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

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.

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.

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.

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.