title: Clinical models to compare the safety and efficacy of inhaled corticosteroids in patients with asthma.
abstract: There is no consensus on the methods to compare the clinical efficacy of different inhaled corticosteroids. A comparison needs to be made in terms of relative potency, and studies should include two-, or preferably, three-dose comparisons. A number of clinical models and outcomes are available; they have their relative advantages and disadvantages. While measurements of symptoms and spirometry are easy and readily available, they show a flat dose-response relationship. Measurements of bronchial hyper-responsiveness to exercise and adenosine monophosphate, allergen-induced airway responses, and measurements of inflammation in sputum and exhaled air show steep dose-response relationships, particularly to low doses of inhaled steroids. An uncontrolled asthma model followed by stabilization with a short course of additional steroid, with measurements of airway responsiveness and airway inflammation, in a crossover study seems more promising than the other models. Drug deposition studies and mathematical modelling of drug pharmacokinetics in the airway may provide complementary information to clinical drug relative potency studies. Fine particle dose and emitted doses, rather than the nominal dose, should be considered in the estimation of clinical and systemic effects, respectively. When a second entry (generic) drug is being evaluated in comparison with the innovator drug (same compound and same device), it may be appropriate to consider accepting a generic as bioequivalent if it satisfies pharmaceutical equivalence.
authors.affiliation: Asthma Research Group, Firestone Institute of Respiratory Health, St Joseph's Healthcare and Department of Medicine, McMaster University, Hamilton, Ontario.
authors.forename: Krishnan
authors.initials: K
authors.lastname: Parameswaran
authors.forename: Richard
authors.initials: R
authors.lastname: Leigh
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Kelly
authors.forename: Charlie H
authors.initials: CH
authors.lastname: Goldsmith
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Hargreave
authors.forename: Myrna
authors.initials: M
authors.lastname: Dolovich
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023381:Endpoint Determination; D005541:Forced Expiratory Volume; D006801:Humans; D015233:Models, Statistical; D010366:Peak Expiratory Flow Rate
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents