The New Opioid REMS: The FDA View

Laurie Scudder, DNP, NP; Gerald J. Dal Pan, MD, MHS


September 19, 2012

Editorial Collaboration

Medscape &

Editor's Note:
The growing problem of misuse and abuse of extended-release and long-acting (ER/LA) opioid medications has resulted in a serious public health crisis of addiction, overdose, and death. In 2009, there were nearly 425,000 emergency department visits involving nonmedical use of these products and over 15,000 deaths.[1]

In July 2012, the US Food and Drug Administration (FDA) approved a Risk Evaluation and Mitigation Strategy (REMS) for these products, the goal of which is to reduce inappropriate prescribing while ensuring continued access to these medications for patients who need them. This new REMS requires that manufacturers make available training for healthcare professionals who prescribe ER/LA opioid analgesics on proper prescribing practices and safe use of these powerful pain medications. Medscape spoke with Gerald J. Dal Pan, MD, MHS, Director of the Office of Surveillance and Epidemiology at the FDA, about this issue.

Medscape: Why did the FDA decide on a REMS that primarily focused on prescriber education?

Dr. Dal Pan: The FDA took a careful, comprehensive approach to developing the REMS for the ER/LA opioid analgesics. We met with stakeholders in industry and sought advice at numerous public meetings with patient stakeholders and health professionals. In 2011, multiple meetings were held with manufacturers of these products to discuss how to design and implement the REMS to help minimize the risks of ER/LA opioid analgesics, without placing an unreasonable burden on the healthcare system. Not surprisingly, there was a variety of different opinions, but one thing about which all the stakeholders were unanimous was the need for prescriber education. That was a clear, consistent, unanimous message, and is the reason we focused on prescriber education.

Medscape: Why is this program voluntary rather than mandatory?

Dr. Dal Pan: It is important to understand that it is mandatory for manufacturers of the ER/LA opioid analgesics to offer prescriber education based on the blueprint provided by the FDA. We expect that the sponsors will meet this obligation by supplying educational grants to accredited continuing education providers, who will then offer training to prescribers.

We expect companies to ensure that at least 60% of the approximately 320,000 prescribers of ER/LA opioid analgesics will take the training course within 4 years of the start of the training. As part of the REMS, companies will report periodically on actions taken to implement the REMS, including training provided by continuing education providers, the number of grants that the companies have awarded to providers, the number of prescribers trained, and other relevant information about the program. The FDA will review these REMS assessments and may require additional elements in the future if needed to achieve the goals of the program.

For prescribers, participating in these educational programs is voluntary but strongly encouraged. We believe that other stakeholders in the healthcare delivery system, such as state medical boards, hospital credentialing committees, and medical liability insurers, will provide additional incentives to prescribers to complete the training.

It is important to understand that this is part of a larger, comprehensive plan to address the epidemic of prescription drug abuse. In April 2011, the Obama administration endorsed a mandatory training program for prescribers of ER/LA opioid analgesics that would be linked to Drug Enforcement Agency (DEA) registration. However, a mandatory approach linking DEA registration to prescriber education would require legislative changes. While the FDA continues to support and endorse that approach, absent such legislation, we chose to exercise our authority to require companies to make voluntary prescriber training available. We think that will be an important step to help curb the misuse and abuse of ER/LA opioid analgesics without being overly burdensome.

Medscape: Prescriber behavior is obviously one outcome measure, but what about patient outcomes? How will those be measured? Fewer adverse events and deaths? Less addiction? Less diversion? How will that be determined?

Dr. Dal Pan: First, I think it is getting back to basics. It is important to understand that our foremost goal has been, and continues to be, reducing the risks of these medicines while preserving continued access for patients who need them. The REMS is designed to help prescribers prescribe these products safely. The focus of the REMS is not simply about the volume of prescribing. Rather, it is on ensuring that prescribing is appropriate and that prescribers and patients take the steps necessary to ensure the safe use of ER/LA opioid analgesics.

The FDA will monitor various sources of data that assess trends in the reporting of serious adverse events associated these medications, and we will also monitor data on the impact of the REMS on access to them by patients with chronic pain. The FDA and industry will monitor the progress of the training and take further steps as needed to ensure its success in making meaningful reductions in the risk posed by the opioid medications. If we determine that the REMS is not meeting its goals, we can reevaluate the program.

It is important to understand that the REMS is only one part of a multipart strategy on the part of the government and other stakeholders to address the problem of misuse and abuse of ER/LA opioid analgesics.

In response to your question about diversion, I would say that our focus is on ensuring proper prescribing and safe use. Diversion is a criminal activity, and the responsibility of that is with the DEA and other federal, state, and local enforcement agencies. We will continue to work in partnership with these organizations to support their law enforcement efforts and to share information and expertise.

Medscape: What is unique about these new safety measures? Will this REMS result in behavior changes when other strategies have not been successful? Are there other strategies under consideration to address this concern?

Dr. Dal Pan: One thing to understand about what's new with this REMS is that the FDA developed core messages to be communicated to prescribers in the FDA Blueprint for Prescriber Education. The FDA previously had not created a blueprint for an educational program, so that is something quite new with this program.

The FDA Blueprint will be used by continuing education providers of REMS-compliant training with funding, such as educational grants, from manufacturers. Education programs will be made available to prescribers at no or nominal cost. We anticipate that many of the providers of REMS-compliant training will be accredited providers who will develop and offer continuing education courses; these courses will be subject to an independent audit to ensure that their content and messages conform to the FDA Blueprint and are free of commercial influence.

The REMS is just one of several strategies being implemented to address the problem of prescription drug abuse. Other strategies reside mainly in the Office of National Drug Control Policy action plans and include legislative initiatives and state-based prescription monitoring programs, which are not managed primarily by the FDA.

Medscape: Why are short-acting products not included in this new effort? Is it possible that use of immediate-release products is "masking" the true size of the problem of inappropriate long-term use? In other words, will this REMS address all possible parts of the problem? Why is the FDA requiring a REMS for only ER/LA opioids?

Dr. Dal Pan: That is a good question that has come up in advisory committee meetings. The FDA is requiring the REMS for the ER/LA opioid analgesics because we have concluded that there is a disproportionate public safety problem associated with these products that must be addressed. The amount of an opioid analgesic in an ER/LA tablet or capsule is greater because these products are designed to release the opioid analgesic over a longer period, compared with the immediate-release opioid analgesics. Although improper use of any opioid can result in serious side effects, including overdose and death, this risk is magnified with the ER/LA opioid analgesics. That is why we focused on these products. Most of the prescribing principles in the FDA Blueprint can be applied to all opioids. That is important to understand.

Medscape: How are potential disruptions to appropriate patient access being addressed?

Dr. Dal Pan: The FDA does not expect that the REMS will affect patient access to their pain medicines. However, part of the REMS assessment will focus on drug utilization patterns, including evaluation of prescribing behavior and changes in patient access. We are not linking patient access to any part of the REMS and do not expect that there will be any effect on patient access, but we will be monitoring that.

Medscape: What about the parallel issue of patients self-limiting use of opioids because of fears of addiction? Is the FDA addressing that issue?

Dr. Dal Pan: Appropriate patient education is something that is very important to the FDA, and one of the features of the REMS is a 1-page medication guide that is designed to communicate key messages about the safe use of ER/LA opioid analgesics to patients. The medication guide is required to be issued to patients with each prescription. In addition, the REMS includes a patient counseling document that will be available to prescribers to use when counseling their patients on safe use of ER/LA products.

Medscape: You have noted that some of the key messages from the REMS are applicable to all opioids. Is that also the case with the patient education tools, or are they more specifically tailored to ER/LA products?

Dr. Dal Pan: Although many of the messages in the medication guide are applicable to the immediate-release products, each product has its own medication guide that is tailored to that specific product.

Medscape: Any concluding advice for our members?

Dr. Dal Pan: We believe that this REMS achieves an appropriate balance in ensuring safe prescribing of the ER/LA opioid analgesics while at the same time providing access to treatment for appropriately selected patients with chronic pain and minimizing the burden on the healthcare system. We see the REMS as one component in a multipronged strategy to address the societal problem of abuse and misuse of these ER/LA opioid analgesics. We are actively working with the sponsors of these products to implement the new REMS in a timely way, and we will be monitoring the success over time. If the goals are not met, we will consider other options to ensure that the benefits of the ER/LA opioid analgesics exceed their risk.