title: Variability and lack of predictive ability of asthma end-points in clinical trials.
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), beta-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 FEV1 and PEFAM; DSS and FEV1; and DSS and beta-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.
authors.affiliation: Dept of Clinical Biostatistics and Clinical Research, Merck Research Laboratories, Rahway, NJ 07665, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Yu
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: T F
authors.initials: TF
authors.lastname: Reiss
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic