了解实用试验结果和亚组分析的异质性：FIAT的例子

IF 1.5 4区医学 Q4 CLINICAL NEUROLOGY

Neurochirurgie Pub Date : 2025-05-19 DOI:10.1016/j.neuchi.2025.101683

Jean Raymond , Tim E. Darsaut

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引用次数: 0

摘要

背景和目的实用主义试验结果本质上是异质的，解释性试验的范式判断所基于的“平均治疗效果”可能不足以将试验结果转化为适用于实践的有临床意义的结论。检查不同的亚组是有问题的，因为他们有假阴性和假阳性结果的风险。方法我们总结了FIAT，一项实用护理试验，对多个亚组进行了检查。本文回顾了平均治疗效果和相互作用试验的概念，以便更好地理解它们在实用试验中的应用。结果该试验显示血流转移优于标准治疗，但结果并不适用于所有颅内动脉瘤。当存在多个比较干预和临床异质性时，“真正的平均治疗效果”的概念很难适用。尽管进行了负相互作用试验，但仍对不同的亚组进行了检查，以帮助解释试验结果。只要子群体的发现不是依赖于数据的“钓鱼考察”，它们就是可信的。预先指定有意义的临床亚组，并将其纳入随机化方案和功率计算，可提供最可信的结论。结论非预先设定的数据依赖亚组分析存在较高的错误风险，不应用于临床决策。然而，对预先指定的亚组分析的批判性评估可以帮助解释异质的实用试验结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Understanding heterogeneity of pragmatic trial results and subgroup analyses: The FIAT example

Background and purpose

Pragmatic trial results are intrinsically heterogeneous and the ‘average treatment effect’, on which the paradigmatic verdict of explanatory trials is based may not suffice to translate trial results into clinically meaningful conclusions applicable in practice. Examining various subgroups is problematic because they are at risk of both false negative and false positive results.

Methods

We summarize FIAT, a pragmatic care trial on flow diversion where multiple subgroups were examined. The notions of average treatment effect and interaction tests are reviewed to better understand their application in pragmatic trials.

Results

The trial showed flow diversion to be superior to standard treatments, but the results do not apply to all intracranial aneurysms. The notion of a ‘true average treatment effect’ can hardly apply when there are multiple comparator interventions and clinical heterogeneity. Various subgroups were examined in spite of negative interaction tests, to help interpret the trial results. Subgroup findings can be credible so long as they are not data-dependent ‘fishing expeditions’. Meaningful clinical subgroups that have been pre-specified and integrated into the randomization scheme and power calculation provide the most credible conclusions.

Conclusion

Non-prespecified data-dependent subgroup analyses are at high risk of being incorrect and should not be used to make clinical decisions in practice. A critical assessment of pre-specified subgroup analyses can nonetheless help interpret heterogeneous pragmatic trial results.

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来源期刊

Neurochirurgie 医学-临床神经学

CiteScore

2.70

自引率

6.20%

发文量

100

审稿时长

29 days

期刊介绍： Neurochirurgie publishes articles on treatment, teaching and research, neurosurgery training and the professional aspects of our discipline, and also the history and progress of neurosurgery. It focuses on pathologies of the head, spine and central and peripheral nervous systems and their vascularization. All aspects of the specialty are dealt with: trauma, tumor, degenerative disease, infection, vascular pathology, and radiosurgery, and pediatrics. Transversal studies are also welcome: neuroanatomy, neurophysiology, neurology, neuropediatrics, psychiatry, neuropsychology, physical medicine and neurologic rehabilitation, neuro-anesthesia, neurologic intensive care, neuroradiology, functional exploration, neuropathology, neuro-ophthalmology, otoneurology, maxillofacial surgery, neuro-endocrinology and spine surgery. Technical and methodological aspects are also taken onboard: diagnostic and therapeutic techniques, methods for assessing results, epidemiology, surgical, interventional and radiological techniques, simulations and pathophysiological hypotheses, and educational tools. The editorial board may refuse submissions that fail to meet the journal''s aims and scope; such studies will not be peer-reviewed, and the editor in chief will promptly inform the corresponding author, so as not to delay submission to a more suitable journal. With a view to attracting an international audience of both readers and writers, Neurochirurgie especially welcomes articles in English, and gives priority to original studies. Other kinds of article - reviews, case reports, technical notes and meta-analyses - are equally published. Every year, a special edition is dedicated to the topic selected by the French Society of Neurosurgery for its annual report.