Access to the PPM Journal and newsletters is FREE for clinicians.

Are REMS Effective for Preventing Overdose Deaths from Extended-Release and Long-Acting Opioids?

January 27, 2020
Quantifying FDA's risk-mitigation program and its impact on opioid-related overdoses is proving difficult.

Few data are available that can accurately assess the impact of the Risk Evaluation Management Strategies (REMS) program for extended release/long-acting (ER/LA) opioids since its introduction by the FDA in July 2012. Provisional data reported by the CDC show a 5.1% drop in total drug overdose deaths from 2017 to 2018, which is the first decrease in more than two decades.1 Yet In 2017, opioid overdoses killed more than 47,000 people, and just over 17,000 of those deaths involved prescription opioids.2

The question remains whether the REMS program has made a measurable impact on mitigating risks from opioids. In a study published in late December 2019, researchers at the Johns Hopkins Bloomberg School of Public Health analyzed more than 9,700 REMS-related documents from inside the agency.3 They claimed that the effectiveness of the REMS program could not be adequately assessed because of flaws in study designs and data tracking. FDA, noting that there is still much work to do to bring down opioid abuse, responded back in a statement to FDANews, noting that the study’s authors “erroneously state that FDA abandoned efforts to evaluate the impact of the ER/LA opioids REMS program on prescriber behavior and patient outcomes.”4

Are Education and Compliance Working?
FDA originally proposed the REMS initiative to curb increases in prescription opioid abuse. Since 2013, opioid manufacturers have contributed millions of dollars to an education fund, known as the REMS Program Compliance (RPC), that was designed to create independent continuing medical education (CME) courses on safe prescribing. The program has been held up as a model of collaboration between the public and private sectors. Since 2013, 108 different CME providers have created more than 943 REMS-compliant activities according to the Accreditation Council for Continuing Medical Education (ACCME).5

However, because of an inability to measure outcomes of the education, it is nearly impossible to tell whether these programs have improved outcomes at the patient level. The ACCME measures the validity of CME programming according to a stepwise level of outcomes. Changes in learning and competence are measurable at the time of a CME activity. But the highly desired Level 5 outcome (performance), which measures whether performance changes identified by learners at the time of the activity were actually made, are more difficult to assess.6

“We can show that people are learning, and they are changing their behavior in practice, but we can’t demonstrate improved outcomes,” according to Norm Kahn, MD, convener of the Conjoint Committee on Continuing Education, which leads the education initiative. One reason is that it is difficult to get learners to complete follow-up surveys after completing a CME activity. Moreover, access to patient data is nearly impossible to obtain and linking the training to changes in opioid deaths is also difficult.

Whether FDA's REMS policy has impacted opioid overdoses remains unclear. (Image: iStock)

Quantifying Change

A few studies have attempted to quantify such changes. Esposito and colleagues analyzed rates of emergency department visits or hospitalizations due to opioid overdose among patients receiving one or more ER/LA opioids during the periods from July 2010 to June 2012 (before REMS) and July 2013 to September 2016 (after REMS).3 Data were taken from the HealthCare Integrated Research Database (HIRD) linked to the National Death Index and US Medicaid claims from four states.7

Incidence rates of opioid overdose did not meaningfully decrease after introduction of the REMS among the commercially insured patients, and they declined slightly in the Medicaid population. A slight decrease in overdose deaths was observed for the commercially insured. The authors found the higher rates of opioid overdose in Medicaid patients compared to commercially insured patients particularly striking. They speculated that certain patient characteristics were responsible for this discrepancy, such as a higher prevalence of psychiatric comorbidities and greater use of ER/LA opioids for opioid dependence maintenance therapy rather than pain management in the Medicaid population. In addition, this study did not measure whether health care providers completed REMS-compliant continuing education and could not account for the impact of other concurrent interventions targeting opioid analgesics.  

In another study of changes in mortality rates in ER/LA opioid analgesics after the implementation of REMS in three states, researchers estimated decreases in mortality rates ranging from 18.96% to 29.43%.However, these decreases were not statistically different from those for other drugs generally involved in overdose deaths but not impacted by the REMS initiative. In fact, when adjusted for the number of prescriptions dispensed, a significant decrease was observed only in Washington, one of the states whose data were analyzed. According to Black and colleagues, this finding suggests that the mortality rate corresponds to the general availability of the drug, as is supported by studies indicating that an increase in heroin use occurs concurrently with a decrease in prescription drug abuse.9

Data from the NIH do show decreases in prescription opioid-related deaths between 2012 and 2017,10 suggesting that prescribers have become more cautious in their opioid prescribing practices. Nevertheless, the amount of opioids prescribed per person, measured in morphine milligram equivalents (MME), was still three times higher in 2017 than it was in 1999.11 In 2017, more than 17% of Americans had at least one opioid prescription filled, with an average of 3.4 prescriptions dispensed per patient.12

Still Missing a Bottom Line

Whether REMS education was solely responsible for the decreases in prescription opioid deaths is unknown. FDA affirms in their statement to FDANews that, “the REMS program is just one strategy in a multi-faceted national effort led by the US Department of Health and Human Services (including the FDA) to reduce the risk of abuse, misuse, addiction, overdose and deaths due to prescription opioid analgesics, while still providing appropriate pain management to patients with critical medical needs.”4  Other interventions, including prescription drug monitoring programs, published prescribing guidelines, expanded treatment for opioid use disorder, and increased law enforcement efforts may have played a part as well.


Last updated on: March 12, 2020
close X