The analysis of titration studies in phase III clinical trials.
Clinical trials commonly employ the titration design for certain drugs such as antihypertensives. In a Phase III trial the design has purposes distinct from those of a Phase I or II trial, as well as from those of a trial with a parallel design. In this paper we compare the titration design with the usual parallel design in their respective purposes for Phase III trials, explore the relevant questions addressed, and examine typical data from such trials. We also discuss work which focuses primarily on the Phase I or II titration trials. We formulate the problem in the framework of one-way contingency table augmented with incomplete data and obtain the maximum likelihood estimates of the parameters and their estimated variances/covariances via the EM algorithm. An example of a Phase III study of an antihypertensive agent illustrates the proposed procedure.
Shih
W J
WJ
Investigative Research, Biostatistics and Research Data System, Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065-0914.
Gould
A L
AL
Hwang
I K
IK
D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000008:administration & dosage; D002986:Clinical Trials as Topic / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation / Q000379:methods; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D011336:Probability; D012107:Research Design
D000959:Antihypertensive Agents