Q&A: New tool may help guide drug development for pediatric migraine

A new FDA-funded registry developed by researchers at the Duke Clinical Research Institute and partners could help answer important questions about an understudied area in medicine: pediatric migraine.

Christoph Hornik, MD, PhD, MPH, co-principal investigator for the Pediatric Migraine Registry, and colleagues created the registry to better understand how pediatric patients with migraine respond to current therapies. Information in the registry could be used to support drug labeling and clinical trials investigating new drugs and drug classes in this patient population.

The registry — developed in collaboration with the nonprofit organization Miles for Migraine — has been implemented in 20 sites across 15 states in the U.S. It recently met its initial enrollment goal of 200 children aged 4 to 17 years.

Healio spoke with Hornik, who is also an associate professor of pediatrics in the division of critical care medicine and chief of the division of quantitative sciences at Duke University School of Medicine, to learn more about the purpose of the registry and how physicians in the United States can use the data that are being collected.

What prompted the development of this registry?

It was prompted by an assessment of the need to identify new tools to help pediatric migraine drug development. We conducted a comprehensive analysis of what we thought were the challenges of getting drugs approved for kids with migraine. We looked at those challenges to try to identify potential solutions and design tools to implement those solutions. A registry seemed like a good fit.

What are some of the barriers to drug development for pediatric migraine?

There are several obstacles to clinical trials. First, there is the issue of the placebo effect, which is quite significant in the migraine population. This creates some potential challenges in assessing response to therapy in traditional placebo controlled trials. The trials need to be large or designed to accommodate this placebo effect. We thought that a registry would be a good way to gather baseline patient data that could potentially allow investigators to prepare for clinical trials. Collecting more detailed information from patients before entering them into a clinical trial helps give a better sense of what their disease is currently like, how stable it is, and how they respond to current therapies. This may allow researchers to select patients who are more likely to respond to new treatments.

Second, migraine is a chronic disease that is debilitating in part because of its lack of predictability, which leads to a lot of life interruptions. So, we think that a particularly attractive way to study migraine going forward is to design trials that are directly between the study team and the patient. We try to minimize the number of times that participants need to visit a hospital or clinic to be enrolled in the trial. It’s certainly a type of disease that lends itself well to telehealth and direct-to-patient trials, which are trials where the interaction happens directly in the patient’s home with the help of technology or in-home visits. If we wanted to develop these types of studies in the future, getting more information about the patient without fully relying on clinic interaction might be a good idea.

In this registry, patients have the option to consent at the time of enrollment to allow us to recontact them if there is any opportunity for them to participate in future research. So, patients are effectively able to enroll themselves in trials that they are informed about through the registry.

What kind of information is stored in the registry?

It’s real-world data. We don’t collect any information that clinicians would not typically use. We built a series of questionnaires about migraine history, treatment and response to treatment. We use the PedMIDAS questionnaire to assess migraine-related disability. In addition to that, we collect typical demographics.

Patients have the option to consent for biospecimen collection and biobanking. We currently do not have any active analyses of biological specimens in the registry, but if patients wanted to, we could collect samples — blood, saliva or urine — and store them. At this stage, we do not have many samples, but this is a least a feature of the registry that we could expand upon if need be.

We use app-based migraine diaries to collect and integrate patient-reported data into our registry database. The app-based migraine diary is free-of-charge and commercially available; we did not create it for the registry.

One important thing to note is all the data are collected in a regulatory-compliant manner. The database is 21 CFR part 11 compliant, so if the FDA wanted to review these data to support drug labeling or any other regulatory recommendations, the data would theoretically meet those standards of data collection.

What are the next steps now that the initial enrollment goal of 200 participants was met?

We are actively working toward creating a virtual trial site for the registry, which would allow for participants to consent and enroll into the registry without having to be seen at a clinical site. It might be a hybrid design where patients continue to see their own migraine providers and enroll in the registry from home through an electronic consent module. Subsequently, they would be followed up through technology-based interactions with the study team. We call this a virtual expansion of the registry. It is another step toward this idea of direct-to-patient trials to minimize the interactions that patients need to have with the health care system as much as possible.

The registry itself is a drug development tool that is designed to support other efforts, so we are currently conducting projects with participant data. We have a series of interviews coming up with registry participants to look at clinical trial endpoint evaluations. We are also doing some work around trying to look at how closely patient-reported data in the migraine diary actually resembles what participants report to their practitioners in the clinic. It’s not really a validation of the migraine diary, but it’s an experiment. We are also actively looking to leverage the registry to conduct clinical trials of various designs. The registry addresses several limitations of past migraine trials, and it is flexible enough that it would provide value for a variety of different trial designs. So, while we think that the virtual direct-to-patient approach is highly promising in this disease area, we understand there might be cases where a site-based trial is going to be important. In addition to the data that we collect from patients, another important element of this registry is that it created a network of 20 U.S. sites that have enrolled participants and provided regulatory-grade data on those participants, which I think confers some level of confidence that these sites will be able to enroll participants in future clinical trials.

We have discussed the idea of an international expansion of the registry. There is nothing about the registry itself that prevents international expansion, and there is some interest. However, there are some funding considerations that make the timeline for that murky.

How can physicians in the U.S. use the data that are being collected?

All the participating sites have the option to request the data, and some sites are already using the data. We have visualization dashboards that pull data from the registry and summarize information that registry sites can use to benchmark themselves against other sites.

Registry sites and physicians who are not currently involved in the registry but want to access the data to answer a clinical question can send a request to our steering committee. The committee would review the request to see if the question being asked of the data is reasonable. To date, we have not received outside requests for data — so far, we have only processed requests for data within the participating sites.

However, this is absolutely a tool that we want the community to be able to use. We are open to requests and collaboration opportunities that maximize the registry’s value to patients going forward.

What kind of drugs can be developed based on information from the registry?

One of the reasons why we chose to focus on this therapeutic area is because there is a need for drugs in this population and there are obstacles to getting drugs labeled for kids. We thought this registry might be a good tool to develop innovations to overcome these obstacles. But another reason why we are focusing on pediatric migraine is because the timing seemed good, due to the fact that there are a number of drugs being studied and approved in the adult population, including entirely new classes of drugs such as CGRP pathway-related agents as well as new formulations of existing drugs.

Theoretically, any type of drug could be developed based on this registry. We know what drugs patients are taking, and we think that treatment is likely dynamic and changing over time. It is extremely common for newly approved drugs in adults to be quickly used off-label in children even before the safety and efficacy has been demonstrated in this population.

I should also mention there is research on nonpharmacological treatments for migraine, including device-based therapy, which is important. Information from the registry is not limited to research for pharmacologic agents but could also support device and behavioral intervention research.

Disclosures: Hornik reports receiving financial support for research from the non-profit Burrhoughs Wellcome Fund, the FDA, the National Institute for Child Health and Human Development, the National Heart Lung and Blood Institute and Purdue Pharma. He also reports receiving consulting or other service fees from Anavex Life Sciences, Purdue Pharma and Sarfez Pharmaceuticals.