title: Clinical trials bureaucracy: unintended consequences of well-intentioned policy.
abstract: BACKGROUND
  As randomized controlled trials have become the 'gold standard' for medical research, a complex regulatory structure for the conduct of clinical trials has emerged. However, this structure has not been adequately assessed to ensure that regulations governing human subjects research actually produce the desired effects.
  
  
  OBJECTIVE
  Our purpose is to identify some of the major shortcomings in the current regulatory system of human clinical trials oversight, and to propose some potential solutions to these problems.
  
  
  METHODS
  We discuss the evolution of the current US regulatory environment and its application in the context of several widely-used drug therapies.
  
  
  RESULTS
  Despite numerous randomized controlled trials, performed within a structure of extensive documentation and data collection, serious shortcomings in a number of pharmaceutical therapies were not detected until after the drugs were approved and widely adopted by clinicians.
  
  
  CONCLUSIONS
  The current system of regulatory bureaucracy in clinical trials has led to an extremely expensive research paradigm that, in spite of complex systems of oversight and exhaustive data collection, cannot be shown to adequately ensure the integrity of the research process and the protection of human research subjects. Some parts of the system, including Research Ethics Review Boards, may not be well-suited to carrying out their core mission of overseeing research conduct, and other aspects of clinical trials regulatory structure, such as monitoring/auditing review and adverse event reporting, may constitute a waste of money and resources. Misdirected data collection and adverse events reporting divert valuable resources and hamper development of large, simple clinical trials powered to definitively answer important research questions. Careful scrutiny of the utility of current or proposed regulatory schemes is required to ensure the integrity of human subjects research and to enhance the effectiveness of research dollars.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA. calif001@mc.duke.edu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000458:organization & administration; D017277:Drug Approval / Q000331:legislation & jurisprudence / Q000458:organization & administration*; D028744:Ethics Committees, Research / Q000458:organization & administration; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000191:economics / Q000331:legislation & jurisprudence / Q000379:methods*; D014481:United States; D014486:United States Food and Drug Administration