臺灣博碩士論文加值系統

慢性肉芽腫是一個罕見的免疫系統遺傳性疾病，但死亡率也高達2%至5%，1989年經實驗證實丙型干擾素能有效降低慢性肉芽腫病患情況，衛生署也在1999年2月將丙型干擾素列為慢性肉芽腫患者的治療藥物。而我們感興趣的是丙型干擾素對於慢性肉芽腫病患復發事件的療效，本篇使用國際肉芽腫組織128個慢性肉芽腫病患的資料，焦點放在多維事件存活時間的三種邊際模型(marginal model：AG、PWP、WLW)與脆弱模型(frailty model)的比較，並探討使用丙型干擾素療程，對於慢性肉芽腫病患復發的次數以及時間的影響。

Chronic Granulomatous Disease (CGD) is a rare inherited disorders of the immune function,but the annual death rate also reaches as high as 2% to 5%. It has been confirmed that the gamma interferon (IFN-r) can reduce the frequency and severity of infections in CGD disease effectively after experiment in 1989. The department of Health in Taiwan has listed gamma interferon as the chronic granuloma patient’s treatment medicine in 1999 February. We are interested in the treatment effects of gamma interferon to the 128 CGD patients’recurrence. To investigate this research problem, we focus on three marginal models (AG model, WLW model and PWP model) and frailty models approaches of multivariate survival data analysis. In addition to compare the performance of the these approaches, we also study the effect of gamma interferon to CGD patients’recurrence and survival times under different models.

第一章緒論. . . . . . . . . . . . . . . . . . . . . . . .1
1.1 慢性肉芽腫病. . . . . . .. . . . . . . . . . . . . 1
1.2 研究方法文獻回顧. . .. . . . . . . . . . . . 4
1.2.1 邊際模型. . . . . . . . . . . . . . . . . . . . 5
1.2.2 脆弱模型. . . . . . . . . . . . . . . . . . . . . 6
1.3 研究架構. . . . . . . . . . . . . . . . . . . . 7
第二章模型方法. . . . . . . . . . . . . . . . . . . .8
2.1 符號定義與基本假設. . . . . . . . . . . . . . . . 8
2.2 邊際模型. . . . . . . . . . . . . . . . . 9
2.2.1 PWP邊際模型. . . . . . . . . . . . . . 12
2.2.2 AG邊際模型. . . . . . . . . . . . 12
2.2.3 WLW邊際模型. . . . . .. . . . . 13
2.2.4 適當的模型配適. . . . . . .. . . 14
2.3 邊際模型參數估計. . . . . . .. . . . . . . 15
2.3.1 夾擠變異數估計量. . . . . . . . 16
2.4 脆弱模型. . . . . . . . . . . . . . . . . . 17
2.4.1 脆弱模型參數估計. . . . . . . . . . . . . 19
2.4.2 PPL演算法. . . . . . . . . . . . . . 20
2.4.3 脆弱參數分佈與懲罰函數. . . . . . . . . . . 22
第三章模擬研究. . . . . . . . . . .23
3.1 模擬方法設定. . . .. . . . . . . . . . . . . 23
3.2 模擬結果. . . .. . . . . . . . . . . . . . . . 24
3.2.1 每個觀測者事件發生之間相互獨立. . . . . . . . . . 24
3.2.2 同一個個體事件發生之間含有相關性. .. . . . . . . 26
3.2.3 總結. . . . . . . . . . . . . . . . . . . . . 27
第四章實例分析. . . . . .. . . . . . . . . .28
4.1 資料說明. . . . . . . . . . . . . . . . . . . . . . 28
4.2 敘述性資料分析. . . . . . . . . . . . . . . . . . . 29
4.3 無母數方法分析. . . . . . .. . . . . . . . . . 31
4.3.1 Kaplan-Meier 估計量. . . . . . . . . . . . . . 31
4.3.2 無母數假設檢定. . . . . . . . . . . 33
4.4 模型估計. . . . . . . . . . . . . . . 34
4.4.1 PWP模型. . . . . . . . . . . 35
4.4.2 脆弱模型. . . . . . . . . . . . . 37
第五章結果與結論. . . . . . . . . . .39
參考文獻. . . . . . . . . . . . . . . . . . 41

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