Full text not available from this repository.

Abstract

Background: Frequency of moderate and severe chronic obstructive pulmonary disease exacerbations is animportant endpoint in clinical trials, but makes them large and lengthy when powered to evaluate it. We aimedto develop a composite endpoint (COPDCompEx) that could predict treatment effect on exacerbations, enablingthe design of shorter early phase clinical trials requiring fewer patients.Methods: In this post hoc analysis, data from 20 randomized controlled trials were used to develop and testCOPDCompEx. Diary events were tested against predefined threshold values for peak expiratory flow, relievermedication use, and symptoms. A COPDCompEx event was defined as first occurrence of a diary event, amoderate or severe exacerbation, or a study dropout. Ratios of event frequency, treatment effect and future trialsample size were compared between COPDCompEx and moderate and severe exacerbations.Findings: At 3 months, the proportion of patients experiencing COPDCompEx events increased over 3-fold versusexacerbations alone. All components contributed to COPDCompEx event rate. Treatment effects at 3 monthswere closely matched between COPDCompEx and exacerbations, and the large net gain in power substantiallyreduced the required sample size.Interpretation: may be used to predict treatment effect on moderate and severe exacerbations ofchronic obstructive pulmonary disease. This may enable the design of shorter Phase 2 clinical trials requiringfewer patients when compared with current exacerbation studies, with exacerbations as a key Phase 3 endpoint.This would, therefore, allow more efficient decision-making with reduced burden and risk to study participants.

Item Type:	Article
Authors/Creators:	Vogelmeier, CF and Fuhlbrigge, A and Jauhiainen, A and Scheepers, LEJM and Bengtsson, T and Peterson, S and Karlsson, N and Sethi, T and Locantore, N and Tal-Singer, R and Rennard, S and Fageras, M and Da Silva, CA
Keywords:	COPD, clinical trial endpoints, exacerbation, treatment effect, drug development
Journal or Publication Title:	Respiratory Medicine
Publisher:	W B Saunders Co Ltd
ISSN:	0954-6111
DOI / ID Number:	10.1016/j.rmed.2020.106175
Copyright Information:	Copyright 2020 Elsevier Ltd.
Item Statistics:	View statistics for this item

Actions (login required)

Item Control Page