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为何在临床试验中需要效应指标来定义治疗效果。

Why estimands are needed to define treatment effects in clinical trials.

机构信息

KeeneONStatistics, Maidenhead, UK.

Biostatistics, Novo Nordisk A/S, Bagsværd, Denmark.

出版信息

BMC Med. 2023 Jul 27;21(1):276. doi: 10.1186/s12916-023-02969-6.


DOI:10.1186/s12916-023-02969-6
PMID:37501156
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10375689/
Abstract

BACKGROUND: The estimand for a clinical trial is a precise definition of the treatment effect to be estimated. Traditionally, estimates of treatment effects are based on either an ITT analysis or a per-protocol analysis. However, there are important clinical questions which are not addressed by either of these analyses. For example, consider a trial where patients take a rescue medication. The ITT analysis includes data after use of rescue, while the per-protocol analysis excludes these patients altogether. Neither of these analyses addresses the important question of what the treatment effect would have been if patients did not take rescue medication. MAIN TEXT: Trial estimands provide a broader perspective compared to the limitations of ITT and per-protocol analysis. Trial treatment effects depend on how events occurring after treatment initiation such as use of alternative medication or discontinuation of the intervention are included in the definition. These events can be accounted for in different ways, depending on the clinical question of interest. CONCLUSION: The estimand framework is an important step forward in improving the clarity and transparency of clinical trials. The centrality of estimands to clinical trials is currently not reflected in methods recommended by the Cochrane group or the CONSORT statement, the current standard for reporting clinical trials in medical journals. We encourage revisions to these guidelines.

摘要

背景:临床试验的评估指标是对拟评估的治疗效果的精确定义。传统上,治疗效果的估计是基于意向性治疗分析(ITT 分析)或符合方案分析(per-protocol analysis)。然而,这些分析并不能解决一些重要的临床问题。例如,考虑一项试验,患者服用抢救药物。ITT 分析包括使用抢救药物后的数据,而符合方案分析则完全排除了这些患者。这两种分析都没有回答如果患者没有服用抢救药物,治疗效果会是怎样的重要问题。

主要文本:与 ITT 和符合方案分析的局限性相比,试验评估指标提供了更广泛的视角。试验治疗效果取决于在治疗开始后发生的事件(如使用替代药物或停止干预)如何被纳入定义。这些事件可以通过不同的方式来处理,具体取决于感兴趣的临床问题。

结论:评估指标框架是提高临床试验清晰度和透明度的重要一步。评估指标对临床试验的重要性目前并没有反映在 Cochrane 小组或 CONSORT 声明等方法中,后者是医学期刊中报告临床试验的当前标准。我们鼓励对这些指南进行修订。

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本文引用的文献

[1]
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JAMA. 2021-9-14

[2]
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Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial.

Lancet Respir Med. 2021-10

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Pharm Stat. 2020-9

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