title: Determining the clinically important difference in visual analog scale scores in abuse liability studies evaluating novel opioid formulations.
abstract: OBJECTIVE
  This study determined how the magnitude of change in positive subjective responses predicts clinical outcome in a treatment setting. Specifically, we attempted to define what constitutes a clinically important difference (CID) in subjective responses.
  
  
  METHODS
  A 100-mm visual analog scale (VAS) measured subjective ratings of drug "high," calculated via an anchor-based method with published data from participants receiving sustained-release naltrexone (NTX) and heroin in a laboratory setting. The data were then compared to clinical outcomes in a treatment trial with sustained-release naltrexone. A distribution-based method subsequently analyzed data from participants who received ALO-01 (extended-release morphine with sequestered NTX) to predict its abuse liability.
  
  
  RESULTS
  Differences in ratings of drug high of approximately 10 mm on a 100-mm line were clinically significant. By extrapolation, CIDs were also found between crushed or intact ALO-01 and immediate-release morphine sulfate (IRMS). No CIDs were found between intact and crushed ALO-01.
  
  
  CONCLUSIONS
  From laboratory and treatment trial data involving naltrexone, calculation of CIDs in subjective ratings of high is possible. Consequently, crushing/swallowing or injecting ALO-01 produces clinically significantly less drug high than oral or intravenous morphine alone, suggesting that ALO-01 has lower abuse liability by those routes than morphine formulations.
authors.affiliation: Analgesic Solutions, Inc, 232 Pond St, Natick, MA 01760, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Eaton
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Comer
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Revicki
authors.forename: Jeremiah J
authors.initials: JJ
authors.lastname: Trudeau
authors.forename: Richard G
authors.initials: RG
authors.lastname: van Inwegen
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Stauffer
authors.forename: Nathaniel P
authors.initials: NP
authors.lastname: Katz
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use; D003932:Heroin; D006801:Humans; D009271:Naltrexone / Q000627:therapeutic use; D009293:Opioid-Related Disorders / Q000188:drug therapy / Q000523:psychology*
chemical_list: D000701:Analgesics, Opioid; D009271:Naltrexone; D003932:Heroin