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.