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An Endpoint for Worsening Asthma: Development of a Sensitive Measure and its Properties

  • Clinical and Non-Clinical Drug Development
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Abstract

The measurement of clinical efficacy in asthma lacks a validated endpoint for worsening asthma outcome. We propose a standard measure of worsening asthma and investigate its measurement characteristics. Data from two clinical trials were used to develop a composite endpoint that incorporated the following parameters on any study day: (1) decrease from baseline in peak expiratory flow (PEF) of >20%; (2) increase above baseline in β-agonist use of >70% (≥2 puffs/day); (3) increase above baseline in symptom score of >50%; (4) >2 nighttime awakenings; (5) PEF <180 L/min (adults); or (6) oral corticosteroid rescue or unanticipated visits to the physician, emergency room, or hospital. This novel endpoint demonstrated sufficient test/retest reliability (p = 0.67), prospectively exhibited a dose-response profile consistent with different dose levels of mon-telukast (a leukotriene antagonist), and was significantly correlated with forced expiratory volume in one second, quality of life, and global evaluations. The endpoint appears to be a valid and sensitive measure of day-to-day worsening of asthma and is appropriate for use in clinical trials.

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Authors and Affiliations

  1. Clinical Biostatistics and Clinical Research, Merck Research laboratories, Rahway, New Jersey, USA

    Ji Zhang PhD, Cindy Song MS & Theodore F. Reiss MD

Authors
  1. Ji Zhang PhD
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  2. Cindy Song MS
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  3. Theodore F. Reiss MD
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Corresponding author

Correspondence to Ji Zhang PhD.

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Supported by a grant from Merck Research Laboratories.

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Zhang, J., Song, C. & Reiss, T.F. An Endpoint for Worsening Asthma: Development of a Sensitive Measure and its Properties. Ther Innov Regul Sci 38, 5–13 (2004). https://doi.org/10.1177/009286150403800103

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  • DOI: https://doi.org/10.1177/009286150403800103

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