title: A comparison between enriched and nonenriched enrollment randomized withdrawal trials of opioids for chronic noncancer pain.
abstract: BACKGROUND
  An enriched enrollment randomized withdrawal (EERW) design excludes potential participants who are nonresponders or who cannot tolerate the experimental drug before random assignment. It is unclear whether EERW design has an influence on the efficacy and safety of opioids for chronic noncancer pain (CNCP).
  
  
  OBJECTIVE
  The primary objective was to compare the results from EERW and non-EERW trials of opioids for CNCP. Secondary objectives were to compare weak versus strong opioids, subgroups of patients with different types of pain, and the efficacy of opiods compared with placebo versus other drugs.
  
  
  METHODS
  MEDLINE, EMBASE and CENTRAL were searched up to July 2009, for randomized controlled trials of any opioid for CNCP. Metaanalyses and meta-regressions were conducted to compare the results. Treatment efficacy was assessed by effect sizes (small, medium and large) and the incidence of adverse effects was assessed by a clinically relevant mean difference of 10% or greater.
  
  
  RESULTS
  Sixty-two randomized trials were included. In 61 trials, the duration was less than 16 weeks. There was no difference in efficacy between EERW and non-EERW trials for both pain (P=0.6) and function (P=0.3). However, EERW trials failed to detect a clinically relevant difference for nausea, vomiting, somnolence, dizziness and dry skin⁄itching compared with non-EERW. Opioids were more effective than placebo in patients with nociceptive pain (effect size=0.60, 95% CI 0.49 to 0.72) and neuropathic pain (effect size=0.56, 95% CI 0.38 to 0.73).
  
  
  CONCLUSIONS
  EERW trial designs appear not to bias the results of efficacy, but they underestimate the adverse effects. The present updated meta- analysis shows that weak and strong opioids are effective for CNCP of both nociceptive and neuropathic origin.
authors: Department of Medicine, University of Toronto, Toronto, Canada. afurlan@iwh.on.ca
authors: Andrea
authors: A
authors: Furlan
authors: Luis E
authors: LE
authors: Chaparro
authors: Emma
authors: E
authors: Irvin
authors: Angela
authors: A
authors: Mailis-Gagnon
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D059350:Chronic Pain / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
chemical_list: D000701:Analgesics, Opioid