Sensitivity analyses of the change in FVC in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis

David J. Lederer, Williamson Z. Bradford, Elizabeth A. Fagan, Ian Glaspole, Marilyn K Glassberg Csete, Kenneth F. Glasscock, David Kardatzke, Talmadge E. King, Lisa H. Lancaster, Steven D. Nathan, Carlos A. Pereira, Steven A. Sahn, Jeffrey J. Swigris, Paul W. Noble

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)196-201
Number of pages6
JournalChest
Volume148
Issue number1
DOIs
StatePublished - Jul 1 2015

Fingerprint

Idiopathic Pulmonary Fibrosis
Therapeutics
Information Storage and Retrieval
pirfenidone
Placebos
Clinical Trials
Safety

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Lederer, D. J., Bradford, W. Z., Fagan, E. A., Glaspole, I., Glassberg Csete, M. K., Glasscock, K. F., ... Noble, P. W. (2015). Sensitivity analyses of the change in FVC in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis. Chest, 148(1), 196-201. https://doi.org/10.1378/chest.14-2817

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 journalArticle

Lederer, DJ, Bradford, WZ, Fagan, EA, Glaspole, I, Glassberg Csete, MK, Glasscock, KF, Kardatzke, D, King, TE, Lancaster, LH, Nathan, SD, Pereira, CA, Sahn, SA, Swigris, JJ & Noble, PW 2015, 'Sensitivity analyses of the change in FVC in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis', Chest, vol. 148, no. 1, pp. 196-201. https://doi.org/10.1378/chest.14-2817
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. / Sensitivity analyses of the change in FVC in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis. In: Chest. 2015 ; Vol. 148, No. 1. pp. 196-201.
@article{a5371ec268ab4a24a693d2611a0369ff,
title = "Sensitivity analyses of the change in FVC in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis",
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",
author = "Lederer, {David J.} and Bradford, {Williamson Z.} and Fagan, {Elizabeth A.} and Ian Glaspole and {Glassberg Csete}, {Marilyn K} and Glasscock, {Kenneth F.} and David Kardatzke and King, {Talmadge E.} and Lancaster, {Lisa H.} and Nathan, {Steven D.} and Pereira, {Carlos A.} and Sahn, {Steven A.} and Swigris, {Jeffrey J.} and Noble, {Paul W.}",
year = "2015",
month = "7",
day = "1",
doi = "10.1378/chest.14-2817",
language = "English (US)",
volume = "148",
pages = "196--201",
journal = "Chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "1",

}

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

UR - http://www.scopus.com/inward/record.url?scp=84937574973&partnerID=8YFLogxK

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 -