论文标题

两阶段的单臂试验很少有足够的报告

Two-stage single-arm trials are rarely reported adequately

论文作者

Grayling, Michael J., Mander, Adrian P.

论文摘要

目的:在II期肿瘤学中通常使用两阶段的单臂试验设计,以推断二元主要结果的治疗效果(例如肿瘤反应)。必须有效地设计,分析和报告此类研究。但是,几乎没有关于这种情况的可用证据,特别是对于关键的统计考虑。因此,我们全面审查了此类试验,并根据报告的特殊质量进行了检查。方法:在5年内使用了“西蒙的两阶段设计”,已确定并审查了使用“西蒙两阶段设计”的肿瘤学试验。评估了文章是否报告了是否报告了足够的设计细节,例如所需的样本量和分析细节,例如置信区间(CI)。重新分析了未调整其纳入临时分析推断的文章,以评估对其报告的点估计和CI的影响。结果:包括报告单个治疗臂结果的四百二十5篇文章。其中,有47.5%提供了确保设计可重复性的五个组件。只有1.2%和2.1%的报告分别报告了调整后的估计值或CI。只有55.3%的试验规定最后阶段拒绝约束,表明许多试验未检验设计的假设。对试验的重新分析表明,报道的点估计值低估了治疗效果,而报道CI的估计值太窄。结论:两阶段单臂试验的关键设计细节通常未报告。尽管定期进行推断,但很少这样做,以消除临时分析引入的偏差。为了最大程度地提高其价值,未来的研究必须改善对其进行分析和报告的方式。

Purpose: Two-stage single-arm trial designs are commonly used in phase II oncology to infer treatment effects for a binary primary outcome (e.g., tumour response). It is imperative that such studies be designed, analysed, and reported effectively. However, there is little available evidence on whether this is the case, particularly for key statistical considerations. We therefore comprehensively review such trials, examining in particular quality of reporting. Methods: Published oncology trials that utilised "Simon's two-stage design" over a 5 year period were identified and reviewed. Articles were evaluated on whether they reported sufficient design details, such as the required sample size, and analysis details, such as a confidence interval (CI). The articles that did not adjust their inference for the incorporation of an interim analysis were re-analysed to evaluate the impact on their reported point estimate and CI. Results: Four hundred and twenty five articles that reported the results of a single treatment arm were included. Of these, 47.5% provided the five components that ensure design reproducibility. Only 1.2% and 2.1% reported an adjusted point estimate or CI, respectively. Just 55.3% of trials provided the final stage rejection bound, indicating many trials did not test the hypothesis the design is constructed to assess. Re-analysis of the trials suggests that reported point estimates underestimated treatment effects and that reported CIs were too narrow. Conclusion: Key design details of two-stage single-arm trials are often unreported. Whilst inference is regularly performed, it is rarely done so in a way that removes the bias introduced by the interim analysis. In order to maximise their value, future studies must improve the way that they are analysed and reported.

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