Design and Analysis of Studies to Assess the Effect of Inhaled Corticosteroids on Growth

Assessment of child growth is problematic: growth is nonlinear in the long-term, and unpredictable in the short-term; growth is subject to a number of environmental as well as genetic influences; and growth is difficult to measure reliably. The potential for growth delay as an effect of asthma is established, although it has proved difficult to quantify how great an impact this has on height, growth velocity, or final attained height. In the treatment of asthmatic children, there remain uncertainties as to the effect of inhaled corticosteroids on growth, given the great number of factors affecting growth. In this paper we present recommendations for the design and analysis of trials to assess the effect of regular treatment with inhaled corticosteroids on growth in asthmatic children. Design recommendations are articulated for study duration, entry criteria, other factors that may affect growth, measuring height, measuring growth, study objectives, and considerations relating to confounding between treatment allocation and the effect of the disease on growth. Special attention is given to analyses that address both the intra-subject correlation arising from multiple measurements in longitudinal studies of growth and the potential bias in treatment comparisons due to dropouts, especially those due to treatment failure.