Lederer David J, Bradford Williamson Z, Fagan Elizabeth A, Glaspole Ian, Glassberg Marilyn K, Glasscock Kenneth F, Kardatzke David, King Talmadge E, Lancaster Lisa H, Nathan Steven D, Pereira Carlos A, Sahn Steven A, Swigris Jeffrey J, Noble Paul W
Columbia University Medical Center, New York, NY.
InterMune, Inc, Brisbane, CA.
Chest. 2015 Jul;148(1):196-201. doi: 10.1378/chest.14-2817.
FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF.
Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) study. Sensitivity analyses were conducted to assess whether alternative statistical tests and methods for handling missing data influenced the observed magnitude of treatment effect on the primary end point of change from baseline to week 52 in FVC.
The distribution of FVC change at week 52 was systematically different between the two treatment groups and favored pirfenidone in each analysis. The method used to impute missing data due to death had a marked effect on the magnitude of change in FVC in both treatment groups; however, the magnitude of treatment benefit was generally consistent on a relative basis, with an approximate 50% reduction in FVC decline observed in the pirfenidone group in each analysis.
Our results confirm the robustness of the statistical finding on the primary end point of change in FVC in the ASCEND trial and corroborate the estimated magnitude of the pirfenidone treatment effect in patients with IPF.
ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov.
特发性肺纤维化（IPF）临床试验中的用力肺活量（FVC）结果会受到分析方法和缺失数据处理方式的显著影响。在一项评估吡非尼酮治疗成年IPF患者的3期试验中，我们进行了一系列敏感性分析，以评估关于FVC变化这一主要终点的统计结果的稳健性以及治疗效果大小估计值的稳定性。
源数据包括在“吡非尼酮治疗特发性肺纤维化疗效与安全性评估（ASCEND）”研究中随机接受吡非尼酮或安慰剂治疗的所有555名研究参与者。进行敏感性分析以评估替代统计检验和处理缺失数据的方法是否会影响观察到的从基线到第52周FVC变化这一主要终点的治疗效果大小。
两个治疗组在第52周时FVC变化的分布存在系统性差异，且在每次分析中均有利于吡非尼酮。用于推算因死亡导致的缺失数据的方法对两个治疗组的FVC变化幅度均有显著影响；然而，相对而言治疗益处的大小总体上是一致的，在每次分析中吡非尼酮组FVC下降幅度约降低50%。
我们的结果证实了ASCEND试验中关于FVC变化主要终点的统计结果的稳健性，并确证了吡非尼酮对IPF患者治疗效果的估计大小。
ClinicalTrials.gov；编号：NCT01366209；网址：www.clinicaltrials.gov。
