Adjusted regression trend test for a multicenter clinical trial.
Studies using a series of increasing doses of a compound, including a zero dose control, are often conducted to study the effect of the compound on the response of interest. For a one-way design, Tukey et al. (1985, Biometrics 41, 295-301) suggested assessing trend by examining the slopes of regression lines under arithmetic, ordinal, and arithmetic-logarithmic dose scalings. They reported the smallest p-value for the three significance tests on the three slopes for safety assessments. Capizzi et al. (1992, Biometrical Journal 34, 275-289) suggested an adjusted trend test, which adjusts the p-value using a trivariate t-distribution, the joint distribution of the three slope estimators. In this paper, we propose an adjusted regression trend test suitable for two-way designs, particularly for multicenter clinical trials. In a step-down fashion, the proposed trend test can be applied to a multicenter clinical trial to compare each dose with the control. This sequential procedure is a closed testing procedure for a trend alternative. Therefore, it adjusts p-values and maintains experimentwise error rate. Simulation results show that the step-down trend test is overall more powerful than a step-down least significant difference test.
Quan
H
H
Clinical Biostatistics, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Capizzi
T
T
D000368:Aged; D019386:Alendronate / Q000627:therapeutic use; D001699:Biometry; D015519:Bone Density / Q000187:drug effects; D003198:Computer Simulation; D005260:Female; D006801:Humans; D015233:Models, Statistical; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012044:Regression Analysis
D019386:Alendronate