Run-in periods and treatment outcomes in asthma trials: A narrative review

IF 1.4 Q4 MEDICINE, RESEARCH & EXPERIMENTAL

Contemporary Clinical Trials Communications Pub Date : 2024-10-15 DOI:10.1016/j.conctc.2024.101382

Emilio Pizzichini , Guy Brusselle , Dawn Edwards , Peter G. Gibson , Huib A. Kerstjens , Alison Moore , David Slade , Robert A. Wise , Shiyuan Zhang

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引用次数: 0

Abstract

Background

The run-in period is an important element of randomized controlled trials, and is often used in respiratory disease trials. The design of the run-in period can greatly impact results and data interpretation, and as such should be designed carefully.

Methods

In this review, we describe the design of run-in periods across six phase 3A trials of triple therapy in asthma, and discuss how differences in run-in period design (specifically the duration, treatment, and reporting of run-in results) may have the potential to alter the interpretation of study outcomes.

Results

We found that the duration of run-in periods ranged between 2 and 7 weeks, with some studies including a combination of screening, run-in and stabilization periods, and others including a run-in period only. Run-in treatment also varied, with some studies running in patients on their previous inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) therapy, and others harmonizing treatment by switching to the same ICS/LABA combination used in the on-treatment phase, or a different ICS/LABA combination entirely. Most of the studies included did not report any changes to study outcomes seen prior to randomization.

Conclusion

We discuss the potential implications associated with the various trial designs, and propose that run-in periods should be consciously designed to meet the goals of the specific study. We also propose that standardized reporting of run-in changes would further allow for differentiation between improvements due to improved adherence and true treatment benefits, and aid with comparing data from different clinical trials.

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哮喘试验中的运行期和治疗结果：叙述性综述

背景磨合期是随机对照试验的重要组成部分，通常用于呼吸系统疾病试验。方法在本综述中，我们描述了六项哮喘三联疗法 3A 期试验的磨合期设计，并讨论了磨合期设计的差异（特别是磨合期的持续时间、治疗和结果报告）可能会如何改变研究结果的解释。结果我们发现，磨合期的持续时间从2周到7周不等，有些研究包括筛选期、磨合期和稳定期，有些研究只包括磨合期。磨合期的治疗方法也不尽相同，有些研究让患者继续使用之前的吸入性皮质类固醇/长效β2-受体激动剂（ICS/LABA）治疗，而有些研究则通过改用与在治疗阶段相同的 ICS/LABA 组合或完全不同的 ICS/LABA 组合来协调治疗。结论我们讨论了与各种试验设计相关的潜在影响，并建议应有意识地设计磨合期，以实现特定研究的目标。我们还建议，对运行期的变化进行标准化报告将进一步区分因依从性提高而带来的改善和真正的治疗效果，并有助于比较不同临床试验的数据。

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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来源期刊

Contemporary Clinical Trials Communications Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

2.70

自引率

6.70%

发文量

146

审稿时长

20 weeks

期刊介绍： Contemporary Clinical Trials Communications is an international peer reviewed open access journal that publishes articles pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from a wide range of disciplines including medicine, life science, pharmaceutical science, biostatistics, epidemiology, computer science, management science, behavioral science, and bioethics. Contemporary Clinical Trials Communications is unique in that it is outside the confines of disease specifications, and it strives to increase the transparency of medical research and reduce publication bias by publishing scientifically valid original research findings irrespective of their perceived importance, significance or impact. Both randomized and non-randomized trials are within the scope of the Journal. Some common topics include trial design rationale and methods, operational methodologies and challenges, and positive and negative trial results. In addition to original research, the Journal also welcomes other types of communications including, but are not limited to, methodology reviews, perspectives and discussions. Through timely dissemination of advances in clinical trials, the goal of Contemporary Clinical Trials Communications is to serve as a platform to enhance the communication and collaboration within the global clinical trials community that ultimately advances this field of research for the benefit of patients.