Department of Medicine, University of Calgary, Calgary, Canada.
Seattle Children's Research Institute, Seattle, WA USA.
J Cyst Fibros. 2023 Jul;22(4):669-673. doi: 10.1016/j.jcf.2023.05.014. Epub 2023 Jun 5.
Although work to date in cystic fibrosis (CF) has elucidated frequencies and characteristics of adverse events, the accuracy of attribution of relatedness to study drug by investigators has not been assessed. We aimed to determine whether there was an association of attribution by group allocation in CF clinical trials.
We conducted a secondary analysis from 4 CF trials of all persons who experienced an AE. Our primary outcome was the odds of an AE related to active study drug and predictor of interest was the treatment allocation. We constructed a multivariable generalized estimating equation model allowing for repeated measures.
A total of 785 subjects (47.5% female, mean age 12 years) had 11,974 AEs, of which 430 were serious. AE attribution was greater with receipt of active study drug as compared to placebo but did not reach statistical significance (OR 1.38, 95% CI 0.98-1.82). Significantly associated factors included female sex (OR 0.58, 95% 0.39-0.87), age (OR 1.24, 95% CI 1.06-1.46) and baseline lung function (per 10%, OR 1.16, 95% CI 1.05-1.28).
In our large study, there was a non-significant but greater odds of AE attribution (a key element of clinical trial reporting) to active study drug based on assigned treatment to study drug or control which suggests that there is a trend in physicians to attribute blinded safety data to the active drug. Interestingly, females were less likely to have AE attribution to study drug and warrants further work in development and validation of monitoring guidelines and processes.
尽管迄今为止在囊性纤维化（CF）中的研究已经阐明了不良事件的频率和特征，但研究人员归因于研究药物的相关性的准确性尚未得到评估。我们旨在确定 CF 临床试验中分组分配是否与归因有关。
我们对 4 项 CF 试验中的所有出现 AE 的人进行了二次分析。我们的主要结局是与活性研究药物相关的 AE 的可能性，预测指标是治疗分配。我们构建了一个多变量广义估计方程模型，允许重复测量。
共有 785 名受试者（47.5%为女性，平均年龄为 12 岁）发生了 11974 次 AE，其中 430 次为严重 AE。与接受安慰剂相比，接受活性研究药物的 AE 归因更大，但未达到统计学意义（OR 1.38，95%CI 0.98-1.82）。显著相关的因素包括女性（OR 0.58，95%CI 0.39-0.87）、年龄（OR 1.24，95%CI 1.06-1.46）和基线肺功能（每 10%，OR 1.16，95%CI 1.05-1.28）。
在我们的大型研究中，根据分配给研究药物或对照药物的治疗，AE 归因（临床试验报告的关键要素）与活性研究药物的可能性更大，但无统计学意义，这表明医生有将盲法安全性数据归因于活性药物的趋势。有趣的是，女性不太可能将 AE 归因于研究药物，这需要进一步制定和验证监测指南和流程。
