Assessing the efficacy-effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population-based, real-world data for contemporary parenteral cancer therapeutics
Assessing the efficacy-effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population-based, real-world data for contemporary parenteral cancer therapeutics
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DOI：
10.1002/cncr.32697
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发表时间：
2020-01-08
期刊：
影响因子：
6.2
通讯作者：
Chan, Kelvin K. W.
中科院分区：
文献类型：
--
作者：
Phillips, Cameron M.;Parmar, Ambica;Chan, Kelvin K. W.
背景尽管越来越多的证据表明临床试验（CT）和真实世界证据（RWE）之间存在疗效-有效性差距，但据作者所知，这种差异的程度仍不充分。本研究的目的是量化CT和RWE在当代癌症全身治疗中的生存率和毒性差异。方法确定接受安大略癌症护理新药资助计划（NDFP）资助的癌症治疗的患者。确定了具有关于每种药物适应症的生存期和不良事件（AE）数据的标志性CT。通过加拿大基于人群的数据库确定了治疗期间生存率和住院率的RWE。每种药物适应症的疗效-有效性差距计算为中位总生存期（OS）、1年OS的RWE和CT数据之间的差异，以及Kaplan-Meier OS曲线生成的风险比（HR）和95% CI。毒性差异计算为住院率RWE与CT严重AE率之间的差异。结果共纳入20种系统治疗的29种适应症。29种适应症中有28种（97%）显示RWE的生存率较差，中位OS差异为5.2个月（四分位距，3.0-12.1个月）。通过OS风险比为1.58（95% CI，1.39-1.80）的荟萃分析也证明了RWE的有效性较低。住院率和CT严重AE的RWE之间的中位差异为14%（95% CI，9%-22%）。结论：现代癌症系统治疗存在疗效-效果差距，与CT数据相比，RWE中观察到的中位OS低5.2个月。这些数据支持使用RWE来更好地告知关于使用癌症全身治疗的真实决策。
Background Although increasing evidence has suggested that an efficacy-effectiveness gap exists between clinical trial (CT) and real-world evidence (RWE), to the authors' knowledge, the magnitude of this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies. Methods Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population-based databases. The efficacy-effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1-year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan-Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates. Results Twenty-nine indications from 20 systemic therapies were included. Twenty-eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0-12.1 months). Lower effectiveness in RWE also was demonstrated through a meta-analysis of an OS hazard ratio of 1.58 (95% CI, 1.39-1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%-22%). Conclusions An efficacy-effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2-month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real-world decision making regarding the use of cancer systemic therapies.