Epigraph Vol. 25 Issue 2, Spring 2023

How and why to address medication adherence: Dr. Avani Modi and Dr. Desiree Williford

Reported, edited and produced by Nancy Volkers, ILAE communications officer

Most people with epilepsy have difficulty always taking their medications as prescribed. How can clinicians and patients talk about the issue and find solutions? Sharp Waves spoke with Dr. Avani Modi and Dr. Desiree Williford.

Listen below or download the episode.

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Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Podcast Transcript

00:00:00] ILAE: So thanks to both of you for, for joining me this morning.

And if you could maybe each of you introduce yourselves and you know, tell us a little bit about you. 

[00:00:12] Avani Modi: I'm Avani Modi. I am a clinical psychologist with a specialty in pediatric psychology. I'm a professor at Cincinnati Children's Hospital and the University of Cincinnati College of Medicine and I lead our center for Adherence and Self Management at Cincinnati Children's Hospital.

My primary role is research, clinical research in particular. And I've been conducting studies and had NIH-funded trials in pediatric epilepsy to improve adherence for the last 15 years. I'm very passionate about that population and the work that we do. 

[00:00:53] Desiree Williford: And then I'm Desiree Williford. I am a, post-doctoral research fellow, in my last year of training before I start my research faculty position. A lot of my work has also focused around adherence and self-management. I've been working really closely with Dr. Modi on some studies. And I'm also really interested in social determinants of health, which are really the conditions that surround our life and everything that affects our, our health behavior. So really excited to be here. 

[00:01:22] ILAE: Thanks to both of you. So we're talking about medication adherence in pediatric epilepsy. And can you talk about how common that is and what some of the consequences might be of not taking medication as prescribed? 

Avani Modi
Dr. Avani Modi (USA)

[00:01:39] Avani Modi: Yeah, so some of the first work I did really focused on understanding and pediatric epilepsy in particular what rates of non-adherence looked like and what we uncovered through a two year natural history study was that adherence rates are quite variable amongst kids with epilepsy. And we really found that about 60% of patients have some difficulty taking medicine as prescribed. Some of those patients may miss a few doses here and there while other patients are missing a substantial amount of doses.

So what that tells us is that there are lots of things that we can do to help in that space, but. Overall, it's about 60% non-adherence for the group, and unfortunately, the consequences of non-adherence are not good. We know that it can lead to increased seizures. We know that it could lead to increased hospitalizations and emergency room visits. We know there is almost a 300-billion-dollar cost associated with non-adherence globally. And we know that it certainly affects the symptoms that kids experience. Not just the seizures, but sometimes, you know, other symptoms that they may be experiencing from having continued seizures due to the non-adherence.

[00:02:59] ILAE: Great. Thank you. So when you say non-adherence, how do you define that? Is it, is it different in different studies or is there sort of an overarching agreement of what non-adherent means? 

[00:03:12] Avani Modi: That is a great question, Nancy. There have been a lot of terms used over the years. Some people used to use the term compliance. We've really moved away from that. We like the word adherence because it connotes this idea that. The physician or the healthcare provider and the patient are, have a shared understanding of what the treatment should be. And non-adherence is defined by, for example, oral medications, the number of pills, dose doses missed of a medication divided by the number of pills they're supposed to be taking.

The general, you know, cutoff people use is 80%, but that has really come from the adult hypertension literature in the seventies. And so what we know is across different pediatric conditions, what that bar is different. In HIV, for example, it is 95 to 98%. You need that level of adherence to have low viral load. In epilepsy in adults, we don't know that exact metric, but some of my own work, we've determined that 95% is the level that we need because we find a difference in the risk of seizures for those that are above 95% versus below 95% with higher risk in those below 95%.

[00:04:30] ILAE: Okay, so that's a pretty high bar we're talking about then. 

[00:04:33] Avani Modi: It is.

[00:04:34] ILAE: Just trying to establish where we were there. Okay. So the paper, you recently published a paper on sort of family-based adherence problem solving, and it used data from something called the STAR Trial, which I don't remember what STAR stands for, but I'm sure one of you could tell me what it stands for and what the, the objective of the trial was and why you started it.

[00:05:01] Avani Modi: So the STAR trial, which is Supporting Treatment Adherence Regimens, that's what the R is for. I almost forgot myself actually, was our first trial that we did that was fairly large here at Cincinnati Children's Hospital where we were testing a behavioral family systems therapy, where we teach families problem solving to address their adherence barriers.

And the, the goal behind it is really to have the families engage in a process to address barriers as they come up. So we were really looking at what the family's own individual barriers were. Some families might say they forget, some families might say their kid is throwing a temper tantrum when they give medications.

 And so we worked with each family on their identified barrier and taught them steps. To figure out solutions to that and then have them test whatever solution that they picked. And Desiree can talk more about this.

 And then sort of followed up with them over time on the solutions that they tested and tried. The work really stems from a larger literature in pediatric chronic conditions where this problem-solving approach has been helpful to improve adherence in self-management. And so it had never been applied to epilepsy and so we thought it was, it was time to test that, given the studies that we had done earlier on, showing that adherence was a problem. And there were no major interventions that had been developed for kids and families with epilepsy. So this was really our first shot at testing out an intervention to see if this approach would work.

It was also built off multiple pilot studies that we did. So before we launched a very large NIH trial, we wanted to get a sense like, do families like this, are they engaged? Will they do it? And so we had a lot of data to show that they liked it. And then, then we launched the randomized controlled trial.

[00:06:57] ILAE: Got it. Great. So how did you determine barriers to adherence in these families? And maybe what were some of the most common ones? 

Headshot of Dr. Desiree Williford
Dr. Desiree Williford (USA)

[00:07:07] Desiree Williford: Yeah, it's a great question. So just to back up a second, just in case and I know Dr. Modi gave really good examples, but we're thinking about barriers.

We're really just thinking about anything that gets in the way of taking their medication. And so because of the amazing studies that Dr. Modi and colleagues have done in the past, we really knew that there were already a lot of barriers that get in the way. 

 So for example, there is a paper that is, has been done by Dr. Anna Gutierrez-Colina and colleagues, including Dr. Modi, that really looked at adherence barriers across the trajectory of development. So going all the way from preschool age all the way to young adulthood and really reporting what the most common barriers that get in the way in epilepsy adherence.

And so what we see is that kind of around that earlier developmental period, the preschool age, things like medication taste parents forgetting that those behavioral concerns Dr. Modi mentioned. Those are what's most common. 

So at school age, we still see things like taste and parental forgetting, but we also see that doses start to move towards pill form. And so swallowing difficulties become a concern for a lot of caregivers at that age. As we move towards adolescence we see that again, taste is still a concern for medications, but also a lot of the social related factors like feeling embarrassed or different because of their condition and having to take medicine like around their friends, or just in other situations.

We also see things like just generally adolescents are forgetting and they're taking on more responsibility for the regimens and it's hard for them when their caregivers have been doing that more. And also just being forgetful around like refilling their prescription and actually running out of the medication themselves when they need it, and that leading to gaps in when they take their medication.

 And then again, as we move towards like young adulthood, we see again, more independence that's happening, less caregiver involvement. And so things like access to pharmacies become more of a concern kind of those competing activities, things going on that they're taking on more adult responsibilities.

And then still a lot of, some of those common barriers like forgetting that happened as well. So we started kind of looking at what was known in the literature, created a list of barriers we expected to see, and then we combine that with something that we call a qualitative approach, which is really focused on looking at the voices or the perspectives of patients and families that were in this study. So we went back, did something called a secondary data analysis, which is when you just dive deeper into data that's already analyzed and really get more nuanced information for it and really try to understand what are the barriers that patients and families are reporting and do they map on to those things that we were existing.

 And so we had a total of 10 different barriers that came up and nine different solutions that we addressed during the sessions. And again, there were some that were common, like forgetting. Those competing activities that were really there. But we also had things that came up that were new, like the transition of responsibility between a child and a caregiver as they're taking on more independence and things like medication not being a major priority for them. So things that weren't, that were, haven't been known from a clinical standpoint, but maybe were not the most common barriers addressed in prior research. 

[00:10:57] ILAE: Cool. Thank you. So you said you came up with solutions. Did you do that with the families or, or how was that done? And maybe if you could describe a couple of the solutions that seem to work just for examples would be great.

[00:11:14] Avani Modi: Maybe I can start by walking us through how the problem-solving session works, and then Dr. Williford can provide examples of the solutions in her paper. And so when we teach problem solving to families, we ask them one to identify the problem. Two, we ask them to brainstorm anywhere from eight to 10 solutions.

And sometimes the therapist helps brainstorm, but we really want the child and the parent to do the brainstorming because if it comes from them, they will be much more engaged in what solution they pick. Then they evaluate the solution. So each person in the family that's involved says plus or minus or smiley face or frowny face, depending on the age of the child.

And they're allowed to say whatever they want. No judgment. So we really set the stage for families that people are allowed to have their own opinion. So what we then try to do is look at all the solutions that the family members picked that were positives for everyone, and then we have them go through and pick the solution that they may want to try as a family.

And we drill down to how are they going to try it? When are they going to try it? Where are they going to try it? Who's going to have which role and how will they know it's working? And so it's really taking a very systematic process to addressing that barrier with a lot of family buy-in, including the child themselves.

And I will tell you, some of our kids come up with amazing solutions. We might say like, we'll give them, you know, a treat for taking their medicine. And the kids might be like, well, I'll just take an M&M and the parent is like, “I didn't know that would work.”

And so Dr. Williford can talk more about this particular study and the solutions that families came up with. 

[00:12:57] Desiree Williford: Yeah, absolutely. So yeah, so a lot of the solutions that our families worked on together were right in line with some of the things that we've already talked about.

 But some common ones I think were things like, environmental cuing was a big one. So what we mean by that is really thinking about having something in your environment that helps you to remember to take your medication. So things like keeping your medication in a certain spot that's visually appealing for you. Doing sticky notes so that you remind yourself, or setting an alarm on your phone to help remind you to take your medicine at a certain time were common. We also saw for some of our younger kiddos that reward systems and positive reinforcement, like we're talking about with the M&M, were really, really important. So even things as small as sticker charts went a long way for helping kind of overcome barriers like forgetting, like refusal and kind of the behaviors that got in the way of taking medication. 

We also had a lot of families that did something that we call multi-pronged solutions, which I thought was really unique, which is when they took pieces of different solution types and put them together. So those two that I gave you as an example were really common where a caregiver might say, “Hey, I'm forgetting too, so I'm going to put a reminder on my phone to remind me to remind my child to take their medication. But I'm also going to use a sticker chart so that they're feeling really engaged and that they can feel like they're making positive progress towards taking care of their illness too.”

 So as part of the, our process of looking at the solutions, we also kind of labeled the target of the intervention. So whether it was caregiver focused, child focused, or it was a joint solution. And we've actually found that the ones that were successful in doing really well, were actually the collaborative joint solutions that patients and families were working on together.

[00:15:03] ILAE: I've been reading some, some literature about adult adherence and there's, there's very definite group that forgets, right? So it's not, they don't mean to not take their medication, they just forget or they're busy or whatever.

And then there are people who don't take it on purpose. They intentionally, they're afraid of the side effects. They don't like the way it makes them feel. Is there intentional non-adherence or whatever you would want to term it in at least older children who have some agency over, whether they are taking their, their medication or not, does that occur and how do you handle that, versus someone who just forgets or is very busy? 

[00:15:48] Avani Modi: Yeah, that's a, it's a great question. And we would use the term, or sometimes we use the term volitional non-adherence, right? It's this active choice not to take your medicine for all the reasons that you said, Nancy - side effects. They don't, you know, like the way it makes them feel, they've done a risk benefit that it's not worth it because they haven't had seizures in a long time and so then why do they need to be on the medicine? 

You know, interventions for folks in that group are harder because the intervention is not behavioral to help as a reminder, it's to engage with them to help them understand why the medication is important and the foundation of that is good education.

That being said, they are also families and kids who sometimes then don't come back to clinic. And so it is really hard to engage them because if they don't think they need the medicine, and we have seen this even in younger kids, if parents don't feel they need it, they don't engage with the medical system until something happens like another seizure.

And so, we will see patients who completely disengage and then reengage when a symptom or a seizure occurs. And then that's when we'll start to sort of work with them much more purposefully around their decision making and talking to them about what their decision-making process was around why they chose not to take it.

We may change their mind, we may not, unfortunately. That is a very hard area to tackle because of engagement with the medical system as a whole. Now we do have teenagers who tell their parents they take their medicine and then sometimes parents will say, “I found the whole bottle under their bed.” And so that is also a different conversation and the ways that we engage those families is, the way I like to think about it is like you would never give your kid keys to start driving at the age of 15, right? There's a learner's permit and there's a transition process. They drive with you. They drive, you know, maybe only during the day, then maybe at night with you. And that teenage time is really where teens need a lot of scaffolding. So it may be more check-ins, it may be much more oversight with the oversight decreasing as the teen starts to show that they can demonstrate those good self-management and adherence behaviors.

And so it's really much more of a collaborative partnership like a, the triadic team of the healthcare provider, the teen and the parent. 

[00:18:24] ILAE: Thank you. So I guess my next question is about the, the population that you studied is a pretty high touch population, for lack of a better term. They're at a comprehensive epilepsy center. They're getting education, they're seeing multiple healthcare professionals. Certainly there are children who don't have that level of care for their epilepsy. So can you talk a little bit about your findings, I guess, and how, how can those be applied or can they be applied to families who are interacting with, say, a primary care provider most of the time, or, you know, maybe even a nurse or someone in a remote area who's doing a lot of things virtually. How can your results help those families? 

[00:19:21] Avani Modi: Another great question. I am very passionate about ensuring that resources and strategies around barriers actually reach as many people as possible. And so I've been working or have worked with the Epilepsy Learning Health Network, which is a network of several pediatric and adult hospitals and academic institutions, even some small private practices and local epilepsy foundations where we created a toolkit that allows folks in their individual practices, even if they're low resourced and it's just one primary care doc or a neurologist, to assess adherence barriers in a very simple checklist fashion.

And we created strategies to go with each of those barriers, which are actually posted online on the Epilepsy Foundation website with the idea that if you say you forget the provider, whoever that might be, can download or print out strategies around forgetting to provide to both families and to adults.

And so the idea was, depending on what your barrier is, can we give you resources to take with you to help you figure out strategies on your own. So it's not problem solving and family problem solving, like we think about, it's taking all the things that we've learned from this research and putting all those strategies down on paper so families and adults and teens can choose what solution makes sense for them if they are experiencing an adherence barrier.

[00:20:55] ILAE: Thank you. That's great. We'll put links to those resources in the show notes and the transcript for this episode. Are there any strategies for clinicians that you could share now, for those who are listening? 

[00:21:11] Avani Modi: I think you know, one thing that we've always worked with our providers on here is how you ask patients. It's very easy to say, "You take your medicines, right? And the family goes, "Yeah, sure we do." And what we've really advised folks is to, and healthcare professionals in particular, is to give families permission to not be perfect, because I think it's a very high bar to expect somebody to be a hundred percent adherent a hundred percent of the time.

I myself, as an adherence researcher, am not even 100% adherent 100% of the time. And so we really say, "We know it's hard to take medicines." By asking about the barriers, it opens the conversation to really say what gets in the way for you? What makes it hard? And that question is very different than, "How often do you miss your doses?" And so we've really encouraged providers to start with this open-ended question about what gets in the way. And we have learned from clinicians who started doing that, that patients that they've had for 20 years, for the first time were saying things like, “Well, it's really expensive, right?” Or “I really don't like taking this medicine three times a day.” And it changed the clinical decision making and the clinical care. And so I think it's just a reframe on how we can give families and adults permission to tell us that they're not able to do this all the time, and then problem solve and give them strategies around whatever they may identify.

And sometimes those are systems level barriers that we are unaware of. If you can't get to the pharmacy, if your medication costs too much, if the generic is much cheaper than the, you know, brand name, then it's really important to know these things because patients struggle for those reasons too. 

[00:23:04] Desiree Williford: I just think that in addition to it, just not only asking in those types of ways, but also asking often. We know that barriers can change over time, and so even if a family at one point told a barrier and they're doing really well and successful in telling you that barrier is gone for them at the moment, it does not necessarily mean that that barrier can't reemerge, or a new barrier could come up.

 I cannot even articulate how many conversations I've had with families where they get a little bit disappointed when they've worked on a barrier and then a new barrier comes up and it just feels like the next thing, the next thing that keeps coming. And sometimes they don't want to necessarily bring that up on their own because you know, their team is telling them how proud they are that they've been working on it, or that they've been doing a great job and now they feel disappointed in themselves and disappointing their team. 

And so I think papers like ours where we know that these are so common and we have examples of the things that families are, are challenged by and then entering a conversation that says, “I know that this area, you said that things have been doing really well. Here's a list of some things that other families have reported get in the way of taking medications sometimes. Do any of these ever come up or have they come up for you recently?”

 It just normalizes the experience. We know that adherence doesn't just like go at a straight line up or down, that there's lots of ebbs and flows of it. And all of that is okay and human and normal and natural.

[00:24:41] Avani Modi: Sometimes we've had this way of providing care that's don't ask, don't tell, and I get that. If a provider asks and they don't know what to do with that information, that's not super helpful to the family.

That's why some of the strategy sheets that I was referring to earlier give them some solutions to provide to families. And I think, you know, all our clinicians and healthcare providers want to help our families, but they don't always have the answers behaviorally on, on what to do. And so to have these tools in place, whether your clinical setting is a well-resourced academic, you know, medical center, or an “n of 1” neurology practice, they're applicable across the board.

[00:25:27] ILAE: So you've done a lot of work in pediatric adherence, which is a little different because we have a younger person who needs to take the medication and an older caregiver who is, is helping them do that. Are these findings at all applicable to adults? And what could adult care providers and clinicians take away from this research? 

[00:25:57] Avani Modi: Barriers are pretty universal for most folks, and they may change with some aspects of development as Dr. Williford, you know, referred to embarrassment is really like a very teen, young adult focused issue. But you know, forgetting is universal. Not being able to swallow pills when you're elderly can become a problem. And so I think there is an ebb and flow to the types of barriers folks experience, but they apply to adults equally as children.

 And the strategies around them are very, very similar. And so part of the work that we did with the Epilepsy Learning Health System was to ensure that we created tools that worked across the entire developmental lifespan.

[00:26:40] Desiree Williford: Absolutely. I would completely agree. Sometimes when we think of even some strategies that tend to feel more child focused, like reward systems and things like that, I think often sometimes are still very relevant and real for adults too. I often will say to families Or adults that I've worked with, Hey, if we didn't get paid to go to work, would we go to work?

Probably not. As much as you might love your job, like there's other incentives that are in place. And so just helping them think about what are the natural incentives for them and what helps motivate them in order to take their medication. 

[00:27:21] Avani Modi: And I think building off of that, it makes me also think that the context around adults is different too. So things like sleep play a role in having seizures, right. Alcohol use. Staying up, you know, very late at night and alcohol is like a double whammy. And so I think we provide different context cues around strategies for adults than we do obviously for a five-year-old.

[00:27:48] ILAE: Great, thank you. So I noticed in the study that you included children who were on monotherapy, is there research on monotherapy versus polytherapy and is it easier to remember to take four medications or do other issues come up, or is it basically the same rodeo but just with more medications?

[00:28:16] Avani Modi: I think the data would suggest the more complex your regimen and the more medications you take, the harder it is to follow the regimen. We started with kids on monotherapy because we also started with kids who were newly diagnosed.

And so by virtue of them being newly diagnosed, most of them only started on one medication. That being said, across the trial, many of them did go on second medications over time. And, you know, for purposes of the study, we were looking at electronic pill bottles and pill boxes to monitor their, monitor, their adherence.

And so we really just picked their primary medication for that purpose. But what we know is that if patients are taking, you know, two medicines and they're taken at the same time of day, then the issues are very similar. When you start having regimen complexity, like one is only in the AM and one is in the AM and the PM or one has to be taken with food one only taken on an empty stomach, you can imagine that then the complexity of that and trying to remember all those things gets more difficult, and so those are extra barriers that happen when you're on polytherapy versus monotherapy. But the strategies and the things that we've talked about related to the barriers apply across the board.

[00:29:42] ILAE: Got it. Thank you. Did any of you, either of you have anything you wanted to add that we didn't discuss or anything about the trial that you wanted to mention?

[00:29:54] Desiree Williford: I just wanted to reiterate again for, for our listeners just how hard and complicated this all is and just normalize that again, we're expecting a lot on you that we know is really complicated. And so I think just if you're out there, and feeling like taking medication is challenging for you or that you're facing some of these barriers, you're not alone.

And it's okay to feel these things and to know that there's tons of people out there that are experiencing the same thing. And if you feel comfortable talking to your team about the things that get in the way, I think that's going to be the most helpful in the long run going forward.

[00:30:34] ILAE: It seems in certain areas, the clinician is waiting for the patient to bring up the topic and the patient is waiting for the clinician to bring up the topic. So no one talks about the topic. And this seems like maybe it's one of those areas where each party is waiting for the other party to say something. “Well, if they have a problem, they'll say something. Right. If the person is having a problem, then they'll, they'll mention it” and, you know, the patient is thinking, “Well, if it's important, the clinician would ask me about it. And if they don't ask me, then it must not be important.” And so then nothing happens. 

[00:31:18] Avani Modi: I think that's very right, and I think what folks don't realize is that then when there are symptoms, our doctors may increase the dose. Because they think the medicine's not working, when in fact it was the non-adherence or the difficulties taking the medicine that was contributing to the seizures.

Right? And so without a discussion around this, clinical decisions are made in the absence of full information. And we did a study many, many years ago where 25% of the time, a dosing change or a med change happened when it was actually non-adherence and not the symptom. Twenty-five percent, that's one in four, right? Those patients are having some change to their regimen that could have been addressed with some adherence solutions if we had taken the time to understand the barriers and help the families in a pediatric sample.

[00:32:14] ILAE: What about research on intermittent adherence? So people who are taking their medication as directed, but then they stop and then they start again and then they stop. 

[00:32:26] Avani Modi: We do worry sometimes that folks who start, stop, start, stop, almost create this intractability for themselves. Because their brains are a little confused.

Like, wait, I have some protection. I don't have some protection. And so we don't know if that happens, but that is one hypothesis that, you know, this intermittent adherence or this sporadic adherence can almost be as equally bad as not taking it at all. Again, not fully tested, but we do have some data that shows that the worst outcomes, when we look at trajectories of adherence over time, are actually for those kids who are much more intermittent and sporadic versus just a few missed doses or complete adherence or even the kids that who don't take it at all. There was a paper we published in Neurology around that. 

[00:33:22] ILAE: Thanks for joining me. 

[00:33:23] Avani Modi: Thank you for giving us the space and time to talk about our work.