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UM E-Theses Collection (澳門大學電子學位論文庫)

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Title

二代測序多基因面板在乳腺癌和卵巢癌篩檢的貝葉斯成本效果分析

English Abstract

Objective: To model and assess the cost-effectiveness of next generation sequencing (NGS) panel over conventional BRCA testing and no testing for the screening of breast cancer (BC) and ovarian cancer (OC) amongst UK Ashkenazi Jews (AJ) women with Bayesian decision-analytic method. Methods: A Bayesian decision-analytic model was developed to compare lifetime costs and health effects associated with NGS panel and BRCA testing. The costeffectiveness was analyzed from a payer’s perspective across a lifetime horizon. Multiple sources including meta-analyses, observational studies were used for estimating cancer incidence, costs, life-years, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). Costs were reported at 2014 prices and discounted at 3.5% as well as effects. Probabilistic sensitivity analysis (PSA) based on Bayesian Markov Chain Monte Carlo simulations as well as deterministic sensitivity analysis were performed to evaluate the robustness of model. Results: In the base-case analysis, compared with “no testing” strategy, multigene panel testing lowered the cancer incidence by 0.93% (0.79% for BC, 0.13% for OC), and gained an additional 0.72 years and 0.74 QALYs, resulting in a Bayesian posterior ICER of £8547/QALY (95%Crl, £5146/QALY~£18226/QALY). Considering 70% testing uptake, this led to 635 fewer cases in breast cancer and 106 fewer cases in ovarian cancer. BRCA1/2 testing reduced cancer incidence by 0.62%, saved 497 cancer cases (391 for BC, 106 for OC), gained an additional 0.70 years and 0.71 QALYs, resulting in a Bayesian ICER of £6090/QALY (95%Crl, £3701/QALY~£13109/QALY). Since there was a considerable overlap of 95%Crl between NGS panel and BRCA testing, the significance difference could not be determined, which suggested that NGS panel was not necessarily worse in costeffectiveness than BRCA testing. While compared with traditional BRCA testing, NGS panel testing was more costly and less effective with a Bayesian ICER of £72203/QALY (95%Crl, £36407/QALY~£182784/QALY), which was far over the threshold of £30000/QALY. One-way sensitivity analysis indicated that the model was robust to variations for most of individual model parameters, and the mutation rate of breast cancer susceptibility genes was an important factor impacting overall results. PSA showed that both the probabilities for NGS panel testing and BRCA vii testing being cost-effective at the threshold of £25000/QALY were over 95%, compared with “no testing” strategy. Conclusion: NGS panel was still less cost-effective than BRCA1/2 testing. BRCA1/2 testing was the most cost-effective strategy, especially for those AJ women with high mutation rates.

Chinese Abstract

目的:以英國德系猶太婦女人群為研究對象,用貝葉斯決策分析方法評估多基 因面板檢測和 BRCA檢測在乳腺癌與卵巢癌篩檢上的成本效果。 方法:結合英國人口流行病學及成本等數據,建立貝葉斯決策模型來評估兩種 檢測策略在人群中的長期成本和健康效果。採用付費者的角度,從文獻中獲取 相關數據,使用貝葉斯後驗分佈來估計總成本、生命年、質量調整生命年等參 數,進行增量成本效果分析。成本以 2014 年價格為基準,所有的成本和結果都 採用 NICE 推薦的 3.5%的年貼現率進行貼現。通過確定性敏感性分析和蒙特卡 洛模擬估計的概率敏感性分析來評估參數的不確定性對模型輸出結果的影響。 結果:在基線分析中,與無基因檢測相比,多基因面板檢測降低了 0.93%的癌 症發生率,挽救了 635 例乳腺癌和 106 例卵巢癌發病,延長了 0.72 個生命年和 0.74 個質量調整生命年,貝葉斯後驗增量成本效果比為 £8547/QALY(95%Crl, £5146/QALY~£18226/QALY)。BRCA 檢測則降低了 0.63%的癌症發生率,挽 救了 497 例癌症(391 例乳腺癌,106 例卵巢癌),延長了 0.70 個生命年和 0.71 個質量調 整生 命年, 貝葉斯 增量 成本效 果比為 £6090/QALY(95%Crl, £3701/QALY~£13109/QALY)。由於 NGS 面板和 BRCA 檢測的 95%Crl互相重 疊,兩者之間的差異的顯著性不能確定,即 NGS 面板不一定比 BRCA 的成本 效果明顯差。多基因面板相對於 BRCA 檢測成本更高,貝葉斯增量成本效果比 為增量成本效果為 £72203/QALY(95%Crl,£36407/QALY~£182784/QALY), 不具備成本效果。單因素敏感性分析顯示模型對大多數參數敏感性並不高,乳 腺癌易感基因突變率是影響模型的重要因素。概率敏感性分析顯示多基因檢測 和 BRCA檢測在閾值範圍內都具有 95%以上的成本效果概率。 結論:與 BRCA 單基因檢測相比,多基因面板檢測還不具備成本效果。 BRCA1/2 檢測相對於多基因檢測和無基因檢測策略是目前最具有成本效果的措 施,尤其是對於 BRCA1/2 突變率較高的德系猶太族。

Issue date

2017

Author

杜春艷

Faculty

Institute of Chinese Medical Sciences

Degree

M.Sc.

Subject

Breast -- Cancer -- Prevention

乳房 -- 癌症 -- 預防

Ovaries -- Cancer -- Prevention

卵巢 -- 癌症 -- 預防

Supervisor

梁少偉

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