title: Clinical trials for authorized biosimilars in the European Union: a systematic review.
abstract: In 2006, Omnitrope (by Sandoz) was the first approved biosimilar in Europe. To date, 21 biosimilars for seven different biologics are on the market. The present study compared the clinical trials undertaken to obtain market authorization.
  
  
  
  We summarized the findings of a comprehensive review of all clinical trials up to market authorization of approved biosimilars, using the European public assessment reports (EPARs) published by the European Medicines Agency (EMA). The features compared were, among others, the number of patients enrolled, the number of trials, the types of trial design, choice of endpoints and equivalence margins for pharmacokinetic (PK)/pharmacodynamic (PD) and phase III trials.
  
  
  
  The variability between the clinical development strategies is high. Some differences are explainable by the characteristics of the product; if, for example, the PD marker can be assumed to predict the clinical outcome, no efficacy trials might be necessary. However, even for products with the same reference product, the sample size, endpoints and statistical models are not always the same.
  
  
  
  There seems to be flexibility for sponsors regarding the decision as to how best to prove biosimilarity.
authors: Statistical Methodology, Novartis Pharma AG, 4056, Basel, Switzerland.
authors: Johanna
authors: J
authors: Mielke
authors: Department of Clinical Pharmacology, Medical University of Vienna, 1090, Vienna, Austria.
authors: Bernd
authors: B
authors: Jilma
authors: Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, 1090, Vienna, Austria.
authors: Franz
authors: F
authors: Koenig
authors: Statistical Methodology, Novartis Pharma AG, 4056, Basel, Switzerland.
authors: Byron
authors: B
authors: Jones
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D017277:Drug Approval; D023381:Endpoint Determination; D005062:European Union; D006801:Humans; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D059451:Biosimilar Pharmaceuticals
keywords: EMA; EPAR; biosimilar drug development programmes; biosimilarity; biosimilars; trial design