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

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Abstract
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), β-agonist use, and morning peak expiratory flow (PEFAM) 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 FEV1and PEFAM; DSS and FEV1; and DSS and β-agonist use. The overall predictive values for FEV1and 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.