非小细胞肺癌靶向治疗试验中设计与结果的吻合度：一项 meta 研究
Design-Outcome Concordance in Targeted-Therapy trials in Non-Small cell lung cancer: a Meta-Research study.
作者
作者单位
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
- Department of Geriatrics, Orthopedics and Rheumatological Sciences, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy.
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS Rome, Italy.
- Department of Oncology, University of Turin, Turin, Italy.
- Biostatistics Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
- Phase 1 Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
摘要
中文
在生物标志物筛选的非小细胞肺癌（NSCLC）中,靶向治疗往往带来显著的生存改善。我们系统综述了驱动基因阳性 NSCLC 的 III 期随机对照试验（RCT）,以评估设计假设与观察到的治疗效应之间的吻合度。检索了 MEDLINE、Embase 和 Cochrane 中心试验注册库（2005 年 1 月 1 日至 2025 年 2 月 1 日发表）的 III 期 RCT,纳入转移性或局部晚期、生物标志物筛选的 NSCLC 患者,采用优效性设计比较靶向药物与标准方案。主要终点为无进展生存期的风险比（HR）。统计分析包括 meta 分析与 meta 回归；回顾性设计的检验效能、Type S 错误率和效应夸大比；设计与结果的吻合度；以及限制性平均生存时间（RMST）。共筛选了 1987 条记录,最终纳入 45 项研究。所有 RCT 的主要终点均为无进展生存期。预期 HR 中位数为 0.64（IQR 0.61–0.67）。观察合并 HR 为 0.47（95% CI 0.40–0.54）,标准误较大的研究倾向于报告更大的治疗效应（P < 0.001）。38 项（84%）RCT 报告了统计学显著结果。按原始假设,中位回顾设计检验效能为 0.78（IQR 0.72–0.88）；采用观察 HR 后,中位检验效能为 1.00（IQR 0.98–1.00）。观察/预期 HR 比合并值为 0.76（95% CI 0.66–0.87）。贝叶斯分析中,17 项（41%）试验超过预设 HR 的概率小于 1%。8 项试验（19%）违反比例风险（PH）假设。HR/RMST 比合并值为 1.40（95% CI 1.29–1.52）。本研究支持报告回顾设计指标、最小临床重要差异以及预期效应大小,并系统性地纳入 RMST。
English
In biomarker-selected non-small cell lung cancer (NSCLC) targeted therapies often produce substantial improvements in survival outcomes. We conducted a systematic review of phase III randomized controlled trials (RCTs) in oncogene-driven NSCLC to evaluate the concordance between design assumptions and observed treatment effects. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for phase III RCTs published between January 1, 2005, and February 1, 2025, enrolling patients with metastatic or locally advanced, biomarker-selected NSCLC, comparing targeted agents versus standard regimens in a superiority design. Hazard ratios (HRs) for progression-free survival were considered. Statistical analyses included meta-analyses with meta-regression; retrodesign analysis of power, type S error, and exaggeration ratios; design-outcome concordance; and restricted mean survival time (RMST). 1987 records were screened, and 45 studies included. Progression-free survival was the primary outcome in all RCTs. Median expected HR was 0.64 (IQR 0.61-0.67). Pooled observed HR was 0.47 (95% CI 0.40-0.54), studies with higher standard errors were associated with larger treatment effects (P<.001). Statistically significant results were reported in 38 (84%) RCTs. Under original assumptions, median retrodesign power was 0.78 (IQR 0.72-0.88), and using the observed HR, median power was 1.00 (IQR 0.98-1.00). Pooled observed-to-expected HR ratio was 0.76 (95%CI 0.66-0.87). In Bayesian analyses, 17 (41%) trials had <1% probability of exceeding planned HR. Proportional hazards (PH) assumption was violated in 8 trials (19%). Pooled HR/RMST ratio was 1.40 (95% CI 1.29-1.52). Our work supports reporting retrodesign metrics, the minimal clinically important difference alongside the anticipated effect size, and systematic inclusion of RMST.
分类与指标
- 研究类型
- 综述Meta
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 7.7
- 新锐分区
- 1区