How to design a pre-specified statistical analysis approach to limit p-hacking in clinical trials: the Pre-SPEC framework
How to design a pre-specified statistical analysis approach to limit p-hacking in clinical trials: the Pre-SPEC framework
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DOI：
10.1186/s12916-020-01706-7
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发表时间：
2020-09-07
期刊：
影响因子：
9.3
通讯作者：
Cro, Suzie
中科院分区：
文献类型：
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作者：
Kahan, Brennan C.;Forbes, Gordon;Cro, Suzie
如果研究者在看到试验数据后选择他们的分析方法，那么临床试验的结果可能容易受到偏倚的影响，因为这可以让他们进行多次分析，然后选择提供最有利结果的方法（通常称为“p-黑客”）。预先指定计划的分析方法对于帮助减少此类偏倚至关重要，因为它确保在看到试验数据之前选择分析方法。因此，SPIRIT（标准方案项目：干预性试验建议）和ICH-E9（人用药品技术要求国际协调会议）等指南要求在试验方案中预先规定试验主要结局的统计方法。然而，预规范只有在不允许p-黑客攻击的情况下才有效。例如，研究人员可能预先指定某种统计方法，如多重插补，但很少详细说明如何实施。由于有许多不同的方法来执行多重插补，这种预先指定的方法是无效的，因为它仍然允许调查人员在决定最终方法之前以不同的方式分析数据。在本文中，我们描述了一个五点框架（Pre-SPEC框架），用于设计不允许p-hacking的预先指定的分析方法。该框架基于SPIRIT和ICH-E9指南中的原则设计，预期与这些指南结合使用，以帮助研究者设计试验方案中试验主要结局的统计分析策略。
Results from clinical trials can be susceptible to bias if investigators choose their analysis approach after seeing trial data, as this can allow them to perform multiple analyses and then choose the method that provides the most favourable result (commonly referred to as 'p-hacking'). Pre-specification of the planned analysis approach is essential to help reduce such bias, as it ensures analytical methods are chosen in advance of seeing the trial data. For this reason, guidelines such as SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and ICH-E9 (International Conference for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) require the statistical methods for a trial's primary outcome be pre-specified in the trial protocol. However, pre-specification is only effective if done in a way that does not allow p-hacking. For example, investigators may pre-specify a certain statistical method such as multiple imputation, but give little detail on how it will be implemented. Because there are many different ways to perform multiple imputation, this approach to pre-specification is ineffective, as it still allows investigators to analyse the data in different ways before deciding on a final approach. In this article, we describe a five-point framework (the Pre-SPEC framework) for designing a pre-specified analysis approach that does not allow p-hacking. This framework was designed based on the principles in the SPIRIT and ICH-E9 guidelines and is intended to be used in conjunction with these guidelines to help investigators design the statistical analysis strategy for the trial's primary outcome in the trial protocol.