title: Environmental exposure chambers in allergen immunotherapy trials: Current status and clinical validation needs.
abstract: As required by the European Medicines Agency and the US Food and Drug Administration for pivotal trials involving allergen immunotherapy (AIT) products, clinical efficacy assessment is currently based on double-blind, placebo-controlled field studies with natural allergen exposure during the allergen season. However, this study design is associated with several drawbacks, such as the high variability of allergen exposure in different trial sites or seasons and the presence of confounding environmental factors. On the contrary, environmental exposure chambers (EECs) aim to operate with a stable and reproducible allergen exposure under highly standardized environmental conditions. Technical validation parameters for different EECs worldwide have been published by several groups. However, full clinical validation of EEC study outcomes is required for their classification as an appropriate alternative to natural allergen exposure for AIT product efficacy assessment. Some clinical validation parameters have already been addressed for EEC units. The reliability of provoked symptoms in repeated EEC sessions is high, but the predictive power of EEC settings for the clinical response on natural exposure and the impact of seasonal priming on test results still have to be validated systematically, as does the inter-EEC variability. Thus the authors recommend a continued in-depth validation of EECs to exploit the potential of this technology for future AIT product development.
authors.affiliation: Division of Allergology, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Rösner-Friese
authors.affiliation: Division of Allergology, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany. Electronic address: Susanne.Kaul@pei.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kaul
authors.affiliation: Division of Allergology, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vieths
authors.affiliation: Center for Rhinology and Allergology Wiesbaden and the Department of Otorhinolaryngology, Head and Neck Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: oliver.pfaar@allergiezentrum.org.
authors.forename: Oliver
authors.initials: O
authors.lastname: Pfaar
mesh_terms: D000485:Allergens / Q000276:immunology*; D001273:Atmosphere Exposure Chambers / Q000592:standards*; D002986:Clinical Trials as Topic; D003888:Desensitization, Immunologic / Q000379:methods; D004781:Environmental Exposure; D005060:Europe; D006801:Humans; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D014481:United States; D054928:Validation Studies as Topic
chemical_list: D000485:Allergens
keywords: Environmental exposure chamber; allergen immunotherapy; clinical validation; pivotal studies