Study design implications of death and hospitalization as end points in idiopathic pulmonary fibrosis.

Published

Journal Article

BACKGROUND: The feasibility of an interventional clinical trial in idiopathic pulmonary fibrosis (IPF) using death and hospitalization as primary end points is an area of uncertainty. Using data from a large well-characterized clinical trial population, this article aims to illustrate the impact of cohort enrichment and study duration on sample size requirements for IPF clinical trials in which death alone or death plus hospitalization serve as the primary end point. METHODS: Event rate estimates for death and hospitalization were determined from patients enrolled in National Institutes of Health-sponsored IPF Clinical Research Network clinical trials. Standard equations were applied to estimate the total sample size required for varying gender, age, and pulmonary function (GAP) stage-based cohorts. RESULTS: Risk estimates for death and hospitalization in the clinical trial cohort were substantially lower than those published. An IPF trial with death as its primary end point enrolling subjects designated as GAP stage 1 and 2 over 1 year with a minimum follow-up of 1 year would require an estimated 7,986 subjects to achieve 90% power for a hazard ratio of 0.70. Alternatively, an IPF trial with death plus hospitalization as its primary end point enrolling subjects with GAP stage 2 and 3 over 2 years with a minimum follow-up of 1 year would require an estimated 794 subjects for the same power and hazard ratio. CONCLUSIONS: Study design decisions, in particular cohort enrichment strategies, have a substantial impact on sample size requirements for IPF clinical trials using time-to-event primary end points such as death and death plus hospitalization.

Full Text

Duke Authors

Cited Authors

  • Collard, HR; Brown, KK; Martinez, FJ; Raghu, G; Roberts, RS; Anstrom, KJ

Published Date

  • November 2014

Published In

Volume / Issue

  • 146 / 5

Start / End Page

  • 1256 - 1262

PubMed ID

  • 25144827

Pubmed Central ID

  • 25144827

Electronic International Standard Serial Number (EISSN)

  • 1931-3543

Digital Object Identifier (DOI)

  • 10.1378/chest.14-0492

Language

  • eng

Conference Location

  • United States