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系統識別號 U0026-0907201013521800
論文名稱(中文) 組合藥品之有效性檢定與區間估計
論文名稱(英文) Testing the Efficacy in Fixed-Dose Combination Drug Studies
校院名稱 成功大學
系所名稱(中) 統計學系碩博士班
系所名稱(英) Department of Statistics
學年度 98
學期 2
出版年 99
研究生(中文) 陳建斌
研究生(英文) Jian-Bin Chen
學號 r2697105
學位類別 碩士
語文別 中文
論文頁數 33頁
口試委員 指導教授-杜宜軒
口試委員-張升懋
口試委員-黃錦輝
中文關鍵字 臨床試驗  組合試驗  最小檢定  正確區間估計 
英文關鍵字 Clinical trial  Combination trial  Min test  Exact confidence interval 
學科別分類
中文摘要 常見的臨床試驗有三種試驗:優越性試驗 (superiority trials)、非劣等試驗 (noninferiority trials)、組合試驗 (combination trials)。在組合試驗下,美國食品與藥品管理局 (U.S. Food and Drug Administration; FDA) 的規範 (21 CFR 300.50) 中,規定使用新的複方藥必須證明“任何組成的單方藥必需對複方藥療效有貢獻”。為了滿足上述的規定,需證明複方藥比其組成單方藥有效。Wang 與 Hung (1997) 提出當反應變數為二元變數時,在單一劑量下組合兩種藥品療效的檢定方法。在實務中,可能不只組合兩種藥品,因此,本論文第一部分是推廣 Wang 與 Hung (1997) 的方法加入與第三個單方藥的比較。當臨床試驗人數不多,無法符合大樣本的條件時,本論文的第二部分提供在小樣本時複方藥療效的正確區間估計。
英文摘要 There are three major types of clinical trials: superiority trials, non-inferiority trials, and combination trials.To determine a combination drug is effective in the combination trials, the U.S. Food and Drug Administration (21CFR 300.50) regulates that the new combination drug must show that "each component makes a contribution to the claimed effect". In other words, this regulation requires that the combination drug must br more effective than its components. Wang and Hung (1997) developed large sample tests for binary outcomes in fixed-dose combination two drugs trials. In practice, it may need to combine more than two drugs. Thus, the first part of this thesis extends their method by including the third drug. In addition, the sample size of clinical trials sometimes may not be large enough to use Wang and Hung (1997)'s method. Therefore, the second part of this thesis constructs confidence intervals of effect size in small samples.
論文目次 第1章 緒論 1
第2章 文獻回顧 4
2.1 大樣本二元變數檢定方法 4
2.2 區間估計 7
第3章 大樣本漸近檢定 11
3.1 檢定方法 11
3.2 模擬 13
3.3 應用 19
第4章 參數之區間估計 20
4.1 估計方法 20
4.2 模擬 24
4.3 應用 26
第5章 結論與建議 27

參考文獻 28

附錄一 30
附錄二 32
參考文獻 1. Chan, I. S. F. (1998). Exact tests of equivalence and efficacy with a non-zero lower bound for comparative studies. Statistics in Medicine, 17, 1403-1413.

2. Chan, I. S. F. and Zhang, Z. (1999). Test-based exact confidence intervals for the difference of two binomialproportions. Biometrics 55, 1202-1209.

3. Clopper, C. J. and Pearson, E. S. (1934). The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 26, 404-413.

4. Haber, M. (1986). An exact unconditional test for the 2 x 2 comparative trials. Psychological Bulletin 99, 129-132.

5. Hung, H. M. (1992). On identifying a positive dose-response surface for combination agents. Statistics in medicine 11, 703-711.

6. Hung, H. M., Ghi, G. Y. H., and Lipicky, R. J. (1993). Testing for the Existence of a Desirable Dose Combination. Biometrics 49, 85-94.

7. Rohatgi, V. K. (1984). Statistical Inference. New York: John Wiley.

8. Soulakova, J. N. (2009). Comparison of several testing strategies for combination drug efficacy trials based on the closure principle. Statistics in medicine 28, 260-273.

9. Soulakova, J. N. and Sampson, A. R. (2009). On identifying minimum efficacious doses in combination drug trials. Statistics in Biopharmaceutical Research: Vol. 1, No. 1.

10. Suissa, S. and Shuster, J. J. (1985). Exact unconditional sample sizes for the 2 x 2 binomial trial. Journal of the Royal Statistical Society, Series A 148, 317-327.

11. U.S. Food and Drug Administrations policy (2006), "Fixed-Combination Prescription Drugs for Humans," Code of Federal Regulations, Title 21, Volume 5 (21 CFR 300.50).

12. Wang, S-J and Hung, H. M. (1997). Large sample tests for binary outcomes in fixed-dose combination drug studies. Biometrics 53, 498-503.
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