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arXiv 2006.05795stat.ME
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理解和调整从概念验证研究到更验证性研究的选择偏差

Understanding and adjusting the selection bias from a proof-of-concept study to a more confirmatory study

Yongming Qu, Yu Du, Ying Zhang, Lei Shen

摘要:

长期以来,人们一直注意到,在小型早期研究中观察到的疗效通常优于在后来的大型研究中观察到的疗效。从历史上看,早期概念验证研究的疗效结果的膨胀要么被忽略,要么使用频率论或贝叶斯方法进行经验调整。本文从测量误差模型和选择偏倚的角度系统地解释了小型早期研究中疗效结果膨胀的根本原因。建立了一个系统的方法来调整早期的研究结果,从频率和贝叶斯的角度。提出了一种分层模型来估计化合物组合的疗效分布,其可以用作贝叶斯方法的先验分布。我们通过理论表明,系统调整为化合物组合的真实平均疗效提供了无偏估计量。该调整适用于早期小型和后来大型研究中一组化合物在糖尿病和免疫学中的有效性的配对数据。调整后,早期小型研究中的偏差似乎有所减少。

英文摘要:

It has long been noticed that the efficacy observed in small early phase studies is generally better than that observed in later larger studies. Historically, the inflation of the efficacy results from early proof-of-concept studies is either ignored, or adjusted empirically using a frequentist or Bayesian approach. In this article, we systematically explained the underlying reason for the inflation of efficacy results in small early phase studies from the perspectives of measurement error models and selection bias. A systematic method was built to adjust the early phase study results from both frequentist and Bayesian perspectives. A hierarchical model was proposed to estimate the distribution of the efficacy for a portfolio of compounds, which can serve as the prior distribution for the Bayesian approach. We showed through theory that the systematic adjustment provides an unbiased estimator for the true mean efficacy for a portfolio of compounds. The adjustment was applied to paired data for the efficacy in early small and later larger studies for a set of compounds in diabetes and immunology. After the adjustment, the bias in the early phase small studies seems to be diminished.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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