title: From the trenches: a cross-sectional study applying the GRADE tool in systematic reviews of healthcare interventions.
abstract: BACKGROUND
  GRADE was developed to address shortcomings of tools to rate the quality of a body of evidence. While much has been published about GRADE, there are few empirical and systematic evaluations.
  
  
  OBJECTIVE
  To assess GRADE for systematic reviews (SRs) in terms of inter-rater agreement and identify areas of uncertainty.
  
  
  METHODS
  Cross-sectional, descriptive study.
  
  
  METHODS
  We applied GRADE to three SRs (n = 48, 66, and 75 studies, respectively) with 29 comparisons and 12 outcomes overall. Two reviewers graded evidence independently for outcomes deemed clinically important a priori. Inter-rater reliability was assessed using kappas for four main domains (risk of bias, consistency, directness, and precision) and overall quality of evidence.
  
  
  RESULTS
  FOR THE FIRST REVIEW, RELIABILITY WAS: κ = 0.41 for risk of bias; 0.84 consistency; 0.18 precision; and 0.44 overall quality. Kappa could not be calculated for directness as one rater assessed all items as direct; assessors agreed in 41% of cases. For the second review reliability was: 0.37 consistency and 0.19 precision. Kappa could not be assessed for other items; assessors agreed in 33% of cases for risk of bias; 100% directness; and 58% overall quality. For the third review, reliability was: 0.06 risk of bias; 0.79 consistency; 0.21 precision; and 0.18 overall quality. Assessors agreed in 100% of cases for directness. Precision created the most uncertainty due to difficulties in identifying "optimal" information size and "clinical decision threshold", as well as making assessments when there was no meta-analysis. The risk of bias domain created uncertainty, particularly for nonrandomized studies.
  
  
  CONCLUSIONS
  As researchers with varied levels of training and experience use GRADE, there is risk for variability in interpretation and application. This study shows variable agreement across the GRADE domains, reflecting areas where further guidance is required.
authors.affiliation: Department of Pediatrics, Alberta Research Centre for Health Evidence, University of Alberta, Edmonton, Canada. hartling@ualberta.ca
authors.forename: Lisa
authors.initials: L
authors.lastname: Hartling
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Fernandes
authors.forename: Jennifer
authors.initials: J
authors.lastname: Seida
authors.forename: Ben
authors.initials: B
authors.lastname: Vandermeer
authors.forename: Donna M
authors.initials: DM
authors.lastname: Dryden
mesh_terms: D015982:Bias; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003430:Cross-Sectional Studies / Q000706:statistics & numerical data*; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000379:methods*; D012107:Research Design / Q000706:statistics & numerical data; D012984:Software; D016896:Treatment Outcome