Statistical evaluation of individual bioequivalence

Drug switchability requires the evidence of individual bioequivalence which -refers to the comparison of the closeness between the two distributions of the pharmacokinetic (PK) responses from the same subject obtained under the repeated administrations of the test and reference formulations. Advantages and drawbacks of the current statistical procedures for assessment of individual bioequivalence are discussed with emphasis on the aggregate-based criteria, An intersection-union test based on disaggregate criteria is proposed for the evaluation of individual bioequivalence. In addition, a modified aggregated criterion is suggested to overcome the drawbacks suffered by aggregate criteria. The relationships among different criteria are examined, and the performance of the procedures will be compared. A numerical example is given to illustrate the proposed procedures.     

Assessing switchability for biosimilar products: modelling approaches applied to children's growth

The present paper describes two statistical modelling approaches that have been developed to demonstrate switchability from the original recombinant human growth hormone (rhGH) formulation (Genotropin^®) to a biosimilar product (Omnitrope^®) in children suffering from growth hormone deficiency. Demonstrating switchability between rhGH products is challenging because the process of growth varies with the age of the child and across children. The first modelling approach aims at predicting individual height measured at several time‐points after switching to the biosimilar. The second modelling approach provides an estimate of the deviation from the overall growth rate after switching to the biosimilar, which can be regarded as an estimate of switchability. The results after applying these approaches to data from a randomized clinical trial are presented. The accuracy and precision of the predictions made using the first approach and the small deviation from switchability estimated with the second approach provide sufficient evidence to conclude that switching from Genotropin^® to Omnitrope^® has a very small effect on growth, which is neither statistically significant nor clinically relevant. Copyright © 2015 John Wiley & Sons, Ltd.