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.

中文翻译：

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评估癌症疗法的疗效-疗效差距：比较临床试验与当代肠胃外癌症疗法基于人群的真实数据之间的总体生存率和毒性。

背景技术尽管越来越多的证据表明，临床试验（CT）与真实证据（RWE）之间存在功效-功效差距，但据作者所知，这种差异的程度仍未得到很好的体现。当前研究的目的是量化CT和RWE之间当代癌症全身疗法的生存率和毒性差异的幅度。方法确定接受安大略省癌症护理新药资助计划（NDFP）资助的癌症治疗的患者。确定了具有每种药物适应症生存和不良事件（AE）数据的地标性CT。通过加拿大人口基数据库确定治疗期间生存率和住院率的RWE。计算每种药物适应症的疗效-效果差距，方法是：RWE和CT数据之间的中位数总生存期（OS），1年OS和产生的危险比（HRs）之间的差异由Kaplan-Meier OS曲线得出，CI为95％。毒性差异计算为住院率的RWE与CT严重AE率之间的差异。结果包括来自20种全身疗法的29种适应症。29个适应症中有28个（97％）表现出RWE生存较差，OS中位数差异为5.2个月（四分位间距为3.0-12.1个月）。通过对OS危险比为1.58（95％CI，1.39-1.80）进行荟萃分析，也证明了RWE的有效性较低。RWE的住院率与CT严重不良事件之间的中位数差异为14％（95％CI，9％-22％）。结论当前的癌症系统疗法存在疗效-有效性差距，与CT数据相比，RWE的中位OS降低了5.2个月。这些数据支持RWE的使用，以更好地指导有关癌症全身疗法使用的现实世界决策。