Establishing the onset of action of intranasal corticosteroids: is there an ideal study design?

Intranasal corticosteroids (INs) are considered the most effective pharmaceutical treatments for nasal allergic rhinitis (AR) symptoms and are recommended as first-line therapy for moderate-to-severe symptoms. United States Food and Drug Administration (FDA) guidelines for clinical development of drug products for AR describe three study types used to determine medication onset of action: (1) standard phase 3 efficacy studies, (2) park-setting studies, and (3) environmental exposure chamber studies. This study was designed to review the U.S. FDA guidelines and discuss published studies of each type examining INS onset of action. Medline searches were conducted using the terms "onset of action" and each of the following: "beclomethasone," "budesonide," "ciclesonide," "fluticasone furoate," "fluticasone propionate," "mometasone furoate," and "triamcinolone." Studies included in the analysis were of subjects with seasonal or perennial AR; were double-blind, placebo-controlled, and randomized; and reported onset-of-action data. Published studies of all three types describing INS onset of action vary widely in compliance with guideline recommendations and in the calculated onset of these medications. The usefulness of the study types used to assess AR therapies-standard efficacy, park setting, and environmental exposure chamber-can be assessed based on each study's ability to reproduce real-world settings, limit variability of allergen exposure, limit variation in study design, and ensure patient adherence to study drug. Studies conducted in an environmental exposure chamber to determine onset of action for INSs may be of superior design because outcomes are significantly less variable and more reproducible than those of other types.