title: Assessing switchability for biosimilar products: modelling approaches applied to children's growth.
abstract: 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.
authors.affiliation: Integrated Quantitative Sciences (IQS), Novartis Pharma AG, Basel, Switzerland.
authors.forename: Rossella
authors.initials: R
authors.lastname: Belleli
authors.affiliation: Integrated Quantitative Sciences (IQS), Novartis Pharma AG, Basel, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Fisch
authors.affiliation: Hexal AG, Sandoz Biopharmaceuticals, Holzkirchen, Germany.
authors.forename: Didier
authors.initials: D
authors.lastname: Renard
authors.affiliation: Integrated Quantitative Sciences (IQS), Novartis Pharma AG, Basel, Switzerland.
authors.forename: Heike
authors.initials: H
authors.lastname: Woehling
authors.affiliation: Integrated Quantitative Sciences (IQS), Novartis Pharma AG, Basel, Switzerland.
authors.forename: Sandro
authors.initials: S
authors.lastname: Gsteiger
mesh_terms: D000293:Adolescent; D000367:Age Factors; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D001827:Body Height / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical; D002648:Child; D002657:Child Development / Q000187:drug effects*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D057915:Drug Substitution / Q000706:statistics & numerical data*; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D012107:Research Design / Q000706:statistics & numerical data*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D059451:Biosimilar Pharmaceuticals; D019382:Human Growth Hormone
keywords: Switchability; biosimilar; interchangeability; statistical modelling