iPLEDGE Updates for Dermatologists

In this podcast episode, host Larry Green, MD, speaks with Klint Peebles, MD, about the latest updates in the iPLEDGE program for isotretinoin. 

Dr Green is a clinical professor of dermatology at George Washington University School of Medicine in Washington, DC, and Dr Peebles is a dermatologist with Kaiser Permanente, Mid-Atlantic Permanente Medical Group in Washington, DC, and suburban Maryland.

Transcript
Dr Larry Green:  Hello, everyone. This is Larry Green, Clinical Professor of Dermatology at George Washington University School of Medicine. Welcome to another podcast with The Dermatologist.

Lucky enough to be joined here by Klint Peebles, dermatologist from the Mid-Atlantic Permanente group to talk about something very timely, and that's what's going on with iPLEDGE and what is iPLEDGE and what are we doing to keep iPLEDGE rolling for our patients.

Dr Peebles, thank you for being with us. I know you've been very active in this. Let's give us some background real quick about iPLEDGE. Why was it originally pursued? Why has it been there in place, and how long has it been in place?

Dr Klint Peebles:  Sure. Thank you for having me. First of all, as we know, isotretinoin or what used to be called Accutane, many years ago, that has another a lot of different forms. Now, it's been used as treatment for severe cystic acne for almost three decades now, a bread and butter to most dermatologists.

It's FDA approved, considered to be the most effective treatment for severe acne, but it's also used for other conditions like some of our genodermatoses like ichthyosis, among others. This medicine is something that has an FDA-mandated REMS program attached to it, and a REMS program is a risk evaluation and mitigation strategy. That is, as I said, mandated by the FDA, and it's been around for this particular medicine since 2005.

This is in place so that we are able to prevent fetal exposure to the drug because it is highly transgenic, can cause severe birth defects even after short exposure. It's been around solely to prevent unintended pregnancies, and it will link prescribers, pharmacists, and patients in a way that it results in counseling and information that's regulated to talk about the drugs serious risks and safe use conditions.

Dr Green:  Thanks. Let me ask you a question, Dr Peebles. Do you know if iPLEDGE, over the years, it's been around actually reduced isotretinoin-exposed fetuses?

Dr Peebles:  It's a great question. One of the interesting things is that we don't have any of iPLEDGE's data directly, and that has been a sticking point where we haven't been able to get data directly from them, but there are studies that have looked at this in a few other ways.

Most notably, in 2011, we had a study out of California that determined that the program did not greatly reduce the number of children with birth defects to parents taking Accutane or isotretinoin.

To the best of our knowledge, we have not seen that this program has actually done what it was originally intended to do. That's one of many reasons that many dermatologists, over the years, are so frustrated with the program, let alone the issues that we're seeing with this new rollout.

Dr Green:  Yes, I agree. I've personally have always been very frustrated with the program. It's not so easy to get a patient on therapy and to get things approved, especially if they've previously been enrolled and never started or never finished.

Now the last week or two, we all know it's become a major headache for us dermatologists. I can give you an example. My patients who take isotretinoin are now off because I cannot get into iPLEDGE. I try and follow the instructions to resign up, as they suggest, and nothing's accepted.

I called today, for example, at 9:00 AM when it opens to try and speak to someone live. Three and a half hours later, we're still on hold waiting for someone to answer that side of the staff listening for that. There's no way to get in. There's no way for patients to be taking their isotretinoin, so everyone's on a drug holiday right now, medication holiday.

What have you heard from the rest of the group? I know you're very involved in this. What have you heard from the rest of the country of dermatologists? Was it done to your patients’ and their patients’ care?

Dr Peebles:  A similar experience to you. Most of us are in that same boat throughout the course of the week. As you mentioned, it's been an evolving situation. There is some success that people are having shriveling throughout the week as they continue to try to access the site, but in general, it is well characterized as an access emergency.

That website, on Monday, when it rolled out, has been completely inaccessible or dysfunctional not just for prescribers but also pharmacists who are unable to get the RMA numbers that they need from the program to dispense the medicine, even if prescribers are able to confirm patients over prescribe it.

Also, provided patients are able to log on particularly those who can become pregnant and are able to answer their questions on the site. Existing patients have been missing from physician profiles. For instance, there are patients who were under my care that I had been prescribing up to the rollout, and now when I'm able to log back in, they're no longer there. Then on top of that, there are patients now on my list that haven't been active with me in years. As you mentioned, the whole times are averaging several hours, sometimes getting messages that the number prescribers are dialing is not in service.

Up until very recently, just today, for me personally, the links to the paper consent forms on the site were broken, not working. Then there's been some issues with being able to transfer among prescribers and providers for those who are relocating or something like that. It has definitely been a headache.

I am like you. I have a lot of patients who are starting their holiday travel, and they are not able to get their medication. Based on how this rolls out and where they're traveling to and how long they're going to be away, it may be a month or two before they're even able to get their medicine at best.

Dr Green:  It sounds like I'm trying to get it on the first step. I can't even re-enroll as prescribers. My patients can't get there. Even when I was able to do that, it seems like there's headache after headache after headache.

Dr Peebles:  Exactly. Right.

Dr Green:  That's great news. It's reality. Tell me what is happening, how can we get...Let's start with what our American Academy of Dermatology Association is doing to try and help us.

I know they've been very heavily involved in this trying to stop this since the AADA found out it was happening a little over a month ago and writing letters and letters. If you can walk us up to what's been happening with the AADA and what's been going on, I'd really appreciate that.

Dr Peebles:  First, it's very important for everyone to know that AADA has been working on this issue for a very long time, not just with this rollout issue that happened earlier this week. There's been a great deal of advocacy related to iPLEDGE for a very long time because we've all recognized there's been undue burdens and various issues affecting our practices in patient care associated with various sticking points of the program.

One of the issues is that this is something where we've had to learn how to advocate not just to advocate for the issues that are inherent to the program but also learning how to do that at all. What I mean by that is that universally shared here is a frustration about finding out exactly how iPLEDGE works, how it's organized and operated, and who's actually responsible for its day-to-day operations.

Getting that information has not been easy, and it's taken a lot of advocacy in and of itself. The process is convoluted in lots of transparency not all of which may be intentional but possibly sometimes related to non-disclosure details of private contracts.

As I mentioned earlier, REMS programs are FDA mandated, but the FDA doesn't otherwise have much to do with them other than that. Putting together, the REMS program is the responsibility of the drug manufacturers or the sponsors as they're called in this case for isotretinoin. There's a little more than half a dozen of them who have to put together a program that satisfies the FDA requirements for a REMS program.

For iPLEDGE, the sponsors have contracted out to Syneos Health for administration of iPLEDGE, but it actually still remains unclear as to whether Syneos is directly responsible for iPLEDGE or whether they in fact have further contracted out to another vendor to actually operate the website.

Syneos is claimed that there are up to two other system contractors responsible for maintaining the website and its call center. So far, to my knowledge, we really have no idea who these other contractors are. One of the reasons that Syneos gives for this December 13th switch was a change in vendor for the website. We still really don't have great confirmation about what's actually going on there, and that's one of the main issues that we're having with the transparency and how all of this works.

Over the last several years, the Academy has made a lot of inroads in finding out this information and advocating for some of these changes, whether that be gender neutrality and iPLEDGE patient categorization models or efforts to reduce access station frequencies for patients who can't become pregnant and other issues making it more amenable to working with patients via telemedicine.

We've made a lot of headway, but just in the last several months, it was announced that a change would be forthcoming, but dermatologists were not at the table. We were basically talking to them, but that was rather a one-way street with the FDA and Syneos and the drug sponsors, but there's changes were not made with any dermatologist or advocates at the table. All of this was behind the scenes.

Then they released some information about this bit by bit over the last few months. There was a lot of alarm there because we were very concerned about the rollout and all of the access and burden issues that it would present and despite the fact that we were reassured by FDA, by Syneos, by the sponsors, that this rollout would be seamless. It was anything but, in a word it was disastrous, as many have said.

There has been quite a bit of advocacy many letters written from AADA. There was an emergency meeting yesterday with FDA and the sponsors. Syneos was not at that meeting to my knowledge though. The FDA did verbalize that they were sharing our concerns. We're committed to coming out with the solution as best they can and working with the sponsors and Syneos.

There was also a commitment to working on a way for us to be at the table actively and have ongoing dialogue, but also AADA has been working on various media outlets, getting the word out, so the public knows what's going on.

We can reassure patients, reassure our dermatologist, and broader community that we are working as hard as we can to come up with a solution here. As you mentioned, as everyone knows, at this point, it has definitely been quite a trying time.

Dr Green:  Thank you very much. Thank you for that updates. Very informative. It seems like to summarize Syneos, which is a health organization of some sort, they have some activity in clinical trials as well. It seems to be the main administrator that subcontracts out to people we don't know, who may or may not be responsible for everything going on. It all goes back to Syneos where we had no input what was going on. The FDA had no input. Everything was contracted out to them, and they did everything on their own without any input from anyone else. Now, they're reaping the rewards of not involving everyone, it looks like.

Dr Peebles:  That's exactly correct. It's important to clarify again that the contracting to Syneos was done by the drug sponsors. FDA does not contract out to anybody. Congress basically gives FDA the authority to require these programs, as well as to suspend them but very little beyond that. That's why the FDA has had a limited role in a lot of this just because they don't really have the authority to address some of these issues directly and certainly not the day-to-day operations of iPLEDGE.

What we have asked—one of the major asks from AADA—is that we work on trying to suspend the program at least temporarily, because each day this goes on, patients are losing access, and the access problem is just amplified.

Even if we were to get a solid commitment to working on this now, it would obviously be several days, if not much longer, before we actually get back to a steady baseline with everyone being able to access iPLEDGE and do what it's intended to do. Especially even for individuals who are not able to become pregnant, having that suspension would be an important way forward, and that is one of the asks coming from AADA now, but it remains to be seen.

It's also worth noting that other aspects of organized medicine have been working on this too. American Medical Association, for instance, has had a conversation with FDA. A lot of people are concerned about this and working on it.

Dr Green:  That's one of the reasons why I know the AADA has asked the FDA to shut iPLEDGE down, at least temporarily suspend it, I should say, because the FDA, like you said, does have that authority, and those discussions are ongoing. I know over 1000 members of the AAD received the call-to-action letter from Ken Tomecki, our AADA president, and sent a letter the FDA knowing the problems. Hopefully, that's helping.

I hope everyone listening to this podcast will do the same. Go to the AADA President Ken Tomecki's letter from a few days ago and respond to that call-to-action to send a letter to the FDA because the more voices are heard, the more hopefully the FDA will listen.

Dr Peebles:  Absolutely. I think that prior to the meeting yesterday, the AADA's call-to-action center online had a way of making your voice heard, and still, it always helps to amplify this message on social media with pressure on all of these entities and stakeholders, whether it be FDA, Syneos, the sponsors. Hopefully, we'll be learning more about this process and get more transparency as the days go by.

My understanding now is that largely a lot of this is in the FDA's court right now as far as that suspension possibility. Then certainly the sponsors working with Syneos and Syneos working with these other contractors that may or may not exist, with these other vendors to try and make sure that there is a solution, but we are all hoping that it's coming sooner rather than later because, as I said, with every day, this is just getting worse.

As you mentioned, there are still many dermatologists who simply do not have access to the site. Really, just getting access to the site is the tip of the iceberg.

Because there's many issues that can come after that in terms of your patients being there, in terms of getting the consents done, finding the patients on the list, pharmacies being able to dispense, patients having their passwords and login information to go into the system and do what they need to do, definitely a lot of issues to be worked out.

Dr Green:  Thanks, Klint. What else can we, as dermatologists, do as well now working on for hours beyond whole? Since one of those dermatologists is at the tip of the iceberg group came in log in anymore, what else can us dermatologist do to help the situation, to get involved, and to move things forward?

Dr Peebles:  As always, this really drives home the point that, as dermatologists and as doctors, we don't work in a vacuum. We are subject, like it or not, to regulatory policies, government bureaucracy, all of that. Advocacy is just incredibly important.

Learning about these processes that we take for granted and participate in every day without really having a solid understanding of how they work, so learning more about those—voicing our concerns, taking time to participate in the academy, get involved, send letters and statements to your elected officials and working through organized medicine, whether that be AAD, AMA or whatever organization that you choose to work with.

Beyond that, certainly reassuring your patients that the medicine part of this has not changed. We are still using the medicine. We're still comfortable with the medicine, that access will hopefully not change once this issue has been sorted out, but just reassuring everyone that we're doing the best as we can to get this resolved as quickly as possible. Just to be a broader lesson, that advocacy is important, and it takes a village. We've had a lot of voices working on this.

I'm fairly certain that this would have been a much greater disaster and would be a much larger disaster had it not been for the very passionate involvement of the AADA, the leadership, the committee's access, the iPLEDGE workgroup, the AMA, all of their stakeholders that have been working very hard.

Dr Green:  I agree. Thank you so much, Klint. I know they've really been working tirelessly on that, all those people you mentioned. Thank you for your time. Thanks to dermatologists for putting this out. This is very timely information. Hopefully, guys, we'll have a good resolution to talk to you about in the near future.