Tuesday, July 10, 2012

U.S. FDA Launches the Long-Awaited Opioid REMS

Opioid REMSIn a long-expected, but rather anticlimactic, announcement, the U.S. Food and Drug Administration (FDA) approved a shared Risk Evaluation and Mitigation Strategy (REMS) for all extended-release (ER) and long-acting (LA) opioid analgesics. This program has been in the works for more than 3 years and is a prudent, but possibly inadequate, step in the right direction.

According to an FDA press release [here], “the REMS is part of a federal initiative to address the prescription drug abuse, misuse, and overdose epidemic. The REMS introduces new safety measures designed to reduce risks and improve the safe use of ER/LA opioids, while ensuring access to needed medications for patients in pain.” FDA Commissioner Margaret A. Hamburg, MD, stated, “The FDA’s goal with this REMS approval is to ensure that health care professionals are educated on how to safely prescribe opioids and that patients know how to safely use these drugs.”

The new REMS will affect more than 20 manufactures of ER/LA opioid analgesics who will be required to make education programs available to prescribers based on a newly finalized “FDA Blueprint for Prescriber Continuing Education” that is the cornerstone of the program [PDF available here]. It is expected that manufacturers will meet their obligation by providing educational grants to continuing education providers, who will develop and deliver the training to prescribers nationwide. Plus, there are some other responsibilities assigned to manufacturers.

The FDA describes three key components of the ER/LA-Opioid REMS:

  1. Training for prescribers: Based on the FDA’s Blueprint, continuing education (CE) programs for prescribers of ER/LA opioids will include information on weighing the risks and benefits of opioid therapy, choosing patients appropriately, managing and monitoring patients, and counseling patients on the safe use of these drugs. In addition, the education — expected to contain 3 hours of core content — will include information on how to recognize evidence of, and the potential for, opioid misuse, abuse, and addiction, and general and specific drug information for ER/LA opioid analgesics.

  2. Updated Medication Guide and patient counseling document: These materials will contain consumer-friendly information on the safe use, storage, and disposal of ER/ LA opioid analgesics.

  3. Assessment/auditing: Manufacturers will be expected to achieve certain FDA-established goals for the percentage of prescribers of ER/LA opioids who complete the training, as well as to assess prescribers’ understanding of important risk information over time. The assessments also cover whether the REMS is adversely affecting patient access to necessary pain medications, which manufacturers must report to FDA as part of periodically required assessments. After FDA review of these assessments, the agency may require additional elements to achieve the goals of the program.

It is anticipated that the first CE activities under this REMS will be available to prescribers no later than March 1, 2013. Of the 320,000 prescribers of ER/LA opioids in the U.S., it is expected that 25% will complete the CE course by the end of the first year, 50% after 2 years, and 60% within 3 years. As courses become available, they will be posted at a special website, here: www.ER-LA-opioidREMS.com (currently under construction).

Presently, the FDA notes, the ER/LA-Opioid REMS is a voluntary-participation program: there is no mandatory requirement that prescribers take the training and no precondition to prescribing ER/LA opioids to patients. However, the Obama Administration endorsed a mandatory training program on responsible opioid prescribing practices in April 2011 as part of its comprehensive plan to address the so-called “epidemic” of prescription drug abuse. The program, which would be linked to DEA registration by providers, would require legislative changes that are being pursued by the Administration.

According to the press release, “The FDA continues to support this [DEA registration] approach, but absent the needed legislation, intends to exercise its authority to require mandatory elements for companies and voluntary elements for prescribers — all of which are important and necessary steps to help curb the misuse and abuse of ER/LA opioid analgesics, without being overly burdensome.”

More information is available in several additional documents from the FDA:
> Opioid Drugs and Risk Evaluation and Mitigation Strategies
> Opioid REMS Questions and Answers
> Consumer Update

COMMENTARY: Apparently, finalization of the “Blueprint” document triggered these current announcements from the FDA and the official start of CE-course development. We first began writing about this REMS initiative several years ago, in 2009 [here], and it has been a long and tortuous path to this point, with many delays along the way.

The FDA’s process was slow and deliberative, listening to and taking into account input from all stakeholders: manufacturers, patient advocates, and the many associations, organizations, and special interest groups that might be affected. After all the chest-thumping and sword-rattling along the way, the FDA should be commended for finally settling on rational and conservative first steps that focus on education; the REMS requirements could have been much more burdensome and restrictive had not common sense prevailed.

The new shared REMS for ER/LA opioid analgesics will supersede individual REMS that already have been developed for some but not all of these products. Certainly, more and better (and, ideally, evidence-based) education on opioid safety — for healthcare providers and patients — is a prudent and potentially effective strategy for change. However, we still have some reservations about the decided-upon approach:

  • First, at various times, some factions advocated for including both short-acting (eg, immediate-release) and longer-acting (ER/LA) opioids in a totally comprehensive REMS. In response, the FDA’s contention has been that most of the problems are associated with the longer-acting medications; yet, prescriptions for ER/LA opioids account for roughly less than 10% of all opioid analgesic prescriptions annually.

    Some authorities claim that, despite their vastly lower prescribing rates, ER/LA opioids comprise a disproportionately large share of the annual 15,000 opioid-overdose deaths in recent years. While this may be the case with methadone, for specific reasons discussed in a recent UPDATE [here], evidence supporting inordinately high mortality rates with most other ER/LA opioids is of poor or questionable quality.

    Still, we can appreciate that, if nothing else, at this stage of the “opioid-REMS experiment” the FDA did not want to take a chance on disrupting the much-needed prescribing of short-acting opioids for acute pain conditions, such as after surgical or dental procedures. This seems wise.

  • Second, it seems that the government could have developed and implemented educational programs concerning these issues long ago; perhaps not the FDA, but other agencies have stepped forward in the past in providing such education. When the government wanted to support and aggressively promote the use of buprenorphine as an opioid-addiction therapy, the Substance Abuse and Mental Health Services Administration (SAMHSA) developed and extensively conducted around the country, for years, a one-day course free-of-charge for all interested prescribers.

    In the case of ER/LA opioids, the entire burden is being placed on product manufacturers, with no support from government agencies. Manufacturers must fund REMS program components but, to avoid undue influence or bias, the actual development and implementation of educational content is expected to be by third-party CE providers, such as professional associations, academic centers, or medical education firms. Therefore, manufacturers carry the full weight of responsibility for costs and outcome success, but with no authority to control development, implementation, and audience participation.

  • Third, what the government clearly would prefer is for the REMS professional-education component to be mandatory and a part of DEA registration that permits only those qualified to prescribe ER/LA opioid medications. This was done with buprenorphine for addiction, noted above, and the mere 3 hours of training presently required by the ER/LA REMS, if used as a contingency for a DEA waiver to prescribe these products, should not be burdensome for healthcare providers.

    In almost all states, healthcare providers are required to participate in extensive continuing education anyway to maintain licensing. In fact, we wonder if longer than a 3-hour course in safe ER/LA-opioid prescribing would be more appropriate and effective in achieving goals of the REMS program. Practitioners who are reticent to invest the relatively modest time in completing opioid-REMS education possibly should not be treating chronic pain conditions with these strong medications in the first place.

It will be interesting to see how this opioid-REMS experiment proceeds and if it will, hopefully, help rather than hinder the care of patients with chronic pain. Meanwhile, the FDA appears to be in “watchful waiting” mode — ready to step in with more extensive requirements if this current approach fails to meet expectations.

eNotifications Don’t Miss Out. Stay Up-to-Date on Pain-Topics UPDATES!
Register [here] to receive a once-weekly e-Notification of new postings.