Opioid labelling debated at FDA Hearing

Advocates and pain management groups aired concerns recently over a citizen petition to change opioid labeling during the first of a 2-day FDA hearing.

Speaking on behalf of the American Pain Society, Edward Michna, MD, an anesthesiologist at Brigham & Women’s Hospital in Boston, cited an anecdote in which an insurance company had denied payment of opioid therapy for a patient because the petition noted a lack of evidence for use in chronic pain.

“You can see how insidious this is,” Michna said. “Insurance companies will use any evidence they can to deny access to care.”

Wendy Foster, an advocate for the U.S. Pain Foundation, called the petition’s requests “extreme measures” that would block access for patients in legitimate pain.

The petition, filed last summer by Physicians for Responsible Opioid Prescribing (PROP) and Public Citizen, was signed by nearly 40 doctors, researchers, and public health officials aiming to make it more difficult for drug companies to market opioids for chronic, noncancer pain.

Specifically, it asks FDA to strike the word “moderate” from opioid labels in chronic pain; to include an upper limit (the equivalent of 100 mg of morphine a day) on the daily dose of opioid in this setting; and to limit therapy to 90 days in this group.

Any other uses then would become off-label, preventing companies from promoting the drugs for those uses in advertising, continuing medical education (CME) programs, and in other physician education settings.

FDA held the 2-day hearing largely to discuss the petition and to gather evidence on the safe and effective medical use of opioids, since the petition’s impetus was the lack of evidence for use of opioids in chronic, noncancer pain beyond 12 weeks — the genesis of the 90 days mentioned in the petition.

Directors of various FDA divisions, including anesthesiology, epidemiology, and controlled substances, heard testimony from patients, clinicians, and other entities with interests in opioid drugs.

Andrew Kolodny, MD, chair of psychiatry at Maimonides Medical Center in Brooklyn and co-founder of PROP, said interest groups have misinterpreted the petition as asking FDA to impose prescribing limits.

“That’s not our intention,” Kolodny said during the hearing. “We’re asking for a more narrow indication and more specific instructions on labels such that use beyond the suggested parameters would become off-label.”

He noted that off-label use is appropriate and legal, and at times can be the standard of care. It simply brings to the clinician’s attention the fact that there is a dearth of evidence for the long-term use of opioids in chronic pain, he said.

But Bob Twillman, director of policy and advocacy for the American Academy of Pain Management, charged that the “absence of evidence is not evidence of absence.”

Twillman also cited the challenges of distinguishing cancer pain from noncancer pain, as complications of cancer treatment that linger long after the disease is gone would fall into a gray area — a point cited by other groups that spoke out against the petition, including the American Association of Hospice and Palliative Medicine.

A recurring theme in recent FDA hearings on issues related to opioid prescribing has been striking a balance between access for patients in legitimate pain, and abuse and diversion. Again, patient advocates on both sides of the issue turned out, seemingly pitting families who lost loved ones to addiction against pain patients who feared losing access to their medications.

Gwenn Herman, a social worker with chronic pain and founder of the pain advocacy group Pain Connection, turned away from the panel during her presentation and addressed the bereaved families directly. She acknowledged their grief and apologized for their loss, but noted that their concerns are “two separate issues” that shouldn’t be at opposition.

Other speakers included representatives from Quest Diagnostics, maker of urine screens for toxicology analysis, and Covectra, which produces electronic technology to track prescriptions. These groups provided alternative approaches to risk management other than changing the label, according to Douglas Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research (CDER), who conducted the meeting.

Several public health researchers also presented evidence of addiction and overdose death rates that have tracked increases in prescribing of opioids over the last 10 years.

Kolodny referenced a similar panel held by FDA about 10 years ago that asked top experts in pain medicine whether opioid labels should be so broad.

“At that time, the people you asked who were working for industry, who were championing this effort, said yes, they wanted the broad label, and you’ve listened to them,” Kolodny said. “I think we have enough evidence today to suggest a very serious mistake was made, and it’s time to fix that mistake.”