Regulatory issues with multiplicity in drug approval: Principles and controversies in a changing landscape

J Biopharm Stat. 2018;28(1):3-9. doi: 10.1080/10543406.2017.1378669. Epub 2017 Oct 24.

Abstract

Recently, new draft guidelines on multiplicity issues in clinical trials have been issued by European Medicine Agency (EMA) and Food and Drug Administration (FDA), respectively. Multiplicity is an issue in clinical trials, if the probability of a false-positive decision is increased by insufficiently accounting for testing multiple hypotheses. We outline the regulatory principles related to multiplicity issues in confirmatory clinical trials intended to support a marketing authorization application in the EU, describe the reasons for an increasing complexity regarding multiple hypotheses testing and discuss the specific multiplicity issues emerging within the regulatory context and being relevant for drug approval.

Keywords: Clinical trials; drug approval; multiplicity.

MeSH terms

  • Clinical Trials as Topic / legislation & jurisprudence*
  • Clinical Trials as Topic / statistics & numerical data*
  • Decision Making
  • Drug Approval / legislation & jurisprudence*
  • Endpoint Determination / statistics & numerical data*
  • European Union
  • Humans
  • Legislation, Drug*
  • Research Design
  • United States
  • United States Food and Drug Administration