Evaluating the effects of asthma therapy on childhood growth: principles of study design.

Inhaled corticosteroids have been established as the most effective treatment for childhood asthma. However, concerns persist regarding their potential effects on growth and, most importantly, final height. To assess their effects on growth, inhaled corticosteroids can be compared with placebo (type 1 study), nonsteroidal anti-asthma therapy (type 2 study), another inhaled corticosteroid (type 3 study) or "real-life" anti-asthma therapy (type 4 study). Owing to the difficulties in obtaining final height data, several different surrogate measures have often been used: short-term lower leg growth, longer-term statural height growth velocity, childhood height and predicted final height. This paper discusses the choice of end point, key trial design issues (including selection and number of subjects in the active and control populations) duration of assessments and methods for measuring height and data analysis, in the context of the different study types. Specific study design recommendations have been developed after consideration of these factors, and these principles will be used to guide the interpretation of previously published growth studies.