臺灣博碩士論文加值系統

背景
醫藥新科技的迅速發展，為人類延長了壽命，也增加了生活品質。然而醫療資源有限，如何將有限資源做最有限分配，就成了近代衛生決策者最大的課題。在這樣的考量下，採取決策分析理論的經濟評估，成為目前發展迅速的學問。為了增進研究之品質，學界及各種決策單位提出了研究共識與建議，將以往較紊亂的研究方向，漸漸改往一致性、高品質的路上邁進。
研究目的
本論文回顧了成本效性研究於醫療衛生應用之起源、角色、及實際執行之各層面，並將之應用於三項衛生研究課題─百日咳疫苗是否該改用非細胞性疫苗、慢性B型肝炎患者使用干擾素療法之成本效性研究、以及慢性C型肝炎患者使用干擾素及ribavirin合併療法之經濟評估。
結果
1. 臺灣地區十八個月大幼兒所施打之第四劑白喉百日咳破傷風疫苗，若以非細胞性疫苗置換目前使用的傳統性疫苗，每減少一個不良反應須多花90~130元。而以生活品質評分來看，每增加一單位幼兒生活品質評分，需多花上1,500~2,000元；如果要增加一單位家庭品質評分，則需多出1,800~2,500元。對於這樣的結果是否支持全面換用，還得視衛生決策者總預算的考量。
2. 由慢性B型肝炎患者接受干擾素療法之經濟評估結果看來，一位35歲的患者接受干擾素治療之後，其平均餘命為29.08年，比接受一般支持性療法的平均餘命28.67年，多了0.41年。如果考慮健康生活品質，則為0.18調整品質後存活年。假設3%的折現率之下，差異成本效性比為492,000元/調整品質後存活年。經由敏感度分析的結果所估計出，差異成本效性比的信賴區間為65,000~683,000元/調整品質後存活年，而90%的模擬結果會小於413,000元/調整品質後存活年。
3. 按照我們所提出的研究模式、參數及研究假設，如果一群45歲的慢性C型肝炎患者接受干擾素及ribavirin合併療法24週，其平均餘命為30.56年；如果這群病人依照基因型不同而使用不同治療長度的療法，則平均餘命可達31.26年；而接受一般支持性療法的病患其平均餘命，為30.17年。此三種方法之終身肝病相關醫療成本分別預測為975,000、709,000、及677,000元（以3%折現率計算）。以兩種合併療法來與一般支持性療法比較，合併療法長期而言比一般療法還節省醫療費用。如果以基因型不同而使用不同長度之合併療法，比上24週合併療法，則有一差異成本效性比93,255元/調整品質後存活年。單維及蒙地卡羅敏感度分析之結果，也都支持相同的趨勢。
結論
新科技、新藥的成本效性評估在國內仍是一個新興的學門，然而如果予以善加執行與應用，可以為我國衛生政策、藥價制訂等制度帶來正面的影響。目前在臺灣地區仍在萌芽階段的經濟評估研究，還需要許多方面的努力。本論文試著將目前成本效性研究最新的發展帶進國內，除了將它應用在疫苗評估的衛生政策制訂方面外，並就新藥療效及成本的評估進行研究。公共衛生的研究最終是希望能帶給國人健康，如何能將新科技、新藥合理的引進使用於病患身上，自然是公共衛生一大課題。成本效性研究不只是斤斤計較成本，對於病人生命的延長與生活品質的提升也是同樣的重視，企希這種概念能早日應用於政策制訂中。

Background
Along with aging of the population, industrialization of the society, and implementation of the National Health Insurance, the Taiwan health care system is facing the same challenge as in all industrialized countries, which is to equitably and optimally allocate limited health care budget. Cost-effectiveness analysis, the scientific method that takes into account all available evidence of viable alternatives, has been widely used in the formulation of health care policy in many countries.
Objectives
This disseration aimed to bring in the concept and experiences of cost-effectiveness analysis to aid health care decision-making. Three consecutive studies utilizing the methodology has therefore proposed: 1) the economic evaluation for the use of the 4th dose of acellular (DTaP) or whole-cell Diphtheria-Tetanus-Pertussis (DTP) vaccine; 2) the cost-effectiveness analysis of interferon alpha therapy in the treatment for chronic hepatitis B; 3) the cost-effectiveness analysis of alpha interferon / ribavirin as initial treatment for chronic hepatitis C.
Methods
1) A decision tree was built to calculate the expected costs and consequences of the DTP and DTaP vaccine alternatives. Using a societal perspective, the cost per adverse event averted and cost per life quality score gained were estimated. 2) For the evaluation of the interferon therapy in chronic hepatitis B patients, a Markov model was constructed. Through systematic reference searches and reviews, the parameters were decided and utilized in the model. The discounted lifetime costs and quality-adjusted life years for the competing alternatives were simulated. The incremental cost-effectiveness ratios (ICERs) were used as the primary endpoint. Utilizing one-way sensitivity analysis, the influential parameters were identified. The uncertainty of the ICERs was estimated from Monte Carlo simulations. 3) In the evaluation of the interferon/ribavirin combination therapy for chronic hepatitis C patients, we also utilized the Markov model approach. ICERs were the analysis endpoint; cost per QALY gained has been therefore estimated. Both one-way sensitivity analyses and probability sensitivity analyses were done to assess the uncertainty of the results. Acceptability curves were presented for comparing the alternatives.
Results
1) Total medical expenses related to the vaccinations were higher in DTaP, but the effectiveness and utility scores were also higher. Since the adverse reaction (ADR) rate is lower in DTaP group, the results for the cost-effectiveness analysis was 90~130 NT dollars (about US$ 3~4) per ADR prevented. However, the ADRs studied here were rather mild, therefore the gains in quality of life were quite small. The cost-utility analysis resulted in a NTD 1,500~2,000 (US$ 45~60) cost per one baby’s quality of life score gained, as well as a NTD 1,800~2,500 (US$ 55~76) cost per one family’s quality of life point gained. 2) For the base case, a 35-year-old chronic hepatitis B patient treated with interferon in Taiwan would have life expectancy of 29.08 years, versus 28.67 years for those who did not receive interferon. Corresponding to this gain in life expectancy of 0.41 years (or 0.18 QALYs), the ICER was 492,000 NTD per QALY with an annual 3% discount rate. Based on Monte Carlo simulation that takes into account the range of plausible values for all model parameters, 95% of the ICERs lied in the range of 65,000 NTD/QALY to 683,000 NTD/QALY, and 90% of the ICERs were below 413,000 NTD/QALY. 3) In the base case analysis, a 45-year-old chronic hepatitis C patient in Taiwan would have a life expectancy of 30.56 years, or 31.26 years if he/she receives the 24-week or the genotype-dependent combination therapies, comparing with 30.17 years from the standard no antiviral treatment. The lifetime costs for the three groups were estimated to be NTD 975,000, 709,000, and 677,000, respectively. While the two combination therapies compares with no treatment are cost-saving options, the genotype-dependent combination therapy has an ICER about 93,255 NTD/QALY when comparing with the 24-week combination therapy. Both one-way sensitivity analysis and probabilistic sensitivity analyses supported the robustness of the study results.
Conclusions
New technology in health care and medicine may prolong lives and improve life quality. “At what prices”, however, is the main issue for the decision makers nowadays. There has been very little work presented about economic evaluation for new drugs/technology in Taiwan. This dissertation serves as a first step to rigorously evaluate the relative merit of public health interventions or disease management regimens in this area.

摘　要 1
英 文 摘 要 3
第一章 前 言 6
第二章 文 獻 回 顧 8
1. 評估方法 9
1.1. 起源 9
1.2. 各種經濟評估 11
1.3. 決策分析與成本效性分析 13
1.4. 經濟評估的步驟 13
2. 研究指引／共識 15
3. 研究執行 19
3.1. 研究目標 19
3.2. 評估方式之選擇 21
3.3. 謹慎選擇比較方案 22
3.4. 架構模式 23
3.5. 估計模式參數 27
3.6. 效性指標 30
3.7. 成本 35
3.8. 成本效性評估指標 38
3.9. 不確定性與敏感度分析 39
3.10. 電腦模擬 48
4. 報告結果及提出結論 50
4.1. 結果報告 50
4.2. 結論 52
第三章 研 究 目 的 55
第四章 實例研究一：「白喉百日咳破傷風疫苗第四劑之經濟評估 — 非細胞性疫苗與傳統疫苗之比較」 57
第五章　實例研究二：「臺灣地區以干擾素治療慢性B型肝炎患者之成本效益評估研究」 68
第六章　實例研究三：「臺灣地區以干擾素及RIBAVIRIN合併療法治療慢性C型肝炎患者之成本效益評估研究」 96
第七章　綜合討論與建議 127
1. 三項應用研究之綜合評估與檢討 128
1.1. 研究一「百日咳疫苗之評估」 128
1.2. 研究二「慢性B型肝炎之治療」 133
1.3. 研究三「慢性C型肝炎之治療」 138
2. 現況與未來 142
2.1. 研究者目前面臨的問題 142
2.2. 未來努力的方向 143
3. 總結 145
第八章　參 考 文 獻 146

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