title: Erythropoietin, uncertainty principle and cancer related anaemia.
abstract: BACKGROUND
  This study was designed to evaluate if erythropoietin (EPO) is effective in the treatment of cancer related anemia, and if its effect remains unchanged when data are analyzed according to various clinical and methodological characteristics of the studies. We also wanted to demonstrate that cumulative meta-analysis (CMA) can be used to resolve uncertainty regarding clinical questions.
  
  
  METHODS
  Systematic Review (SR) of the published literature on the role of EPO in cancer-related anemia. A cumulative meta-analysis (CMA) using a conservative approach was performed to determine the point in time when uncertainty about the effect of EPO on transfusion-related outcomes could be considered resolved.
  
  
  METHODS
  Patients included in randomized studies that compared EPO versus no therapy or placebo.
  
  
  METHODS
  Number of patients requiring transfusions.
  
  
  RESULTS
  Nineteen trials were included. The pooled results indicated a significant effect of EPO in reducing the number of patients requiring transfusions [odds ratio (OR) = 0.41; 95%CI: 0.33 to 0.5; p < 0.00001;relative risk (RR) = 0.61; 95% CI: 0.54 to 0.68]. The results remain unchanged after the sensitivity analyses were performed according to the various clinical and methodological characteristics of the studies. The heterogeneity was less pronounced when OR was used instead of RR as the measure of the summary point estimate. Analysis according to OR was not heterogeneous, but the pooled RR was highly heterogeneous. A stepwise metaregression analysis did point to the possibility that treatment effect could have been exaggerated by inadequacy in allocation concealment and that larger treatment effects are seen at hb level > 11.5 g/dl. We identified 1995 as the point in time when a statistically significant effect of EPO was demonstrated and after which we considered that uncertainty about EPO efficacy was resolved.
  
  
  CONCLUSIONS
  EPO is effective in the treatment of anemia in cancer patients. This could have already been known in 1995 if a CMA had been performed at that time.
authors.affiliation: Interdisciplinary Oncology Program H, Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa, FL, USA. clark@evidencias.com
authors.forename: Otavio
authors.initials: O
authors.lastname: Clark
authors.forename: Jared R
authors.initials: JR
authors.lastname: Adams
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Benjamin
authors.initials: B
authors.lastname: Djulbegovic
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000628:therapy; D017707:Erythrocyte Transfusion; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D007700:Kinetics; D009369:Neoplasms / Q000150:complications*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin