帕金森氏症病人接受傳統性藥物治療合併Exenatide療效之成本效益分析

Abstract

研究背景: 帕金森氏症是慢性進展的運動障礙性疾病，其症狀會隨著時間進展逐漸惡化。現行的傳統藥物僅能針對症狀進行治療，無法有效的延緩疾病病程以及治癒疾病。最近研究指出，在傳統藥物治療下，合併使用exenatide能在帕金森氏症病人身上產生極佳的療效。同時很多的研究證據也顯示在帕金森氏症前罹患第二型糖尿病可能會增加帕金森氏症的發生率以及加快帕金森氏症的疾病進程。Exenatide能同時治療第二型糖尿病以及帕金森氏症，而至今可同時治療兩種疾病的成本效益尚未與現行傳統藥物治療進行比較。 研究目的: 了解帕金森氏症病人在臺灣的醫療花費，以及評估帕金森氏症病人與帕金森氏症病人在第二型糖尿病共病下，在傳統藥物治療中合併使用exenatide與傳統治療的成本效益。 研究方法: 首先，以基隆整合式社區篩檢資料庫進行回溯性研究，了解帕金森氏症病人在不同疾病分期下的醫療花費。其後，再根據此回溯性研究與其他文獻獲得的資料進行後續的成本效益評估。 1. 帕金森氏症病人的醫療花費 收納自民國88年至民國90年在臺灣基隆地區的整合式社區篩檢資料庫中的帕金森氏症病人，藉由其資料庫中提供的病人基本資料，H-Y (Hoehn & Yahr)分類，串聯至民國88年到民國94年的健保資料庫來了解其在不同帕金森氏症期別下的醫療花費 2. 帕金森氏症病人中合併使用exenatide的成本效益分析 本研究應用以一年為長度的馬可夫模型來模擬傳統藥物合併使用exenatide相較於傳統藥物之成本效益。本研究之馬可夫模型模擬之時間長度為35年，假設所有帕金森氏症病人於55歲進入研究，依照上個研究中的期別分布至不同的H-Y期別，隨著時間的演進可能會留在原本的期別、進入下個期別或是進展至死亡。死亡再進一步分成帕金森氏症相關之死亡或是其他原因之死亡。 3. 一般族群中，罹患帕金森氏症或是第二型糖尿病，合併使用exenatide的成本效益分析 本研究應用以一年為長度的馬可夫模型來模擬傳統藥物合併使用exenatide相較於傳統藥物之成本效益。本研究之馬可夫模型模擬之時間長度為50年，假設所有健康的人於40歲進入研究，在被納入研究時處於”正常”或是”糖尿病” (依照該年齡之糖尿病盛行率) 的狀態，隨著時間的演進可能會保持正常、罹患糖尿病、罹患帕金森氏症、以及罹患糖尿病合併帕金森氏症或是進展致死亡。死亡再分成帕金森氏症相關之死亡、糖尿病相關之死亡或是其他原因之死亡。 所有套入上述兩研究的馬可夫模型之相關數據如疾病發生率、疾病進展速度、疾病相關花費、生活品質盡可能來自基隆整合式社區篩檢資料庫、健保資料庫以及臺灣文獻。所有的花費計算以新臺幣 (NT$) 為基準，並且引入每年3%的折現率。除了基準值分析外，本研究亦引入單維敏感度分析 (One-way sensitivity analysis)、機率性敏感度 (Probabilistic analysis)分析來測試模型的不確定性對於結果之影響。 研究結果: 1. 帕金森氏症病人的醫療花費 研究一共納入82位帕金森氏症病人，再進一步將病人分成帕金森氏症以及帕金森氏症共病第二型糖尿病。在帕金森氏症病人當中，醫療花費分別為H-Y 第二期:NT$52,439，第三期: NT$56,339，第四期以上: NT$133,558。在帕金森氏症共病第二型糖尿病的病人，醫療花費分別為H-Y 第一期:NT$21,822，H-Y 第二期:NT$67,961，第三期: NT$71,097，第四期以上: NT$148,741。 2. 帕金森氏症病人中合併使用exenatide的成本效益分析 以社會觀點而言，在35年的研究區間下，傳統藥物合併使用exenatide相對於傳統藥物而言，平均每人可以增加1.12個品質校正生活年 (Quality-adjusted life year, QALY) 及NT$492,574的額外花費，而增加成本效益比 (Incremental cost-effectiveness ratios, ICER) 為NT$438,998，代表每多增加一品質校正生活年需多花費NT$438,998。 3. 一般族群中，罹患帕金森氏症或是第二型糖尿病，合併使用exenatide的成本效益分析 以社會觀點而言，在50年的研究區間下，傳統藥物合併使用exenatide相對於傳統藥物而言，平均每人可以增加0.39個品質校正生活年以及NT$104,700的額外花費，而增加成本效益比為NT$268,218，代表每多增加一品質校正生活年需多花費NT$268,218。 依據世界衛生組織的建議，若增加成本效益比小於人均國民所得，則該醫療方案相對於其他對照方案為非常符合經濟效益。在我們研究中的兩種不同研究模型中，均小於2016年臺灣之人均國民所得NT$728,314，因此合併使用exenatide為非常符合經濟效益之方案。同時敏感度分析顯示，以人均國民所得做為閾值下，合併使用exenatide在帕金森氏症病人有96.9%的機率會是非常符合經濟效益的;在帕金森氏症與第二型糖尿病共病病人中有100%的機率非常符合經濟效益。 結論: 本研究證明在傳統藥物治療中，合併使用exenatide在帕金森氏症的病人與帕金森氏症病人併有第二型糖尿病在臺灣經濟評估效益所使用的閾值下(臺灣之人均國民所得NT$728,314)是非常符合經濟效益的。在目前研究顯示第二型糖尿病可能是其他退化性疾病的危險因子干擾之下，exenatide在帕金森氏症合併糖尿病的病人中，同時展現了極佳的臨床療效以及經濟效益

Background: Parkinson’s disease (PD) is a chronic and progressive movement disorder, the symptoms continue and worsen over time. Nearly all of the available treatments now are symptomatic in nature and do not appear to slow or reverse the natural course of the disease. Recently, studies suggested that add-on exenatide to the conventional pharmacotherapy provided clinical benefits in patients with PD. Meanwhile, there are growing evidences suggested that preceding type 2 Diabetes Mellitus (DM) may increase the risk and progression of PD. As a drug treating both diseases, its cost-effectiveness compared to conventional pharmacotherapy has not been evaluated. Objectives: To investigate the medical utilization in patients with PD and the cost-effectiveness of the add-on exenatide to conventional pharmacotherapy in patients with PD and patients with PD and DM. Methods: We first used the KCIS (Keelung and Community-based Integrated Screening) databases to understand medical utilization in different H-Y (Hoehn & Yahr) stages of patients with PD. Subsequent cost-effective analyses were performed with these patients and data from literatures. 1. Medical utilization in patients with PD An integrated model of community-based multiple screening was designed and conducted between 1999 and 2001 in Keelung, Taiwan. The data extracted from the original screening datasets including the patients’ identification (ID), baseline characteristics and the H-Y stage. We further connected these patients to NHIRD (National Health Insurance Research Database) between 1999 and 2005 for understanding their medical utilization. 2. Cost-Effectiveness analysis of the add-on exenatide in patients with PD A Markov model with a one-year cycle length and 35-year time horizon was used to assess the cost-effectiveness of the add-on exenatide to conventional pharmacotherapy compared to conventional pharmacotherapy alone. Patients with PD entered the hypothetical cohort at the age of 55 with the H-Y stage according to our cohort and were then staying in the same H-Y stage or progress to advanced stage or death. The death was split into PD-related and other cause. 3. Cost-effectiveness analysis of add-on Exenatide for patients with PD or DM in the general population A Markov model with a one-year cycle length and 50-year time horizon was used to assess the cost-effectiveness of the add-on exenatide to conventional pharmacotherapy compared to conventional pharmacotherapy alone. Healthy people entered the hypothetical cohort at the age of 40 and were then staying normal or progress to DM, PD and PD combined with DM. The death in this model was split into PD-related, DM-related and other cause. The likelihood of incidences, disease progression, costs, utilities in these two models were derived from KCIS databases, NHIRD, Taiwanese studies if applicable. All the costs were adjusted to the value of New Taiwanese dollar (NT$) and discounted with a rate of 3%. One-way sensitivity analysis and probabilistic analysis were performed to test the robustness of results. Results: 1. Medical utilization in patients with PD 82 patients were enrolled in the study, further divided into patients with PD only and patients with PD and DM. Medical utilization was NT$69,074, NT$71969, NT$133,558 from H-Y 2 to H-Y 4+, respectively in patients with PD only. As for patients with PD and DM, medical utilization was NT$21,821, NT$90,217, NT$77,079, NT$148,741 from H-Y 1 to H-Y 4+, respectively. 2. Cost-Effectiveness analysis of the add-on exenatide in patients with PD From societal perspective the add-on exenatide brought an average of 1.12 QALYs (Quality-adjusted life year) gained and a cost increment of NT$492,574 per person in a 35-year horizon compared to the conventional pharmacotherapy. The Incremental cost-effectiveness ratios (ICER) was NT$438,998 per QALY gained. 3. Cost-effectiveness analysis of add-on Exenatide for patients with PD or DM in the general population From societal perspective the add-on exenatide brought an average of 0.39 QALYs gained and a cost increment of NT$104,700 per person in a 50-year horizon compared to the conventional pharmacotherapy. The ICER was NT$268,218 per QALY gained. As the ICER was less than a gross domestic product (GDP) per capita (NT$728,314), the add-on exenatide was considered to be very cost-effective in two model according to the World Health Organization (WHO) recommendation. Add-on exenatide had a 96.9% probability of being cost-effective in patients with PD, 100% probability of being cost-effective in patients with PD and DM. Conclusion: Under the threshold of GDP of Taiwan in 2016 (NT$728,134), the add-on exenatide was demonstrated to be very cost-effective in PD and in PD combined with DM. With concern that DM may be a risk factor of neurodegenerative disease, Exenatide provide both clinical benefits and cost-effectiveness when taking PD and DM into account.