機率性馬可夫決策模型於巴金森氏症治療之經濟評估

Abstract

研究背景及目的: 巴金森氏症是老年人神經退化疾病最常見的疾病之一，主要會產生肢體僵硬、非自主性顫抖、行動遲緩等症狀發生，進而影響病患日常生活起居之困難。藥物是主要治療方式但仍有治療上的極限且有其副作用，腦部深層刺激術(STN-DBS)是另一治療選擇，然而腦部深層刺激術初期成本相當昂貴，是否長期追? 後之成效所得之效益會比初期成本經過時間折價之後來得大，在醫療決策上形成感興趣之經濟評估主題。因此，本研究為台灣首次針對以腦部深層刺激術等不同巴金森氏症治療方式進行成本效益分析。 材料及方法: 本研究首先收集巴金森氏症以腦深層電刺激術、多巴胺用藥及延遲治療等不同治療效益之文獻，包括巴金森氏症Motor score, UPDRS score, 日常生活功能(ADL), 肢體運動障礙(dyskinesia)及存活等多項效益指標，利用文獻資料獲得不同治療於不同時間之成效，並以我國醫療程序及成本等進行腦部深層刺激術成本支出計算，利用機率性 決策分析分析方法，以馬可夫模型(Markov Model)模擬巴金森氏症Hoehn Yahr 階段進展之自然病史，進行長期成本效益評估，以增加成本效益比、淨效益指標、有效治療數等指標呈現結果。 結果: 忽視治療的延遲治療組病患在平均三年的追蹤期間，其UPDRS 的平均分數為53.24 分，明顯高於STN-DBS 組的19.73 分及Medication 組的36.71 分。腦部深層刺激術 3 年之追蹤結果，日常生活功能可由52.5 分增加至73.1 分，增加效益達39.2%。服藥治療增加效益僅達33.3%。在腦部深層刺激術3 年之追蹤結果，肢體運動障礙可由0.92 分降至0.80 分，而服藥治療僅降至0.84 分。成本效益結果顯示若以整體三萬名巴金森氏症世代追蹤十年來看， DBS-STN 組則為128,567 美元，相較於延遲治療組，每欲降低1 分的UPDRS Motor Score，STN-DBS與用藥組相對於延遲治療組都是節省成本(Cost-saving)的策略。STN-DBS 若與用藥相比，則每欲降低1 分的UPDRS Motor Score，STN-DBS 需多花費約903 美元。每欲多拯救一個QALY，STN-DBS 與用藥組相對於延遲治療組均為節省成本(Cost-saving)的策略。若與用藥相比，則每欲多拯救一個QALY，STN-DBS 需多花費約7994 美元。當願付成本在10,000 美元之下，用藥組較STN-DBS 有較高的機會具成本效益，但願付成本逐漸增加之後，STN-DBS 具有成本效益的機會將凌駕於用藥組。 結論: STN-DBS 比延遲治療組可以多拯救113,487 人年命，而STN-DBS 比用藥組可以多拯救48,885 人年命，以臺灣目前GDP 為18,000 USD 計算，STN-DBS 相較於用藥組，則每投資一美元，可回收約2.12 美元。腦深層電刺激術相較於延遲治療具成本效益，與用藥組相比較，在願付成本增加至10,000 美元以上，則腦深層電刺激術可有較用藥組高的機會具成本效益。

Background and propose: Parkinson’ disease (PD) is one of the most common neurological diseases in elderly. The clinical manifestations of PD are resting tremor, bradykinesia, rigidity and postural instability. Antiparkinsonism agents such as levodpar and doperminergic agonists are widely used for treatment of PD. However, dyskinesia and fluctuation may develop after long-term medication treatment. Subthalamic nucleus deep brain stimulation (STN-DBS) by stereotaxic surgery is one of alternative treatments of PD. Although STN-DBS is an expensive procedure, clinical reports have proved the effectiveness of STN-DBS in PD. In this study, we evaluate the long-term cost-effectiveness between medication and STN-DBS for PD in Taiwan. Materials and methods: We divided patients with PD into three treatment groups: medication, STN-DBS and delayed treatment groups. We searched the published articles by the key words of Parkinson’s disease, deep brain stimulation, subthalamus, randomized clinical trail form PubMed data base. We collected the information of treatment responses such as unified Parkinson disease rating score (UPDRS) motor score, Hoehn-Yahr (H-Y) stage, activity of daily life (ADL), dyskinesia and survival results in different follow-up intervals as the effectiveness parameters. We searched for the expense of medication or surgical procedure form National Health Insurance as the parameters of cost for PD. The probabilistic economic evaluation with Markov decision model was used to simulate the natural history of PD by H-Y stage. As a measure of long-term cost-effectiveness, we calculated the incremental cost-effectiveness ratio (ICER), incremental net benefit index, number need to treatment and life years gained adjusted by healthrelated quality of life (QALY). Results: In the three years follow-up period, the UPDRS scores were 53.24 in delayed treatment group which was higher than 19.73 of STN-DBS and 36.71 of medication groups. As compared with delayed treatment group, the ADL improved 39% in STN-DBS and 33% in mediation groups. The survival rates were decreased to 67% (95%CI: 65.96%-67.55%) in STN-DBS and 34% (95%CI: 33.15%-34.51%) in medication groups as compared with delayed treatment group. The cost-effectiveness analysis revealed cost of 128,567 USD in STN-DBS, 115,119 USD in medication and 169,777 USDin delayed treatment groups based on thirty thousand patients with PD with long-term follow-up for 10 years. Comparing the ICER needed to obtain an improvement of one point in the UPDRS score with delayed treatment group, both STN-DBS and medication groups were cost-saving strategy. In comparing with medication group, the ICER needed to obtain an improvement of one oint in the UPDRS score was of 903 USD in STN-DBS patients. Both STN-DBS and medication groups were cost-saving strategy for improving of QALY than delayed treatment group. In comparing with medication group, for improving one QALY was of 7,994 USD in STN-DBS patients. The STN-DBS group has higher probability of cost-effectiveness than medication group when the cost of will-to-pay more than 10,000 USD. Conclusion: STN-DBS group can save 113,487 life-year than delayed treatment group and 47,694 life-year than medication group. DBS-STN group is more cost effectiveness than delayed treatment group. The STN-DBS group has higher probability of cost-effectiveness than medication group when the cost of will-to-pay more than 10,000 USD.