Multiple Comparison Procedures for Non-inferiority Clinical Trials with Heterogeneous Variances and Multiple Standard Treatments

  • 黃 莉晴

Student thesis: Doctoral Thesis

Abstract

The objective of a non-inferiority (NI) trial is to affirm the efficacy of a new treatment compared with a standard treatment by verifying that the new treatment maintains a considerable portion of the treatment effect of the standard The marginal loss of efficacy (NI margin) of adopting the new treatment has to be justified by its other benefits such as the alleviation of side effects the lowering of costs and the simplification of intricate treatment regimens A popular approach is to express the NI margin in terms of the efficacy difference between the new treatment and the standard treatment Based on this approach statistical procedures that simultaneously conduct NI tests of several new treatments have been proposed However these procedures were formulated on the assumption of equal variances In this thesis the first objective is to discuss the undesirable effect on the familywise error rate using these procedures under the situation of heterogeneous variances Two new procedures are proposed to alleviate the problem A simulation study of the familywise error rate and power is conducted to compare different procedures It is found that the proposed procedure that used a plug-in method is superior The second objective of this thesis is to extend previous statistical methods for NI trials that only focus on testing of treatments with a single standard treatment In practice NI trials sometimes compare new treatments with multiple standard treatments and the appropriate testing procedure is derived Further the power function together with the strategy to determine the optimal sample size are discussed Clinical trial examples are presented to illustrate our proposed procedure
Date of Award2015 Jan 12
Original languageEnglish
SupervisorMiin-Jye Wen (Supervisor)

Cite this

Multiple Comparison Procedures for Non-inferiority Clinical Trials with Heterogeneous Variances and Multiple Standard Treatments
莉晴, 黃. (Author). 2015 Jan 12

Student thesis: Doctoral Thesis