Core outcome measures for opioid abuse liability laboratory assessment studies in humans: IMMPACT recommendations

Abstract

A critical component in development of opioid analgesics is assessment of their abuse liability (AL). Standardization of approaches and measures used in assessing AL has the potential to facilitate comparisons across studies, research laboratories, and drugs. The goal of this report is to provide consensus recommendations regarding core outcome measures for assessing abuse potential of opioid medications in humans in a controlled laboratory setting. Although many of the recommended measures are appropriate for assessing the AL of medications from other drug classes, the focus here is on opioid medications because they present unique risks from both physiological (e.g., respiratory depression, physical dependence) and public health (e.g., individuals in pain) perspectives. A brief historical perspective on AL testing is provided and then those measures that can be considered primary and secondary outcomes and possible additional outcomes in AL assessment are discussed. These outcome measures include: (1) subjective effects (some of which comprise the primary outcome measures, including drug liking); (2) physiological responses; (3) drug self-administration behavior; and (4) cognitive and psychomotor performance. Prior to presenting recommendations for standardized approaches and measures to be used in AL assessments, the appropriateness of using these measures in clinical trials with patients in pain is discussed.

The ALERRT® instrument: a quantitative measure of the effort required to compromise prescription opioid abuse-deterrent tablets

“…The consistency in the ALERRT ratings by the four laboratory technicians was high but with some of the variability that would be expected under real-world conditions. Drug liking is considered a reliable assessment of the likelihood of abuse of a drug, and human abuse potential studies can be used to analyze the likability of various intact and physically manipulated formulations of drugs (16,17). As drug users attempt to manipulate prescription drugs to change the route of administration and produce greater euphoria (17), a significant increase in time and effort required to achieve maximal euphoria may play a role in decreasing the likelihood of abuse of a given drug formulation.…”

“…In the United States, overdose with opioids, including heroin, resulted in 28,647 deaths in 2014, with a 14% increase in the age-adjusted rate of drug overdose deaths compared with 2013 (4). Prescription drugs were associated with 22,767 overdose deaths in 2013; 71.3% of these deaths (16,235) involved the use of opioids, the most frequently prescribed drug category in the United States and the most common treatment for chronic pain (3,5).…”

Instruments to Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: An ACTTION Systematic Review

“…Further, we examine whether the instruments provide sufficient data regarding cross-sectional reliability and construct validity, longitudinal construct validity (ie, hypothesized relationships between concepts over time), 58 ability to detect change, and responder definitions to meet regulatory standards for assessing benefits and risks in clinical trials. 21,58, 60 We do not review measures for abuse liability assessment in early-phase studies with substance abusers 16 or those designed to predict the development of inappropriate medication use. 14,57 It is important to acknowledge that most instruments reviewed were developed for other purposes (eg, diagnosis of substance use disorders), rather than identifying current inappropriate medication use events occurring in clinical trials.…”

A critique of Minozzi et al.'s pain relief and dependence systematic review, and authors' response

“…They concluded that: 'The available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk of developing dependence'. The proposition that taking opioids long term for pain compared to taking them for nontherapeutic purposes is markedly less likely to cause a drug use disorder has implications for addiction theory, policy, diagnosis, liability assessment and counseling [10,[22][23][24].…”