Podcast – Beyond the Pill Methodology in Dementia Clinical Trials

Voice Over:

The Dementia Researcher Podcast talking careers, research, conference highlights, and so much more.

Dr Annalise Rahman-Filipiak:

Hello and welcome to the Dementia Researcher Podcast. In this episode, we are exploring methodology in dementia clinical trials, particularly, what it is like for early career researchers entering this field, and how trials extend much further than medicines.

I'm Dr. Annalise Rahman-Filipiak from the research programme on cognition and neuromodulation-based interventions at the University of Michigan, and I am delighted to be hosting this week's show.

Clinical trials are often viewed as a domain of pharmacology, yet, in dementia research, trials include behavioural interventions, sensory environments, sleep and activity interventions, and many other approaches. These studies require careful design, strong methods and collaboration, and many early career researchers tell us that they feel unprepared when first entering this work.

So, today that's what we want to get into. To explore this, I am joined by three guests who each work on clinical trials in different ways, and who are part of ISTAART's clinical trials and advancement of methods PIA.

First, Dr. Elizabeth Rhodus, assistant professor at the University of Kentucky, whose work focuses on multisensory and home environment interventions to support people living with dementia. Hello, Elizabeth.

Dr. Inga Antonsdottir, researcher at Johns Hopkins University, whose work examines sleep, circadian rhythms, and neuropsychiatric symptoms with a growing programme of trial methods. Hi, Inga.

And finally, Dr. Elisa França Resende, neurologist and researcher at the Federal University of Minas Gerais in Brazil, whose research explores cognitive reserve, literacy, and dementia prevention, including applied trials in diverse populations. Hello, Elisa.

Dr Elisa França Resende:

Hello, everyone. Thank you for having me here.

Dr Annalise Rahman-Filipiak:

Okay. So, thank you again for joining us. To start us off, could I ask each of you to introduce yourself in your own words. Maybe we can start with you, Elizabeth.

Dr Elizabeth Rhodus:

Sure. Yeah. Thank you so much. I, clinically, have a background as an occupational therapist, and my training started in paediatrics and neurodevelopment. So, I come to the stage in dementia care, or in Alzheimer's disease and related dementia is really with this idea of neurodevelopment to neurodegeneration, and how do we support both sides of the lifespan through an environmental and sensory-based approach?

So, we would ... If we have a baby, who is having a hard time calming itself down, we naturally swaddle that baby. Right? We give it full body [inaudible 00:02:39] input to regulate its nervous system. We rock the baby. We sing to the baby. We give lavender-infused lotions to the baby.

So, we care for this brand-new nervous system in a way that's environmental and sensory based. How can we rigorously design and assess and test a similar type of intervention for older adults? We're not going to swaddle our elders. But how can we create an environment that's going to provide similar input in that way? So, that's really my research and my experience thus far.

Dr Annalise Rahman-Filipiak:

Honestly, Elizabeth, that sounds fantastic for all of us. So, very excited to hear more. Inga, what about you?

Dr Inga Antonsdottir:

Thank you so much for having us today. So, I'm Inga Antonsdottir. I'm actually a post-doctoral research fellow at Johns Hopkins. And my research interests lie at the intersection of Alzheimer's disease and related dementias and then sleep and circadian rest activity rhythms in people living with dementia, but also in their carer partners. So, tailoring interventions to make it as easy as possible for us to treat any type of sleep disorder or disruption.

And then I'm also a nurse practitioner in our memory clinic. So, I'm able to see, treat, and assess people with memory disorders as well as other neurodegenerative diseases. So, a beautiful way to combine that clinical practise, and the research, and see where the gaps might be.

Dr Annalise Rahman-Filipiak:

Fantastic. So glad you're here. Elisa?

Dr Elisa França Resende:

Yes. I'm Elisa Resende. I'm a neurologist from Brazil. And when I was a medical student, I was impressed by the fact that many of our older adults with dementia, they were illiterate. And then my curiosity began about how illiteracy can be a risk factor for dementia. So, I built my career research around understanding this in their brains and then developing a trial to understand if literacy given to older adults could improve brain health.

Dr Annalise Rahman-Filipiak:

Fantastic. So, I'd love to start our conversation today by talking about early career research and entering this field. So, many early career researchers say they feel unprepared for trial design and conduct. So, let's begin with your own journeys. Elizabeth, Inga, and Elisa, could you each describe how you found yourselves working in clinical trials? Was that a deliberate decision or just something that developed gradually?

Dr Inga Antonsdottir:

Yeah. So, I could definitely start off. I was incredibly lucky in my pre-doctoral work to slowly, but surely get introduced to different clinical trials, and we were doing community-based trials. So, Dr. Quincy Samus, who had recently closed up her project Mind at Home, and we were just starting Memory Core, which was in association with the Alzheimer's Association. And then also Szanton, who was adapting one of her clinical trials, her clinical programmes.

But being exposed to those programmes so early on, and how you can go into the home, how you're able to work with people living with dementia, memory disorders, and their care partners, and adapt things in a way that's going to do what's best for them, but also still giving them this beautiful intervention that's going to help our knowledge of what to do at home versus what to do in clinic.

I was just very fortunate that that's how my pre-doctoral work started, and I've been able to have a foot in the door at every step of the way. And now I get to hopefully build my own practise and understanding of how to develop these trials.

Dr Annalise Rahman-Filipiak:

That's so interesting. So, you came in with very pragmatic community trials as opposed to some of the trials that we hear about that are purely lab-based. I'm wondering if you could share if there were surprises or challenges in that pragmatic trial space that you didn't expect.

Dr Inga Antonsdottir:

Yes. So many different surprises, and just as you're ... It's amazing to learn the book side of clinical trials, and then what happens in the real world, and realising that life can be messy, and that's okay, but the methodology, we have to make sure that we're putting rigour into our trials, even though, life gets messy, so, that when we look back and we get that data, it's as clean as possible, so, that we can generalise what we've found to other people and make sure that it's reproducible.

That was definitely ... Doing home visits, it's such a privilege to be able to be invited into somebody's home, and to try and help figure things out, and into their lives generally. And I'm sure the other researchers on this call have had some of those experiences where you just learn that one thing will work for someone, and it might not work for another. And we have to adjust and everything is personal.

And so, it deserves to have a personal touch, but we also have to maintain the rigour of our methods and make sure that we're able to reproduce what we're creating in this [inaudible 00:07:43].

Dr Annalise Rahman-Filipiak:

Thanks so much. I really appreciate you talking about that, because I think that is a misconception that we have about trials is that sometimes we take away the human, or interactional piece of it, but your work is such a great testament to the fact that we can do both.

Elizabeth, how did you come into this space?

Dr Elizabeth Rhodus:

Yeah. I would love to follow up on what Inga was saying, as an occupational therapist, I'm based in Kentucky and was working in eastern Kentucky. We don't have a whole lot of resources. It's Appalachia. Right?

So, in going into these homes and using the programmes that Inga was actually involved in developing these manualized programmes, that had an occupational therapy component, I was recognising that we were adapting the home, we were improving safety, we were trying all that we could, but there was still something missing. There was something missing related to the caregiver training that this nervous system is now degenerating and dying, and how do we accept that?

There was something missing about regulating behaviours through this sensory-based approach. None of the research 15 years ago was talking about that. And so, I went in, I decided at that point, "Let's get a PhD. Let's see what I can figure out." But I had never wanted to be a doctor, or a PhD, or any of this space. I was a clinician, and I still ... Even though, I'm faculty, I still see myself as someone who really cares about this clinical aspect.

And so, I want to improve care. I came into this space saying, "I'm going to get a PhD. I'm going to do a clinical trial with a sensory-based intervention that we've seen productive and useful in autism spectrum disorder, and I'm going to do it in people with dementia."

Thankfully, I had some really good mentors, and they said, "No. You're not. You have to prove the fact that you can use a paediatric intervention in a dementia population with basic science showing this level of interaction first."

So, during my PhD I actually worked with the University of Kentucky Alzheimer's disease research centre, that carries a longitudinal cohort of up to 700 people, and we survey people who had a diagnosis with dementia. So, over 350 people. And we found that this group of population, or these group of people also had behaviours characteristic of autism spectrum disorder that aren't already collected or analysed in our basic neuropsychiatric symptom inventory. And we actually followed people to autopsy, and their brains in the pathology distribution actually looked different.

So, we're working with a group of people that have behavioural symptoms. We don't have any treatment. Let's think outside of the box. At that point, Dr. Greg Jicha at the University of Kentucky is a world-renowned clinical trialist and really designs the pharmaceuticals. He designs the mechanisms to create the medications to cure and treat Alzheimer's disease.

He liked what I was doing, but he wasn't sure ... He would call it Rhodus magic sometimes. But I would come in, and I would say, "Well, here's my protocol." And he would ask me questions. And I'd say, "Well, the therapist is just going to use their clinical judgement ." And he said, "To hell they are. That's not rigorous. You have to put down exactly what you're going to do in your protocol, and you have to measure that."

So, it took me about a year and a half of asking, "How do we operationalize an individualised intervention?" And through that, it's really about assessments, and decision matrices. If this person scores this on this assessment, then we're going to treat them this way. If they score this, then they're presenting this way, then we're going to give them this group of intervention supplies or tools or whatever it might be.

So, that really opened the door for me to understand how we can use this idea that people are using precision-based medicine to tailor medications based on genetics and really dial in at the pharmaceutical level. How do we develop and implement precision-based care? How do we create an environment and care systems that are really tailored to that individual to maximise success, but how do we do it in a rigorous way that we can replicate over and over and over?

So, that's my space and how I've gotten here. I've had three clinical trials now that are all in this idea of behavioural intervention and caring for people in their homes. They've been all funded by the National Institute on Health. So, I've been really fortunate to have great training, to have great funding and support, and see where it goes.

Dr Annalise Rahman-Filipiak:

That's an incredible story. And what I really like about it is that it's a somewhat non-traditional pathway towards trials, and I love that you're applying so much from your clinical background. I think that really helps develop new ideas and bring a new perspective to the work that's done.

You mentioned something that I do want to return to, which is this idea of mentorship. I think mentorship and sponsorship is really what can help an early career person have the confidence to move forward, and sometimes the resources and infrastructure as well. Would you be willing to talk a little bit about just how mentorship played a role in you being so successful at this point?

Dr Elizabeth Rhodus:

Absolutely. I've told Dr. Jicha so many times that he opened doors for me that I didn't even know existed. I was in a health profession, I was doing evidence-based care out in the field, but I didn't know ... I was not trained in a school that had a path for research. I went to a smaller school. It was not an R1. So, I've never really been in a lab. I didn't know what this looked like.

So, without that mentorship, without that little piece of him believing in me, and then kicking me along, with me kicking and screaming, literally, because I didn't see the world how he saw it. And he's a renowned neurologist. He's also the clinical side. Right? He understands how clinicians think and provides resources, but he also has that PhD and leads clinical trials, and really strong science. And through his mentorship and training, I really was able to tailor and learn my space, and place in this.

But I also had multiple different types of mentors. I would go to him for the really science-based things, and then I would have the other mentors that I'd be texting at night, like, crying, like, "I can't do this. I'm lost. I don't know what to do." Or the next person of, "How do I really make sure that my career is blossoming and that I'm well-rounded and I'm getting all the skills that I need, but not burning at both ends?" And making sure that ... I'm young, I still have a two-year-old at home. Right? So, how do I blend this space of advancing my academic career, leading a field in clinical trials within occupational therapy, and being true to myself as a mom and a wife, and me. Right?

So, I think that that mentorship landscape really was what helped create me and allowed me to get to this point.

Dr Inga Antonsdottir:

I want to piggyback on that. I second everything that Elizabeth is saying, and mentorship is so important, and that team-based approach. I love how you describe that it's not always one person that you go to everything for, it's very much a team of people who lift you up, and help you understand different aspects of the research, different aspects of work/life balance.

I, too, have been just absolutely incredibly lucky with the mentorship teams that have become my village, for lack of a better word, and just to be able to go to people and ask questions. And then finding mentorship outside of academia. There are different groups, and we're going to talk about this a little bit later with the clinical trials PIA. You can find different PIAs for different areas of research that you want and finding those people that you're able to go to that are at different universities, or in different spaces in life.

There's another one, IMPACT AD, where Elizabeth and I actually got to meet, and you're able to surround yourself with other researchers either at your stage, or a little bit above, or a little bit below. And it's amazing just being able to chat with people and have those ideas spur off of one another. And really just learn from each other and make the science and the research space just keep evolving and keep getting better.

Dr Annalise Rahman-Filipiak:

I think that's excellent advice.

Dr Elizabeth Rhodus:

I have to throw out there that Inga's father is another world-renowned clinical trialist at the University of Rochester [inaudible 00:15:50]. He is one of my mentors for my ... I have a career development award through the NIH, and he is one of my mentors. So, he is one of those people that I call every other month of like, "What am I doing? Are you sure I can do this? Fantastic." I just wanted to put that plug in for him as well.

Dr Inga Antonsdottir:

It's a beautiful small world. We all like each other, we all learn and grow from each other, and I think that's one of the best things. Elisa, I feel like I'm talking over everyone, though.

Dr Annalise Rahman-Filipiak:

Yeah. Great notes about a mentoring network. I think that's excellent advice. Elisa, I'm really interested to hear how you came into this field.

Dr Elisa França Resende:

Yeah. So, my path is a little bit different, because in Brazil, it's really hard to do clinical trials. That's the truth, because of the rigour, because of the ethical approval is very long. It sometimes can take two years to have an ethical approval here.

So, I started trying to understand why illiteracy was a risk factor. So, I was looking into the MRI, so, to correlate the MRI with memory, and to see if there is a correlation between illiteracy and poor memory.

So, I found a lot of evidence that, yes, they had poor memory, they had poor brain connections, but everybody was asking me, "Do you know ... It's interesting that they have poor memory, but what else? If you do something, can you do something about it?"

And I think all of you talked a little bit about we want to improve patients and peoples' lives. So, there is no point of discovering something, and then you cannot put that into practise to improve their lives. So, that's how I entered this world, a little bit afraid, to be honest, because I was like, "Oh my God. I'm going to do a clinical trial." When I was writing clinical trials like, "I'm not sure if I'm doing a clinical trial."

But, anyway, so, I had incredible support from mentors, my mentor here in Brazil, he led a lot of clinical trials here, medicine, behavioural interventions. So, he had a lot of experience. He helped. And I had the Global Brain Health Institute Training, that some of you may know, it was a wonderful experience, and I learned a lot about leadership, team management, some things that are really important in running a clinical trial, respect, involvement with the community.

And also, I had the IMPACT AD training. And I think it was ... I did a clinical trial before, and when I did the IMPACT AD training, it was like, "Oh my God." I made a lot of mistakes, and they said, "No. It's okay." I said, "Okay." So, the papers, they're, like, "There's this, this, this, and that. I'm so sorry."

But, anyways, I learned a lot. And I entered this work to actually to show, so, to prove, and to bring this to public policy, because some schools here in Brazil, they were about to close for adult literacy training, because the government said, "They don't do anything. They just go there. They don't learn."

And I was trying to show that, no, they learn. Their brains get better. So, you should invest in this approach here. So, that's how. And I agree with all of you, like, mentorship is incredibly important, and I had ...

And I think I have to say about women here, because I had a male mentor. He's amazing, but he doesn't understand [inaudible 00:19:50] stuff. [inaudible 00:19:51]. And one of my mentors, she had three children, and I was like, "Okay. If she can do it, I can do it." So, I also had two children, three I think is too much, but I had two. And she helped me with managing career, as Elizabeth said, career and being a clinician, and also the clinical trials, the research part.

And funding is very important. So, my first, first trial, pilot trial was from the Alzheimer's Association. So, the grant. So, I think we should go there and find grants. And to truly start you need to do a pilot. Right? A small pilot that's a few people, visibility, and then you go over into a larger one.

Dr Annalise Rahman-Filipiak:

Thank you so much. I really want to point out, A, that all of us, to some extent, experienced or talked about some imposter syndrome entering this space, and I think that's for a lot of reasons. But we also talked about some of the tools we've relied on or benefited from in order to overcome that.

I want to shift the conversation a little bit to a new topic, which somewhat relates to imposter syndrome. I think coming into the trial space there was so much emphasis on medicines or pharmacology as the true trials, yet each of you works on interventions that are so far beyond that and incredibly important, and translational, and affecting policy.

So, I'd love to hear a little more about that. Elizabeth, could you tell us more about your multi-sensory and home environment work, and how applying trial methodology has shaped that?

Dr Elizabeth Rhodus:

Absolutely. Thank you for that question. If we think about, at least, within the United States landscape, insurance and Medicare and Medicaid pay for interventions that are evidence-based. Evidence-based really boils down to the gold standard of clinical trial methodology. If we, as clinicians, have anecdotal interventions and programmes, and things that we see are working in the field, but that don't necessarily have that gold standard to back it up from an evidence-based standpoint, then we can't change policy. We can't show up and say, "These are what we need to do, because here's the evidence." You can't deny facts. Right?

So, thinking about how do we take this concept of we each have these ideas and we want to change and improve care, but we have to do it within a space of evidence-based care that boils down to clinical trial methodology, but a lot of our professions may not be developing and designing clinical trials at the level of medicine. So, how do we boil that down?

There are actually several different models that have really been integrated into how I've developed my interventions and how I use the environment. The NIH has the stage model and behavioural intervention development. So, it talks about the stage zero of the basic understanding or mechanisms that are influencing what you're going to measure.

Stage one is then looking at the pilot, and the feasibility. Stage two is similar to a phase two clinical trial of the medicine, which you're looking at the efficacy. In ideal situations, can you actually show a difference because of your intervention? The third is looking at the effectiveness. Then we're moving into implementation and sustainability. And really looking at this full circle of how do we create a manualized intervention regardless of if it's how people sleep, and prepare to sleep, or how they exercise, or how they design their home environment, it's about creating a manual, a protocol that you can measure.

And if you need to tailor it here or there, do that, but put that in your measures, in your rigour, so, that you can replicate it over and over. So, going back to the question of, specifically, how does multi-sensory and home environment come into play?

I mentioned earlier this idea of assessments. So, let's understand the personal preferences, and the personal processing ability or capacity of that individual's brain. For example, we had an individual who was refusing to take showers. And we did the adult sensory profile with him, and we found out that he had tactile defensiveness. He didn't want to be touched, especially, in his feet, he didn't want to be touched on his feet.

So, we talked to the occupational therapist, talked to the wife, and said, "Have you ever heard or considered using water shoes?" Those little non-skid shoes that people wear to the beach, or whatever. And she laughed and said, "We used to go to the lake every summer, and he would never take his shoes off. He always had water shoes on, and we still have four pairs in the closet." So, the OT said, "Well, why don't you put them next to the shower to create an environment that's prepared for him with the tools that he needs?"

The man independently put on his water shoes, got in the shower, gave himself a shower, and got out without any behavioural problems or resistance. He could still independently give himself a shower. He couldn't communicate the need that he didn't want his feet wet or touched. And he didn't have the resources anymore, the capacity to go ahead and independently seek out the shoes or set up that environment in a way that's prepared for what his specific needs are.

So, creating an environment or a home using these sensory elements are really thinking about these individual needs, figuring out how do we make it fit, and then training the caregivers to really be the tool to implement these spaces, because like Inga mentioned earlier, everybody is different, and every care situation is different.

We don't have manuals on how to raise children. We don't have manuals on how to help support people through the terminal process of dementia, but we can find these little ingredients that will make things a little bit easier and a little bit smoother as we go.

Dr Annalise Rahman-Filipiak:

That's amazing. And thank you for sharing that story. And I think another aspect that I really love to bring up is involving participants from the beginning, because of stories just like this where we don't know what's happening in every single situation or every single family. And there's so many things that people have already figured out, that can then help another family or another person. And so, involving people who are living with dementia, or their care partners, or their clinicians who maybe have insight into what might work, what might not work from the beginning just to see is this something that people would actually respond to, or that they would like, or are we delivering it in a way that is helpful? Or is it actually more of a burden?

And I think that's a really important aspect of methodology and trial design, and having a community advisory board, because, in the end, we're trying to do good on our patients, we're trying to do good for people, and we're trying to make these interventions really work and be accessible.

And I think involving people from the get-go, and having stories like the one you just told is so important, because we wouldn't know that if we didn't have that story attached to everything. And that was absolutely beautiful. So, thank you so much for sharing that. I think-

Dr Elizabeth Rhodus:

Yeah. Thank you for your compliments. I will say there's one other element to that too of when we're putting people in clinical research, it's hard. It's hard to do things, it's hard to track your behaviours, it's hard to learn something new. And so, making sure that we're compensating and supporting caregivers, but in the very beginning of this journey that I've been on, I had social support teams tell me they weren't going to refer people to my clinical trial, because I was asking them to do too much, that it was going to be too burdensome on people that were already burdened.

Thankfully, we talked through it, and we did end up getting full involvement for the trial, but we tracked caregiver burden. What we found is that burden didn't get worse. It actually improved. People felt better. And we know that from other evidence as well, that when we give caregivers the tools and the techniques to provide the care and teach them how to understand this process, their burden doesn't go away completely. It's hard to care for people. But it gets better. It's not as stressful. It's not as strenuous. And they can be able to repair and adapt and live this life the best they can with the tools that they need with less stress and higher satisfaction.

Dr Annalise Rahman-Filipiak:

I really appreciate the attention to patient-oriented and community-oriented work, and how you're integrating that into your trials. I think this is a great point to bring Elisa in given all of the work that you've been doing. I'm sure community partnership is such a massive part. Would you tell us more about that? And maybe other methodological considerations that come up in your trials.

Dr Elisa França Resende:

Yeah. Sure. So, I'm a neurologist. And I decided to work with literacy training. So, the first challenge was how to deliver literacy. So, I had to engage with an educator, a teacher, a pedagogue, and she's specialised in adult education. And I showed her ... I didn't do this first part of community engagement, the first time. So, I showed her my protocol, and it was like, "Oh, [inaudible 00:28:45] very small letters, and not in capital letters." And she said, "The participants will never do that. It's impossible. They are illiterate." And I said, "Oh, no. I never realised."

So, I had to spend the time with her, developing the protocol, and then I spent time with the teachers, the teachers in their room, the teaching room, to ask them, "What would work? The assessments, the outcomes that would be important for them and for these students." And then I also, like Elizabeth, spent almost one year developing the protocol. Because it was from the beginning, my initial protocol was totally wrong.

And at the same time, I needed to have [inaudible 00:29:31] and tools that were already published in the literature. And that was another challenge, because it is in Portuguese. It has to be in Portuguese, because it's in Brazil. They speak Portuguese. They won't say anything in English. And there was not a lot of literature out there in validating instruments that were validating some things.

So, we had to develop a lot of instruments, and the teacher that I engaged with, the leader, she developed a protocol to teach adults, and she published, because of the trial. So, we had this care of publishing things that we used, so, people could understand and our trial could be reliable and with the [inaudible 00:30:27] that it needed.

But I'm also I have to say that I am very touched about Elizabeth's story. As a neurologist who takes care of people with dementia, I see this a lot. And sometimes it's really hard during the consultation to understand these small details, but it has a lot of difference, and the easy part is to give a pill. Right?

So, to just run a clinical trial for pills, for behavioural problems, but you have this very interesting and multi-sensory intervention that it's safe, and it makes a lot of difference.

Dr Inga Antonsdottir:

As you were talking, I had this thought, if it's okay, I'll just throw it out there, we talk about health disparities a lot. Right? And the differences that people have with access to care, and all the things that lead into health disparities.

But as you're talking, Elisa, there's this element of ... I don't know if we would call it disparities, but disparities in trial readiness for clinicians and researchers across the world.

We have different levels of accessibility. Like, validated tools and assessments in English that you have to overcome those hurdles, or I can get an IRB passed in two to three weeks compared to two years. Right?

So, there's these elements that really facilitate and allow ... It, kind of, changes the landscape of how easy it is. Everything is hard. Behavioural trials are hard. Period. But I feel like there's so many different elements that make it even more hard based on the environment that you're in. So, kudos to you for being able to overcome so many barriers, and that push, and that will just keep going.

I think it ties into early career researchers across the world, and how do you get started. But I guess making sure that we're identifying the resources and maybe we need to start writing up and talking about the barriers to becoming a clinical trialist just at that really basic level.

Dr Annalise Rahman-Filipiak:

Yeah. No. Absolutely. Gone through so many different challenges, and just the resilience it takes to keep going, and to have this idea and say, "This is so worthwhile and we need this." And to keep that moving. I think that's absolutely beautiful.

Dr Elisa França Resende:

Yeah. That's true for early careers, especially, now in the U.S. [inaudible 00:32:48] Europe, let's say. I know Europe is also challenging. It's not so easy some places. Right?

But so, non-U.S. and non-north-based, we face a lot of challenges. So, language. And the preparedness of the participants too. There is some misconception about participating in a trial, and saying, "You're going to be a ..." I forgot the name in English. A pygmy? No.

Dr Inga Antonsdottir:

A guinea pig.

Dr Elisa França Resende:

A guinea pig. That's it. "I don't want to be a guinea pig." And it is really hard to get their trust, because they were excluded from life from the beginning of their lives. So, for 50 years, they don't know how to read and write. So, everything they had to ask people, they are very ashamed of that to say that they don't read.

And in their school, they are shown that. But if you go to the community, and you show, for example, a prescription, a doctor's prescription, and sometimes the participants say, or the patient looks at the prescription and they'll say, "Do you know how to read?" And the person says, "No."

So, this person, to engage this person in the clinical trial is really hard. So, go to the MRI and to do this paper pencil tests. So, this is a disparity that we have to face, but I said, "I didn't want to give up, because I wanted to try to give this step, so, other people can come through and give [inaudible 00:34:22]."

But it's really a challenge. But I think everyone in their early career [inaudible 00:34:28], especially in the non-U.S. and Europe, don't give up. Go for it. You're going to do it.

Dr Inga Antonsdottir:

So, even just talking about an IRB being passed in two or three weeks versus two years, and sometimes it's up ... Depending on the trial, it's a little bit longer. Early career researchers trying to break into the clinical trial space, clinical trials take a long time.

And I think that's a huge barrier when you're just starting to get into it, in your early career, you have to look at the promotions committee, and "How am I going to get that next job?" Because a clinical trial won't generate any data for papers for several years.

And I think that's a big thing that if you have a great mentor, they can talk about that early on. I'm extremely fortunate. I have [inaudible 00:35:15] has taught me from my very early stages of career to, "Hey. You have to have different streams of research. You have to have papers that you're putting out, so, that you can show that you're growing as a researcher, so, you can show expertise, so, that you can show that there is this progression."

And I think, Elisa, you talked about that, that you needed certain papers, and certain aspects of your trial taken care of before you could go to the clinical trial. And then you can build your clinical trial, but it almost has to be on the side. So, a clinical researcher, especially, early career has to wear two hats. You have to be progressing in your field on some other stream, so, that you can show that you are moving forward and learning those skills. But then you also have to be working on that trial in the background, because you know it's going to take two, three, seven years for you to then get that data, and put that data out there, and analyse it. And I think it's a barrier we forget about, because time just keeps moving.

Dr Elizabeth Rhodus:

I really appreciate you bringing this up, and we have gotten to it, but I was going to ask about next, which is you're all involved in ISTAART, and we all share that we're IMPACT AD alums. Shout-out to IMPACT AD. Amazing programme.

These all seem like great ways to get people skilled, ready to conduct trials, but you're also giving some fantastic advice about other practical steps that people might take, or considerations for starting as an early career researcher in this.

I will just add for myself, I think a massive challenge to overcome was just understanding all the regulatory pieces of trials, that could have been a year or two of my career alone just getting up to speed on all of the different regulatory bodies, the differences between needing an independent safety officer versus a safety monitoring board, what your institutional regulations might look like versus things at the funding level.

So, that was really overwhelming for me, and I did find taking specific course work on that was incredibly helpful.

Dr Annalise Rahman-Filipiak:

From your own perspectives, any other titbits of advice beyond what you've already talked about for early career listeners who want to enter clinical trials? Maybe we can start with you, Elisa.

Dr Elisa França Resende:

Yeah. Sure. I think we should talk about ISTAART, because I began my career at ISTAART. So, I was at the reserve and resilience professional interest area, the PIA. And I was doing the programme chair, and then communications chair. So, I got involved, and as an early career researcher from other countries, from Brazil, this involvement with the leadership there in the United States and Europe was very important. And I participated in the meetings and the webinars. They are very helpful, the clinical trials PIA. They have a lot of webinars teaching this kind of [inaudible 00:38:17].

And I think to engage in these opportunities, to engage in the PIA, in this case, the clinical trials PIA is really helpful. Other opportunities I engaged that it was really important was the mentor's breakfast, and also the aware PIA. So, we are all women here, again. And there is this aware PIA at ISTAART. They have this breakfast. And you go there and you listen, you [inaudible 00:38:50] some women that it's a researcher, very famous in consolidating the field. And you can talk a little bit about this challenge that you don't have the opportunity to ask in the talk or something like that. And it's really important not only to understand the science, but also what do you need to do the science properly?

So, I think to engage these communities and go for and show up, and don't be afraid of getting risks that ... For a clinical trial, it's a risk from the beginning, but believe in what we're doing with the rigours of the science.

Dr Annalise Rahman-Filipiak:

Awesome. Elizabeth, what about you?

Dr Elizabeth Rhodus:

Yeah. I think I have two thoughts that really stand out. The first is this idea of knowing your why, because things get really, really, really hard, and like we mentioned earlier, we have lots of internal challenges and thought processes that can slow us down or stop us.

So, if you really think about, and you embody your why, that will help you overcome the barriers and the challenges, and the days where you have to stay up to 1:00 in the morning to get a grant submission in, or whatever it might be.

My other thought to that, tied in but it's this idea of seeing failure outside of your own identity, that failure is actually learning, and we call them growing pains, because it literally is painful to grow, but we don't learn and grow without that level of failure, because I know those tests that you failed, or whatever, that paper that got rejected, whatever it might be, some of those might be standing out the most in your memory. But then you learn and you grow above that and beyond that.

So, not having those rejections and the failures, whatever you might call that, it's not tied to your identity and who you are. You are sound, you are smart, you're brilliant and doing great things in the world to make an impact for people who need it the most, but it really lies into our ability to be resilient and overcome those hard times to stay focused on our why, to help us carry through to be able to celebrate all the wins, and the great opportunities to connect to people, to go into people's houses, and sit on their couch and talk about how their quilting is going. Those are the elements, the humanistic side of why we do what we do.

Dr Annalise Rahman-Filipiak:

Incredible advice. I am, officially, asking you to be a peer mentor at this point. Inga, let's end with you.

Dr Inga Antonsdottir:

It's a tough act to follow. That was beautiful, and I agree with everything that's been said so far. So, I think what I can add is just also making sure that you're trying, and putting yourself out there, and asking for ... It's not the easiest thing to email someone, or cold email, but the field is just such a lovely place where people are really excited to mentor. They're excited to help.

And so, I think if there's any kind of hesitation of, "I'm not sure," or imposter syndrome, I know we talked a little bit about that, just jumping over it, it takes 30 seconds of courage, and just build it up, and hit send, and see what happens. And so, I think it's getting yourself a little bit of experience even if it's collecting data or analysing the data with a team. Those little aspects of experience build over time, and they compound, and then you're going to build that confidence and start feeling more and more ready and then joining these different programmes.

I think the different programmes and ISTAART, so, IMPACT AD, ISTAART, all these things, those are the catalyst to really bring you to the next level, especially, in this field, and it's just a really collaborative, beautiful environment.

Dr Annalise Rahman-Filipiak:

Fantastic advice.

So, we are almost out of time. Before we finish, I'd like to end on something a little bit fun. I'm going to ask that in the interest of time, you keep your answers to just the research question, but if you could run a trial on absolutely anything at all, no matter how unrealistic, somewhat whimsical or silly, what would you test? So, this could be the effect of your favourite snack on productivity, whether dogs in meetings improve team morale, or just anything that makes you smile. So, one research question. And Inga, I'm putting you on the spot first.

Dr Inga Antonsdottir:

Well, I am a huge fan of dogs. So, actually, that one really resonated with me, and, honestly, I would love to see how dogs just impact people's ability to live their best life. So, I know we're keeping it short.

Dr Annalise Rahman-Filipiak:

Awesome. Fellow dog lover here. Elizabeth?

Dr Elizabeth Rhodus:

Yeah. I'm a music nut. And we know that the music you like from the ages of 15 to 25 is the music you're going to like for the rest of your life. Right? So, we can see that those genre are generational. So, I listened to hardcore rap when I was 16, my grandpa is not going to have the same response to that.

If I could do a research question or trial, it would really be to look at the functional MRI and the imaging, and the neurochemical release of listening to your favourite song from that generational era, and what does that do in your brain? And how does that correlate to behavioural response?

Dr Annalise Rahman-Filipiak:

The elder emo in me loves that answer so much. And last but not least, Elisa, what's your research question?

Dr Elisa França Resende:

Oh my God. That's so fun. I would say that the question the teachers ask me, "Why some people don't learn?" So, my research question was the best teaching strategy for adults who are difficult learners, let's say, and using this functional MRI to understand their brains while they are learning.

Dr Annalise Rahman-Filipiak:

Fantastic. Well, thank you all so much Elizabeth, Inga, and Elisa for joining me today, and to all of you for listening. As ever, you can find more information, links to resources, and details on our website at www.DementiaResearcher.NIHR.AC.UK.

Do also check out our community app where we continue these conversations, and share news events, blogs, and podcasts. This has been an amazing discussion. I feel like you've all shared incredible information, both as early career researchers and those getting fantastic trials off the ground and finished in some cases.

We heard about your dedication to patient-oriented and community-oriented outcomes, your ability to balance the rigour of trials with things like more tailored individualised interventions. We heard about mentoring networks and how you might build them.

But I think what I'm taking away is just this idea of all of you taking chances and putting yourselves out there, taking those opportunities that are in front of you to learn, but also to really grow in your own skillset. So, so appreciative of your willingness to share that advice and that wisdom with all of us.

I am Annalise Rahman-Filipiak. You have been listening to the Dementia Researcher Podcast. Bye.

Dr Elisa França Resende:

Thank you.

Dr Inga Antonsdottir:

Thank you so much.

Dr Elizabeth Rhodus:

Thank you. Bye.

Voice Over:

The Dementia Researcher Podcast was brought to you by University College London with generous funding from the UK's National Institute for Health Research, Alzheimer's Research UK, Alzheimer's Society, Alzheimer's Association, and Race Against Dementia. Please subscribe, leave us a review, and register on our website for full access to all our great resources. www.Dementia Researcher.NIHR.AC.UK.