Browsing by Author "Hsiao, Chin-Fu"

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An alternative phase II/III design for continuous endpoints
(2011-03-01)
Huang, Wong-Shian
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Liu, Jen-pei
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Hsiao, Chin-Fu
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統計學研究所
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Institute of Statistics
The success rate of drug development has been declined dramatically in recent years and the current paradigm of drug development is no longer functioning. It requires a major undertaking on breakthrough strategies and methodology for designs to minimize sample sizes and to shorten duration of the development. We propose an alternative phase II/III design based on continuous efficacy endpoints, which consists of two stages: a selection stage and a confirmation stage. For the selection stage, a randomized parallel design with several doses with a placebo group is employed for selection of doses. After the best dose is chosen, the patients of the selected dose group and placebo group continue to enter the confirmation stage. New patients will also be recruited and randomized to receive the selected dose or placebo group. The final analysis is performed with the cumulative data of patients from both stages. With the pre-specified probabilities of rejecting the drug at each stage, sample sizes and critical values for both stages can be determined. As it is a single trial with controlling overall type I and II error rates, the proposed phase II/III adaptive design may not only reduce the sample size but also improve the success rate. An example illustrates the applications of the proposed phase II/III adaptive design. Copyright (C) 2010 John Wiley & Sons, Ltd.
Non-lethal Candida albicans cph1/cph1 efg1/efg1 mutant partially protects mice from systemic infections by lethal wild-type cells
(2009-03-01)
Yang, Yun-Liang
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Wang, Chih-Wei
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Chen, Chiung-Tony
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Wang, Min-Hsien
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Hsiao, Chin-Fu
Although Candida albicans cph1/cph1 efg1/efg1 mutant cells are not lethal to mice, they proliferated in infected mice instead of simply being cleared by the host immune system. Here, we have shown that the cph1/cph1 efg1/efg1 mutant partially protects mice from systemic infections by the lethal wild-type Candida albicans cells. Our results further indicate that a second dose of the cph1/cph1 efg1/efg1 mutant did not boost the degree of protection. (c) 2008 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
Sample size determination for a specific region in multiregional clinical trials with multiple co-primary endpoints
(2017-06-30)
Huang, Wong-Shian
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Hung, Hui-Nien
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Hamasaki, Toshimitsu
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Hsiao, Chin-Fu
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統計學研究所
Recently, multi-regional clinical trials (MRCTs), which incorporate subjects from many countries/ regions around the world under the same protocol, have been widely conducted by many global pharmaceutical companies. The objective of such trials is to accelerate the development process for a drug and shorten the drug's approval time in key markets. Several statistical methods have been purposed for the design and evaluation of MRCTs, as well as for assessing the consistency of treatment effects across all regions with one primary endpoint. However, in some therapeutic areas (e.g., Alzheimer's disease), the clinical efficacy of a new treatment may be characterized by a set of possibly correlated endpoints, known as multiple co-primary endpoints. In this paper, we focus on a specific region and establish three statistical criteria for evaluating consistency between the specific region and overall results in MRCTs with multiple co-primary endpoints. More specifically, two of those criteria are used to assess whether the treatment effect in the region of interest is as large as that of the other regions or of the regions overall, while the other criterion is used to assess the consistency of the treatment effect of the specific region achieving a pre-specified threshold. The sample size required for the region of interest can also be evaluated based on these three criteria.