Determining the clinically important difference in visual analog scale scores in abuse liability studies evaluating novel opioid formulations

• Published in: Quality of life research Vol. 21; no. 6; pp. 975 - 981
• Main Authors: Eaton, Thomas A., Comer, Sandra D., Revicki, Dennis A., Trudeau, Jeremiah J., van Inwegen, Richard G., Stauffer, Joseph W., Katz, Nathaniel P.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.08.2012; Springer Netherlands; Springer Nature B.V
• Subjects: Analgesics; Analgesics, Opioid - therapeutic use; Brief Communication; CLINICAL AND POLICY APPLICATIONS; Controlled substances; Datasets; Dosage; Drug abuse; Drug dosages; Heroin; Humans; Laboratories; Liability; Medication administration; Medicine; Medicine & Public Health; Methods; Morphine; Naltrexone - therapeutic use; Narcotics; Opioid analgesics; Opioid-Related Disorders - drug therapy; Opioid-Related Disorders - psychology; Pain measurement scales; Placebos; Product development; Public Health; Quality of Life Research; Ratings & rankings; Retention; Sociology; Standard deviation; Substance abuse treatment; Opioid; Drug high; Morphine; Abuse liability; Analgesics; Drug formulations
• ISSN: 0962-9343; 1573-2649
• DOI: 10.1007/s11136-011-0012-7

Purpose 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.