balaam's design being most efficient. In case of insufficient knowledge on the dropout rate or ρ, a maximin strategy is devised: choose the design that minimizes the maximum variance of the treatment estimator. Such maximin designs are derived for each type of carry-over.
在考察治疗A与治疗B的效果时，在平行组设计、AA/BB设计、AB/BA交叉设计和巴兰设计之间可能存在选择。对于线性混合效应回归，从所涉及成本的灵活函数出发并考虑受试者退出的情况，考察哪种设计在估计这种效果时效率最高。对于无残留效应的情况，只要第二次测量时的退出率不超过2ρ/(1 + ρ)（ρ为组内相关系数），AB/BA交叉设计就是最有效的。对于稳态残留效应，根据所涉及的成本、退出率和ρ，平行设计或AA/BB设计可能是最有效的。对于允许自身残留效应的残留效应类型，关注的是直接治疗效果加上自身残留效应，此时AA/BB设计或巴兰设计是最有效的。在对退出率或ρ了解不足的情况下，设计了一种极大极小策略：选择使治疗估计量的最大方差最小化的设计。针对每种残留效应类型都推导出了此类极大极小设计。
