Crossover design and its application in late-phase diabetes studies.
Crossover design has been widely used in late-phase clinical studies, as well as in pharmacokinetic and pharmacodynamic, bioequivalence, and medical device studies; however, its interpretability and applicability continue to be debated. Herein we provide discussions around a crossover design's scientific benefit, applicability, and how it can be implemented in late-phase diabetes studies by properly handling key issues: carryover effect, washout period, and baseline selection. Specifically, detailed considerations are provided about the validity and situations of having appropriate length of study duration to deal with carryover effects so that a washout period may not be needed. A simulation study and data mining results on 12 crossover late-phase insulin clinical trials are presented to examine the discussion points and proposals.
Eli Lilly and Company, Insulin and Device Development, Indianapolis, Indiana, USA.
Tao
T
Wang
Eli Lilly and Company, Insulin and Device Development, Indianapolis, Indiana, USA.
James
J
Malone
Eli Lilly and Company, Insulin and Device Development, Indianapolis, Indiana, USA.
Haoda
H
Fu
Eli Lilly and Company, Insulin and Device Development, Indianapolis, Indiana, USA.
Cory
C
Heilmann
Eli Lilly and Company, Insulin and Device Development, Indianapolis, Indiana, USA.
Yongming
Y
Qu
Eli Lilly and Company, Insulin and Device Development, Indianapolis, Indiana, USA.
William J
WJ
Huster
D035843:Biomedical Research / Q000379:methods / Q000592:standards; D001786:Blood Glucose / Q000378:metabolism*; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000145:classification / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use*; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin
carryover effect; crossover design; diabetes; late-phase clinical trials; washout period; 交叉设计; 实施效果; 晚期阶段临床试验; 洗脱期。; 糖尿病