Correlation of airway obstruction and patient-reported endpoints in clinical studies.
To establish the correlation among asthma efficacy parameters over a long period, data from over 1,500 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" beta-agonist 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.
Shingo
S
S
Dept of Clinical Biostatistics, Merck Research Laboratories, Rahway, NJ 07065, USA.
Zhang
J
J
Reiss
T F
TF
D000085:Acetates / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D002986:Clinical Trials as Topic; D003521:Cyclopropanes; D003545:Cysteine / Q000037:antagonists & inhibitors; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D015289:Leukotrienes; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D012123:Pulmonary Ventilation / Q000187:drug effects*; D011804:Quinolines / Q000627:therapeutic use; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011804:Quinolines; D013440:Sulfides; C112381:cysteinyl-leukotriene; D003545:Cysteine; C093875:montelukast