Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 334-338 |
| Number of pages | 5 |
| Journal | Therapeutic Innovation and Regulatory Science |
| Volume | 52 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - May 1 2018 |
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Keywords
- Bayesian design
- rare cancer
- single-arm trial
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
- Public Health, Environmental and Occupational Health
- Pharmacology (medical)
Cite this
Utility of Bayesian Single-Arm Design in New Drug Application for Rare Cancers in Japan : A Case Study of Phase 2 Trial for Sarcoma. / Hirakawa, Akihiro; Nishikawa, Tadaaki; Yonemori, Kan; Shibata, Taro; Nakamura, Kenichi; Ando, Masashi; Ueda, Takafumi; Ozaki, Toshihumi; Tamura, Kenji; Kawai, Akira; Fujiwara, Yasuhiro.
In: Therapeutic Innovation and Regulatory Science, Vol. 52, No. 3, 01.05.2018, p. 334-338.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Utility of Bayesian Single-Arm Design in New Drug Application for Rare Cancers in Japan
T2 - A Case Study of Phase 2 Trial for Sarcoma
AU - Hirakawa, Akihiro
AU - Nishikawa, Tadaaki
AU - Yonemori, Kan
AU - Shibata, Taro
AU - Nakamura, Kenichi
AU - Ando, Masashi
AU - Ueda, Takafumi
AU - Ozaki, Toshihumi
AU - Tamura, Kenji
AU - Kawai, Akira
AU - Fujiwara, Yasuhiro
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
KW - Bayesian design
KW - rare cancer
KW - single-arm trial
UR - http://www.scopus.com/inward/record.url?scp=85042348654&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042348654&partnerID=8YFLogxK
U2 - 10.1177/2168479017728989
DO - 10.1177/2168479017728989
M3 - Article
C2 - 29714533
AN - SCOPUS:85042348654
VL - 52
SP - 334
EP - 338
JO - Therapeutic Innovation and Regulatory Science
JF - Therapeutic Innovation and Regulatory Science
SN - 2168-4790
IS - 3
ER -