title: Reporting of meta-analyses of randomized controlled trials with a focus on drug safety: an empirical assessment.
abstract: BACKGROUND
  Due to the sparse nature of serious drug-related adverse events (AEs), meta-analyses combining data from several randomized controlled trials (RCTs) to evaluate drug safety issues are increasingly being conducted and published, influencing clinical and regulatory decision making. Evaluation of meta-analyses involves the assessment of both the individual constituent trials and the approaches used to combine them. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting framework is designed to enhance the reporting of systematic reviews and meta-analyses. However, PRISMA may not cover all critical elements useful in the evaluation of meta-analyses with a focus on drug safety particularly in the regulatory-public health setting.
  
  
  OBJECTIVE
  This work was conducted to (1) evaluate the adherence of a sample of published drug safety-focused meta-analyses to the PRISMA reporting framework, (2) identify gaps in this framework based on key aspects pertinent to drug safety, and (3) stimulate the development and validation of a more comprehensive reporting tool that incorporates elements unique to drug safety evaluation.
  
  
  METHODS
  We selected a sample of meta-analyses of RCTs based on review of abstracts from high-impact journals as well as top medical specialty journals between 2009 and 2011. We developed a preliminary reporting framework based on PRISMA with specific additional reporting elements critical for the evaluation of drug safety meta-analyses of RCTs. The reporting of pertinent elements in each meta-analysis was reviewed independently by two authors; discrepancies in the independent evaluations were resolved through discussions between the two authors.
  
  
  RESULTS
  A total of 27 meta-analyses, 12 from highest impact journals, 13 from specialty medical journals, and 2 from Cochrane reviews, were identified and evaluated. The great majority (>85%) of PRISMA elements were addressed in more than half of the meta-analyses reviewed. However, the majority of meta-analyses (>60%) did not address most (>80%) of the additional reporting elements critical for the evaluation of drug safety. Some of these elements were not addressed in any of the reviewed meta-analyses.
  
  
  CONCLUSIONS
  This review included a sample of meta-analyses, with a focus on drug safety, recently published in high-impact journals; therefore, we may have underestimated the extent of the reporting problem across all meta-analyses of drug safety. Furthermore, temporal trends in reporting could not be evaluated in this review because of the short time interval selected.
  
  
  CONCLUSIONS
  While the majority of PRISMA elements were addressed by most studies reviewed, the majority of studies did not address most of the additional safety-related elements. These findings highlight the need for the development and validation of a drug safety reporting framework and the importance of the current initiative by the Council for International Organizations of Medical Sciences (CIOMS) to create a guidance document for drug safety information synthesis/meta-analysis, which may improve reporting, conduct, and evaluation of meta-analyses of drug safety and inform clinical and regulatory decision making.
authors.affiliation: Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 30993, USA. tarek.hammad@fda.hhs.gov
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Hammad
authors.forename: George A
authors.initials: GA
authors.lastname: Neyarapally
authors.forename: Simone P
authors.initials: SP
authors.lastname: Pinheiro
authors.forename: Solomon
authors.initials: S
authors.lastname: Iyasu
authors.forename: George
authors.initials: G
authors.lastname: Rochester
authors.forename: Gerald
authors.initials: G
authors.lastname: Dal Pan
mesh_terms: D064420:Drug-Related Side Effects and Adverse Reactions; D015201:Meta-Analysis as Topic; D011643:Publishing / Q000592:standards*; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D012107:Research Design / Q000592:standards*