Overall Survival and Quality-of-Life Superiority in Modern Phase 3 Oncology Trials: A Meta-Epidemiological Analysis.

However, alternative end points are often not valid surrogates for overall survivaland quality of life (QOL) and may be less relevant to patients.

然而，这些替代终点往往不能有效替代总生存期和生活质量（QOL），对患者的相关性可能较低。

Background

To determine the proportion of phase 3 RCTs with overall survivalor QOL superiority.

确定第三阶段随机对照试验中总生存或生活质量优势的比例。

design_and_setting

Meta-epidemiological study of 2-group, superiority-design, interventional phase 3 oncology RCTs screened from ClinicalTrials.gov and published between 2002 and 2024.

对2002年至2024年间在ClinicalTrials.gov筛选并发表的两组、优效设计、干预性第三阶段肿瘤学随机对照试验进行的荟萃流行病学研究。

main_outcomes_and_measures

Alternative end-point, overall survival, and QOL superiority in the experimental group vs the reference/control group according to prespecified statistical criteria for each RCT.

根据预先设定的统计标准，评估实验组与参考/对照组在替代终点、总生存和生活质量方面的优势。

A secondary goal was to evaluate the quality of QOL analyses, since approaches unadjusted for baseline scores may bias results.

次要目标是评估生活质量分析的质量，因为未调整基线得分的方法可能会导致结果偏差。

Results

A total of 791 RCTs representing 555 580 enrolled patients were included.

共纳入了791项随机对照试验，代表了555,580名已登记患者。

Alternative primary end points were most common (n = 495 [63%]).

替代的主要终点最为常见（n = 495 [63%]）。

The primary end point was met in 53% of the RCTs (n = 420); alternative end-point superiority was shown in 55% (n = 434).

主要终点在53%的随机对照试验（RCTs）中得到满足（n = 420）；替代终点的优势在55%中得到显示（n = 434）。

Overall survivalsuperiority was shown in 28% (n = 221).

总生存的优势在28%中得到显示（n = 221）。

Patient-reported outcomes were collected in 61% of the RCTs (n = 482), but global QOL results were published in only 34% (n = 271).

在61%的随机对照试验中收集了患者报告的结果（n = 482），但只有34%的试验发表了全球生活质量结果（n = 271）。

Most between-group global QOL analyses did not adjust for baseline scores (223 [82%]).

大多数组间全球生活质量分析未对基线得分进行调整（223 [82%]）。

Global QOL superiority was shown in 11% (n = 84).

11%（n = 84）的研究显示了全球生活质量（Global QOL）的优势。

Among all RCTs, 32% (n = 257) demonstrated either overall survivalor global QOL superiority.

在所有随机对照试验（RCTs）中，32%（n = 257）显示了总生存（overall survival）或全球生活质量（Global QOL）的优势。

Superiority of both overall survivaland global QOL was shown in 6% (n = 48).

在6%（n = 48）的病例中，总生存和全球生活质量均显示出优越性。

Among 434 RCTs with a positive alternative end point, only a minority showed superiority of either overall survival(185 [43%]) or global QOL (67 [15%]).

在434个具有积极替代终点的随机对照试验中，只有少数显示出总生存（185 [43%]）或全球生活质量（67 [15%]）的优越性。

conclusions_and_relevance

Findings of superiority-design phase 3 oncology RCTs are commonly interpreted as positive.

优势设计的III期肿瘤学随机对照试验（RCTs）的结果通常被解释为阳性。

However, this is mostly based on improvements in alternative end points.

然而，这主要基于替代终点的改善。

Gains in either overall survivalor QOL are uncommon, even when alternative end-point findings are positive.

即使替代终点的研究结果为阳性，总生存或生活质量的改善也是不常见的。

QOL appears both underevaluated and underreported; furthermore, the majority of phase 3 QOL analyses are unadjusted for baseline scores, which lose efficiency and add bias compared with adjusted analyses.

生活质量似乎被低估和报道不足；此外，大多数第三阶段的生活质量分析没有根据基线得分进行调整，这与调整后的分析相比，效率降低，偏倚增加。

To increase the meaningfulness of late-phase research, future trial designs and regulatory processes should be refocused toward overall survivaland QOL improvements.

为了提高晚期研究的意义，未来的试验设计和监管流程应重新聚焦于总生存和生活质量的改善。