REMS Redesign: FDA's Opening Statement to Stakeholders

Center for Drug Evaluation & Research Director Janet Woodcock kicked off FDA's two day feedback meeting on the REMS July 27 with a construction analogy: FDA is still in the process of building a new house, but it is clear that there needs to be a redesign. Here are her opening remarks, from the official transcript of the meeting.

We've had about two and a half years of experience with the FDA Amendments Act REMS provisions. We've heard concerns about the program from many affected parties, from industry, from prescribers, from pharmacy groups, patient groups and others. So we realize this program is not perfect. It's not meeting all the needs of all the groups involved. And it's on everyone's list to discuss as a part of PDUFA-V.

But in the meantime, we have to continue to approve drugs, and we need risk management programs for some of those drugs. So while we are continuing construction of the house, so to speak, we evaluate the need for redesign. This meeting is about how we might remodel our house.

The Rationale for REMS

Why do we need REMS? What is REMS fundamentally intended to do and why do we have them? Well, if you recall, once upon a time, many of us believed that prescribers could know everything and did know everything, and that they would be able to pick the perfect patients for any given intervention, make sure to remember all the tests and monitoring that were required to keep the people safe and so forth.

Now we know, and some researchers have always known, that was never true. But, in fact, with the plethora of drugs and other interventions that are available and the complexity of the modern health care system, patient safety is much more of a challenge even than it used to be.

So REMS are really a way to keep people safe when using drugs that are especially risky, given that health care is challenged to do that unassisted. Now we all understand that health care needs more systemic methods to keep people safe. The patient safety movement, in fact, is trying to bring that about, as well as many other efforts like for electronic health records, e-prescribing and many other interventions.

But we are far from where we should be.

So the ideal of prescribing, where the prescriber knows all the facts about the drugs that are being prescribed, and all the facts about the patients, everything a patient is taking, all the pertinent information about the patient's condition, we do not live in that world.

So if we want to introduce drugs with serious risks into that environment, we need other ways to keep patients safe. That was really the genesis of our restrictive distribution programs, and that is the thinking underlying the REMS.

The Benefits of REMS

Now REMS have benefits and liabilities or costs. Let me go over some of them. I'm sure they will be discussed in great detail today, by many of you with more direct experience.

On the benefits side, without these risk management programs, given the possibility of errors that would lead to very serious adverse events, some drugs would not be approved that can be approved with the REMS. So that's kind of a fundamental benchmark here. These drugs that come onto the market with restrictions of different sorts, in fact, they would not be approved unless they had those elements attached. Because right now, we have no other way to ensure that people will be kept safe, with the knowledge that we already have about how to protect people from the various risks of these drugs.

REMS are enforceable by the FDA. So compliance by all parties is more likely than with voluntary programs of different kinds. This is a benefit, because these are restrictions we've deemed are necessary.

Assessments of the effectiveness of the REMS are a required part of the REMS program, and this will help. I mean, you should never do interventions unless you have a plan to see whether or not they have been effective. The REMS, the statute and the program we've implemented, include assessments that are required to see whether the program is meeting its metrics, and if not, why not.

So those are all positives for the REMS programs that we have.

The Downsides

However, there are liabilities and downsides and tradeoffs that all of us have had to deal with.

First of all, the REMS must be imposed on the sponsors or the drug manufacturers, because that's who we, the FDA, regulate.

Given that this is partly an issue of safety and health care, that's a little bit of an awkward arrangement. Obviously, I think most people would feel a manufacturer who is introducing and marketing a drug that has potential serious liabilities should probably assume some of the burden for managing those liabilities. However, because FDA regulates the sponsors and then the sponsors are asked to influence health care—the prescribers, patient behavior, pharmacies—this is a somewhat awkward arrangement. The drug manufacturers are not in the best position to influence health care in that manner.

Secondly, the proliferation of REMS with elements to assure safe use—and we've had 14 approved since the Amendments Act was put in place—in addition to the 16 pre-Amendment Act deemed REMS.

These have led to a lot of confusion, which I think we will hear about today, because many of these are not identical to one another. Instead of having one system that we're operating, we're having a proliferation of different systems, of restrictions and other elements, all of which are directed at patient safety, but in different ways.

We know from human factors analysis that the more complicated programs we put into place, and the more that providers, pharmacists, health care professionals in general have to deal with complex programs, the higher the potential for error.

So there has to be some limit on the number of types of REMS programs that could be implemented. In addition, this multiplicity of individual programs that require physician and patient enrollment, as well as have different pharmacy systems are burdensome on our already burdened health care system, and we are very sensitive to that.

Again, these REMS would not be put into place unless we actually could not approve the drugs, absent some system for assuring that those risks are managed. So all of this adds up to added cost for health care.

Doctors have to be educated. Pharmacists and patients need educational programs. They need to use their time to come to grips with these programs and restrictions. The enrollment, confirming enrollment in such programs, monitoring of patients and it's not clear how much of these costs are borne actually by health care versus the drug manufacturer.

Some of them obviously are borne by the various participants, because it's their time and effort that has to be put in.

Because of the way the statute works and also the drug approval system works, each program is proposed by the drug sponsor. Then it's negotiated between the sponsor and the FDA, and is uniquely tailored to the risks of that particular drug. So we don't have a kind of standardization and consistency of the programs that would be ideal.

We have limited data to show how effective these REMS interventions are, and what is the cumulative effect of the burden and other effects of these programs on health care in general, as well as on health, on patient safety. We are working on a plan to assess the overall impact of the program, but we are not there yet.

We really look forward to input today on many of these issues. We will be initiating efforts in the fall to look at how to better integrate these risk management activities into quality improvements in health care, and to have some type of standardized and consistent approach to this.

So I strongly feel this is where we need to go, into a more single system for health care that can be utilized by various sponsors to initiate REMS.

MedGuide REMS, Role of Generics Pose Burdens on FDA

In addition, some provisions in the statute have proven challenging for us. There is something called a Medication Guide-Only REMS. This means that any time there's a Medication Guide, all the provisions of the REMS are triggered, and this has a fair amount of paperwork, for the sponsors and the FDA, and procedural aspects. We're not sure whether this is adding additional value.

We also know that MedGuides are not the optimum way to provide patients with information. We can all be united on one point: that we can do better than the current MedGuide format. We intend to move forward with a patient information leaflet that will use modern communication science and be much more informative.

Now there's also a requirement for a communication plan around the REMS. It can only be directed to health care providers, according to statute, not patients. So it's a communication plan about the drug.

But what's particularly problematic for FDA is that generics can't be required to have a communication plan, and FDA must implement the communication plan for innovator and generic drugs once generics are approved.

In FDA, of course, our resources are quite strained in many areas, and for us to implement communication plans to the health care community around specific drugs and maintain those communication plans and keep those lines of communication open is burdensome. I'm not sure how we actually could do that for a significant number of drugs.

Then with the presence of generics, of course, which is a good thing for health care costs, but it's challenging within the REMS program. REMS can't be required until after a REMS for the innovator is approved. So there's a sequencing. First, if we find out an innovator drug needs a REMS, we can negotiate with the innovator, get the REMS, then require it on the generics.

The generic and innovator are supposed to use a single shared system, and this gets back to some of the issues about this proliferation of different systems. Congress wanted to avoid that. But cost and issues of who controls this system have been impediments to timely implementation of shared systems.

In FDA, it's really not a good use of our time, although that's what we're having to do, is to broker these multiparty agreements on how a shared system for a given drug might be implemented amongst various generics and an innovator company.

Generics are not required to have a timetable for assessment of their aspects of the program. When you consider that generic prescriptions are about 75 percent of the U.S. market, you could see where this might put some type of a void into the whole REMS system.

So those are some of the provisions as we have been implementing this whole statutory framework that we have found very challenging.

I think that the turnout shows that there's a tremendous amount of interest in getting this right in our redesign, and making sure that we design a REMS system that really serves patients and prescribers in this country.

So today, our panel really welcomes your comments. Believe me, we will take them all very seriously under consideration as we try to move forward into a system that truly meets the needs of all the parties.