Postmarketing studies program to assess the risks and benefits of long-term use of extended-release/long-acting opioids among chronic pain patients.

Background: Among patients with chronic pain using long-term opioid therapy, the incidence of opioid abuse, addiction, overdose, and associated death are not well quantified. The range of estimates for these adverse outcomes varies drastically and may depend on how they are measured (i.e. study definitions of outcomes) and on patient characteristics and opioid-use factors (e.g. regimen, daily dose).Methods: Based on a review of the literature, the US Food and Drug Administration (FDA) required companies that manufacture and sell extended-release/long-acting (ER/LA) opioids conduct as a postmarketing requirement (PMR) a series of observational studies to estimate the rates of treatment-emergent misuse, abuse, addiction, overdose, and death using validated measures. The companies formed a consortium, the Opioid PMR Consortium (OPC), to conduct the studies.Results: The FDA initially requested four observational studies (a cohort study, a questionnaire validation study, a code validation study, and a doctor-shopping validation study), but in order to achieve the FDA's goals of the 4 studies, OPC and FDA agreed to 10 observational studies (a prospective cohort study, a retrospective database cohort study, three questionnaire validation studies, two code validation studies, and three doctor-shopping validation studies). The studies are continuing through 2020.Conclusions: A series of 10 observational studies was or are being conducted in response to the FDA's postmarketing requirement. All studies have been feasible to conduct, although a validated algorithm for measuring abuse and addiction in databases was not successful.

Development and impact of prescription opioid abuse deterrent formulation technologies.

BACKGROUND: Millions of patients are treated with opioid analgesics (OpAs) to relieve pain. Unfortunately, these medications are subject to abuse and/or unintended misuse. Abuse deterrent formulations (ADFs) represent an intervention strategy to decrease abuse/misuse without affecting patient access. The Food and Drug Administration (FDA) has issued Draft Guidance "Abuse deterrent opioids, Evaluation and Labeling" and is currently actively pursuing scientific input on this issue. METHODS: The development of ADF technologies was reviewed using peer reviewed journals describing OpA post marketing studies, web sites containing FDA announcements on product approvals and manufacturer product use profiles. RESULTS: Reviewed is the FDA recent approval of a product label describing the abuse deterrent characteristics of OxyContin(®) (physical barrier formulation), and the FDA determination that studies were insufficient for an Opana(®) (physical barrier) ADF label. Additional reviewed marketed OpAs with ADF technologies include: Suboxone(®) and Embeda(®) (opioid agonist/antagonist combinations), Oxecta(®) (aversion technology), and Nucynta(®) (physical barrier). Reviewed ADF technologies currently in development include: new physical barrier and aversion technologies, an innovative extended release formulation as well as novel polymer-opioid conjugates. As ADF technologies are part of a comprehensive intervention strategy to promote safe OpA use, additional components including governmental, community, and educational initiatives are reviewed. CONCLUSIONS: The outcomes of the recent ADF labeling applications for OxyContin(®) (Tier 3 approval) and Opana(®) (non-approval) suggest that the threshold for ADF labeling will be appropriately high. The presented findings indicate that ADF technologies can be a critical component of a comprehensive strategy to promote the safe and effective use of OpAs.