Correlation between a pollen challenge chamber and a natural allergen exposure study design for eliciting ocular and nasal symptoms: Early evidence supporting a paradigm shift in drug investigation?

Abstract

Environmental exposure units (EEUs) have been used extensively for well over 25 years. Initially, they were used to investigate occupational exposures but were subsequently adapted to investigate treatment of seasonal allergic rhinitis (SAR) and, more recently, perennial allergic rhinitis with antihistamines, nasal corticosteroids, nasal antihistamines, and immunotherapy. Studies investigating treatments for SAR were able to successfully demonstrate the onset of action and efficacy of these different therapeutic agents compared with placebo. Clinical trials designed with EEUs have several distinct advantages for conducting SAR studies over traditional study designs, which typically are conducted in a park setting over 24 to 48 hours or over a 2to 4-week timeframe during the natural allergy season. First and foremost, the EEU can eliminate confounding variables, such as other potential airborne allergens (eg, mold spores), and environmental factors (eg, air pollution and weather conditions) that cannot be regulated during the natural allergy season. Second, the EEU allows for the delivery of precise levels of airborne pollen in a controlled atmosphere (eg, temperature, humidity, and barometric pressure) to ensure adequate exposure during the study exposure period. This is important because many park studies or longitudinal SAR studies often are hampered by unpredictable pollen levels that can frequently thwart attempts to compare drug efficacy with pollen exposure. Although there are several well-designed EEUs in the United States, Canada, and Europe, there has been little effort thus far to validate the use of these EEUs as surrogates for investigating SAR therapies. A recent workshop that convened June 18, 2010, at the National Institutes of Health in Bethesda, Maryland, to discuss the clinical study design and reliability of outcome measurements of EEUs cited several unmet needs required for validation of EEUs. These included (1) determination of the reproducibility and therefore reliability of EEU clinical trials for assessing treatments for