Some Aspects on Comparative Efficacy Studies with Inhaled Corticosteroids in Asthma

Olof      Selroos

Abstract

This review evaluates dose-response and comparative studies with inhaled corticosteroids (ICS) in asthma. A dose-response relationship for lung function variables has been demonstrated for some ICS, but not for all. Measurements of anti-inflammatory properties, e.g. bronchial challenge with adenosine 6-monophosphate, may provide better possibilities to detect dose-response relationships and differences between ICS. Studies with the same ICS delivered by different inhalers with different lung deposition characteristics show that efficacy is strongly related to the amount of drug deposited in the airways. Comparative studies with different ICS using different inhalers have often used doses resulting in effects at the top of the dose-response curve. However, a lack of statistically significant difference between treatments does not mean therapeutic equivalence. Comparative clinical studies should be performed with dose-response curves of both products and the relative dose ratio should be estimated. The minimum criterion is to use one dose of one product and fit the result of that treatment to a dose-response curve of the other. Down titration represents an alternative, clinically reliable study design. Clinically relevant differences between doses and treatments should be defined prior to the study; a proper power calculation has to be performed; and comparisons should be made on the dose scale rather than the effect scale.

Keywords: Asthma, comparative studies, dose scale, dose-response, down titration, single-dose comparison

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