| Summary: | 碩士 === 國立中央大學 === 統計研究所 === 103 === In the development of a new drug, to reduce the cost and shorten the time of the phase I and II clinical trials, a study of combining the above two phase trials is investigated. Traditionally, the phase I trial which takes about 6 months is to find the maximal tolerate dose (MTD) of the drug under study under specific dose-limiting toxicity (DLT). The phase II clinical trial, taking about 18 months, is to evaluate the short term effectiveness of the drug at the MTD above, based on binary outcomes. This thesis considers a two-stage combined trial. The first stage concerns with the safety of the drug, where the temporary MTD is determined by applying the Bayesian method. The second stage considers both the safety and effectiveness which is proceeded in batch and the dose applied to next batch is adjusted based on a Bayesian analysis. Note that the two-stage design may take care of the late-onset toxicity since the MTD is adjusted at the second stage. Through an appropriate design, the proposed trial may save time with less patients for futility drugs or effective drugs. Finally, a simulation study is conducted to investigate the required number of patients and the needed time for implement the combined trials under a variety of toxicity-dose and dose-response models under different distributions of reaction times to toxic or effectiveness.
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