FDA Releases Final Risk Evaluation and Mitigation Strategies (REMS) for Extended Release/Long Acting Opioids Including a Prescriber Education Program

After three years of work the Food and Drug Administration (FDA) released its final Risk Evaluation and Mitigation Strategies (REMS) for extend-release (ER) and long-acting (LA) opioid medications.   This is the first time that the FDA has mandated a class wide REMS and much of what is recommended will be looked at closely for future class REMS. 

ER/LA opioids are highly potent drugs that are approved to treat moderate to severe persistent pain for serious and chronic conditions (list of ER/LA opioid products). The misuse and abuse of these drugs have resulted in a serious public health crisis of addiction, overdose, and death. 

After input from many stakeholders dating back to November 2011, the Food and Drug Administration (FDA) also released the “Blueprint for Prescriber Continuing Education Program” regarding the use of opioids.  The Blueprint contains core messages intended for use by continuing education (CE) providers to develop educational materials to train prescribers of long-acting and extended release opioids under the required risk evaluation and mitigation strategy (REMS) for these products (Opioid REMS).  

A REMS is a risk management plan that goes beyond requirements in the drug prescribing information to manage serious risks associated with a drug.  The Food and Drug Administration Amendments Act of 2007 gave FDA the authority to require companies to develop and implement a REMS when necessary to ensure that the benefits of a drug or biological product outweigh its risks.  

The CME Coalition offered its strong support for FDA’s efforts.  Andrew Rosenberg, Senior Advisor to the CME Coalition stated, “When there is a public health imperative, such as the abuse of long acting opioids, continuing education of providers is integral to improving patient outcomes and advancing the health of the country.”  Rosenberg continued, “We are pleased that the FDA views CME as a change agent and valuable resource to improve caregiver behavior in this vital area.” 

FDA’s final REMS is important because it marks a crucial step in federal health care agencies for recognizing the importance of CE and continuing medical education (CME).  The Agency’s logical and reasoned approach towards working with industry and accredited CE providers is a significant step in the right direction not only for patients and physicians but for the future of our healthcare system.  The opioid REMS represents the cross-collaboration of CE providers, industry, consumers, patients, and FDA.  Moving forward, FDA and these stakeholders should look at other opportunities to collaborate and use CE/CME to improve patient outcomes, reduce healthcare costs, and lower safety risks. 

Background 

Opioids are widely prescribed and carry a risk of abuse, misuse and death.  In 2009, there were nearly 425,000 emergency department visits involving non-medical use of opioid analgesics. According to estimates from the Centers for Disease Control and Prevention, 14,800 Americans died from overdoses involving opioid pain relievers in 2008.  In 2009, there were 15,597 deaths involving an opioid medication. 

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 is requiring a REMS for ER/LA opioid analgesics because FDA has concluded that there is a disproportionate safety problem associated with these products that must be addressed. 

“Misprescribing, misuse, and abuse of extended-release and long-acting opioids are a critical and growing public health challenge,” said FDA Commissioner Margaret A. Hamburg, M.D. “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.” 

All ER/LA opioid analgesics will be required to have a REMS.  The new ER/LA opioid REMS will affect more than 20 companies that manufacture these opioid analgesics.  Under the new REMS, companies will be required to make education programs available to prescribers based on an FDA Blueprint.  It is expected that companies will meet this obligation by providing educational grants to accredited continuing education (CE) providers to offer training to prescribers at no or nominal cost.  These CE activities must cover the content and messages of a blueprint developed by FDA for this purpose. 

The REMS also will require companies to make available FDA-approved patient education materials on the safe use of these drugs. The companies will be required to perform periodic assessments of the implementation of the REMS and the success of the program in meeting its goals. The FDA will review these assessments and may require additional elements to achieve the goals of the program. 

“We commend the FDA for taking action to save lives by increasing access to prescriber education,” said Gil Kerlikowske, director of the Office of National Drug Control Policy. “Since day one, the Obama Administration has been laser focused on addressing the prescription drug abuse epidemic and today’s action is an important contribution to this comprehensive effort.”  The new ER/LA opioid analgesics REMS is also part of the national prescription drug abuse plan announced by the Obama Administration in 2011 to combat prescription drug misuse and abuse. 

ER/LA opioid analgesics are widely prescribed medicines with an estimated 22.9 million prescriptions dispensed in 2011, according to IMS Health, which provides services and information to the health care and pharmaceutical industries. It is estimated that more than 320,000 prescribers registered with the Drug Enforcement Administration (DEA) wrote at least one prescription for these drugs in 2011. 

ER/LA opioid analgesics are associated with serious risks of overuse, abuse, misuse and death and the numbers continue to rise. According to the Centers for Disease Control and Prevention, 14,800 Americans died from overdoses involving opioids in 2008. In 2009, there were 15,597 deaths involving these medications – nearly four times as many deaths compared to 1999. 

“There are a limited number of options available for the treatment of pain.  Opioids are one option, but they carry a significant risk of misuse, abuse, overdose and death,” says Sharon Hertz, M.D., deputy director of FDA’s Division of Anesthesia, Analgesia and Addiction Products. “We’re trying to help physicians manage the risks and improve the safety of using these medicines.” 

“Misuse and abuse of prescription opioids is a complex problem and demands a holistic response,” said John Jenkins, M.D., director of CDER’s Office of New Drugs. “The new REMS program is one component of a multi-agency, national strategy to address this important public health issue.” 

Role of CME 

The central component of the ER/LA opioid analgesics REMS is an education program for prescribers (e.g., physicians, nurse practitioners, physician assistants).  There are approximately 320,000 prescribers of ER/LA opioid analgesics in the United States, and FDA expects companies to train 25% of these prescribers at the end of the first year following implementation of the program, 50% after two years, and 60% of them within three years of the start of training.  

It is expected that the first continuing education activities under the REMS will be offered to prescribers by March 1, 2013.  The FDA expects the training to take approximately 3 hours, but the CE providers will determine the number of CE credit hours that will be offered for the courses based on established standards for such determinations.  Key components of the ER/LA opioid analgesics REMS include: 

• Training for prescribers. Based on an FDA Blueprint, developed with input from stakeholders, educational 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 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. 
• Updated Medication Guide and patient counseling document. These materials contain consumer-friendly information on the safe use, storage and disposal of ER/ LA opioid analgesics. Included are instructions to consult one’s physician or other prescribing health care professional before changing doses; signs of potential overdose and emergency contact instructions; and specific advice on safe storage to prevent accidental exposure to family members and household visitors. 
• Assessment/auditing. Companies 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 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 periodic required assessments. 

It is expected that the first continuing education activities under the REMS will be offered to prescribers by March 1, 2013.  

Follow-up surveys will be conducted to assess prescriber understanding of the important safety information and assess whether the REMS is adversely affecting patient access to necessary pain medications.  Companies plan to offer additional funding to CE providers as an incentive to identify and track prescribers who take the REMS-compliant training and to perform follow-up surveys to assess the amount of information retained. 

As part of the REMS, companies will report periodically on actions taken to implement the REMS, including, for training provided by CE providers, the number of grants awarded to CE providers, the number of prescribers trained, and other relevant information.  If FDA determines that the REMS is not meeting its goals, the Agency will re-evaluate the 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 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. 

The FDA continues to support this 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. 

For patients, the benefit is two-fold. First, Hertz notes that health care professionals who participate in the REMS program will have more knowledge and awareness and can have frank conversations with their patients about the risks and appropriate use of opioids. A new patient counseling document will be available for prescribers to use when talking to their patients about these medications. 

The REMS also includes an updated Medication Guide—a paper handout for patients that the pharmacist will provide when a patient receives an ER/LA opioid medication.  This document, Hertz says, is written in plain language to simply explain how to safely use ER/LA opioid medicines. 

The American Academy of Pain Medicine, which represents 2,600 pain physicians and treatment teams, issued a statement supporting FDA’s issuance of the REMS for opioids, calling it a “huge leap forward.” 

 “Through proper education and training, opioids can be administered safely to patients and continue to be an important option in the treatment of chronic and debilitating pain that is suffered by millions of Americans.”  AAPM will also shortly be issuing a series of best practices for both patients and prescribers that can further reduce adverse outcomes associated with opioids. 

Purdue Pharma L.P., maker of several opioids including OxyContin®, also announced its support for FDA’s REMS for opioids.