Treatment Effect Reanalysis of the Randomized Individual Screening Trial of Innovative Glioblastoma Therapy in Newly Diagnosed Glioblastoma With External Control Data.

We reanalyzed the three experimental arms of the Individual Screening Trial of Innovative Glioblastoma Therapy (INSIGhT), a randomized phase II platform trial in newly diagnosed O6-methylguanine-DNA methyltransferase-unmethylated glioblastoma (ClinicalTrials.gov identifier: NCT02977780).

我们重新分析了个体筛查试验的创新性胶质母细胞瘤治疗（INSIGhT）的三个实验组，这是一个针对新诊断的O6-甲基鸟嘌呤-DNA甲基转移酶未甲基化的胶质母细胞瘤的随机II期平台试验（ClinicalTrials.gov注册号：NCT02977780）。

To evaluate the validity of using external data sets, we compared treatment effect estimates based on internal INSIGhT control data and matched external control data.

为了评估使用外部数据集的有效性，我们比较了基于内部INSIGhT对照数据和匹配的外部对照数据的治疗效果估计。

Methods

The three experimental arms of INSIGhT (abemaciclib [n = 72], neratinib [n = 80], and CC-115 [n = 12]) did not improve survival compared with internal controls (standard chemoradiation [n = 70]).

INSIGhT的三个实验组（阿贝西利[n=72]、尼拉替尼[n=80]和CC-115[n=12]）与内部对照组（标准化放化疗[n=70]）相比，并没有改善生存率。

We derived external control patient-level data from multiple real-world and clinical trial data sets.

我们从多个真实世界和临床试验数据集中派生出外部对照的患者级数据。

We applied propensity score matching and Cox proportional hazards models to estimate treatment effects with external controls.

我们应用倾向得分匹配和Cox比例风险模型来估计外部对照的治疗效果。

Additionally, using this glioblastoma (GBM) data collection, we specified simulation scenarios to evaluate trial designs that integrate external controls.

此外，利用这个胶质母细胞瘤（GBM）数据集，我们指定了模拟情景来评估整合外部对照的试验设计。

Results

After matching to external controls, no survival benefit was observed for patients receiving abemaciclib (hazard ratio[HR], 1.00 [95% CI, 0.75 to 1.34]), neratinib (HR, 0.93 [95% CI, 0.70 to 1.24]), or CC-115 (HR, 0.88 [95% CI, 0.41 to 1.88]).

在与外部对照匹配后，接受abemaciclib（风险比[HR]，1.00 [95% 置信区间，0.75 至 1.34]）、neratinib（HR，0.93 [95% 置信区间，0.70 至 1.24]）或CC-115（HR，0.88 [95% 置信区间，0.41 至 1.88]）的患者未观察到生存益处。

Simulations, together with the INSIGhT data and a collection of GBM data sets, allowed us to examine efficiencies and risks of clinical trial designs that leverage external control data.

通过模拟、INSIGhT数据集以及一系列胶质母细胞瘤(GBM)数据集，我们能够检验利用外部对照数据的临床试验设计的效率和风险。

Conclusions

The use of carefully matched external controls, to replace or augment the internal controls of INSIGhT, produced treatment effect estimates that were similar to previously published analyses.

使用经过仔细匹配的外部对照，来替代或增强INSIGhT的内部对照，产生的治疗效果估计与先前发表的分析相似。

Single-arm trial designs and hybrid randomized designs incorporating propensity score-matched external control data evaluated treatment effects in the early-phase testing of experimental therapies in newly diagnosed GBM.

单臂试验设计和结合倾向得分匹配外部对照数据的混合随机设计评估了在新诊断的胶质母细胞瘤中实验性治疗的早期测试效果。

The validity of this approach and risks of bias depended on the availability of comprehensive and accurate data on all potential confounders, in the absence of unmeasured confounding.

这种方法的有效性和偏差风险取决于所有潜在混杂因素的全面和准确数据的可用性，不存在未测量的混杂因素。