Qiao Nan, Insinga Ralph, de Lima Lopes Junior Gilberto, Cook John, Sénécal Martin
Center for Observational and Real-World Evidence, Merck & Co., Inc., Kenilworth, NJ, 07033, USA.
Clinical Oncology Sector, University of Miami, 1120 NW 14th St, Suite 650J, Miami, FL, 33136, USA.
Pharmacoecon Open. 2021 Sep;5(3):365-383. doi: 10.1007/s41669-020-00255-2. Epub 2021 Jan 19.
Pembrolizumab monotherapy or combination therapy is an approved treatment for various advanced non-small cell lung cancer (NSCLC) indications. We review published cost-effectiveness analyses (CEAs) of pembrolizumab as treatment for NSCLC and provide in-depth assessment of their methodologies. Fourteen studies were selected through searches of the PubMed database. Modeling approaches, survival and cost estimation, and utility analyses were compared and evaluated. These publications covered regulatory-approved pembrolizumab NSCLC indications based on the following randomized clinical trials: KEYNOTE-010 (one publication), KEYNOTE-024 (six), KEYNOTE-042 (four), KEYNOTE-189 (two), and KEYNOTE-407 (one). Differences were observed in health states (progression free, progressed disease, and death vs stable disease, progressed disease, death, and treatment discontinuation), modeling approaches (partitioned survival vs Markov), survival extrapolation/transition probability estimation, inclusion of additional costs to drug, disease management and adverse event costs (e.g., programmed death-ligand 1 [PD-L1] testing, subsequent treatment, terminal care), treatment duration approaches (trial-based time on treatment vs treat to progression), utility sources (trial data vs literature), and utility analyses (time to death vs progression status). Certain aspects of variability across models were problematic, including deviation from observed treatment utilization within trials and predicted long-term mortality risks for pembrolizumab higher than historical real-world NSCLC mortality data prior to the availability of pembrolizumab. Consequently, results differed even among studies examining the same population and comparator within similar time intervals. Differences in methodology across CEAs may lead to distinct results and conclusions. Payers and policy makers should carefully examine study designs and assumptions and choose CEAs with greater validity and accuracy for evidence-based decision-making.
帕博利珠单抗单药治疗或联合治疗是多种晚期非小细胞肺癌（NSCLC）适应症的获批治疗方法。我们回顾了已发表的关于帕博利珠单抗治疗NSCLC的成本效益分析（CEA），并对其方法进行了深入评估。通过检索PubMed数据库筛选出14项研究。对建模方法、生存和成本估算以及效用分析进行了比较和评估。这些出版物涵盖了基于以下随机临床试验获得监管批准的帕博利珠单抗NSCLC适应症：KEYNOTE-010（1篇出版物）、KEYNOTE-024（6篇）、KEYNOTE-042（4篇）、KEYNOTE-189（2篇）和KEYNOTE-407（1篇）。在健康状态（无进展、疾病进展和死亡与疾病稳定、疾病进展、死亡和治疗中断）、建模方法（分段生存与马尔可夫模型）、生存外推/转移概率估计、药物额外成本、疾病管理和不良事件成本（如程序性死亡配体1[PD-L1]检测、后续治疗、终末期护理）、治疗持续时间方法（基于试验的治疗时间与治疗至进展）、效用来源（试验数据与文献）以及效用分析（至死亡时间与进展状态）等方面观察到差异。模型间变异性的某些方面存在问题，包括偏离试验中观察到的治疗利用率，以及在帕博利珠单抗可用之前，预测的帕博利珠单抗长期死亡率风险高于历史真实世界NSCLC死亡率数据。因此，即使在相似时间间隔内研究相同人群和对照的研究之间结果也存在差异。CEA方法的差异可能导致不同的结果和结论。支付方和政策制定者应仔细审查研究设计和假设，并选择具有更高有效性和准确性的CEA用于基于证据的决策。
