US FDA Advisory Panel Split On Value Of Education In Fentanyl REMS

Some members feel more education has important role in risk management for transmucosal immediate-release fentanyl products, while others think further education will be useless in ensuring the REMS meets its goals. 

Members of the US FDA's Drug Safety and Risk Management Advisory Committee and Anesthetic and Analgesic Drug Products Advisory Committee generally agreed that the goals of the risk evaluation and mitigation strategy (REMS) for transmucosal immediate-release fentanyl (TIRF) products are appropriate, but panelists were split on the value of more education to improving its performance

In a wide-ranging discussion on a series of topics related to the TIRF REMS at an Aug. 3 joint advisory committee meeting, several members lamented the just 30 minutes it takes to for providers to become certified in prescribing TIRF products.

Rutgers New Jersey Medical School Professor Lewis Nelson noted that the certification time for TIRF products is significantly shorter than that for buprenorphine, which he described as a "benign drug" in comparison.  He further complained that less than 100% of prescribers surveyed demonstrated a high level of knowledge across most of the key risk message questions.

"I think we are really doing our patients a big disservice," Nelson said. "You can't imagine asking a doctor where the liver is and having only an 80% chance of getting it right. And when you're giving out a drug this is dangerous, I think you should have to have 100% across the board on everything."

Notably, only 65% of prescribers surveyed by the TIRF REMS Industry Group (TRIG) in the most recent annual TIRF REMS assessment correctly stated that chronic non-cancer pain is not an approved indication for TIRF products. It was also found that these drugs are widely used in non-cancer patients.

But while education is an important component of the REMS, Nelson continued, it is not a solution to ensuring the REMS is meeting its goals.

"We clearly have to educate, but people do a lot of things that they know they shouldn't do," Nelson said. "And I'm not sure no matter what we tell them to do or not to do, they're going to do what they want to do.

"And I don’t know how we are going to be able to fix those things … But really we just have to make sure that these medicines are used safely and appropriately."

FDA noted in its briefing documents that there appeared to be an increase in the prescription-adjusted rate of TIRF abuse from the pre-to-post REMS period, and also an increase in spontaneous adverse event cases ending with a death or overdose. (See sidebar for related story.)

Other topics discussed throughout the meeting included use of TIRF products in opioid non-tolerant patients, the reliability of data used to assess the REMS, switching between non-bioequivalent products and barriers preventing access to TIRF products for patients who legitimately need them.

Is Education A Solution?

Several others also took a more negative view on the value of education, including Ronald Litman, a professor at the University of Pennsylvania's Perelman School of Medicine.

"We have so much physician education," Litman said. "It seems like every other day we are getting an email about another what we call 'learning links.' It takes up a lot of our time. I am very skeptical and cynical about the usefulness of these."

Steve Meisel, system director of medication safety at Fairview Health Services offered a similar assessment. He argued that education is insufficient to ensure that the prescribing and dispensing of TIRF meds to appropriate patients takes place.

"The only way to do that is to change how we do the work," Meisel said, floating the ideas of changing the patient-prescriber agreement form (PPAF) and engaging pharmacists more on the refill process.

Harvard Medical School Professor Martin Kulldorff agreed, adding that TRIG's recommendation to revise the PPAF to include a prescriber attestation confirming that a patient is opioid tolerant "might be much more efficient, in my guess, than many of the educational programs."

But University of New Mexico School of Medicine Professor Joanna Katzman took a different view, contending that "education very much can be helpful." She noted that 79% of patients receiving TIRF meds do not have cancer, and that only 22% of clinicians prescribing TIRF medications are in the oncology realm.

"So there's a huge disconnect going on right now with an undertreatment with patients who probably need cancer pain meds and then an overtreatment of patients getting opioids, really really potent opioids, who probably don't need them," Katzman said.

"If we really wanted to hone in and give these medicines to the patients who it's really designed for, maybe the patients with acute cancer pain, we need to do a much better job of educating oncologists and mid-level providers working in the cancer field that this is how it's used," she added.

Raeford Brown, a professor at the University of Kentucky College of Medicine, also argued in favor of more education in terms of time and exposure beyond the 30 minutes it currently takes to become a certified TIRF prescriber.

"I'm concerned that if we don't improve the education of these people that are prescribing TIRFS, that we'll begin to see an increase in prescriptions and more adverse outcomes," Brown said.

Goals Are Good, But Are They Being Achieved?

Several of the panelists feel the goals of the TIRF REMS – which include ensuring appropriate use, preventing inappropriate conversion, preventing accidental exposure, preventing accidental exposure and educating stakeholders – are appropriate.

But there were nevertheless concerns from those same members that the goals are not being met. Brown, for example, pointed to the inherent limitations of surveillance data, which include spontaneous adverse event reports.

"I see that after going through all this data how difficult it is to make an assessment on surveillance data," Brown said. "And I'm a little bit concerned that the TRIG may not have the availability of all the data that's required to continue to do that good work that you're currently doing."

Elizabeth Joniak-Grant, a sociologist at the National Coalition of Independent Scholars and the panel's patient representative, said the goals were "good," but raised concerns that only 43% of patients surveyed in the most recent assessment of the REMS correctly stated that they have to stop use of the TIRF product if they stop taking around-the-clock opioids. She further questioned whether the prescriber certification actually takes 30 minutes.

"We keep talking about this 30-minute training," Brown said. "I highly doubt that it's 30 minutes. Whenever anyone gets those video things … they never take 30 minutes. They take 15, maybe 20 at the most. So I think we should also be mindful of that."

More broadly, Litman said that "I think they are worthy goals, of course, but I don’t think they are effective. I don't see any evidence that they are."