US FDA Launches Study Of Prescriber Perceptions About Abuse-Deterrent Opioids

The agency is assessing whether to use different language to describe addiction and abuse deterrence.

The US FDA is attempting to answer a question central to its approach to the opioid epidemic: do physicians understand the limitations of abuse-deterrent opioid formulations?

The agency is funding a study to assess the knowledge, attitudes, and behaviors about abuse-deterrent formulations (ADFs) among opioid prescribers and pharmacists, including their understanding of the meaning of addiction and abuse deterrence. It will also explore possible alternative language for describing these products.

Sharon Hertz, director of FDA's Division of Anesthesia, Analgesic, and Addiction Products, noted the research project at the Nov. 14 joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and Drug Safety and Risk Management Advisory Committee. At that meeting the panel voted 10-7 for approval of Mallinckrodt PLC's abuse deterrent formulation of immediate release oxycodone. (Also see "Mallinckrodt's Abuse Deterrent Oxycodone IR Narrowly Wins US FDA Panel Backing" - Pink Sheet, 14 Nov, 2018.)

"We have heard concerns from past committee members and other sources that prescribers are not reading the label and for some reason they are perceiving a Schedule II opioid as either not addictive anymore or that the formulation makes it abuse proof," Hertz said. "We have a formal study looking at the extent of these misperceptions. And then we are going to do some work to try and figure out if we need to change the terminology" so that products can't be assumed to do something that the terms are not meant to convey.

FDA told the Pink Sheet that the agency contracted with RTI International to conduct the research under an existing competitive Blanket Purchase Agreement, and the agency's Project Advisory Group "will be intimately involved in all research tasks throughout this project." The group consists of several experienced social and behavioral scientists, as well as opioid and ADF subject matter experts, including physicians from the Center for Drug Evaluation and Research's Office of New Drugs and Office of Surveillance and Epidemiology.

The research project consists of three iterative phases that will build on the findings of each previous phase. The first phase involves focus groups, which will be followed by a survey aimed at getting more representative findings. The last phase will be an experimental study in which ADF-related content, including that related to the terminology, will be compared experimentally.

Concern ADFs Will Increase Opioid Prescribing

In discussing the potential public health impact of Mallinckrodt's product, advisory committee members expressed concern that there would be a misperception that the abuse-deterrent formulation of oxycodone is safe.

"My primary concern with these products is the effect of these formulations on prescribing behavior," Brandon Marshall, Brown University School of Public Health, stated. "We can imagine maybe a 20% reduction in diversion and abuse due to this formulation that can be completely offset by a 25% increase in inappropriate prescribing due to misperceptions of the safety of the ADF formulation in the prescribing community."

Jeanmarie Perrone, Perelman School of Medicine at the University of Pennsylvania, agreed with Marshall. "There is absolutely a huge risk of increasing opioid prescribing," she said. "This really might cause a crazy shift in the other direction," with people who've routinely been prescribed hydrocodone shifting to this product because of the ADF label.

"I think it's the doctors reading headlines problem. These things seem like they're safer" and that is the misperception that is going to get escalated all throughout clinical practice, Perrone added. "People who read the subtext may understand that these are not any safer, or maybe a fraction safer, but not the risk of overprescribing."

Hertz noted that the agency does not have any data that suggests there is increased prescribing of extended release formulations with abuse-deterrent properties over previous non-ADF products. "In spite of a number of approved abuse-deterrent formulations, the prescribing numbers overall are dropping, including the prescribing numbers of abuse-deterrent formulations such as OxyContin," she said.

The agency has approved 10 opioid analgesics with abuse-deterrent labeling, nine extended-release products and one immediate release product.

Steven Meisel, Fairview Health Services/Healtheast Care System in Minneapolis, pointed to the need for FDA to define the term abuse and what constitutes sufficient data. He said the agency needs to rethink its guidance to industry on developing opioid products with potentially abuse deterrent properties, which was issued in 2015.

"The agency needs to go back and sort of rethink the model and strategy as to what exactly is intended to be accomplished. Because every applicant will have a different frame of reference for what we mean, or the agency means, by the term 'abuse' and what population, what situation, what settings" it applies to, Meisel stated.