Carl L. Roland

Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations

Abstract Terminology related to prescription drug misuse and abuse is inconsistently defined. An expert panel developed consensus classifications and definitions for use in clinical trials. Abstract As the nontherapeutic use of prescription medications escalates, serious associated consequences have also increased. This makes it essential to estimate misuse, abuse, and related events (MAREs) in the development and postmarketing adverse event surveillance and monitoring of prescription drugs accurately. However, classifications and definitions to describe prescription drug MAREs differ depending on the purpose of the classification system, may apply to single events or ongoing patterns of inappropriate use, and are not standardized or systematically employed, thereby complicating the ability to assess MARE occurrence adequately. In a systematic review of existing prescription drug MARE terminology and definitions from consensus efforts, review articles, and major institutions and agencies, MARE terms were often defined inconsistently or idiosyncratically, or had definitions that overlapped with other MARE terms. The Analgesic, Anesthetic, and Addiction Clinical Trials, Translations, Innovations, Opportunities, and Networks (ACTTION) public–private partnership convened an expert panel to develop mutually exclusive and exhaustive consensus classifications and definitions of MAREs occurring in clinical trials of analgesic medications to increase accuracy and consistency in characterizing their occurrence and prevalence in clinical trials. The proposed ACTTION classifications and definitions are designed as a first step in a system to adjudicate MAREs that occur in analgesic clinical trials and postmarketing adverse event surveillance and monitoring, which can be used in conjunction with other methods of assessing a treatment’s abuse potential.

The Abuse Potential of Remoxy®, an Extended‐Release Formulation of Oxycodone, Compared with Immediate‐ and Extended‐Release Oxycodone

OBJECTIVES Remoxy(®) is a water-insoluble, highly viscous oral formulation of oxycodone extended release (ER) currently in development. The primary objective was to determine the abuse potential of Remoxy under fed conditions relative to oxycodone ER and immediate release (IR) under fasted conditions and compared with placebo (treatment group X). A secondary objective was to evaluate abuse potential under reversed fed/fasted conditions (treatment group Y). DESIGN   Phase I randomized double-blind triple-dummy placebo- and active-controlled 6-way crossover study. Setting.  A single US site. PATIENTS.  Healthy men and women aged 18-50 years who were nondependent, recreational opioid users. Interventions.  Remoxy 40 mg whole and chewed, oxycodone ER 40 mg whole and crushed, oxycodone IR 40 mg crushed, and placebo. OUTCOME MEASURES The primary endpoint was the drug liking subscale of the drug effects questionnaire assessed by various pharmacodynamic parameters. Secondary endpoints included additional pharmacodynamic measures, chewing duration, and safety measures. RESULTS In treatment group X, Remoxy whole (fed) and chewed (fed) had a significantly lower abuse potential compared with oxycodone ER (crushed, fasted) and IR (fasted) based on the majority of pharmacodynamic parameters of interest for the primary endpoint (drug liking subscale) as well as secondary endpoints. Treatment group Y showed generally similar results. CONCLUSIONS The abuse potential of Remoxy when taken whole or chewed was significantly lower than two comparators with known abuse potential, including oxycodone IR and crushed oxycodone ER, under the fed/fasted conditions tested. Remoxy may be associated with a reduced risk potential for abuse.

A double-blind, randomized, placebo-controlled trial of a diazepam auto-injector administered by caregivers to patients with epilepsy who require intermittent intervention for acute repetitive seizures

A diazepam auto‐injector (AI) has been developed for intramuscular administration to treat acute repetitive seizures (ARS). The objective of this study was to evaluate the efficacy and safety of the diazepam AI when administered by caregivers to control an episode of ARS (ClinicalTrials.gov identifier NCT00319501).

Economic Burden of Prescription Opioid Misuse and Abuse: A Systematic Review

ABSTRACT A 2009 systematic review found that the total cost of prescription opioid abuse in 2001 in the United States was approximately

Research design considerations for clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations

8.6 billion and medical expenses were estimated to be

Safety and effectiveness of long-term treatment with diazepam auto-injector administered by caregivers in an outpatient setting for the treatment of acute repetitive seizures

15,884 for opioid abusers and

A clinical trial to determine if corelease of morphine and naltrexone from crushed extended-release capsules induces withdrawal in opioid-dependent patients: a descriptive analysis of six patients.

1,830 for nonabusers. A search was conducted for English publications on the cost of prescription opioid abuse and misuse from 2009 to 2014. The initial literature search identified 5,412 citations. Title and abstract review selected 59 for further review. The final review process resulted in 16 publications for inclusion that examined cost from the payer perspective. Mean costs to the payer for abusers were

Clinical Outcomes during Opioid Titration following Initiation with or Conversion to Remoxy®, an Extended-Release Formulation of Oxycodone

23,000–

Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration

25,000 per year and excess costs approximately

Prevalence of Prescription Opioid Misuse/Abuse as Determined by International Classification of Diseases Codes: A Systematic Review

15,000 per patient. Three papers were identified that presented societal costs, including direct and indirect costs such as criminal justice costs and costs associated with lost productivity. The strongest evidence suggests that societal cost is in excess of