Selecting the best method to evaluate bronchodilation when analysing bronchodilator studies

Changes in lung function (that is, FEV(1)) are commonly expressed as a percentage of the predicted value. The question is whether this parameter is best suited for statistical analysis. A total of 2199 bronchodilation tests were selected and pre- and post-dilator FEV(1), age, height and sex extracted. Predicted FEV(1) values, the difference between pre- and post-dilator FEV(1) and the change as percentage of predicted or baseline FEV(1) were calculated. The latter parameters were subjected to analysis of variance and pre- and post-dilator FEV(1) to analysis of covariance. The statistical power of these four approaches and the residual structure were used to select the best approach. Analysis of variance of the change as percentage of predicted and covariance analysis of pre- and post-dilator FEV(1) offers the best performance. The residuals of the analysis of variance showed a funnel shaped structure. The latter causes residual heterogeneity, resulting in a loss of power and deviations between the actual and nominal alpha-level. This is not taken into account when calculating sample sizes using the standard equations, which implicitly assume lack of these problems. Analysis of covariance does not suffer from these problems. The best way to evaluate bronchodilation in trials is to use analysis of covariance.