Assessment of equivalence on multiple endpoints.
Some clinical trials aim to demonstrate therapeutic equivalence on multiple primary endpoints. For example, therapeutic equivalence studies of agents for the treatment of osteoarthritis use several primary endpoints including investigator's global assessment of disease activity, patient's global assessment of response to therapy, and pain. In this paper, thoughts on simultaneous equivalence assessment on three endpoints are presented. As pointed out by Berger and Hsu (1996), the conventional intersection-union test can be conservative. Simulation and computation are conducted to provide an insight on the conservativeness. We also provide a method to lower the confidence level and at the same time maintain the type I error when endpoints have normal distributions and are independent. If, in a particular analysis, the goal is to demonstrate equivalence on as many endpoints as possible, a step-up procedure can be used for selecting those endpoints for which equivalence may be demonstrated. This step-up procedure at the same time controls experimentwise error rate. The techniques are illustrated by a data example.
Quan
H
H
Clinical Biostatistics and Research Data Systems, Merck Research Laboratories, RY 33-404, P.O. Box 2000, Rahway, New Jersey 07065, USA. hui_quan@merck.com
Bolognese
J
J
Yuan
W
W
D001699:Biometry; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D016001:Confidence Intervals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D010003:Osteoarthritis / Q000188:drug therapy / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases; D013810:Therapeutic Equivalency
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases