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系統識別號 U0026-2007201513151000
論文名稱(中文) 右設限資料下多組試驗之非劣性檢定
論文名稱(英文) Non-inferiority trials with multiple new treatments for right censored data
校院名稱 成功大學
系所名稱(中) 統計學系
系所名稱(英) Department of Statistics
學年度 103
學期 2
出版年 104
研究生(中文) 鄭芳岫
研究生(英文) Fang-Xiu Zheng
學號 R26021045
學位類別 碩士
語文別 中文
論文頁數 41頁
口試委員 指導教授-蘇佩芳
口試委員-嵇允嬋
口試委員-張升懋
中文關鍵字 檢測靈敏度  非劣性檢定  多重檢定  聯合信賴區間 
英文關鍵字 assay sensitivity  non-inferiority test  multiple test  simultaneous confidence intervals 
學科別分類
中文摘要 在藥物的臨床試驗中,非劣性試驗的比例逐漸增加。而臨床試驗需費時好幾年的時間,
且經費龐大,若多種新藥或不同劑量的新藥,可同時進行檢定,則可減少執行臨床試
驗的成本。本文考慮在右設限資料下的非劣性檢定,為了要評估多種新藥的療效,我
們利用Dunnett 多重比較的想法,使整體的型I 誤差率維持一定的顯著水準。進一步
地,我們推導出聯合信賴區間。並藉由模擬研究探討所提出的檢定方法,其型I 誤差
率及檢定力的表現。最後,以一筆資料說明所提出在右設限資料下非劣性檢定方法的
應用。
英文摘要 Non-inferiority (NI) trials are becoming increasingly popular. The main purpose of NI trials is to assert the efficacy of a new treatment compared with a standard treatment by demonstrating that the new treatment is at worst clinically irrelevantly inferior to the standard treatment. In this paper, we develop a statistical method for planning and evaluating NI trials with many new drugs for right censored data. In order to assess the efficacy of many new drugs, we apply the idea of Dunnett's multiple comparison to prevent an increased overall type I error rate. We propose a statistical procedure for many-to-one comparisons of treatments with adjustment for covariates based on the Cox proportional hazards model. The resulting simultaneous confidence intervals (SCI) for the hazard ratios of placebo and new treatments compared with a standard treatment can be interpreted in terms of both statistical significance and clinical importance. Simulation results show that the actual type I error rate and power perform well. Finally, to demonstrate the proposed method, we apply an example in this paper.
論文目次 第一章緒論.............................................1
1.1 研究背景.......................................... 1
1.2 研究動機與目的..................................... 2
第二章文獻回顧..........................................5
2.1 半參數模型下的非劣性檢定............................ 5
2.2 以聯合信區間比較多種新藥與標準藥物的療效.............. 7
第三章統計方法.........................................10
3.1 模型建立.......................................... 10
3.2 檢定問題.......................................... 11
3.3 漸近理論.......................................... 14
3.4 建構聯合信賴區間................................... 16
第四章模擬研究..........................................18
4.1 總體錯誤率的控制................................... 18
4.2 檢定力 ........................................... 23
4.2.1 在一組新藥下檢定力的模擬方法與結果................. 23
4.2.2 在兩組新藥下檢定力的模擬方法結果 .................. 29
第五章資料分析..........................................32
第六章結論與建議........................................36
參考文獻...............................................38
附錄 ..................................................39
參考文獻 Bender, R., Augustin, T., Blettner, M. (2005). Generating survival times to simulate Cox proportional hazards models. Statistics in Medicine 24(11), 1713-1723.
Cox, D.R. (1975). Partial likelihood. Biometrika 62(2), 269-276.
European Medicines Agency (2005). Committee for Medicinal Products for Human Use (CHMP). Guideline on the choice of the non-inferiority margin EMEA/CPMP/EWP/2158/99.
Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. Journal of the Royal Statistical Society 50(272), 1096-1121.
Freitag, G., Lange, S., Munk, A. (2006). Non-parametric assessment of non-inferiority with censored data. Statistics in Medicine 25(7), 1201-1217.
Herberich, E., Hothorn, T. (2012). Dunnett-type inference in the frailty Cox model with covariates. Statistics in Medicine 31(1), 45-55.
Kwong, K.S., Cheung, S.H., Hayter, A.J., Wen, M.J. (2012). Extension of three-arm non-inferiority studies to trials with multiple new treatments. Statistics in Medicine 31(24), 2833-2843.
Kombrink, K., Munk, A., Friede, T. (2013). Design and semiparametric analysis of non-inferiority trials with active and placebo control for censored time-to-event data. Statistics in Medicine 32(18), 3055-3066.
Prentice, R.L. (1973). Exponential survivals with censoring and explanatory variables. Biometrika 60(2), 279-288.
Tsiatis, A.A. (1981). A large sample study of Cox's regression model. The Annals of Statistics 9(1), 93-108.
U.S. Food and Drug Administration (2010). Guidance for industry non-inferiority clinical trials.
吳雅琪(2012,8月)。不劣性試驗統計審查重點。當代醫藥法規,22,1-6。
鄭雅珊(2009)。根據限制平均壽命所做之非劣性檢定。國立中央大學統計研究所碩士論文。
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