Chest
Original ResearchDiffuse Lung DiseaseSensitivity Analyses of the Change in FVC in a Phase 3 Trial of Pirfenidone for Idiopathic Pulmonary Fibrosis
Section snippets
Patients
All study participants who were randomized to treatment with pirfenidone 2,403 mg/d (n = 278) or placebo (n = 277) in the ASCEND study were included in the analyses. Eligibility criteria for the ASCEND study have been previously described.1 Briefly, eligible patients were between the ages of 40 and 80 years with a centrally confirmed diagnosis of IPF at least 6 months prior to randomization. Physiologic eligibility criteria included a baseline percent predicted FVC ≥ 50% and ≤ 90%, percent
Results
A total of 555 patients were included in the analysis. The proportion of patients with missing FVC data at the week 52 study visit is summarized in Table 1. A total of 482 patients (86.6%) completed an FVC assessment at the week 52 study visit (243 [87.4%] in the pirfenidone group and 239 [86.3%] in the placebo group). Fewer patients in the pirfenidone group compared with placebo had a missing value due to death (11 [4.0%] vs 20 [7.2%]), and slightly more patients in the pirfenidone group
Discussion
We found a consistent and statistically persuasive treatment effect of pirfenidone on the change in FVC in patients with IPF in multiple sensitivity analyses using a variety of statistical tests and data imputation methods. In each analysis, the distribution of FVC change from baseline to week 52 in the ASCEND trial was systematically different between the treatment groups and favored treatment with pirfenidone. The strength of the statistical finding was consistent across all analyses and was
Conclusions
In conclusion, our results confirm the robustness of the statistical finding on the primary end point of change from baseline to week 52 in percent predicted FVC in the ASCEND study and corroborate the estimated magnitude of the pirfenidone treatment effect on FVC change in patients with IPF. Additionally, our findings demonstrate the effect of various analytic methods and data imputation strategies on the magnitude of change in FVC, thereby providing benchmarks to facilitate comparisons with
Acknowledgments
Author contributions: D. J. L. is the guarantor of the manuscript and takes responsibility for the integrity of the data and the accuracy of the data analysis. D. J. L., W. Z. B., E. A. F., I. G., M. K. G., D. K., T. E. K., L. H. L., S. D. N., C. A. P., S. A. S., J. J. S., and P. W. N. contributed to the conception and design of the ASCEND study, as well as the acquisition and interpretation of original data, approved the final draft, and vouch for the accuracy of the overall content of the
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2022, The Lancet Digital HealthCitation Excerpt :Evaluation of disease progression in clinical trials and observational studies in patients with idiopathic pulmonary fibrosis is often hampered by missing data on lung function,6–9 affecting the power and accuracy of statistical models for assessing decline of lung function.4,5,10,11 As idiopathic pulmonary fibrosis progresses, missed spirometry visits promote survivor bias by raising the mean FVC because missing values are associated with exacerbation of the condition or mortality among patients.6–8 To mitigate this bias, previous studies have used various methods to adjust for data loss.4–7,10,11
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2017, Revue des Maladies RespiratoiresCitation Excerpt :There was no significant difference in terms of scores of dyspnea, all-cause mortality or IPF mortality [83]. A sensitivity analysis has confirmed the robustness of the statistical difference between pirfenidone and placebo in terms of FVC evolution [86]. A pooled analysis of the CAPACITY and ASCEND trials has shown that, compared to placebo, pirfenidone significantly decreased by 48% the risk of death (HR 0.52; 95% CI: 0.31–0.87; P = 0.01), both in terms of all-cause deaths (P = 0.01) and IPF deaths (P = 0.006) [83].
FUNDING/SUPPORT: This study was sponsored by InterMune (Brisbane, CA).
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