Pizzichini Emilio, Brusselle Guy, Edwards Dawn, Gibson Peter G, Kerstjens Huib A, Moore Alison, Slade David, Wise Robert A, Zhang Shiyuan
GSK, London, UK.
Federal University of Santa Catarina, Santa Catarina, Brazil.
Contemp Clin Trials Commun. 2024 Oct 15;42:101382. doi: 10.1016/j.conctc.2024.101382. eCollection 2024 Dec.
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.
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.
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 β-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.
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.
导入期是随机对照试验的一个重要组成部分，常用于呼吸系统疾病试验。导入期的设计会对结果和数据解读产生重大影响，因此应谨慎设计。
在本综述中，我们描述了六项哮喘三联疗法3A期试验的导入期设计，并讨论了导入期设计的差异（特别是导入期的持续时间、治疗方法以及导入期结果的报告方式）如何可能改变对研究结果的解读。
我们发现导入期的持续时间在2至7周之间，一些研究包括筛查、导入和稳定期的组合，而其他研究仅包括导入期。导入期治疗也有所不同，一些研究让患者继续使用之前的吸入性糖皮质激素/长效β受体激动剂（ICS/LABA）疗法，而其他研究则通过改用治疗期使用的相同ICS/LABA组合或完全不同的ICS/LABA组合来统一治疗。大多数纳入的研究没有报告随机分组前观察到的研究结果有任何变化。
我们讨论了各种试验设计的潜在影响，并建议应精心设计导入期以实现特定研究的目标。我们还建议，对导入期变化进行标准化报告将进一步有助于区分因依从性提高而带来的改善和真正的治疗益处，并有助于比较来自不同临床试验的数据。
