title: Completeness of reporting of patient-relevant clinical trial outcomes: comparison of unpublished clinical study reports with publicly available data.
abstract: BACKGROUND
  Access to unpublished clinical study reports (CSRs) is currently being discussed as a means to allow unbiased evaluation of clinical research. The Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests CSRs from manufacturers for its drug assessments. Our objective was to determine the information gain from CSRs compared to publicly available sources (journal publications and registry reports) for patient-relevant outcomes included in IQWiG health technology assessments (HTAs) of drugs.
  
  
  RESULTS
  We used a sample of 101 trials with full CSRs received for 16 HTAs of drugs completed by IQWiG between 15 January 2006 and 14 February 2011, and analyzed the CSRs and the publicly available sources of these trials. For each document type we assessed the completeness of information on all patient-relevant outcomes included in the HTAs (benefit outcomes, e.g., mortality, symptoms, and health-related quality of life; harm outcomes, e.g., adverse events). We dichotomized the outcomes as "completely reported" or "incompletely reported." For each document type, we calculated the proportion of outcomes with complete information per outcome category and overall. We analyzed 101 trials with CSRs; 86 had at least one publicly available source, 65 at least one journal publication, and 50 a registry report. The trials included 1,080 patient-relevant outcomes. The CSRs provided complete information on a considerably higher proportion of outcomes (86%) than the combined publicly available sources (39%). With the exception of health-related quality of life (57%), CSRs provided complete information on 78% to 100% of the various benefit outcomes (combined publicly available sources: 20% to 53%). CSRs also provided considerably more information on harms. The differences in completeness of information for patient-relevant outcomes between CSRs and journal publications or registry reports (or a combination of both) were statistically significant for all types of outcomes. The main limitation of our study is that our sample is not representative because only CSRs provided voluntarily by pharmaceutical companies upon request could be assessed. In addition, the sample covered only a limited number of therapeutic areas and was restricted to randomized controlled trials investigating drugs.
  
  
  CONCLUSIONS
  In contrast to CSRs, publicly available sources provide insufficient information on patient-relevant outcomes of clinical trials. CSRs should therefore be made publicly available. Please see later in the article for the Editors' Summary.
authors.affiliation: Institute for Quality and Efficiency in Health Care, Cologne, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Wieseler
authors.forename: Natalia
authors.initials: N
authors.lastname: Wolfram
authors.forename: Natalie
authors.initials: N
authors.lastname: McGauran
authors.forename: Michaela F
authors.initials: MF
authors.lastname: Kerekes
authors.forename: Volker
authors.initials: V
authors.lastname: Vervölgyi
authors.forename: Petra
authors.initials: P
authors.lastname: Kohlepp
authors.forename: Marloes
authors.initials: M
authors.lastname: Kamphuis
authors.forename: Ulrich
authors.initials: U
authors.lastname: Grouven
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D012042:Registries; D058028:Research Report