臺灣博碩士論文加值系統

背景：針對大腸直腸癌的篩檢方式，以成本及效益的眼光來看，包括糞便潛血檢驗(FOBT)、適時的乙狀結腸鏡及大腸鏡常有正反不同的意見，而糞便潛血檢查合併DNA分析(AOAD)則是提供另一種大腸直腸癌的篩檢方法。
目標：本研究利用成本效益分析比較AOAD、每年做FOBT、每五年做乙狀結腸鏡檢查及每十年做大腸鏡檢查間的差異。
方法：依據大腸直腸癌之疾病自然史，包括正常、小腺腫、大腺腫、臨床前期Duke A&B、臨床前期Duke C&D、臨床期Duke A&B、臨床期Duke C&D、及死亡等階段，利用馬可夫鏈模式估計各階段轉移速率，並考慮自然死因。而參數值則是經由花蓮門諾醫院在1996-2000年針對1495名(819名男性及676名女性)個案進行大腸鏡檢查作為實證資料的來源。至於決策分析部份則是利用蒙地卡羅模擬來比較不同篩檢方式其效能及效益。而增加成本效益比則是用來計算是否FOBT加上AOAD會比每年做FOBT或是大腸鏡更具效益。
結果：每兩年進行AOAD比每年做FOBT每增加一單位的成本效益比需花新台幣1,631元；而每兩年進行AOAD比乙狀結腸鏡為新台幣6,614元；比大腸鏡則為新台幣27,707元。另一方面，每三年進行AOAD比乙狀結腸鏡每增加一單位的成本效益比需花新台幣3,108元；雖然每三年做AOAD比每年做FOBT加上每三年做AOAD來的具成本效益，而且與每十年做大腸鏡的效益相當。在敏感度分析部份，AOAD的成本會影響分析結果，相對於每年做FOBT、每五年乙狀結腸鏡篩檢、每十年做大腸鏡檢查，如果AOAD所花的成本分別低於新台幣1,145元、新台幣834元、新台幣697元則建議做AOAD。
結論：對於大腸直腸癌而言，AOAD相對於每年做FOBT、每五年做乙狀結腸鏡更具成本效益，而且與每十年做大腸鏡所得到的效益相當，而大腸鏡是目前美國現階段大腸直腸癌篩檢最建議使用的篩檢方式。

Background CRC screening using fecal occult blood test, flexible sigmoidoscopy and colonoscopy has pros and cons in terms of cost and effectiveness. The recent proposal for using fecal occult blood test plus assay of altered DNA (AOAD) from stool provides an alternative method for CRC screening.
Objectives The aim of this study was to perform a series of cost-effectiveness analysis for the comparisons of AOAD with annual FOBT, flexible sigmoidoscopy every five year, and colonoscopy every ten years.
Methods A Markov model was first developed for the progression of neoplasm of CRC, from normal, small adenoma, larger adenoma, pre-clinical Duke A&B, pre-clinical Duke C&D, clinical Duke A&B, clinical Duke C&D, and finally to death, taking natural causes of death into account. Estimation of parameters were based on empirical data from 1495 subjects, 819 males and 676 females, that underwent colonoscopy between 1996 and 2000 in MCH located in Hualien, eastern area of Taiwan. A decision analysis using a Monte Carol computer simulation model based on the Markov model was constructed to compare the efficacy and the effectiveness among a variety of screening regimes. Incremental cost —effectiveness ratio was calculated to assess whether fecal occult blood test plus assay of altered stool DNA is more cost-effective than annual FOBT and comparably cost-effective to colonoscopy.
Results The incremental cost-effectiveness ratios are calculated as NT$1,631 for biennial AOAD against annual FOBT, NT$6,614 for biennial AOAD against flexible sigmoidoscopy, and NT$27,707 for biennial AOAD against colonoscopy. The incremental cost-effectiveness ratio is calculated as NT$3,108 for triennial AOAD against flexible sigmoidoscopy, but triennial AOAD dominates annual FOBT and triennial AOAD, although dominated by, but is comparable to colonoscopy every 10 years. Sensitivity analysis shows cost of AOAD has much influence on the results. Triennial AOAD screening would be preferred over annual FOBT test if cost of AOAD is less than NT$1,145 and would be preferred over sigmoidoscopy every 5 years, and colonoscopy 10 years, if cost of AOAD screening is lower than NT$834, and NT$697, respectively.
Conclusions Colorectal cancer screening with triennial AOAD is more cost-effective than annual FOBT and sigmoidoscopy every five year and is almost as cost-effective as colonoscopy screening every 10 years that has been recommended as the preferred screening strategy for average-risk people in the USA.

Abstract ………………………………………………………………….iv
中文摘要…………………………………………………………………v
I. Introduction….…………………………………………………………1
II. Literature Review……………………………………………………..5
1. The disease natural history and the prognosis of CRC……………..5
2. Options for colorectal cancer screening…………………………….6
3. Cost-effectiveness analysis…………………………………………8
III Methods……………………………………………………………….11
1. Empirical data………………………………………………………11
2. Biological definition of the disease natural history and prognosis of colorectal cancer……………………………………………………12
3. The Markov process for the disease natural history and prognosis of CRC……………………………………………………………..14
4. Parameter Estimation……………………………………………….15
5. Markov decision model……………………………………………..16
6. Cost-effectiveness Analysis…………………………………………19
IV Results………………………………………………………………...22
1. Empirical data……………………………………………………….22
2. Base-case cost-effectiveness analysis………………………………23
3. Sensitivity analysis………………………………………………….25
V Discussion……………………………………………………………..26
1. Major findings and contributions……………………………………26
2. Methodological considerations……………………………………..27
3. Limitations and future studies………………………………………28
Reference ………………………………………………………………...29
Appendix I Transition rates for the Markov process in Figure 1………...33
Appendix II Transition rates for the Markov model II…………………..34
Appendix III Likelihood Function L(.), for estimation of parameters using Markov model II………………………………….35
Table List
Table 1 Descriptive results for subjects underwent colonoscopy between 1996 and 2000 in MCH…………………………………………..36
Table 2 Descriptive results for adenoma and CRC………………………..37
Table 3 Transition history type, transition history, transition probability and number of transition…………………………………………38
Table 4 Estimated results for the Markov modelⅡ………………………39
Table 5 Estimated results for the Markov modelⅠwith the incorporation of Duke stage and classification of pre-clinical and clinical status for subject aged over 50 years.. …………………………………40
Table 6 Sensitivity and specificity by different screening tools and characteristics of neoplasm………………………………………41
Table 7 Base-case estimates for cost- effectiveness analysis………………42
Table8 Simulated results for adenoma <1cm,adenoma≧1cm, pre-clinical Duke A&B, pre-clinical Duke C&D, and CRC death by screening regimes……………………………………………………………44
Table 9 Average cost-effectiveness ratio (ACER) and incremental cost-effectiveness ratio (ICER) by different screening regimes….45
Table 10 Results of incremental cost-effectiveness ratios for AOAD by annual, biennial and triennial screening regimes as compared with annual FOBT, flexible sigmoidoscopy every 5 years and colonoscopy every 10 years………………………………………46
Table 11 Results of sensitivity analysis for ICER for AOAD against annual FOBT compliance rate and cost of screening ……………47
Table 12 Results of sensitivity analysis for AOAD versus flexible sigmoidoscopy every 5 years……………………………………..48
Table 13 Results of sensitivity analysis for AOAD versus colonoscopy every 10 years…………………………………………………….
49
Figure List
Figure 1 Markov Model I. …………………………………………………13
Figure 2 Markov Model II.…………………………………………………15
Figure 3 Markov Decision Model………………………. ………………...50
Figure 4 Markov decision model for the disease natural history………….52

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