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

Abstract

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.

Oral Human Abuse Potential of Oxycodone DETERx® (Xtampza® ER)

“…Moreover, the pharmacodynamic data show that there is a significantly lower abuse potential for both chewed and intact oxycodone DETERx compared with the control, IR oxycodone. Statistically significant differences in abuse potential in clinical studies have been associated with clinical importance . However, the impact of oxycodone DETERx as an abuse‐deterrent formulation will not be fully established until it has been available on the market, allowing for confirmation that a lower abuse potential in controlled studies translates to lower rates of abuse in the community.…”

Assessment of Pharmacodynamic Effects Following Oral Administration of Crushed Morphine Sulfate and Naltrexone Hydrochloride Extended-Release Capsules Compared with Crushed Morphine Sulfate Controlled-Release Tablets and Placebo in Nondependent Recreational Opioid Users

“…In addition, although the primary PD endpoints used in the present study are well accepted as indicators of abuse potential, demonstration of reduction in misuse, abuse, and diversion with MSN awaits evaluation in real‐world epidemiological studies. Only one study to date has examined the relationship between laboratory measures of abuse liability (VAS ratings) and real‐world indicators of misuse and abuse . A retrospective analysis by Eaton et al.…”

Positive subjective measures in abuse liability studies and real-world nonmedical use: Potential impact of abuse-deterrent opioids on rates of nonmedical use and associated healthcare costs

“…2 In 2010, drug overdose was the leading cause of injury death. 3 Of the 22,134 overdose deaths involving pharmaceuticals, 75% involved a prescription opioid. 4 In 2011, nearly one-third of the 1.4 million emergency room visits attributed to the non-medical use (NMU) of pharmaceuticals were related to opioids.…”