Evaluating multiplicity reporting in analgesic clinical trials: An analytical review.

IF 3.5 2区医学 Q1 ANESTHESIOLOGY

European Journal of Pain Pub Date : 2024-11-25 DOI:10.1002/ejp.4756

Maaz S Khan, Lori F Zarmer, Jie Liang, Sepideh Saroukhani, Anthony R Lucas, Colin J L McCartney, Rabail Chaudhry

{"title":"Evaluating multiplicity reporting in analgesic clinical trials: An analytical review.","authors":"Maaz S Khan, Lori F Zarmer, Jie Liang, Sepideh Saroukhani, Anthony R Lucas, Colin J L McCartney, Rabail Chaudhry","doi":"10.1002/ejp.4756","DOIUrl":null,"url":null,"abstract":"Background and objectives: Analgesia trials often demands multiple comparisons to assess various treatment arms, outcomes, or repeated assessments. These multiple comparisons risk inflating the false positive rate. Multiplicity correction in recent analgesic randomized controlled trials (RCTs) remains unclear despite statistical method advancements and regulatory guidelines. Our study aimed to identify reporting inadequacies in multiple analysis adjustments and explanations to understand these deficiencies.Databases and data treatment: This review analysed RCTs from the European Journal of Pain, the Journal of Pain, and PAIN, published between January 2018 and December 2022. We included randomized, double-blind trials focusing on pain outcomes. Data extraction, managed by three researchers using predefined criteria, included trial characteristics, multiplicity presence, and correction methods. Descriptive statistical analyses included Fisher's exact, and Holm method for multiple comparisons.Results: Out of 112 articles, 48 pre-specified a primary analysis plan. Multiple analyses were observed in 65 articles, with 60% adjusting for all comparisons, primarily using the Bonferroni method. Compared with previous studies, no significant changes in multiplicity correction practices were noted when stratified by trial type, size, and sponsor.Conclusions: The study reveals a persistent reliance on multiple comparisons in analgesic clinical trials without a corresponding increase in multiplicity corrections emphasizing a need for enhanced reporting and implementation of statistical adjustments. We acknowledge limitations in categorizing studies, the use of a surrogate for the trial stage, and sourcing data from journal webpages rather than a database.Significance statement: This study flags inadequate reporting on multiplicity correction in analgesic trials, stressing the risk of false positives and the urgent need for enhanced reporting to boost reproducibility.","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ejp.4756","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANESTHESIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and objectives: Analgesia trials often demands multiple comparisons to assess various treatment arms, outcomes, or repeated assessments. These multiple comparisons risk inflating the false positive rate. Multiplicity correction in recent analgesic randomized controlled trials (RCTs) remains unclear despite statistical method advancements and regulatory guidelines. Our study aimed to identify reporting inadequacies in multiple analysis adjustments and explanations to understand these deficiencies.

Databases and data treatment: This review analysed RCTs from the European Journal of Pain, the Journal of Pain, and PAIN, published between January 2018 and December 2022. We included randomized, double-blind trials focusing on pain outcomes. Data extraction, managed by three researchers using predefined criteria, included trial characteristics, multiplicity presence, and correction methods. Descriptive statistical analyses included Fisher's exact, and Holm method for multiple comparisons.

Results: Out of 112 articles, 48 pre-specified a primary analysis plan. Multiple analyses were observed in 65 articles, with 60% adjusting for all comparisons, primarily using the Bonferroni method. Compared with previous studies, no significant changes in multiplicity correction practices were noted when stratified by trial type, size, and sponsor.

Conclusions: The study reveals a persistent reliance on multiple comparisons in analgesic clinical trials without a corresponding increase in multiplicity corrections emphasizing a need for enhanced reporting and implementation of statistical adjustments. We acknowledge limitations in categorizing studies, the use of a surrogate for the trial stage, and sourcing data from journal webpages rather than a database.

Significance statement: This study flags inadequate reporting on multiplicity correction in analgesic trials, stressing the risk of false positives and the urgent need for enhanced reporting to boost reproducibility.

查看原文本刊更多论文

评估镇痛临床试验中的多重性报告：分析综述。

背景和目的：镇痛试验通常要求进行多重比较，以评估各种治疗臂、结果或重复评估。这些多重比较有可能提高假阳性率。尽管统计方法和监管指南不断进步，但近期镇痛随机对照试验（RCT）中的多重性校正仍不明确。我们的研究旨在确定多重分析调整中的报告不足之处，并解释如何理解这些不足之处：本综述分析了2018年1月至2022年12月期间发表在《欧洲疼痛杂志》（European Journal of Pain）、《疼痛杂志》（Journal of Pain）和《疼痛杂志》（PAIN）上的RCT。我们纳入了以疼痛结果为重点的随机双盲试验。数据提取由三位研究人员使用预定义标准进行管理，包括试验特征、多重性存在和校正方法。描述性统计分析包括费雪精确法和用于多重比较的霍尔姆法：在 112 篇文章中，有 48 篇预先指定了主要分析计划。65篇文章进行了多重分析，其中60%的文章对所有比较进行了调整，主要采用Bonferroni方法。与之前的研究相比，根据试验类型、规模和赞助商进行分层后，多重性校正的做法没有明显变化：本研究揭示了镇痛临床试验中对多重比较的持续依赖，而多重性校正却没有相应增加，这强调了加强报告和实施统计调整的必要性。我们承认在对研究进行分类、使用试验阶段的替代物以及从期刊网页而非数据库中获取数据方面存在局限性：本研究揭示了镇痛试验中多重性校正报告的不足，强调了假阳性的风险以及加强报告以提高可重复性的迫切需要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Journal of Pain 医学-临床神经学

CiteScore

7.50

自引率

5.60%

发文量

163

审稿时长

4-8 weeks

期刊介绍： European Journal of Pain (EJP) publishes clinical and basic science research papers relevant to all aspects of pain and its management, including specialties such as anaesthesia, dentistry, neurology and neurosurgery, orthopaedics, palliative care, pharmacology, physiology, psychiatry, psychology and rehabilitation; socio-economic aspects of pain are also covered. Regular sections in the journal are as follows: • Editorials and Commentaries • Position Papers and Guidelines • Reviews • Original Articles • Letters • Bookshelf The journal particularly welcomes clinical trials, which are published on an occasional basis. Research articles are published under the following subject headings: • Neurobiology • Neurology • Experimental Pharmacology • Clinical Pharmacology • Psychology • Behavioural Therapy • Epidemiology • Cancer Pain • Acute Pain • Clinical Trials.