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Regulatory Focus™ > News Articles > 2019 > 2 > Study Evaluates How an Opioid’s REMS Did Not Work as Intended

Study Evaluates How an Opioid’s REMS Did Not Work as Intended

Posted 19 February 2019 | By Zachary Brennan 

Study Evaluates How an Opioid’s REMS Did Not Work as Intended

Research published in JAMA on Tuesday details how a US Food and Drug Administration (FDA) class-wide Risk Evaluation and Mitigation Strategy (REMS) did not prevent the inappropriate prescribing of transmucosal immediate-release fentanyls (TIRFs), which were approved solely for breakthrough cancer pain in opioid-tolerant patients.

The study, conducted by researchers from the Johns Hopkins Bloomberg School of Public Health and the Center for Science in the Public Interest, evaluates how FDA managed the REMS program to maximize appropriate TIRF prescribing and use. Researchers were able to conduct the study by evaluating thousands of FDA documents from 2012 to 2017, accessed via the Freedom of Information Act.

“Analyses of health plan data indicated that thousands of patients receiving TIRFs were opioid-nontolerant,” the study found.

And although surveys of pharmacists, prescribers and patients showed high levels of knowledge about proper TIRF prescribing, some survey items and claims-based analyses “indicated substantial rates of inappropriate TIRF use. Despite these findings, the FDA did not require substantive changes to the program,” the researchers wrote.

In addition, the REMS program had a noncompliance plan, but there were no reports of prescribers being disenrolled for inappropriate prescribing.


Accompanying the study is an editorial from a professor in the Program On Regulation, Therapeutics, And Law (PORTAL) at Harvard Medical School and the deputy editor of JAMA, who explain how the study raises serious questions.

“These findings highlight not just deficiencies with the structure and administration of the TIRF REMS, but problems with the REMS system more generally. Although the FDA has taken steps to improve this system in recent years, including efforts to standardize, integrate, and evaluate REMS programs, additional action is needed,” the editorial says.

The authors outline three necessary reforms:
  • “First, REMS should be designed by the FDA with manufacturer input—not vice versa—and be administered by a neutral third party paid by the FDA with newly instituted REMS user fees.”
  • “Second, REMS assessments submitted to the FDA should be publicly available. It is disturbing that it took 5 years for Rollman et al to secure the FDA documents on which they based their review.”
  • “Third, for REMS to ensure safe use of clinically useful prescription drugs with potentially significant adverse effects, the FDA will need to be more assertive in requesting specific analyses pertaining to the performance of REMS programs and in restructuring ETASU in response to concerns the analyses raise.”
JAMA Study



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Tags: opioid, REMS, TIRF

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