title: Regulatory impediments jeopardizing the conduct of clinical trials in Europe funded by the National Institutes of Health.
abstract: BACKGROUND
  A number of reports have highlighted problems of conducting publicly funded trials in Europe as a consequence of the European Union (EU) Clinical Trials Directive. The impact of the EU Directive on multi-national trials, which include sites in Europe that are funded by the US National Institutes of Health (NIH) have not been described.
  
  
  METHODS
  Four problems in the conduct of two international HIV treatment trials funded by NIH in the EU are described: (1) conflicting regulations on the continuing review of protocols by Institutional Review Boards/Research Ethics Committees; (2) US regulations requiring Federalwide Assurances for sites which are only partially funded by NIH; (3) EU guidance on the designation of studies as a trial of an investigational medicinal product; and (4) EU guidance on trial sponsorship and the requirements for insurance and indemnification. Following the description of the problems, recommendations for improving global collaborations are made to the US Office of Human Research Protections, to NIH, and to the EU and its Member States.
  
  
  RESULTS
  A lack of harmonization of regulations at multiple levels caused enrollment in one study to be interrupted for several months and delayed for one year the initiation of another study aimed at obtaining definitive evidence to guide the timing of the initiation of antiretroviral therapy for individuals infected with HIV. The delays and the purchase of insurance resulted in substantial increases in trial costs and caused substantial disruption at clinical sites among staff and study participants.
  
  
  CONCLUSIONS
  The problems cited and recommendations made pertain to trials funded by NIH and conducted by sites in the EU. There are many other challenges in the conduct of international research, public and private, that global harmonization would alleviate.
  
  
  CONCLUSIONS
  Disharmony, at multiple levels, in international regulations and guidelines is stifling publicly funded global research. International scientific organizations and government groups should make the documentation and solution of these problems a priority.
authors: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55414, USA. jim@ccbr.umn.edu
authors: James D
authors: JD
authors: Neaton
authors: Abdel
authors: A
authors: Babiker
authors: Mark
authors: M
authors: Bohnhorst
authors: Janet
authors: J
authors: Darbyshire
authors: Eileen
authors: E
authors: Denning
authors: Arnie
authors: A
authors: Frishman
authors: Jesper
authors: J
authors: Grarup
authors: Gregg
authors: G
authors: Larson
authors: Jens
authors: J
authors: Lundgren
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D002985:Clinical Protocols; D002986:Clinical Trials as Topic / Q000331:legislation & jurisprudence* / Q000379:methods / Q000592:standards; D004335:Drug and Narcotic Control / Q000191:economics / Q000331:legislation & jurisprudence*; D005060:Europe; D005062:European Union; D033161:Government Regulation; D019983:Guideline Adherence; D017408:Guidelines as Topic; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D038622:Internationality; D015337:Multicenter Studies as Topic; D009316:National Institutes of Health (U.S.); D014481:United States
chemical_list: D019380:Anti-HIV Agents