title: Navigating the maze of requirements for obtaining approval of non-interventional studies (NIS) in the European Union.
abstract: OBJECTIVE
  The purpose of this article is to give an overview of the complexities and unexpected regulatory requirements for obtaining approval of multinational and multicentre non-interventional studies (NIS) in the European Union (EU).
  
  
  METHODS
  The websites of national competent authorities (CAs), ethics committees (ECs) and data protection (DP) authorities were consulted to find regulations and guidance information related to the authorisation of NIS in various member states of the EU.
  
  
  RESULTS
  Many additional hurdles, neither disclosed nor clear in the various regulations/guidances for NIS, were identified. Although approval from the CA is not needed for NIS, in many countries request of CA opinion is nevertheless recommended, prior to submission to the EC, to obtain confirmation that the planned NIS does not fall in the interventional trial category. Clinical trial insurance was required in some countries. In countries like Belgium and Italy, the multicentre NIS required the approval from a central EC and local ECs as a single central EC opinion was not considered sufficient. The EC document requirements for submission and the fees were extremely variable among all member states. Additional approvals from data protection authorities and insurance companies were required in some countries.
  
  
  CONCLUSIONS
  The process of obtaining approval for multicentre and multinational NIS is time consuming due to lack of transparency and the different regulatory requirements among member states. The EU pharmacovigilance legislation and clinical trial regulation No 536/2014 is a step forward in providing a regulatory framework for PASS (post-authorisation safety studies) and low intervention clinical trials, but since regulation No 536/2014 excludes NIS, it will be difficult to enforce harmonization of requirements for approval of NIS among member states.
authors.affiliation: Zerimar Consulting, Munich, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ramirez
mesh_terms: D035843:Biomedical Research / Q000941:ethics / Q000331:legislation & jurisprudence*; D002986:Clinical Trials as Topic / Q000191:economics / Q000331:legislation & jurisprudence*; D028741:Ethics Committees, Clinical; D028744:Ethics Committees, Research; D005060:Europe; D005062:European Union; D006801:Humans; D007341:Insurance; D007391:International Cooperation; D015337:Multicenter Studies as Topic / Q000941:ethics / Q000331:legislation & jurisprudence*
keywords: competent authorities; data protection authorities; ethics committee; non-interventional studies; observational studies; regulatory approval