Trial emulation with observational data in cystic fibrosis.
Trial emulation with observational data in cystic fibrosis.
复制标题
使用囊性纤维化观察数据进行试验模拟。
DOI：
10.1016/s2213-2600(23)00328-4
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Davies G
中科院分区：
文献类型：
--
作者：
Davies G
囊性纤维化研究和临床护理领域正在迅速变化，但仍有许多未解答的问题。虽然随机对照试验（RCT）是产生治疗效果证据的金标准，但它们有局限性，并不总是可行的。在囊性纤维化跨膜传导调节因子（CFTR）调节剂现已被确立为标准治疗的人群中，其他治疗的预期效应量可能较小，需要更大的样本量才能显示疗效。在不适合CFTR调节剂的患者中，传统RCT的潜在参与者数量可能低于实现足够功效所需的数量。允许较小样本量和增加临床试验参与机会的新颖试验设计受到极大欢迎。1然而，实际上，它们仍然不能满足需求，需要传统RCT的强大的补充替代品。另一种方法是用现有的观察数据模拟RCT。2对囊性纤维化患者的注册数据进行试验模拟，可以评估RCT中无法解决的一系列问题。在治疗环境迅速变化的背景下，这种方法特别具有现实意义。詹姆斯·林德联盟确定优先事项的工作突出表明了尚未回答的问题的广度和复杂性。有几个问题与治疗效果有关，包括十大研究重点列表中的以下内容3（2022年更新）：药物（包括CFTR调节剂）对囊性纤维化的长期影响是什么？有哪些有效的方法可以减轻囊性纤维化患者的治疗负担？图中总结了试验仿真过程。该过程从一个研究问题和一个回答该问题所需的目标试验方案开始。下一步是在进行数据设置和分析的最后一步之前，指定如何使用可用的观察数据模拟目标试验方案的每个元素。RCT的关键要素不能直接用观察数据来模拟，
The field of cystic fibrosis research and clinical care is changing rapidly, yet there remain many unanswered questions. Although randomised controlled trials (RCTs) are the gold standard for generating evidence on the effects of treatment, they have limitations and are not always feasible. In populations in which cystic fibrosis transmembrane conductance regulator (CFTR) modulators are now established as standard care, the anticipated effect sizes for other treatments might be smaller, requiring larger sample sizes to show efficacy. In patients who are ineligible for CFTR modulators, the number of potential participants for traditional RCTs could fall below that required to achieve adequate power. Novel trial designs that permit smaller sample sizes and increased opportunity for clinical trial participation are greatly welcomed. 1 However, realistically they will still not meet demand and robust, complimentary alternatives to the traditional RCT are required. An alternative approach is to emulate an RCT with existing observational data. 2 Trial emulation with registry data for patients with cystic fibrosis offers the possibility of assessing a range of questions that are not feasible to address in RCTs. This approach is particularly topical in the context of a rapidly changing treatment landscape. The breadth and complexity of unanswered questions have been highlighted by the James Lind Alliance priority-setting exercises. Several questions pertain to the effects of treatments, including the following from the list of top 10 research priorities3 (2022 refresh): what are the long-term effects of medications (including CFTR modulators) in cystic fibrosis? What are the effective ways of simplifying the treatment burden of people with cystic fibrosis? The trial emulation process is summarised in the figure. The process begins with a research question and a protocol of the target trial desired to answer that question. The next step is to specify how each element of the target trial protocol is to be emulated with available observational data, before proceeding to the final step of data set-up and analysis. The key element of an RCT that cannot be emulated directly with observational data is the
影响因子：
5
作者：
Hernan, Miguel A.;Robins, James M.
通讯作者：
Robins, James M.
影响因子：
10
作者：
通讯作者：
--
影响因子：
4.6
作者：
Granger, Emily;Keogh, Ruth H.;Frost, Freddy
通讯作者：
Frost, Freddy