PD-1/PD-L1抑制劑治療非小細(xì)胞肺癌的成本-效用分析方法學(xué)系統(tǒng)評價(jià)

費(fèi)正洋 張雪珂 王櫻澄 陳平鈺 芮明軍 馬愛霞

中圖分類號 R956 文獻(xiàn)標(biāo)志碼 A 文章編號 1001-0408（2021）20-2499-10

DOI 10.6039/j.issn.1001-0408.2021.20.11

摘 要 目的：為提高我國細(xì)胞程序性死亡受體1（PD-1）/細(xì)胞程序性死亡配體1（PD-L1）抑制劑治療非小細(xì)胞肺癌相關(guān)藥物經(jīng)濟(jì)學(xué)研究的質(zhì)量提供依據(jù)。方法：計(jì)算機(jī)檢索Embase、PubMed、Medline、Cochrane圖書館、中國知網(wǎng)、萬方數(shù)據(jù)、維普網(wǎng)等中英文數(shù)據(jù)庫，搜集PD-1/PD-L1抑制劑治療非小細(xì)胞肺癌的成本-效用研究，檢索文獻(xiàn)的發(fā)表時(shí)間為2016年1月-2021年1月。對納入研究進(jìn)行資料提取，采用衛(wèi)生經(jīng)濟(jì)學(xué)評價(jià)報(bào)告標(biāo)準(zhǔn)共識(shí)清單對其進(jìn)行質(zhì)量評價(jià)后，從模型框架、模型參數(shù)、不確定性分析等方面入手對方法學(xué)相關(guān)數(shù)據(jù)進(jìn)行總結(jié)和對比。結(jié)果與結(jié)論：最終納入17項(xiàng)研究，研究整體質(zhì)量較高，但在方法學(xué)上有著較大的差異。16項(xiàng)研究采用了基于三狀態(tài)的馬爾可夫模型或分區(qū)生存模型;研究時(shí)限最短為5年，最長為終身;模型周期最短為1周，最長為6周;8項(xiàng)研究采用了標(biāo)準(zhǔn)參數(shù)分布的方法進(jìn)行參數(shù)擬合，7項(xiàng)研究同時(shí)結(jié)合了KM曲線或樣條模型等其他參數(shù)估計(jì)方法;有11項(xiàng)研究進(jìn)行了模型外推驗(yàn)證;所有研究均僅考慮了直接醫(yī)療成本，并以質(zhì)量調(diào)整生命年為產(chǎn)出指標(biāo)報(bào)告了對應(yīng)的增量成本-效果比;16項(xiàng)研究同時(shí)進(jìn)行了確定型敏感性分析和概率敏感性分析以提高模型結(jié)果的穩(wěn)健性。建議未來我國的相關(guān)研究應(yīng)保證報(bào)告格式的完整性，選擇合適的陽性對照方案，根據(jù)可獲得的數(shù)據(jù)形式選擇經(jīng)濟(jì)學(xué)評價(jià)模型并建立合理的研究假設(shè)，采用Cholesky分解等方法探索參數(shù)擬合的不確定性，結(jié)合外部數(shù)據(jù)進(jìn)行外推驗(yàn)證，并在缺乏頭對頭臨床試驗(yàn)時(shí)采取適當(dāng)?shù)拈g接比較方法，以提高我國相關(guān)藥物經(jīng)濟(jì)學(xué)研究質(zhì)量。

關(guān)鍵詞 細(xì)胞程序性死亡受體1/細(xì)胞程序性死亡配體1抑制劑;非小細(xì)胞肺癌;經(jīng)濟(jì)學(xué)評價(jià)模型;系統(tǒng)評價(jià);方法學(xué)

Systematic Review of Cost-utility Analysis Methodology for PD-1/PD-L1 Inhibitors in the Treatment of Non-small Cell Lung Cancer

FEI Zhengyang1，ZHANG Xueke1，WANG Yingcheng1，CHEN Pingyu1，2，RUI Mingjun1，MA Aixia1，2（1. School of International Pharmaceutical Business， China Pharmaceutical University， Nanjing 211198， China; 2. Center for Pharmacoeconomics and Outcomes Research， China Pharmaceutical University， Nanjing 211198， China）

ABSTRACT? ?OBJECTIVE： To provide reference for improving the quality of programmed cell death protein 1 （PD-1）/programmed cell death 1 ligand （PD-L1） inhibitors in the treatment of non-small cell lung cancer related pharmacoeconomic studies in China. METHODS： Retrieved from Embase， PubMed， Medline， Cochrane Library， CNKI， Wanfang database， VIP and other Chinese and English database， cost-utility studies about PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer published during Jan. 2016-Jan. 2021 were collected. The data of the included studies were extracted. After the quality of the included studies was evaluated by using the Consolidated Health Economic Evaluation Reporting Standards list， the relevant data were summarized and compared from the aspects of model framework， model parameters and uncertainty analysis. RESULTS & CONCLUSIONS： A total of 17 studies were finally included， the overall quality of them was high but the differences in methodology were great. Markov model or partition survival model based on three states was adopted for 16 studies. The time horizon ranged from 5 years to lifetime; the cycle length ranged from 1 week to 6 weeks. A total of 8 studies used the standard parameter distribution method for parameter fitting， and 7 studies additionally adopted other parameters estimation methods as KM curves or spline models. Eleven studies performed the validation of model extrapolation. All studies considered the direct medical costs and reported the incremental cost-effectiveness ratio using quality-adjusted life years as the health outcome. Sixteen studies conducted the deterministic sensitivity analysis and probabilistic sensitivity analysis to improve the stability of the model. It is suggested that studies should keep the integrity of the report format， choose the appropriate positive comparators， select the health economic model and construct reasonable assumptions according to the available data format， use Cholesky decomposition to explore the uncertainty of the parameter fitting， perform the validation of extrapolation combined with external data and use the appropriate indirect comparison in the absence of the head-to-head clinical trials to improve the quality? of related pharmacoeconomic studies in China.