藥物開發之二元滿足點Phase II/III調適性無縫設計

Abstract

近幾十年來，對於製藥發展來說，如何設計一個臨床試驗、分析其數據，以及評估藥物的效益已成為一門重要課題。成功開發新藥物的價格急劇上升，而且在發展過程中有超過一半的時間和費用被使用於臨床試驗中，因此，臨床試驗不僅費時且費用昂貴。儘管有許多候選藥物，但研究、開發新藥物的成功率卻是令人失望的。因此，迫切需要發展一種快速、經濟且適當的方法以減少藥物發展的時間與花費。此研究中，針對二元滿足點的臨床試驗，提出了一個phase II/III的調適性無縫設計。在phase II試驗中，一試驗藥物的多種劑量皆與一對照組做比較，以便評估新藥的療效。若有一些劑量在此階段被證實是有效的，或是所有的劑量皆無效，則試驗將提早結束；否則這些劑量組被允許進入phase III試驗。在最終資料分析時，我們使用兩階段的數據，如此一來，可節省更多的病患資料及提供更多藥物安全性的訊息。因此，節省資源和成本，縮短臨床試驗發展時間是有可能的。

In recent decades, how to design a clinical trial, to analyze the data, and to evaluate the benefit of drugs as a whole 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. Thus the process of clinical trials is not only time-consuming but also costly. However, the success rate of researching and developing new drugs is disappointing even though there are many potential candidates. As a result, there is an urgent need to conduct a clinical trial by a quick, economical and suitable approach. In this paper, an adaptive phase II/III design which is based on a dichotomous endpoint is proposed in order to reduce the cost and time of developing a drug. At the first stage (the phase II stage), we provide the contrasts between several doses of a test drug and a concurrent control group so that we can evaluate the efficacy of doses of the test drug over the control group. The trial will be stopped early because of efficacy of some doses or futility of all doses. Otherwise, the promising dose groups are permitted to enter the next stage (the phase III stage). We perform the final analysis with the cumulative data from both the phase II stage and the phase III stage so that it can save data form patients and provide more information about safety. Therefore, considerably saving resource and cost and shortening the duration of clinical trials may be possible.