二元滿足點之Phase II/III調適性無縫臨床試驗設計

Abstract

How to design a clinical trial, to analyze the data, and to evaluate the benefit of drugs becomes an important course for pharmaceutical development. The price of successfully developing new drugs has risen steeply, and more than half of the time and expense in the development process are spent in clinical trials. Hence, one challenge in the development of new drug is reducing expenses and time, moreover demonstrating the benefits of a new drug. It is recognized that, in spite of increasing spending of biomedical research does not reflect an increase of the success rate of pharmaceutical development. The success rate of researching and developing new drugs is disappointing even though there are many potential candidates and lengthy process of clinical development. Therefore, there is a reason to find ways in which drug development could be expedited and made more efficient. In this thesis, two adaptive seamless phase II/III designs are developed: one permits early stopping only for futility (Design I), and the other allows early stopping for either efficacy or futility (Design II). The resulting designs are in practice two-stage designs. At the stage one (the phase II stage), several doses of an experiment are compared with a control group so that we can evaluate the efficacy of doses of the experiment over the control group. After stage one (phase II stage), an interim analysis is performed and a decision is made on whether to proceed to stage two (phase III stage). Numerical examples are also given to illustrate our designs.