Woods J R, Williams J G, Tavel M
Methodist Hospital of Indiana, Inc., Indianapolis.
Ann Intern Med. 1989 Apr 1;110(7):560-6. doi: 10.7326/0003-4819-110-7-560.
The crossover design has enjoyed popularity with many clinical researchers, but has been criticized by biostatisticians. The central problem is the inability to derive an unbiased estimate of the treatment effect when differences occur because of the different sequences in which treatments are applied. This problem can be traced to a deficiency of the logic of the crossover arrangement itself. Factors that can invalidate the findings of a crossover trial include nonuniform pharmacologic and psychologic carry-over effects, failure to return patients to their baseline state before the crossover, nonuniform changes in the patients over time, and the use of time-dependent response measures. When these problems can be anticipated, a parallel-groups design should be used instead of a crossover trial.
交叉设计受到了许多临床研究人员的青睐，但却遭到了生物统计学家的批评。核心问题在于，当由于治疗应用顺序不同而出现差异时，无法得出治疗效果的无偏估计。这个问题可追溯到交叉设计本身逻辑的缺陷。可能使交叉试验结果无效的因素包括药理学和心理学方面的非均匀残留效应、在交叉前未能使患者恢复到基线状态、患者随时间的非均匀变化以及使用随时间变化的反应测量指标。当这些问题可以预见时，应采用平行组设计而非交叉试验。
