Department of Equity, Ethics and Policy, McGill University, Montreal, Quebec, Canada.
Department of Medicine, Temple University, Philadelphia, Pennsylvania.
JAMA. 2024 Jun 25;331(24):2105-2113. doi: 10.1001/jama.2024.6281.
Many cancer clinical investigators view clinical trials as offering better care for patients than routine clinical care. However, definitive evidence of clinical benefit from trial participation (hereafter referred to as the participation effect) has yet to emerge.
To conduct a systematic review and meta-analysis of the evidence examining whether patient participation in cancer trials was associated with greater survival benefit compared with routine care.
Studies were found through PubMed and Embase (January 1, 2000, until August 31, 2022), as well as backward and forward citation searching.
Studies were included that compared overall survival of trial participants and routine care patients.
Data extraction and methodological quality assessment were completed by 2 independent coders using Covidence software. Data were pooled using a random-effects model and analyzed based on the quality of the comparison between trial participants and routine care patients (ie, extent to which studies controlled for bias and confounders).
The hazard ratio (HR) for overall survival of trial participants vs routine care patients.
Thirty-nine publications were included, comprising 85 comparisons of trial participants and routine care patients. The meta-analysis revealed a statistically significant overall survival benefit for trial participants (HR, 0.76 [95% CI, 0.69-0.82]) when all studies were pooled, regardless of design or quality. However, survival benefits diminished in study subsets that matched trial participants and routine care patients for eligibility criteria (HR, 0.85 [95% CI, 0.75-0.97]) and disappeared when only high-quality studies were pooled (HR, 0.91 [95% CI, 0.80-1.05]). They also disappeared when estimates were adjusted for potential publication bias (HR, 0.94 [95% CI, 0.86-1.03]).
Many studies suggest a survival benefit for cancer trial participants. However, these benefits were not detected in studies using designs addressing important sources of bias and confounding. Pooled results of high-quality studies are not consistent with a beneficial effect of trial participation on its own.
许多癌症临床研究人员认为临床试验为患者提供的治疗比常规临床护理更好。然而，参与试验带来的临床获益的明确证据（以下简称参与效应）尚未出现。
对评估癌症试验患者参与与常规护理相比是否与更大的生存获益相关的证据进行系统回顾和荟萃分析。
通过 PubMed 和 Embase（2000 年 1 月 1 日至 2022 年 8 月 31 日）以及回溯和前向引文搜索查找研究。
纳入比较试验参与者和常规护理患者总生存率的研究。
使用 Covidence 软件由 2 名独立编码员完成数据提取和方法学质量评估。使用随机效应模型对数据进行合并，并根据试验参与者与常规护理患者之间比较的质量进行分析（即研究控制偏倚和混杂因素的程度）。
试验参与者与常规护理患者的总生存率的风险比（HR）。
纳入 39 篇文献，包括 85 项试验参与者和常规护理患者的比较。荟萃分析显示，当所有研究合并时，试验参与者具有统计学显著的总体生存获益（HR，0.76 [95%CI，0.69-0.82]），无论设计或质量如何。然而，在匹配试验参与者和常规护理患者入选标准的研究亚组中，生存获益减少（HR，0.85 [95%CI，0.75-0.97]），当仅合并高质量研究时，获益消失（HR，0.91 [95%CI，0.80-1.05]）。当对潜在发表偏倚进行调整时，获益也消失（HR，0.94 [95%CI，0.86-1.03]）。
许多研究表明癌症试验参与者具有生存获益。然而，在使用解决重要偏倚和混杂来源的设计的研究中，这些获益并未被发现。高质量研究的合并结果与试验参与本身具有有益影响不一致。
