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Conducting Clinical Trials in Pediatric Migraine, Advances in Care

Christina Szperka, MD, MSCE, the director of the Pediatric Headache Program at CHOP, offered her perspective on the challenges in conducting pediatric migraine trials and the advances made recently.

This is part 3 of this conversation. For part 1, click here. For part 2, click here.

Many neurologic diseases, such as Alzheimer disease and multiple sclerosis, experience challenges in conducting clinical trials of novel therapies because trial criteria force the patient populations to be vastly different from their real-world counterparts. For migraine, this is no different.

When it comes to pediatric migraine, things can be even more complicated. Part of this is because of the infancy of novel therapies in the field, with the lack of long-term data leading to parent hesitation in allowing their children to participate. Additionally, many pediatric patients with migraine report benefit from nonpharmacologic interventions, prompting a lack of interest in participating.

Despite this challenge—and those introduced by the ongoing COVID-19 pandemic—advances in care have still been made. New data have shed light on possible approaches to care, and rapid adjustment to a changing society has produced creative solutions to new problems.

In a conversation with NeurologyLive®, Christina Szperka, MD, MSCE, offered insight into this landscape of clinical trials and advances in pediatric migraine. As the director of the Pediatric Headache Program at Children’s Hospital of Philadelphia, she shared her experience with patient care and how things have changed since early 2020.

NeurologyLive®: When it comes to conducting clinical trials, has it been a challenge to include populations that mimic real-life patients? Has that made conducting trials like CHAMP more difficult?

Christina Szperka, MD, MSCE: It does. I would say that it depends on the study. Quite frankly, some of the studies that we're so excited about with some of these new medications have been relatively difficult to enroll for because they are brand new therapies for which we have no long-term safety data. A lot of parents are reluctant to put their child in a trial like that, with very good reason, right? Particularly if you say, “Well, if I give my child a vitamin for 3 months, they are likely to get benefit,” so why do they necessarily need to expose them to the risks of a brand new, unproven therapy? In many cases, the patients who are coming to me saying, “Can I please be in a trial,” are those who have continuous headache who have failed multiple therapies and are therefore ineligible for the trials. I do think that that is a mismatch. And I understand why the trials are designed to say, “Let's address regular, more straightforward, earlier-on migraine,” because if, as has been the case with the adult studies, they can demonstrate benefit with low risk of adverse effects, then that would be potentially superior to what we have available.

Again, the CHAMP study showed that there were a lot of adverse effects in those meds, particularly topiramate. So, if we have another therapy that does have does ultimately have long-term safety and fewer adverse effects, that's easier in terms of adherence, maybe then, the prescription patterns will eventually shift. But for right now, early on, when they meds have only been approved in adults for a couple of years, it's hard sometimes for parents to say, “I want to put my child in that study.” That's something that we wrestle with, and it just depends. Sometimes it's patients who are more refractory but might just sort of been able to eke into those studies and they are happy to do it. Or sometimes it's like a child whose parent has tried a specific therapy and found it really beneficial, and they want to participate. Those are, sometimes, the ones we're seeing in trials.

In the past couple of years, what's been the biggest advance, despite all the adjustments that have needed to be made amid COVID, in terms of pediatric migraine care?

There have been a couple of things. One, in migraine in general. We, particularly early on, when we had the shutdown period, we couldn't do our usual procedures, and we couldn't have in-person clinics as easily and things like that. A group of us got together and wrote a paper essentially describing other alternative options, and they were clearly off-label, and we stated them as such. Essentially, we gave the evidence where it existed—it was very limited—and said, “Here are some things you might try orally for status migrainosus, if you can't bring a patient in to do IV meds or a nerve block or something like that.” I found that really interesting because, in some ways, it was one of the best received papers I've ever written, even though it had the least data behind it. It was like, “Here's what you can try in real world care if you are getting stuck.” It's the tips and tricks that people whisper down the lane but can't publish because they didn't have enough data. Suddenly, we were like, “Well, here it is. Here are the tricks,” because we all have to help each other. Even in those cases, sometimes, insurance was allowing us to use some of the new medications off label for older teenagers more easily than they had otherwise, which, quite frankly, was the request of the paper to them—to the insurers. Please give us flexibility, both hands are tied, we can't do anything right now that we would usually do can't do, we need a little bit of flexibility. That was really helpful to actually have that flexibility. Some of it has been maintained, some of it has been pulled back. But sometimes, we will say, “Hey, we started this med a couple of years ago, it's really helpful, let’s continue.”

Is there anything else that has changed amid the pandemic?

The other piece that that jumps to mind is honestly, is almost a humility. In general, the philosophy for the majority of us was that we needed to focus on school, and we needed to get children to go to school. I'm speaking in generally, right, because people definitely had different opinions before COVID-19. But to some degree, there was a lot of rigidity of this belief that in-person school is the norm, and therefore if you didn't get in-person school, we must figure out how to do that. Then COVID changed everything. There were some kids who did so much better when they weren't in-person at school. For some of them, it's because they were shy, and they did better when they didn't have to necessarily interact with a huge group. For some of them, maybe it was the lights and the noise and all of those other things. They would come to us and say, “This school building is really hard for me because of all these things.” There were a good chunk of patients who got much better when they were home.

Now, it's important for us to reflect and say, “Okay, maybe we don't need to think about this as a one-size-fits all approach.” Whereas I used to think of cyber school as not a great option for patients, I'm a little bit more forgiving about the concept. Now, maybe it is a good option for you. I'm always very careful to say that “I still want you to be sure that you're maintaining a good schedule you're sleeping, and you're eating, and you're doing all these things, and that you're socializing, and you're exercising because if you're not leaving your house, and you're not seeing friends, that's not a good for your development overall.” But if we can make sure we bring in the positives and don't just restrict it to all the negatives, then maybe we want to think more broadly. I do think that if you look at the rates of kids enrolling in things like cyber school, I think it certainly has gone up over the past year. I am curious to see how that plays out over the next several years.

I also think, to that end, it's important for us to recognize maybe we were wrong, right? We have to keep reevaluating and looking and learning from our patients and saying, “You know what, I thought this was the right way to be and I was wrong before and I'm sorry. Let me learn.”

Transcript edited for clarity.