Background Cystic fibrosis (CF) is a life-threatening genetic disease, affecting around 10 500 people in the UK. Precision medicines have been developed to treat specific CF-gene mutations. The newest, elexacaftor/tezacaftor/ivacaftor (ELEX/TEZ/IVA), has been found to be highly effective in randomised controlled trials (RCTs) and became available to a large proportion of UK CF patients in 2020. Understanding the potential health economic impacts of ELEX/TEZ/IVA is vital to planning service provision. Methods We combined observational UK CF Registry data with RCT results to project the impact of ELEX/TEZ/IVA on total days of intravenous (IV) antibiotic treatment at a population level. Registry data from 2015 to 2017 were used to develop prediction models for IV days over a 1-year period using several predictors, and to estimate 1-year population total IV days based on standards of care pre-ELEX/TEZ/IVA. We considered two approaches to imposing the impact of ELEX/TEZ/IVA on projected outcomes using effect estimates from RCTs: approach 1 based on effect estimates on FEV1% and approach 2 based on effect estimates on exacerbation rate. Results ELEX/TEZ/IVA is expected to result in significant reductions in population-level requirements for IV antibiotics of 16.1% (~17 800 days) using approach 1 and 43.6% (~39 500 days) using approach 2. The two approaches require different assumptions. Increased understanding of the mechanisms through which ELEX/TEZ/IVA acts on these outcomes would enable further refinements to our projections. Conclusions This work contributes to increased understanding of the changing healthcare needs of people with CF and illustrates how Registry data can be used in combination with RCT evidence to estimate population-level treatment impacts. Data may be obtained from a third party and are not publicly available. This work used anonymised data from the UK Cystic Fibrosis Registry, which has Research Ethics Approval (REC Ref: 07/Q0104/2). The use of the data was approved by the Registry Research Committee (Data Request Reference 382). Data are available following application to the Registry Research Committee ().

中文翻译：

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使用患者登记数据结合随机试验的治疗效果，预测三重 CFTR 调节剂疗法对囊性纤维化静脉内抗生素需求的影响

背景 囊性纤维化 (CF) 是一种危及生命的遗传病，影响英国约 10500 人。已经开发出精准药物来治疗特定的 CF 基因突变。最新的 elexacaftor/tezacaftor/ivacaftor (ELEX/TEZ/IVA) 在随机对照试验 (RCT) 中被发现非常有效，并于 2020 年可供大部分英国 CF 患者使用。了解潜在的健康经济影响ELEX/TEZ/IVA 对于规划服务提供至关重要。方法 我们将观察性英国 CF 登记数据与 RCT 结果相结合，以预测 ELEX/TEZ/IVA 对人口水平静脉内 (IV) 抗生素治疗总天数的影响。2015 年至 2017 年的注册数据用于使用多个预测因子开发 1 年期间 IV 天数的预测模型，并根据 ELEX/TEZ/IVA 前的护理标准估计 1 年人口总 IV 天数。我们考虑了两种方法来使用 RCT 的效应估计将 ELEX/TEZ/IVA 的影响强加于预期结果：方法 1 基于 FEV1% 的效应估计，方法 2 基于对恶化率的效应估计。结果 ELEX/TEZ/IVA 预计使用方法 1 和使用方法 2 分别使 IV 抗生素的人群需求量显着减少 16.1%（~17 800 天）和 43.6%（~39 500 天）。这两种方法需要不同的假设。增加对 ELEX/TEZ/IVA 作用于这些结果的机制的理解将使我们的预测进一步完善。结论 这项工作有助于加深对 CF 患者不断变化的医疗保健需求的理解，并说明如何将注册数据与 RCT 证据结合使用，以估计人群水平的治疗影响。数据可能从第三方获得，并且不公开。这项工作使用了来自英国囊性纤维化登记处的匿名数据，该登记处获得了研究伦理批准（REC Ref：07/Q0104/2）。数据的使用得到了注册研究委员会的批准（数据请求参考 382）。向注册研究委员会提出申请后即可获得数据（具有研究伦理批准（REC Ref：07/Q0104/2）。数据的使用得到了注册研究委员会的批准（数据请求参考 382）。向注册研究委员会提出申请后即可获得数据（具有研究伦理批准（REC Ref：07/Q0104/2）。数据的使用得到了注册研究委员会的批准（数据请求参考 382）。向注册研究委员会提出申请后即可获得数据（).