title: Warning letters to sponsor-investigators at academic health centres - the regulatory "canaries in a coal mine".
abstract: OBJECTIVE
  This study highlights Warning Letter (WL) findings issued to sponsor-investigators (S-Is) by the Food and Drug Administration (FDA).
  
  
  METHODS
  The online index of WLs issued from October 1, 2007 through September 30, 2012 was reviewed [1]. Through a manual screening process, letters were evaluated if specifically issued to 'clinical investigators', 'sponsors' or 'sponsor-investigators'. A particular focus was given to S-Is at Academic Health Centres (AHCs). Each letter was scored for the presence of violations in 40 general regulatory categories.
  
  
  RESULTS
  A review of FDA WLs issued over a five-year period (FDA Fiscal Years 2008-2012) revealed that WLs to S-Is represent half of the WLs issued to all sponsors (16 of 32 letters). A review of these letters indicates that S-Is are not aware of, or simply do not meet, their regulatory responsibilities as either investigators or sponsors. In comparing total sponsor letters to those of S-Is, the most cited violation was the same: a lack of monitoring. A review of publicly available inspection data indicates that these 16 letters merely represent the tip of the iceberg.
  
  
  CONCLUSIONS
  This review of the WL database reveals the potential for serious regulatory violations among S-Is at AHCs. Recent translational funding initiatives may serve to increase the number of S-Is, especially among Academic Health Centres (AHCs) [2]; thus, AHCs must become aware of this S-I role and work to support investigators who assume both roles in the course of their research.
authors.affiliation: . erin.oreilly@duke.edu.
authors.forename: Erin K
authors.initials: EK
authors.lastname: O'Reilly
authors.forename: M E
authors.initials: ME
authors.lastname: Blair Holbein
authors.forename: Jelena P
authors.initials: JP
authors.lastname: Berglund
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Parrish
authors.forename: Mary-Tara
authors.initials: MT
authors.lastname: Roth
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Burnett
mesh_terms: D035843:Biomedical Research / Q000331:legislation & jurisprudence*; D015709:Correspondence as Topic; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008297:Male; D014481:United States; D014486:United States Food and Drug Administration