The opioid epidemic in drug safety reporting systems
Last week, the founder of Insys Therapeutics, John Kapoor (76), was sentenced to 66 months in prison for orchestrating a scheme to bribe physicians to prescribe Subsys, a highly addictive form of fentanyl, to patients who did not need this drug. Five corporate executives, including Kapoor, were convicted of racketeering conspiracy. Under his leadership, John Kapoor exercised tight control over all decisions within Insys. At dinner parties, disguised as peer-to-peer educational lunches, prescribers received bribes and kickbacks for Subsys prescriptions and increased dosage. To ensure reimbursement, employees of Insys Reimbursement Center, posing as medical practitioner staff, obtained prior authorization for Subsys prescriptions through misrepresentation of the patients’ diagnoses .
Subsys is a potent opioid intended for use in cancer patients with breakthrough pain who are already on around-the-clock oral opioid painkillers . Transmucosal Immediate-Release Fentanyl (TIRF) Products, including Subsys, are so potent that the FDA requires a Risk Mitigation and Evaluation Strategy for them. The program consists of an educational program for physicians, pharmacists, and patients combined with a series of administrative measures. The program aims at limiting access to non-qualifying patients, prevention of inappropriate conversion, and accidental exposure of others .
In 2018, 10 million Americans misused prescription opioids. Of these, 2 million did so for the first time. Overall, 47,600 people died from overdosing on opioids . Of these, over 17,000 overdose deaths involved a prescription opioid .
The most commonly prescribed opioids are hydrocodone (Vicodin®) oxycodone (OxyContin®, Percocet®), oxymorphone (Opana®), morphine (Kadian®, Avinza®), codeine, and fentanyl . Prescription opioids most commonly involved in overdose are methadone, oxycodone, and hydrocodone . The highest number of reports in FAERS concerned oxycodone, hydrocodone, fentanyl, tramadol, and morphine. Estimating true incidence and prevalence in the population remains a challenge .
The opioid epidemic is a complex problem due to the existing overlap and often transition between prescription medications and street drugs and legitimate supply, misuse, abuse, and diversion. Monitoring and reporting systems are not always fully aligned as opioid reporting is done at the state level while the FDA FAERS database collects information nationwide. Would the epidemic be stalled earlier had better data been available in real-time?
 DOJ. (2020). Founder and Former Chairman of the Board of Insys Therapeutics Sentenced to 66 Months in Prison. Retrieved 3 February 2020, from https://www.justice.gov/usao-ma/pr/founder-and-former-chairman-board-insys-therapeutics-sentenced-66-months-prison
 DailyMed. (2020). DailyMed – SUBSYS- fentanyl spray. Retrieved 3 February 2020, from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=18a413e9-11e0-4a8f-86c0-d33b37b7b771
 Approved Risk Evaluation and Mitigation Strategies (REMS). (2020). Retrieved 3 February 2020, from https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm?event=RemsDetails.page&REMS=60
 HHS. (2020). What is the U.S. Opioid Epidemic?. Retrieved 3 February 2020, from https://www.hhs.gov/opioids/about-the-epidemic/index.html
 Walek, S. (2020). New Study Shows Physician-Targeted Marketing Is Associated with Increase in Opioid Overdose Deaths. Retrieved 4 February 2020, from https://nyulangone.org/news/new-study-shows-physician-targeted-marketing-associated-increase-opioid-overdose-deaths
 NIDA. (2020). Prescription Opioids. Retrieved 3 February 2020, from https://www.drugabuse.gov/publications/drugfacts/prescription-opioids
 CDC. (2020). Overdose Death Maps | Drug Overdose | CDC Injury Center. Retrieved 3 February 2020, from https://www.cdc.gov/drugoverdose/data/prescribing/overdose-death-maps.html
 Veronin, M., Schumaker, R., Dixit, R., & Elath, H. (2019). Opioids and frequency counts in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database: a quantitative view of the epidemic. Drug, Healthcare And Patient Safety, Volume 11, 65-70. doi: 10.2147/dhps.s214771