title: Reporting of industry funded study outcome data: comparison of confidential and published data on the safety and effectiveness of rhBMP-2 for spinal fusion.
abstract: OBJECTIVE
  To investigate whether published results of industry funded trials of recombinant human bone morphogenetic protein 2 (rhBMP-2) in spinal fusion match underlying trial data by comparing three different data sources: individual participant data, internal industry reports, and publicly available journal publications and conference abstracts.
  
  
  METHODS
  The manufacturer of rhBMP-2 products (Medtronic; Minneapolis, MN) provided complete individual participant data and internal reports for all its studies of rhMBP-2 in spinal fusion. We identified publications and conference abstracts through comprehensive literature searches. We compared outcomes provided in the individual participant data against outcomes reported in publications. For effectiveness outcomes, we compared meta-analyses of randomised controlled trials based on each of the three data sources. For adverse events, meta-analysis of the published aggregate data was not possible and we compared the number and type of adverse events reported between data sources.
  
  
  RESULTS
  32 publications reported outcomes from 11 of the 17 existing manufacturer sponsored studies. For individual randomised controlled trials, 56% (9/16) to 88% (15/17) of effectiveness outcomes known to have been collected were reported in the published literature. Meta-analyses of effectiveness data were almost identical for pain outcomes and similar for fusion across the three data sources. A minority of adverse event data known to have been collected were reported in the published literature. Several journal articles reported only "serious," "related," or "unanticipated" adverse events, without defining these terms. Others reported a small proportion of the collected adverse event categories. Around 23% (533/2302) of the total adverse events collected in published randomised controlled trials have been reported in the literature, with randomised controlled trials evaluating the licensed preparation (Infuse) reporting around 11% (122/1108) of collected adverse events.
  
  
  CONCLUSIONS
  The published literature only partially represents the total data known to have been collected on the effects of rhBMP-2. This did not lead to substantially different results for meta-analysis of effectiveness outcomes. In contrast, reporting of adverse event data in trial publications was inadequate and inconsistent to the extent that any systematic review based solely on the publicly available data would not be able to properly evaluate the safety of rhBMP-2. Analysis of individual participant data enabled the most complete, detailed, and in-depth analysis and was not more resource intensive than extracting, collating, and analysing aggregate data from multiple trial publications and conference abstracts. Confidential internal reports presented considerably more adverse event data than publications, and in the absence of individual participant data access to these reports would support more accurate and reliable investigation, with less time and effort than relying on incomplete published data.
authors.affiliation: Centre for Reviews and Dissemination, University of York, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rodgers
authors.forename: Jennifer V E
authors.initials: JV
authors.lastname: Brown
authors.forename: Morag K
authors.initials: MK
authors.lastname: Heirs
authors.forename: Julian P T
authors.initials: JP
authors.lastname: Higgins
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Mannion
authors.forename: Mark C
authors.initials: MC
authors.lastname: Simmonds
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Stewart
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000458:organization & administration*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000009:adverse effects; D004345:Drug Industry / Q000191:economics / Q000379:methods; D006801:Humans; D015201:Meta-Analysis as Topic; D010043:Outcome and Process Assessment, Health Care / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D010147:Pain Measurement / Q000706:statistics & numerical data; D010149:Postoperative Pain / Q000175:diagnosis / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012107:Research Design / Q000592:standards*; D012109:Research Support as Topic; D013123:Spinal Fusion / Q000009:adverse effects / Q000379:methods / Q000706:statistics & numerical data; D013597:Systems Analysis; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2