■大型试验可以在重要问题上提供大规模证据。
■探讨大型试验的结果如何与样本量较小的试验的荟萃分析结果进行比较。
■ClinicalTrials.gov一直在搜索大型试验,直到2023年1月。截至2023年6月,PubMed一直在搜索纳入符合条件的大型试验结果的荟萃分析。
■大型试验如果是非集群非疫苗随机临床试验,则符合资格。样本量超过10,000,并且有同行评审的荟萃分析出版物,介绍了大型试验的主要结局和/或全因死亡率的结果.
■对于每个选定的荟萃分析,我们提取了纳入汇总效应估计的较小试验和大型试验的结果,并使用随机效应分别合并.这些估计值用于计算每个荟萃分析中大型试验和较小试验之间的比值比(ROR)。接下来,使用随机效应组合ROR。我们分析中包括的每项试验都提取了偏倚风险(或在不可用的情况下,仅在大型试验中评估)。数据分析于2024年1月至6月进行。
主要结果是大型试验和小型试验之间的主要结局和全因死亡率的总结ROR。对出版年份进行了敏感性分析,掩蔽,体重,干预类型,和专业。
■在确定的120项大型试验中,41显示了主要结局的显着结果,22显示了全因死亡率的显着结果。在35个主要结果比较(包括来自69个独特的大型试验的85点估计值和来自较小试验的272点估计值)和26个全因死亡率比较(包括来自65个独特的大型试验的70点估计值和来自较小试验的267点估计值)中,大型试验和较小试验的主要结局之间没有差异(ROR,1.00;95%CI,0.97-1.04),也不包括全因死亡率(ROR,1.00;95%CI,0.97-1.04)。对于主要结果,在大型试验之前发表的较小的试验比大型试验有更有利的结果(ROR,1.05;95%CI,1.01-1.10)和随后在大型试验后发表的较小试验(ROR,1.10;95%CI,1.04-1.18)。
■在这项荟萃研究分析中,较小研究的荟萃分析显示,与大型试验的总体结果相当,但是在大型试验之前发表的较小的试验比大型试验给出了更有利的结果。这些发现表明,鉴于发现的大型试验数量相对较少,需要更频繁地进行大型试验,他们的低显著利率,事实上,在大型试验之前发表的较小的试验报告比大型试验和随后的较小的试验更有益的结果。
UNASSIGNED: Mega-trials can provide large-scale evidence on important questions.
UNASSIGNED: To explore how the results of mega-trials compare with the meta-analysis results of trials with smaller sample sizes.
UNASSIGNED: ClinicalTrials.gov was searched for mega-trials until January 2023. PubMed was searched until June 2023 for meta-analyses incorporating the results of the eligible mega-trials.
UNASSIGNED: Mega-trials were eligible if they were noncluster nonvaccine randomized clinical trials, had a sample size over 10 000, and had a peer-reviewed meta-analysis publication presenting results for the primary outcome of the mega-trials and/or all-cause mortality.
UNASSIGNED: For each selected meta-analysis, we extracted results of smaller trials and mega-trials included in the summary effect estimate and combined them separately using random effects. These estimates were used to calculate the ratio of odds ratios (ROR) between mega-trials and smaller trials in each meta-analysis. Next, the RORs were combined using random effects. Risk of bias was extracted for each trial included in our analyses (or when not available, assessed only for mega-trials). Data analysis was conducted from January to June 2024.
UNASSIGNED: The main outcomes were the summary ROR for the primary outcome and all-cause mortality between mega-trials and smaller trials. Sensitivity analyses were performed with respect to the year of publication, masking, weight, type of intervention, and specialty.
UNASSIGNED: Of 120 mega-trials identified, 41 showed a significant result for the primary outcome and 22 showed a significant result for all-cause mortality. In 35 comparisons of primary outcomes (including 85 point estimates from 69 unique mega-trials and 272 point estimates from smaller trials) and 26 comparisons of all-cause mortality (including 70 point estimates from 65 unique mega-trials and 267 point estimates from smaller trials), no difference existed between the outcomes of the mega-trials and smaller trials for primary outcome (ROR, 1.00; 95% CI, 0.97-1.04) nor for all-cause mortality (ROR, 1.00; 95% CI, 0.97-1.04). For the primary outcomes, smaller trials published before the mega-trials had more favorable results than the mega-trials (ROR, 1.05; 95% CI, 1.01-1.10) and subsequent smaller trials published after the mega-trials (ROR, 1.10; 95% CI, 1.04-1.18).
UNASSIGNED: In this meta-research analysis, meta-analyses of smaller studies showed overall comparable results with mega-trials, but smaller trials published before the mega-trials gave more favorable results than mega-trials. These findings suggest that mega-trials need to be performed more often given the relative low number of mega-trials found, their low significant rates, and the fact that smaller trials published prior to mega-trial report more beneficial results than mega-trials and subsequent smaller trials.