title: Comparison of content of FDA letters not approving applications for new drugs and associated public announcements from sponsors: cross sectional study.
abstract: OBJECTIVE
  To describe the content of non-public complete response letters issued by the US Food and Drug Administration (FDA) when they do not approve marketing applications from sponsors (drug companies) and to compare them with the content any subsequent press releases issued by those sponsors
  
  
  METHODS
  Cross sectional study.
  
  
  METHODS
  All applications for which FDA's Center for Drug Evaluation and Research initially issued complete response letters (n=61) from 11 August 2008 to 27 June 2013. Complete response letters and press releases were divided into discrete statements related to seven domains and 64 subdomains and assessed to determine whether they matched.
  
  
  RESULTS
  48% (29) of complete response letters cited deficiencies in both the safety and efficacy domains, and only 13% cited neither safety nor efficacy deficiencies. No press release was issued for 18% (11) of complete response letters, and 21% (13) of press releases did not match any statements from the letters. Press release statements matched 93 of the 687 statements (14%), including 16% (30/191) of efficacy and 15% (22/150) of safety statements. Of 32 complete response letters that called for a new clinical trial for safety or efficacy, 59% (19) had matching press release statements. Seven complete response letters reported higher mortality rates in treated participants; only one associated press release mentioned this fact.
  
  
  CONCLUSIONS
  FDA generally issued complete response letters to sponsors for multiple substantive reasons, most commonly related to safety and/or efficacy deficiencies. In many cases, press releases were not issued in response to those letters and, when they were, omitted most of the statements in the complete response letters. Press releases are incomplete substitutes for the detailed information contained in complete response letters.
authors.affiliation: Office of Public Health Strategy and Analysis, US Food and Drug Administration, Office of the Commissioner, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA peter.lurie@fda.hhs.gov.
authors.forename: Peter
authors.initials: P
authors.lastname: Lurie
authors.affiliation: Office of Public Health Strategy and Analysis, US Food and Drug Administration, Office of the Commissioner, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors.forename: Harinder S
authors.initials: HS
authors.lastname: Chahal
authors.affiliation: Office of Public Health Strategy and Analysis, US Food and Drug Administration, Office of the Commissioner, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Sigelman
authors.affiliation: Office of Public Health Strategy and Analysis, US Food and Drug Administration, Office of the Commissioner, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Stacy
authors.affiliation: Office of Public Health Strategy and Analysis, US Food and Drug Administration, Office of the Commissioner, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Sclar
authors.affiliation: Office of Public Health Strategy and Analysis, US Food and Drug Administration, Office of the Commissioner, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ddamulira
mesh_terms: D003257:Consumer Product Safety / Q000331:legislation & jurisprudence*; D015709:Correspondence as Topic; D003430:Cross-Sectional Studies; D017277:Drug Approval; D004345:Drug Industry / Q000331:legislation & jurisprudence; D006801:Humans; D058028:Research Report; D014481:United States; D014486:United States Food and Drug Administration