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研究生: 顏秀禎
Hsiu-Chen Yen
論文名稱: 聯合長期追蹤與存活資料分析─術後黑色素細胞瘤病患之實例研究
Joint modeling of longitudinal and survival data─ A case study in patients with resected melanoma
指導教授: 曾議寬
Yi-Kuan Tseng
口試委員:
學位類別: 碩士
Master
系所名稱: 理學院 - 統計研究所
Graduate Institute of Statistics
畢業學年度: 99
語文別: 中文
論文頁數: 69
中文關鍵詞: 擴充風險模型聯合模型
外文關鍵詞: Joint model, Extended hazard model
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  • 在本篇文章中,我們利用免疫球蛋白抗體Igg值來評估術後黑色素細胞瘤的復發狀況,並且探討疫苗干擾素α-2b (IFNα-2b) 的加入是否會影響免疫治療劑GMK對於抗體的反應以及混合後疫苗的治療效果。主要利用聯合模型 (joint model) 的概念來對資料做分析,聯合模型同時包含了長期追蹤資料與存活資訊,
    使得估計量具有一致性 (consistency)、有效性 (efficiency)、以及漸近常態 (asymptotic normality) 的良好性質。在第一部分我們使用線性隨機效應模型 (linear random effect model) 來對長期追蹤資料做配適,並利用概似比檢定來診斷長期追蹤模型的適合度;在第二部分使用擴充風險模型 (extended hazard model) 描述變數與存活時間的關係,結合這兩部分建構出聯合概似函數且利用EM演算法 (expectation maximization algorithm) 對參數做估計。由於Cox比例風險模型 (Cox proportional hazards model) 和加速失敗時間模型 (accelerated failure time model) 皆為擴充風險模型的特例,因此可利用Wald type拔靴法、Percentile拔靴法以及BC percentile法建構參數信賴區間來對模型做選擇。


    We utilize immunoglobulin G serologic responses to the vaccine to appraise the
    progression of patients with resected melanoma, and determine whether there are any
    adverse response to GMK and evaluate therapeutic efficacy of the combined-modality
    therapy. The joint model approach has been used to analyze the data, which includes
    both longitudinal and survival data. It makes estimators contains nice properties, such
    as consistency, efficiency and asymptotic normality. In the first part, we fit the longit-
    udinal data with the linear random effects model, and use the likelihood ratio test to
    choose a proper longitudinal model. In the second part, the relationship between the
    longitudinal covariates and the failure time can be assessed by means of the extended
    hazard model, and then use the EM algorithm to obtain the maximum likelihood esti-
    mates. Since the extended hazard model includes two popular survival models, the
    Cox proportional hazards model and the accelerated failure time model, we use Wald
    type bootstrap, Percentile bootstrap and BC percentile method to select the appropriate
    one.

    摘 要 I 英文摘要 II 致謝辭 III 目 錄 IV 表 目 錄 VI 圖 目 錄 VII 符 號 表 IX 第一章 緒論 1 1-1 背景資料 1 1-1.1 疾病介紹 2 1-1.2 疾病病因 4 1-1.3 危險因子 4 1-1.4 診斷指標 5 1-1.5 黑色素細胞瘤的分期 5 1-1.6 治療方式 6 1-2 研究背景 10 1-3 研究目的 14 第二章 統計方法 15 2-1 長期追蹤模型 16 2-2 Cox比例風險模型 18 2-3 加速失敗時間模型 18 2-4 擴充風險模型 20 2-5 聯合概似函數 21 2-6 EM演算法 23 2-7 參數標準差與信賴區間之估計 29 第三章 實例分析 32 3-1 資料介紹 32 3-2 圖形法 34 3-2.1 輪廓圖 34 3-2.2 事件歷史圖 39 3-2.3 3D平滑曲面圖&等高圖 46 3-3 比例風險檢定 53 3-4 聯合模型 55 第四章 結論與討論 63 參考文獻 66

    Ciampi, A. and Etezadi-Amoli, J. (1985). “A general model for testing the proportional hazards and the accelerated failure time hypothesis in the analysis of censored survival data with covariate.” Communications in Statistics, 14, 651-667.
    Cox, D. R. (1972). Regression Models and Life-Tables. Journal of the Royal Statistical Society, 34, 187-220.
    Cox, D. R. and Oakes, D. (1984), Analysis of Survival Data, Chapman and Hall, London, New York.
    Dafni, U. G. and Tsiatis, A. A. (1998). Evaluating Surrogate Markers of Clinical Outcome When Measured with Error. Biometrics, 54, 1445-1462.
    Dubin, J. A., Müller, H. G. and Wang, J. L. (2001). Event history graphs for censored survival data. Statistics in Medicine, 20, 2951-2964.
    Efron, B., Tibshirani, R. J. (1993). An introduction to the Bootstrap. Chapman & Hall, New York.
    Henderson, R., Diggle, P. and Dobson, A. (2000). Joint modeling of longitudinal measurements and event time data. Biostatistics, 4, 465-480.
    Hsieh, F., Tseng, Y. K. and Wang, J. L. (2006). Joint Modeling of Survival and Longitudinal Data: Likelihood Approach Revisited. Biometrics, 62, 1037-1043.
    John M. Kirkwood, Joseph Ibrahim, David H. Lawson, Michael B. Atkins, Sanjiv S. Agarwala, Keirsten Collins, Ruth Mascari, Donna M. Morrissey, Paul B. Chapman, High-Dose Interferon Alfa - 2b Does Not Diminish Antibody Response to GM2 Vaccination in Patients With Resected Melanoma: Results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696, Journal of Clinical Oncology, vol. 19, no. 5, 2001, pp. 1430-1436.
    Jones, M.C. (1990). The performance of kernel density functions in kernel distribution
    function estimation. Statistics and Probability Letters, 9, 129-132.
    Jones, M.C. and Sheather, S.J. (1991). Using non-stochastic terms to advantage in kernel-based estimation of integrated squared density derivatives. Statistics and Probability Letters, 11, 511-514.
    Kaplan, E. L. and Meier, P. (1958). Nonparametric Estimation from Incomplete Observations. Journal of the American Statistical Association, 53, 457-481.
    Laird, N. M. and Ware, J. H. (1982). Random-effects models for longitudinal data. Biometrics, 38, 963-974.
    Prentice, R. L. (1982). Covariate measurement errors and parameter estimation in a failure time regression model. Biometrika, 69, 331-342.
    Schoenfeld, D. (1980). “Chi-Squared Goodness-of-Fit Tests for the Proportional Hazards Regression Model.” Biometrika, 67, 145-153.
    Schoenfeld, D.A. (1982). “Partial residuals for the proportional hazards regression model.” Biometrika, 69, 239-241.
    Tseng, Y. K., Hsieh F. and Wang, J. L. (2005). Joint modeling of accelerated failure time and longitudinal data. Biometrika, 92, 587-603.
    Tsiatis, A. A. and Davidian, M. (2001). A semiparametric estimator for the proportional hazards model with longitudinal covariates measured with error. Biometrika, 88, 447-458.
    Tsiatis, A. A. and Davidian, M. (2004). Joint Modeling of Longitudinal and Time-to-Event Data: An Overview. Statistica Sinica, 14, 809-834.
    Tsiatis, A. A., DeGruttola, V. andWulfsohn, M. S. (1995). Modeling the relationship of survival to longitudinal data measured with error. Applications to survival and CD4 counts in patients with AIDS. Journal of the American Statistical Association, 90, 27-37.
    Wang, Y. and Taylor, J. M. G. (2001). Jointly Modeling Longitudinal and Event Time Data With Application to Acquired Immunodeficiency Syndrome. Journal of the American Statistical Association, 96, 895-905.
    Wulfsohn, M. S. and Tsiatis, A. A. (1997). A Joint Model for Survival and Longitudinal Data Measured with Error. Biometrics, 53, 330-339.
    Zeng, D. and Cai, J. (2005). Asymptotic Results for Maximum Likelihood Estimators in Joint Analysis of Repeated Measurements and Survival Time. The annals of Statistics, 33(5), 2132-2163.
    Zeng, D. and Lin, D. Y. (2007a). Maximum Likelihood Estimation in Semiparametric Regression Models with Censored Data (with Discussion). Journal of the Royal Statistical Society, Series B 69, 507-564.
    Zeng, D. and Lin, D. Y. (2007b). Efficient Estimation in the Accelerated Failure Time Model. Journal of the American Statistical Association, 102, 1387-1396.

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