New Opioid Data May Lowball Harms: FDA Advisors

 New research about the harms of long-acting opioids may underestimate risks, members of two FDA advisory committees said Monday.

Data did not represent large segments of the U.S. population and relied on varying definitions of misuse and abuse, including a pain-adjusted outcome measure for opioid use disorder (OUD), noted members of the FDA's Anesthetic and Analgesic Drug Products and Drug Safety and Risk Management advisory committees at a joint meetingopens in a new tab or window.

"There's a real risk of reporting underestimates of some of these adverse effects and giving the wrong message," said James Floyd, MD, MS, of the University of Washington in Seattle. "Should any of those specific findings go on a label? I would say no."

There's "no compelling robust evidence that long-term therapy with opiates has any efficacy on outcomes that matter to patients," Floyd continued. "That is the most important thing -- and that actually does not show up on the label -- and it changes the equation entirely about how we think about these harms, the potential harms, and trying to estimate the quantity of them."

In a prospective study -- one of two analyses discussed at the meeting -- the 12-month incidence of long-acting opioid misuse was about 22%, the incidence of abuse was roughly 9%, and about 1-6% had moderate-to-severe OUD, depending on the definition. A cross-sectional study suggested about 15% of people on long-acting opioids had misuse, 6% had abuse, and approximately 3-6% had moderate-to-severe OUD.

The studies were postmarketing requirements the FDA requested in 2013 of all companies with new opioid analgesics for chronic noncancer pain, including extended-release, long-acting opioids. The agency called the non-voting meeting this week to ask its advisory committees to discuss and interpret the data.

Allergan, Endo, Hikma, Janssen, Mallinckrodt, Pfizer, Purdue, Rhodes, and Zogenix pharmaceutical companies were in the original postmarketing requirements consortium.

Most participants in the studies were white, and the findings were based on surveys conducted with English-speaking patients. Many participants were recruited at university-affiliated centers or lived in West Coast regions.

Despite limitations, several FDA advisors thought the findings carried a clear message.

"The results are quite consistent," said Krista Huybrechts, MS, PhD, of Harvard Medical School in Boston. "Risk is high, it increases with higher dose, and it increases with longer duration."

The misuse and abuse estimates were "in line with a lot of what we've seen in the published literature. Settling on what numbers to put on a label seems like a big challenge, given that there's going to be a range in the empirical data that we have," said William Becker, MD, of Yale School of Medicine in New Haven, Connecticut.

"I would also like to point to the elephant in the room ... which is the lack of long-term data on effectiveness," Becker emphasized. "If we're talking about the impact a label may have on guiding practice, I think we would have to acknowledge that the label as it currently stands is an implication that there is known effectiveness data, but it truly is not."

Quantitative data from a better-designed study might be warranted on a label, suggested Elizabeth Joniak-Grant, PhD, of the University of North Carolina at Chapel Hill, who attended the meeting as a patient representative.

"In research that I've done with general lay people and also with clinicians, everybody's definition of a high risk or a low risk is exceedingly different. That being said, I don't think this study by itself is sufficient to warrant giving those numbers."

Ascribing a dichotomous risk above a certain dose also can have consequences, observed Adam Gordon, MD, MPH, of the University of Utah in Salt Lake City. "We know that higher doses are always going to contribute higher risk to the patient populations," he said.

"I worry -- and we learned from the CDC guidelines -- that these [numbers] can be weaponized in some ways," Gordon added. "If you have a label change that gives a certain dose as a target dose, we'll have regulators, states, lawmakers, and insurers trying to drive everybody down to that certain dose. And we know that there are some untoward outcomes associated with that action."

https://www.medpagetoday.com/neurology/opioids/115442