HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Permissions Request Permissions Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (32) Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Articles by Reiss, T.F. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by Reiss, T.F.

Variability and lack of predictive ability of asthma end-points in clinical trials

Depts of ¹ Clinical Biostatistics and ³ Clinical Research, Merck Research Laboratories, Rahway, NJ, USA. ² Respiratory, Cell and Molecular Biology Research Division, School of Medicine, University of Southampton, Southampton, UK

CORRESPONDENCE: T. Reiss, Merck Research Laboratories, Pulmonary-Immunology, Mail code RY34B-328, Rahway, NJ 07065, USA. Fax: 1 7325947830. E-mail: theodore_reiss@merck.com

Keywords: asthma, montelukast, predictability of response, variability of asthma

Received: November 29, 2001
Accepted June 20, 2002

This study was supported by a grant from the Merck Research Laboratories.

While a consensus definition of the clinical parameters important in asthma control exists, an adequate objective definition of a response to asthma treatment and parameters for prediction of that response remain undefined. Given that asthma is a complex biological disease and that different parameters may measure dissimilar aspects of the disease status, this study assessed the relationship among several end-points of asthma control, and attempted to select a combination of variables measured before (baseline characteristics) or early in asthma therapy which would be predictive of a long-term clinical response.

Data from two previously reported clinical studies which included montelukast, inhaled beclomethasone, and placebo in mild-to-moderate asthmatics (n=1,576) were analysed. The forced expiratory volume in one second (FEV₁), daily symptoms score (DSS), ß-agonist use, and morning peak expiratory flow (PEF_AM) were recorded during the baseline period and throughout the 12-week treatment period.

For the long-term response, as measured during the last 9 weeks of treatment, there was a large within-patient variability and no more than a moderate correlation between the changes in FEV₁ and PEF_AM; DSS and FEV₁; and DSS and ß-agonist use. The overall predictive values for FEV₁ and DSS were 70–80%.

The results showed that multiple measurements over a length of time are needed to establish a more complete profile of response, and that demographic and early treatment responses had a small but inadequate ability to predict future response. This study demonstrates the complex relationship among asthma end-points and the difficulty of reliably estimating long-term response using common, surrogate clinical markers of asthma control.

This article has been cited by other articles:

				H. K. Reddel, D. R. Taylor, E. D. Bateman, L.-P. Boulet, H. A. Boushey, W. W. Busse, T. B. Casale, P. Chanez, P. L. Enright, P. G. Gibson, et al. An Official American Thoracic Society/European Respiratory Society Statement: Asthma Control and Exacerbations: Standardizing Endpoints for Clinical Asthma Trials and Clinical Practice Am. J. Respir. Crit. Care Med., July 1, 2009; 180(1): 59 - 99. [Abstract] [Full Text] [PDF]

				C. Thamrin, G. Stern, M-P. F. Strippoli, C. E. Kuehni, B. Suki, D. R. Taylor, and U. Frey Fluctuation analysis of lung function as a predictor of long-term response to {beta}2-agonists Eur. Respir. J., March 1, 2009; 33(3): 486 - 493. [Abstract] [Full Text] [PDF]

				L. M. Graham Classifying Asthma Chest, July 1, 2006; 130(1_suppl): 13S - 20S. [Abstract] [Full Text] [PDF]

				J. F. Donohue and J. A. Ohar Effects of Corticosteroids on Lung Function in Asthma and Chronic Obstructive Pulmonary Disease Proceedings of the ATS, November 1, 2004; 1(3): 152 - 160. [Abstract] [Full Text] [PDF]

				D K C Lee and S A Green Urinary leukotriene LTE4 levels in non-responders to antileukotriene therapy Thorax, August 1, 2004; 59(8): 727 - 727. [Full Text] [PDF]

				B. Suki and U. Frey Temporal dynamics of recurrent airway symptoms and cellular random walk J Appl Physiol, November 1, 2003; 95(5): 2122 - 2127. [Abstract] [Full Text] [PDF]

				D.A. Stempel Asthma variability Eur. Respir. J., May 1, 2003; 21(5): 909 - 910. [Full Text] [PDF]

				J. Zhang, C. Yu, S.T. Holgate, and T.F. Reiss From the Authors Eur. Respir. J., May 1, 2003; 21(5): 909 - 910. [Full Text] [PDF]