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Podcast/Transcript: Opioid Drugs and Risk Evaluation and Mitigation Strategies (REMS)


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Moderator: Heidi Marchand
April 20, 2011
12:00 pm CT


Welcome and thank you for standing by. At this time all participants are in a listen-only mode until the question and answer session of today’s conference. At that time you may press star 1 on your Touch-Tone phone to ask a question. I would also like to remind parties that this call is being recorded. If you have any objections, you may disconnect at this time. I would now like to turn the call over to Heidi Marchand. Thank you. You may begin.

Heidi Marchand:
Thank you very much. This is Heidi Marchand from FDA’s Office of Special Health Issues and thank you for joining us this afternoon. The purpose of today’s call is to update you, our healthcare professional stakeholders, patient advocates and industry sponsors, on FDA’s announcement related to the new risk management program for all extended-release and long-acting opioid drugs.

You may be aware a news conference was held yesterday on April the 19th led by the Office of National Drug Control Policy announcing the Administration’s Prescription Drug Abuse Prevention Plan. And a videotape of that replay is available on the National Drug Control Policy’s Web site which can be found at www.whitehousedrugpolicy.gov.

In conjunction, FDA sent a letter to each of the multiple drug sponsors responsible for manufacturing and marketing the extended-release and long-acting opioid drugs to inform them that a risk evaluation and mitigation strategy will be required for these drug products.

An example of the letter that was sent by the FDA to drug sponsors informing them of this new requirement is available on FDA’s Web site at www.fda.gov/drugs.

The letter to the drug sponsors is a link and is described as post-approval REMS notification letter. Also on this FDA Web page you will find a complete list of the products affected and the name of the drug manufacturers also referred to as sponsors that are responsible for marketing those products in the United States.

 With that I would like to introduce the FDA’s panel of experts that are with us today to tell you more about FDA’s program and introducing the new safety measures for certain pain medicines.

With me today is Dr. Janet Woodcock, the Director of FDA’s Center for Drug Evaluation and Research. In a moment Dr. Woodcock will describe to you FDA’s new risk management program for all extended-release and long-acting opioid drugs.

She is also joined by Dr. Douglas Throckmorton, the Deputy Director Center for Drug Evaluation and Research; Dr. Gerald Dal Pan, the Director of Office of Surveillance and Epidemiology and the Center for Drug Evaluation and Research; Dr. Rob Rappaport the Director Division of Anesthesia and Analgesia and Addiction Drug Products and the Center for Drug Evaluation and Research; and Dr. Sharon Hertz, the Deputy Director of the Division of Anesthesia, Analgesia and Addiction Drug Products for the Center of Drug Evaluation and Research. Hello, panel.

Dr. Woodcock will now make some remarks and upon completion of her remarks, we will open the phone lines to address questions you may have. With that, Dr. Woodcock, please proceed.

Dr. Janet Woodcock:           
Thank you and good afternoon everyone. As you probably heard yesterday the Obama Administration announced its Prescription Drug Abuse Prevention Plan, which includes action in four major areas to reduce prescription drug abuse and other harm from drugs, education, monitoring, proper disposal and enforcement.

Yesterday in conjunction with this and as part of the plan, the FDA announced a new risk management program for all extended-release and long-acting opioid drugs. These include hydromorphone, oxycodone, morphine, oxymorphone, methadone, transdermal fentanyl and transdermal buprenorphine. These drugs are used primarily to manage chronic moderate to severe pain.

Our plan is formally called a Risk Evaluation and Mitigation Strategy or REMS and this supports the Administration’s broader plan, particularly the education and drug disposal part.

Let me stop and explain what a REMS is for those of you who are not familiar with this regulatory term. A REMS is a risk management plan that FDA can require of a drug company or companies to manage serious risks associated with the drugs. A REMS goes beyond the drug’s written prescribing information and can include tools such as patient medication guide, a communication plan and other elements to assure the safe use of the drug.

Every REMS is developed to address the unique benefit risk profile of either a drug or a drug class. So each REMS is specific to the problems that it’s trying to address. This new REMS will provide education and tools to doctors and other prescribers for reducing the risks of these drugs but just as important it provides tools on appropriate pain management making sure that patients who need these medications can get them.

The REMS was designed with these two important goals in mind, number one, reduce the risk and, number two, ensure access for patients. And we have tried hard to strike that balance in the REMS. In fact I personally think the REMS as you’ll hear about it that it might actually improve access for patients who are in pain and actually need these medications.

Why is that? It’s not always clear to doctors who should get these drugs and how to best help patients manage their pain but sometimes physicians are reluctant to prescribe these drugs and patients suffer as a result. At other times, prescribers may prescribe the drugs too freely and in large amounts putting patients at risk or potentially others at risk.

So let me talk about the extent of opioid use in this country and why the new REMS is important. The medical use of the extended-release and long-acting opioids is extensive with nearly 23 million prescriptions dispensed. This is out of a total of 257 million opioid prescriptions dispensed in the United States in 2009. But unfortunately abuse and misuse of the drugs is also extensive and also is harm simply from the intended medical use and harmful consequences of intended medical use.

In 2002 we know that over 29 million Americans age 12 and older used extended-release or long-acting opioids for non-medical purposes. By 2007 that number had grown to 33 million. In 2006 there were nearly 50,000 emergency department visits related to opioids. And in 2007 our figures show that nearly 28,000 Americans died from unintended consequence of drug use and of these, nearly 12,000 involved prescription pain relievers. This problem is huge and it continues to grow every year. So it’s clear that we need to take some action.

But we also of course have doctors trying to be responsive to patients in pain. The prescribers have to think about whether the patient should get an extended-release or long-acting drug or not or maybe they should get a different medicine such as an immediate release opioid or a non-opioid pain killer. Or if a physician has a concern that a patient might unintentionally misuse a drug or intentionally abuse it, the patient actually might need referral for treatment for drug addiction, abuse or dependency instead of more opioid prescriptions.

Through the tools provided by this opioid REMS, we hope that all prescribers will become more knowledgeable and feel more comfortable about when to prescribe and when not to prescribe these extended-release and long-acting opioids as well as other opioids and know which patients should get these medicines and under what conditions or circumstances. We think this will lead to better pain management and decrease the overall risks and harm that we’re seeing.

So another part of the opioid REMS relates to drug storage and disposal. A very important aspect of the safety of these drugs is proper storage and disposal. We know that many of the actual drugs that are abused or related to unintended overdoses that are particularly having adolescents and young people in the hospital and dying come from the medicine cabinets of people around the country. So storage and disposal is extremely important.

Long-acting, extended-release opioids because of the amount of drug they contain are especially dangerous and lethal when they get in the wrong hands. So they need to be stored where others can’t get them. And where they’re no longer needed, patients must understand how to dispose of them properly and safely.

So let me go into some of the details of the actual opioid REMS. Yesterday the FDA sent letters to the 32 drug sponsors who market these drugs. There are 16 brand name companies and 17 generic companies stating they will have to meet new requirements to assure the safety of the medicines, requiring all the companies to use a single shared system for their REMS to provide standardization. And this is done specifically to minimize the burden on healthcare of having all these products have a REMS.

The first element of the program is prescriber education and this will include education on patient selection and counseling, for example, how to select appropriate patients, what are the risks of using a product, how to initiate therapy with the drugs and how to counsel patients about product risk and appropriate use.

And the education program will also inform prescribers on how to recognize the potential for and evidence of addiction dependence and tolerance. Although much of the training will apply to all extended-release or long-acting opioids, part of it will focus on communicating specific product information such as specific risks or side effects from a specific opioid.

Now the way this information is going to be transmitted is we’re asking the drug sponsors to develop educational content. And this is based on the outline of the needed content that’s been developed by the FDA and you can find us in the letter that’s posted on our Web site. So we have each line of the content more or less specified.

After this is developed - and we would expect that there be a single content for the general content about recognizing the right patients and many other aspects of the program and then there will be drug-specific information that will be contributed by each sponsor. After this is developed, FDA will review and approve the content, the factual content. So this will be FDA approved and regulated and it will not be promotional or anything like that. It will be factual information.

And in fact there’s some very good examples of information like this that have been developed by say the federation of state medical boards and others that have much of the factual information in there already. So we think much effort and thought has already gone into what do prescribers need to know before they prescribe these.

But we expect with this opioid REMS that the current existing drug information on all of the existing drugs will be added and also if there’s any new drugs approved that fit into this category, that information would be added as well. So the training can be kept up to date on what people need to know about these products.

After we approve the content then we expect that unrestricted grants would be offered to accredited CME providers and other continuing education providers for the appropriate medical and prescriber groups. And we think having the training provided by CME organizations will be an incentive and will not create new burdens on prescribers since they have to be registered and renew their registration on a periodic basis or their licensure or their certifications and so on. So most healthcare professionals are engaged routinely in continuing education activity. And we would expect this training to be provided without cost to the healthcare professionals.

So that’s the educational program along with the content of the education. Now in the educational program there will be discussions of patient prescriber agreements. Patient prescriber agreements are a tool that can be used to help manage pain - individuals who have pain and are using opioids. And these agreements describe the patients responsibility such as the importance of adhering to dosing and how to store and dispose of the drugs and other matters that are important for an agreement between a prescriber and a patient when the patient is taking these kind of medications.

And actually the FDA is working with many other stakeholders, many who are on this call I think, to work to develop a standardized template for patient provider agreements so that they can be used broadly.

Also the educational materials will include a medication guide. This is for patient counseling and this will be a sheet that describes in patient-friendly language the key information needed to use the drug safely. The medication guide must be provided to the patient when the time the drug is prescribed and again when the drug is dispensed at the pharmacy.

And industry monitoring and evaluation is another part of the REMS. The proposed REMS will require sponsors to assess on a specific time table whether the REMS is achieving its goals. And metrics will include pre-specified percentage of prescribers who’ve been trained and also an assessment, an independent audit, of the quality of the educational materials used by the CME providers.

Also sponsors will have to evaluate, and we’ll work with them on this of course, whether the REMS is adversely affecting patient access to necessary pain medication.

Now obviously the overall metric of this program or overall outcome we hope is to reduce some of the adverse consequences that pertain to these drugs. That will be a longer - that evaluation will take longer and in the meantime we’ll be assessing these intermediate metrics.

So as far as what FDA - how FDA will monitor this program, this new REMS is more or less a stepwise approach to ensuring that prescribers are trained in appropriate pain management. The - we have approved at the FDA over the last 15 or so years a wide variety of new dosage forms and new types of powerful pain medications and we want to make sure that all the individuals prescribing these medications are fully up to date and trained on how to use them. And we also need to ensure that patients not only continue to have access but they understand how the use the products as well and particularly store and dispose of them also.

We’ll be working with each sponsor as they implement the REMS and be actively monitoring the entire REMS program and we’ll have metrics for success.

Now this is a stepwise approach and in fact if we determine the REMS program is not meeting expectations, there are more steps that we can take. We also plan to work with outside organizations and we’re doing that under the Safe Use Initiative to pursue non-regulatory activities such as patient provider agreements and so forth that can help improve the safety of these meds.

Now as was announced yesterday, under our REMS, the training - it’s not mandatory for healthcare professionals to take these educational courses that are going to be offered. However, the administration will pursue modification of the Controlled Substance Act and that will require of course a legislative change to incorporate mandatory training for prescribers of opioid drugs as a condition of obtaining DEA registration.

So we strongly support such an approach because we think if people - if individuals are going to write for these controlled substances, they should have the basic knowledge in order to use them well.

Now of course this is contingent on the legislation and if for some reason the legislation doesn’t pass, we do have other ways we can accomplish this goal but we feel this is the most efficient and effective way to accomplish this training.

So to close, on the timeline the drug sponsors must submit a draft REMS within 120 days and the timeline for development and implementation of this will undoubtedly take several - many months and is projected to be completed in early 2012. Very soon we’ll be meeting with drug sponsors who are affected to discuss further the details of the opioid REMS and the implementation.

In the meantime of course healthcare professionals should continue to prescribe these opioids as usual; however, of course we encourage everyone to thoroughly discuss the benefits and risks of these products with their patients as well as their disposal. Patients who are currently taking these drugs should continue to take them as directed and of course patients who have concerns about their medications should consult with their healthcare professionals.

Just to finish we have - this has been a very long and complicated effort that the FDA has been engaged in. Many of you on the call have been working with us in helping us as we struggle with all the issues of maintaining access and dealing with this epidemic that’s occurring. I want to thank all these organizations and the individuals who took time to help us and gave us very valuable advice and we intend to continue this collaboration and remain open to input as we implement this very significant program. Thank you.

Heidi Marchand:      
Thank you, Dr. Woodcock, for those comments. They’re very comprehensive and I know we’ll probably have some good dialogue and questions. But while we’re waiting for your questions to come in, I do invite those folks on the call today to provide feedback to us after the call about how we can best work with your organizations to educate your members about important safety information. We’re also interested in your feedback about how we did on developing the information posted on our Web site.