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Original Research: Diffuse Lung Disease |

Study Design Implications of Death and Hospitalization as End Points in Idiopathic Pulmonary FibrosisStudy End Points in Idiopathic Pulmonary Fibrosis

Harold R. Collard, MD, FCCP; Kevin K. Brown, MD, FCCP; Fernando J. Martinez, MD; Ganesh Raghu, MD, FCCP; Rhonda S. Roberts, MSPH; Kevin J. Anstrom, PhD; for the IPFnet Investigators
Author and Funding Information

From the Department of Medicine (Dr Collard), University of California San Francisco, San Francisco, CA; Department of Medicine (Dr Brown), National Jewish Health, Denver, CO; Department of Medicine (Dr Martinez), University of Michigan, Ann Arbor, MI; Department of Medicine (Dr Raghu), University of Washington, Seattle, WA; and Duke Clinical Research Institute (Ms Roberts and Dr Anstrom), Durham, NC.

CORRESPONDENCE TO: Harold R. Collard, MD, FCCP, Department of Medicine, University of California San Francisco, 505 Parnassus Ave, Box 0111, San Francisco, CA 94143; e-mail: hal.collard@ucsf.edu


Dr Martinez is currently at Weill Cornell Medical Center (New York, NY).

FUNDING/SUPPORT: This study was supported by National Heart, Lung, and Blood Institute [Grants U10HL080513 (data coordinating center), U10HL80413, U10HL80274, U10HL80370, U10HL80371, U10HL80383, U10HL80411, U10HL80509, U10HL80510, U10HL80543, U10HL80571, and U10HL80685 (clinical centers)].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(5):1256-1262. doi:10.1378/chest.14-0492
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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.

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