title: Is the decision on the use of biosimilar growth hormone based on high quality scientific evidence? - a systematic review.
abstract: BACKGROUND
  The authors carried out a systematic and critical review of the scientific literature regarding the possible development of neutralising antibodies developed in patients treated with growth hormone biosimilars (defined as a drug expected to be similar to the originator or original pharmaceutical -European Medicines Agency) as compared to the reference drug. As a consequence, we discovered two major issues, namely, the poor quality of the comparative clinical trials and the poor quality of the antibody assays used during the trials.
  
  
  METHODS
  The literature review was performed according to the principle of the Cochrane Collaboration and SBU. The electronic literature search included the databases PubMed, EMBASE and The Cochrane Library up to December 2012. Two independent reviewers assessed abstracts and full-text articles.
  
  
  RESULTS
  The search identified 1,553 abstracts related to the subject. Only six articles contained data on biosimilar growth hormone or antibody results obtained with appropriate methods. None of the studies fulfilled the criteria for high quality randomised controlled trials. Qualitative rather than quantitative assays were used for monitoring antibody formation.
  
  
  CONCLUSIONS
  It is our firm opinion , that since biosimilars are not identical, emphasis must be placed on the quality of the comparative clinical trials performed and the quality of the analytical studies in order to guarantee patient safety. Clinical trials should follow established quality rules for controlled comparative randomised clinical trials. A whole set of new guidelines is required.
authors.affiliation: SBU, Box 3657, 103 59, Stockholm, Sweden, fryklund45@gmail.com.
authors.forename: Linda
authors.initials: L
authors.lastname: Fryklund
authors.forename: Martin
authors.initials: M
authors.lastname: Ritzén
authors.forename: Göran
authors.initials: G
authors.lastname: Bertilsson
authors.forename: Marianne Heibert
authors.initials: MH
authors.lastname: Arnlind
mesh_terms: D000917:Antibody Formation / Q000276:immunology; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000592:standards*; D017277:Drug Approval / Q000331:legislation & jurisprudence; D019382:Human Growth Hormone / Q000276:immunology / Q000592:standards / Q000627:therapeutic use*; D006801:Humans; D007880:Legislation, Drug; D011994:Recombinant Proteins / Q000276:immunology / Q000592:standards / Q000627:therapeutic use*
chemical_list: D059451:Biosimilar Pharmaceuticals; D011994:Recombinant Proteins; D019382:Human Growth Hormone