To present and analyse primary model designs to optimise the effects of observational allergy trials and to emphasise the latest results of testing networks sponsored by NIAID was the purpose of this study. Three principles are discussed. In the first instance, benefit from prospective longitudinal retrospective trials, which show the latest seasonal results on all rhinitis phenotypes in children with asthma, as well as the preventive impact, in the first year of life, of high-home dust allergen content on asthma growth at age seven. Second, the benefits of extensive (deep) phenotyping, which is shown by the discovery of a MALT1 gene as a powerful genetic connection with peanut allergy and the establishment of a separate skin endotype relative to atopic dermatitis by atopic food allergy. Third, the advantage of study that results in hypotheses in combination with future design and profound phenotypes, as shown by exposing alternative pathophysiological mechanisms to asthma exacerbations in children during a ‘cold.’

If well-designed, observational research can have great effects. Three key design topics that must be addressed during the implementation of the study are longitudinal design, profound phenotyping, and hypothesis generating testing.