The purpose of this study was to determine if different methods for average bioequivalence in high variability drugs coincide or not in their conclusions when applied to the same dataset, and to discuss the method validity and reliability of the conclusions. Different approaches for the evaluation of average bioequivalence were applied to the results of a bioavailability trial on the diuretic drug Furosemide. These methods included widening the bioequivalence limits according to regulatory recommendations, scaling the limits and scaling the bioequivalence statistic, jointly with evaluating alternative bioavailability measures. The methods to establish the bioequivalence limits were also combined with some alternative methods to construct confidence intervals. The decision on bioequivalence depends much more on the bioavailability measures than on the statistical approach. The reliability of the final decision lies mainly in the interpretation of these measures and on the special characteristics of each drug.

Background It is uncertain whether peak flow measurement is best done in the standing or sitting position. Methods In this cross-over study, study participants were randomized to perform the initial peak expiratory flow (PEF) measurement in either standing or sitting position. The highest of three readings in each position were compared using paired t-test. A mean difference of <±25 l/min was set as the equivalence limits. Test of equivalence of standing and sitting PEF measurements was done using MedCalc Software. Test of agreement of standing and sitting PEF was assessed by Lin’s concordance correlation coefficient and Bland–Altman limits of agreement. Results Of the 100 study participants, 50% of them had asthma. There was a statistically significant difference between the standing and sitting PEF in adults suffering from asthma [mean difference 11 l/min, 95% confidence interval (CI) = 4 to 19], but not in the healthy individuals (mean difference 3 l/min, 95% CI = −6 to 12). The observed differences in PEF were small and may not be clinically important. In adults with and without asthma, the standing and sitting PEF were highly correlated and satisfied the test of equivalence. Conclusions The PEF in the standing and sitting positions was equivalent in adults. Therefore, performing PEF in either position is acceptable. However, health care practitioners should be aware of the small reduction in PEF when it is done in the sitting position. It is desirable that the position used is documented and the same position is used wherever possible.