Adopt standard definitions of misuse, abuse, and addiction Conduct studies assessing:
Abuse liability, for example, in recreational substance abusers The likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation Misuse and abuse outcomes within randomized clinical trials enrolling low risk and high risk of abuse pain patients Post-marketing epidemiologic data
Features of a randomized clinical trial of a putative abuse-deterrent formulation ( pADF) to evaluate misuse and abuse outcomes in pain patients that should be considered in the design of the trial include:
Randomization to pADF, equianalgesic dosages of a comparable standard opioid formulation, placebo, and, if possible, a treatment with known low abuse potential; if no standard formulation exists, such as with a new molecular entity, consider comparisons with a well-characterized mu-opioid receptor agonist at what are expected to be equianalgesic dosages Use of a representative, diverse population of pain patients, including high risk patients with histories of abuse Prospective assessments of signs and symptoms of opioid misuse and abuse Trial personnel should be carefully trained to recognize potentially aberrant behaviors Blinding of investigators assessing outcomes Use of validated questionnaires and other measures to detect misuse, abuse, and addiction (e.g., urine drug screening) Clinical evaluation of potential cases Careful evaluation of pain relief in the different treatment groups to ensure that reduced abuse liability is not achieved at the cost of reduced pain relief Reasons for premature terminations from the trial should also be carefully evaluated.
Post-marketing surveillance should be used to examine misuse, abuse, addiction, diversion, and other adverse outcomes
|
