title: Risk of bias and brand explain the observed inconsistency in trials on glucosamine for symptomatic relief of osteoarthritis: a meta-analysis of placebo-controlled trials.
abstract: OBJECTIVE
  To determine whether study sponsor, chemical formulation, brand of glucosamine, and/or risk of bias explain observed inconsistencies in trials of glucosamine's efficacy for treating pain in osteoarthritis (OA).
  
  
  METHODS
  A systematic review and stratified meta-analysis of randomized placebo-controlled trials was performed, and random-effects models were applied with inconsistency (I(2) ) and heterogeneity (tau(2) ) estimated using Review Manager and SAS, respectively. The major outcome was reduction of pain; the standardized mean difference (SMD [95% confidence interval (95% CI)]) served as effect size.
  
  
  RESULTS
  The inclusion criteria yielded 25 trials (3,458 patients). Glucosamine moderately reduced pain (SMD -0.51 [95% CI -0.72, -0.30]), although a high level of between-trial inconsistency was observed (I(2) = 88%). The single most important explanation (i.e., covariate) was brand, reducing heterogeneity by 41% (P = 0.00032). Twelve trials (1,437 patients) using the Rottapharm/Madaus product resulted in significant pain reduction (SMD -1.07 [95% CI -1.47, -0.67]), although a sensitivity analysis of 3 low risk of bias trials using the Rottapharm/Madaus product showed less promising results (SMD -0.27 [95% CI -0.43, -0.12]), which is only a small effect size. Thirteen trials (1,963 patients) using non-Rottapharm/Madaus products consistently failed to show a reduction in pain (SMD -0.11 [95% CI -0.46, 0.24]). The second most important explanation was overall risk of bias (reducing heterogeneity by 32%).
  
  
  CONCLUSIONS
  Most of the observed heterogeneity in glucosamine trials is explained by brand. Trials using the Rottapharm/Madaus glucosamine product had a superior outcome on pain in OA compared to other preparations of glucosamine. Large inconsistency was found, however. Low risk of bias trials, using the Rottapharm/Madaus product, revealed a small effect size.
authors.affiliation: The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Patrick
authors.initials: P
authors.lastname: Eriksen
authors.forename: Else M
authors.initials: EM
authors.lastname: Bartels
authors.forename: Roy D
authors.initials: RD
authors.lastname: Altman
authors.forename: Henning
authors.initials: H
authors.lastname: Bliddal
authors.forename: Carsten
authors.initials: C
authors.lastname: Juhl
authors.forename: Robin
authors.initials: R
authors.lastname: Christensen
mesh_terms: D002986:Clinical Trials as Topic; D005944:Glucosamine / Q000627:therapeutic use*; D006801:Humans; D015588:Observer Variation; D010003:Osteoarthritis / Q000188:drug therapy*; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D005944:Glucosamine