Asthma stability after oral prednisone - A clinical model for comparing inhaled steroid potency

Clinical studies comparing the potency of inhaled corticosteroids require s teep dose-response slopes (b) and minimal response variability (s), as stat istical power is inversely related to the s/b ratio. To evaluate a new stud y model, we performed a randomized, crossover study of 12 adult asthmatics who required 800 to 2,000 mug of inhaled corticosteroids daily, and calcula ted s/b for 21 raw clinical outcomes and 36 mathematically derived variable s based on these raw outcomes. Each of two 21-d treatment periods was prece ded by 4 to 7 d of oral prednisone to maximize asthma control and minimize carry-over of previous inhaled treatment. Treatments were 100 and 800 mu /d of an HIFA-134a beclomethasone dipropionate formulation. Assessments inclu ded daily home spirometry, histamine challenge, inhaled albuterol use, and asthma symptom scores. Efficacy variables with the greatest power (lowest s /b values) were A.M.FEF25-75, A.M.FEV1, and A.M.PEF, (s/b = 0.46, 0.48, and 0.59). Carry-over between treatment periods was not significant. Crossover study sample size calculations using these ratios yielded samples of 23, 2 5, and 37 patients, respectively. Otherwise identical parallel studies woul d require sample sizes of 657, 1,438, and 2,261 patients. These results sup port the use of a crossover asthma stability model after a short course of oral prednisone as a clinical study model for comparing topical potency of inhaled corticosteroids.