Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov
| Original language | English (US) |
|---|---|
| Pages (from-to) | 196-201 |
| Number of pages | 6 |
| Journal | Chest |
| Volume | 148 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 1 2015 |
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ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
- Cardiology and Cardiovascular Medicine
Cite this
Sensitivity analyses of the change in FVC in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis. / Lederer, David J.; Bradford, Williamson Z.; Fagan, Elizabeth A.; Glaspole, Ian; Glassberg Csete, 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.
In: Chest, Vol. 148, No. 1, 01.07.2015, p. 196-201.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sensitivity analyses of the change in FVC in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis
AU - Lederer, David J.
AU - Bradford, Williamson Z.
AU - Fagan, Elizabeth A.
AU - Glaspole, Ian
AU - Glassberg Csete, Marilyn K
AU - Glasscock, Kenneth F.
AU - Kardatzke, David
AU - King, Talmadge E.
AU - Lancaster, Lisa H.
AU - Nathan, Steven D.
AU - Pereira, Carlos A.
AU - Sahn, Steven A.
AU - Swigris, Jeffrey J.
AU - Noble, Paul W.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov
AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov
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UR - http://www.scopus.com/inward/citedby.url?scp=84937574973&partnerID=8YFLogxK
U2 - 10.1378/chest.14-2817
DO - 10.1378/chest.14-2817
M3 - Article
C2 - 25856121
AN - SCOPUS:84937574973
VL - 148
SP - 196
EP - 201
JO - Chest
JF - Chest
SN - 0012-3692
IS - 1
ER -