Statistical considerations for confirmatory clinical trials for similar biotherapeutic products

Biologicals. 2011 Sep;39(5):266-9. doi: 10.1016/j.biologicals.2011.06.006. Epub 2011 Jul 31.


For the purpose of comparing the efficacy and safety of a Similar Biotherapeutic Product (SBP) to a Reference Biotherapeutic Product (RBP), the "Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs)" issued by the World Health Organisation (WHO), states that equivalence or non-inferiority studies may be acceptable. While in principle, equivalence trials are preferred, non-inferiority trials may be considered if appropriately justified, such as for a medicinal product with a wide safety margin. However, the statistical issues involved in the design, conduct, analysis and interpretation of equivalence and non-inferiority trials are complex and subtle, and require that all aspects of these trials be given careful consideration. These issues are important in order to ensure that equivalence and non-inferiority trials provide valid data that are necessary to draw reliable conclusions regarding the clinical similarity of an SBP to an RBP.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Clinical Trials as Topic / methods*
  • Drug Evaluation / methods*
  • Guidelines as Topic
  • Research Design*
  • Statistics as Topic / methods*
  • World Health Organization*