2018年5月1日
Utility of Bayesian Single-Arm Design in New Drug Application for Rare Cancers in Japan: A Case Study of Phase 2 Trial for Sarcoma
Therapeutic Innovation and Regulatory Science
- 巻
- 52
- 号
- 3
- 開始ページ
- 334
- 終了ページ
- 338
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1177/2168479017728989
- 出版者・発行元
- SAGE Publications Inc.
Investigational drugs for rare cancers are often approved based solely on a single-arm phase II trial that primarily evaluates response rate in Japan. Such trials typically use a fixed sample size determined on the basis of the frequentist manner. However, since predicting the speed of patient enrollment is challenging because of the disease rarity, the time needed to complete the enrollment of the fixed number of patients is prolonged in some cases. A Bayesian design without fixing the sample size is useful for single-arm phase II trials of rare cancers. However, the arbitrariness of prior distribution specifications and the frequentist operating characteristics are regulatory issues. We recently started a Bayesian single-arm phase II trial of nivolumab in patients with sarcoma for new drug application in Japan and examined the statistical rationale and design consideration. In the Bayesian design, we specify the minimum and maximum numbers of enrolled patients during the enrollment period and the prior distributions of response rates. Considering these parameters, we obtain the minimum number of responders needed for the positive conclusion of the efficacy of nivolumab for each sample size. Simulation studies demonstrated that the operating characteristics of this design would be acceptable from the frequentist view. The Bayesian design provided an adaptive decision rule for efficacy conclusion for the drug without fixing the sample size. We hope our trial’s success will provide a new drug development option for rare cancers in Japan.
- ID情報
-
- DOI : 10.1177/2168479017728989
- ISSN : 2168-4804
- ISSN : 2168-4790
- PubMed ID : 29714533
- SCOPUS ID : 85042348654