Correlation of airway obstruction and patient-reported endpoints in clinical studies

Abstract

To establish the correlation among asthma efficacy parameters over a long period, data from over 1500 patients in two one-year asthma clinical trials with montelukast, a Cys-LT1 antagonist, were analysed. Airway obstruction measurements, forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF), were measured at clinic visits. Patients recorded daytime symptom score, "as-needed" bagonist use, and PEF on a daily basis.Relationships among these parameters at baseline and during the one-year treatment period were established by correlation analyses. Multiple correlations between the airway obstruction (FEV1 and PEF) and patient-reported measurements were evaluated by canonical correlation analysis.Pairwise correlations of the efficacy parameters over a one-year time period were stable. Canonical correlation between the airway obstruction and patient-reported asthma efficacy endpoints was low, indicating that each category of endpoints measures a distinctively different aspect of the disease.It appears that at least one endpoint from each category should be used in asthma clinical studies. Eur Respir J 2001; 17: 220-224. Asthma is a variable and multifaceted disease. Many efficacy endpoints are measured and reported in asthma clinical trials. Cross-sectional correlations among the most commonly used asthma-related endpoints such as forced expired volume in one second (FEV1), peak expiratory flow (PEF), "as-needed" b-agonist use, and daytime and night-time symptoms have been explored, mostly in a small group of patients over short periods of time, and mild to moderate correlations have been observed [1 -3]. This paper investigates the relationship (over a oneyear period) among the endpoints of FEV1, PEF, "asneeded" b-agonist use, and daytime symptoms, and the relationship between the pulmonary function measurements (FEV1, PEF) and patient-reported efficacy measurement endpoints (daytime symptom, "asneeded" b-agonist use). The relationships were investigated based on a large data set collected over a one-year period, from 1576 patients who entered two large clinical trials, which were conducted as multi-centre, double-blind, placebo-controlled studies to determine the safety, tolerability, and efficacy of one-year continuous treatment of montelukast, a Cys-LT1 antagonist [4,5]. The relationships among these endpoints will provide more information about this multifaceted disease and establish the multi-dimensionality of these endpoints. Methods Study designStudy 1 was a multi-centre, double-blind, parallelgroup, placebo-controlled study comparing montelukast (MNT), inhaled beclomethasone (ICS) and placebo (table 1). The study consisted of a 2-week single-blind placebo run-in period (I), a 12-week, double-blind, active treatment period (II) and a 3-week, double-blind washout period (III). Patients taking concomitant oral theophylline (limited to approximately 25% of patients) were allowed to continue this medication at a constant dose. At the end of Period II, a prespecified subset of patien...

Asthma symptoms in Hispanic children and daily ambient exposures to toxic and criteria air pollutants.

“…This is particularly likely if the patient has been using as-needed β-agonist inhalers. In a large study of more than 1,500 patients in clinical trials, correlation coefficients between airway obstruction (FEV 1 and PEF) and patient-reported end points (asthma symptoms and as-needed β-agonist use) was low (-0.13 to -0.23) (Shingo et al 2001). The within-subject Spearman rank correlations between evening PEF and ordinal symptom score in the present study ranged widely, from 0.46 to -0.62 (mean, -0.07).…”

Evaluation and Comparison of Respiratory Symptoms and Lung Capacities in Tile and Ceramic Factory Workers of Yazd

“…Individuals with impaired lung function do not always have more respiratory symptoms, but a correlation between these two has already been reported (26). The presence of chemical vapours, fumes, odours and other mineral dusts, should also be taken into account, as they may contribute to the respiratory effects.…”

Categorizing Asthma Severity: An Overview of National Guidelines

“…This intuitively makes sense to the clinician, but is difficult to support scientifically because numerous studies have shown that there is poor correlation between reporting of asthma symptoms and objective measures of lung function. 36,38,39 Other observations make it difficult to support scaling symptoms and lung function in the same way. Patients cannot reliably predict changes in their lung function based on the symptoms they experience 40 and physicians cannot accurately predict lung function from examinations of patients with asthma.…”