Latest / Dementia Researcher Vodcast / Beyond the Pill: Methodology in Dementia Clinical Trials

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Beyond the Pill: Methodology in Dementia Clinical Trials · Dementia Researcher Vodcast

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- [Announcer] The Dementia Researcher podcast,
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talking careers, research, conference highlights,
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and so much more.
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- Hello and welcome to the Dementia Researcher podcast.
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In this episode, we are exploring methodology
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in dementia clinical trials, particularly what it is like
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for early career researchers entering this field,
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and how trials extend much further than medicines.
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(upbeat music)
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I'm Dr. Annalise Rahman-Filipiak from the research programme
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on Cognition and Neuromodulation Based Interventions
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at the University of Michigan.
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And I am delighted to be hosting this week's show.
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Clinical trials are often viewed
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as a domain of pharmacology, yet in dementia research,
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trials include behavioural interventions,
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sensory environments, sleep and activity interventions,
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and many other approaches.
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These studies require careful design,
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strong methods and collaboration.
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And many early career researchers tell us
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that they feel unprepared when first entering this work.
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So today that's what we wanna get into.
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To explore this I am joined by three guests
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who each work on clinical trials in different ways
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and who are part of ISTAART's clinical trials
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and advancement of methods PIA.
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First, Dr. Elizabeth Rhodus,
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assistant professor at the University of Kentucky,
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whose work focuses on multisensory
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and home environment interventions
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to support people living with dementia.
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Hello, Elizabeth.
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Dr. Inga Antonsdottir,
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researcher at Johns Hopkins University,
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whose work examines sleep circadian rhythms
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and neuropsychiatric symptoms
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with a growing programme of trial methods.
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Hi, Inga.
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And finally, Dr. Elisa Franca Resende,
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neurologist and researcher
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at the Federal University of Minas Gerais in Brazil,
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whose research explores cognitive reserve,
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literacy and dementia prevention,
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including applied trials in diverse populations.
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Hello, Elisa.
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Hello, everyone, thank you for having me here.
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Okay, so thank you again for joining us.
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To start us off, could I ask each of you
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to introduce yourself in your own words?
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Maybe we can start with you, Elizabeth.
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- Sure, yeah, thank you so much.
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I clinically have a background as an occupational therapist
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and my training started in paediatrics and neurodevelopment.
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So I come to this stage in dementia care
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or in Alzheimer's disease and related dementias
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really with this idea of neurodevelopment
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to neurodegeneration and how do we support
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both sides of the lifespan
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through an environmental and sensory based approach.
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So if we have a baby
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who is having a hard time calming itself down,
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we naturally swaddle that baby, right?
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We give it full body proprioceptive input
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to regulate its nervous system.
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We rock the baby, we sing to the baby,
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we give lavender-infused lotions to the baby.
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So we care for this brand new nervous system
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in a way that's environmental and sensory based.
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How can we rigorously design and assess
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and test a similar type of intervention for older adults?
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We're not gonna swaddle our elders,
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but how can we create an environment
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that's gonna provide similar input in that way?
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So that's really my research and my experience thus far.
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- Honestly, Elizabeth, that sounds fantastic for all of us.
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So very excited to hear more.
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Inga, what about you?
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- Thank you so much for having us today.
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So I'm Inga Antonsdottir.
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I'm actually a postdoctoral research fellow
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at Johns Hopkins.
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And my research interests lie at the intersection
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of Alzheimer's disease and related dementias
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and then sleep and circadian rest activity rhythms
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in people living with dementia,
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but also in their care partners.
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So tailoring interventions to make it as easy as possible
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for us to treat any type of sleep disorder or disruption.
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And then I'm also a nurse practitioner in our memory clinic,
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so I'm able to see, treat,
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and assess people with memory disorders
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as well as other neurodegenerative diseases.
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So beautiful way to kind of combine that clinical practise
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and the research and see where the gaps might be.
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- Fantastic, so glad you're here.
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Now Elisa.
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- Yes, I'm Elisa Resend.
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I'm a neurologist from Brazil.
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And when I was a medical student,
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I was impressed by the fact
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that many of our older adults with dementia,
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they were illiterate.
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And then my curiosity began
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about how literacy can be a risk factor for dementia.
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So I built my career research
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around understanding this in their brains,
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and then developing a child to understand
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if literacy giving to older adults
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could improve brain health.
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Fantastic.
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(upbeat music)
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- So I'd love to start our conversation today
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by talking about early career research
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and entering this field.
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So many early career researchers say they feel unprepared
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for trial design and conduct.
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So let's begin with your own journeys.
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Elizabeth, Inga, and Elisa, could you each describe
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how you found yourselves working in clinical trials?
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Was that a deliberate decision,
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or just something that developed gradually?
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- Yeah, so I could definitely start off.
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I was incredibly lucky in my pre-doctoral work
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to slowly but surely get introduced
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to different clinical trialists.
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And we were doing community-based trials.
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So Dr. Quincy Samus who had recently
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kind of closed up her project mind at home.
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And we were just starting memory corps,
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which was an association with the Alzheimer's Association,
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and then also (indistinct) who was adapting one
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of her clinical trials, her clinical programmes.
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But being exposed to those programmes so early on
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and how you can go into the home,
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how you're able to kind of work
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with people living with dementia,
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memory disorders and their care partners
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and adapt things in a way
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that's going to do what's best for them,
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but also still giving them
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kind of this beautiful intervention
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that's going to help our knowledge
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of what to do at home versus what to do in clinic.
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I was just very fortunate
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that that's kind of how my pre-doctoral work started,
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and I've been able to kind of have a foot in the door
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at every step of the way and now I get to,
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hopefully, build my own practise
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and kind of understanding of how to develop these trials.
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- That's so interesting.
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So you came in with very pragmatic community trials
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as opposed to, you know, some of the trials
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that we hear about that are, you know, purely lab-based.
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I'm wondering if you could share if there were surprises
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or challenges in the pragmatic trial space
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that you didn't expect?
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- Yes, so many different surprises and just as you're,
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it's amazing to learn kind of the book side
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of clinical trials and then what happens in the real world
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and realising that life can be messy and that's okay.
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But the methodology we have to kind of make sure
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that we're putting rigour into our trials,
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even though life gets messy,
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so that when we kind of look back and we get that data,
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it's as clean as possible so that we can generalise
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what we found to other people
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and make sure that it's reproducible.
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That was definitely doing home visits.
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It's such a privilege to be able to be invited
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into somebody's home and to try and help figure things out
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and into their lives generally.
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And I'm sure the other researchers on this call
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have had some of those experiences
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where you just learn that one thing will work for someone
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and it might not work for another,
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and we have to adjust and everything is kind of personal.
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And so, it deserves to have kind of a personal touch,
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but we also have to maintain the rigour of our methods
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and make sure that we're able to reproduce
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what we're kind of creating in this world.
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- Thank you so much, I really appreciate
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you talking about that 'cause I think
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that is a misconception that we have about trials,
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is that sometimes we take away the,
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sort of human or interactional piece of it,
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but your work is such a great testament
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to the fact that we can do both.
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Elizabeth, how did you come into this space?
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- Yeah, I would love to follow up on what Inga was saying.
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As an occupational therapist,
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I'm based in Kentucky and was working in eastern Kentucky.
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We don't have a whole lot of resources.
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It's Appalachia, right?
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So in going into these homes and using the programmes
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that Inga was actually involved
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in developing these manualized programmes
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that had an occupational therapy component,
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I was recognising that we were adapting the home,
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we were improving safety, we were trying all that we could,
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but there was still something missing.
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There was something missing related
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to the caregiver training,
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that this nervous system is now degenerating and dying
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and how do we accept that?
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There was something missing about regulating behaviours
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through this sensory based approach.
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None of the research 15 years ago was talking about that.
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And so I went in, I decided at that point, let's get a PhD,
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let's see what I can figure out.
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But I had never wanted to be a doctor, or a PhD,
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or any of this space.
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I was a clinician and I still,
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even though I'm faculty, I still see myself as someone
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who really cares about this clinical aspect.
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And so, I want to improve care.
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I came into this space saying, I'm gonna get a PhD,
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I'm gonna do a clinical trial
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with a sensory-based intervention that we've seen productive
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and useful in autism spectrum disorder.
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And I'm gonna do it in people with dementia.
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Thankfully, I had some really good mentors and they said,
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"No, you're not.
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You have to prove the fact
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that you can use a paediatric intervention
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in a dementia population with basic science showing
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this level of interaction first."
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So during my PhD, I actually worked with the University
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of Kentucky Alzheimer's Disease Research Centre
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that carries a longitudinal cohort of up to 700 people
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and we surveyed people who had a diagnosis with dementia,
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so over 350 people.
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And we found that this group of population,
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or these group of people also had behaviours characteristic
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of autism spectrum disorder that aren't already collected
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or analysed in our basic neuropsychiatric symptom inventory.
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And we actually follow people to autopsy,
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and their brains and the pathology distribution
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actually look different.
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So we're working with a group of people
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that have behavioural symptoms.
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We don't have any treatment, let's think outside of the box.
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At that point, Dr. Greg Jicha at the University of Kentucky
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is our a world renowned clinical trialist
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and really designs the pharmaceuticals.
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He designs the mechanisms to create the medications
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to cure and treat Alzheimer's disease.
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He likes what I was doing, but it wasn't sure.
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He would call it Rhodus magic sometimes.
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But I would come in and I would say,
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"Well, here's my protocol," and he would ask me questions,
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and I'd say, "Well, the therapist is just gonna use
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their clinical judgement ."
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And he said, "The hell, they are, that's not rigorous.
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You have to put down exactly
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what you're gonna do in your protocol
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and you have to measure that."
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So it took me about a year and a half
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of asking how do we individualise
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or how do we operationalize an individualised intervention?
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And through that it's really about assessments
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and decision matrices.
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If this person scores this on this assessment,
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then we're gonna treat them this way.
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If they score this, then they're presenting this way,
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then we're gonna give them this group
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of intervention supplies or tools or whatever it might be.
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So that really opened the door
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for me to understand how we can use this idea
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that people are using in precision-based medicine
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to tailor medications based on genetics
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and really dial in at the pharmaceutical level.
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How do we develop and implement precision-based care?
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How do we create an environment
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and care systems that are really tailored
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to that individual to maximise success,
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but how do we do it in a rigorous way
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that we can replicate over and over and over?
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So that's kind of my space and how I've gotten here.
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I've had three clinical trials now
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that are all in this idea of behavioural intervention
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and caring for people in their homes.
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I've been all funded by the National Institute on Health,
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so I've been really fortunate to have great training,
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to have great funding and support and see where it goes.
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- That's an incredible story.
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And what I really like about it is that
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it's a somewhat non-traditional pathway towards trials.
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And I love that you're applying so much
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from your clinical background.
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I think that really helps develop new ideas,
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and bring a new perspective to the work that's done.
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You mentioned something that I do wanna return to,
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which is this idea of mentorship.
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I think mentorship and sponsorship
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is really what can help an early career person
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have the confidence to move forward
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and sometimes the resources and infrastructure as well.
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Would you be willing to talk a little bit about
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just how mentorship played a role
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in you being so successful at this point?
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- Absolutely, I've told Dr. Jicha so many times
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that he opened doors for me that I didn't even know existed.
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I was in a health profession,
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I was doing evidence-based care out in the field,
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but I didn't know, I was not trained in a school
12:47
that had a path for research.
12:50
I went to a smaller school, it was not an R1,
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so I've never really been in a lab.
12:54
I didn't know what this looked like.
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So without that mentorship,
12:57
without that little piece of him believing in me
13:01
and then kicking me along,
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with me kicking and screaming, literally,
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because I didn't see the world how he saw it.
13:08
And he's a renowned neurologist,
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he's also the clinical side, right?
13:13
He understands how clinicians think and provides resources,
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but he also has that PhD and leads clinical trials
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and really strong science.
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And through his mentorship and training,
13:24
I really was able to tailor
13:25
and learn my space and place in this.
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But I also had multiple different types of mentors.
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You know, I would go to him
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for the really science-based things
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and then I would have the other mentors
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that I'd be texting at night,
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like, crying, like, I can't do this.
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I'm lost, I don't know what to do.
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Or the next person of, how do I really make sure
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that my career is blossoming and that I'm well-rounded
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and I'm getting all the skills that I need,
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but not burning at both ends
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and making sure that, you know, I'm young,
13:53
I have a 2-year-old at home, right?
13:55
So how do I blend this space
13:57
of advancing my academic career,
13:59
leading the field and clinical trials
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within occupational therapy and being true to myself,
14:05
as a mom and a wife and me, right?
14:07
So I think that that mentorship landscape
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really was what helped create me
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and allowed me to get to this point.
14:15
- Kind of wanna piggyback on that.
14:17
I second everything that Elizabeth is saying,
14:20
and mentorship is so important and that team-based approach.
14:23
I love how you described that,
14:25
you know, it's not always one person
14:27
that you go to everything for.
14:29
It's very much a team of people who lift you up,
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and help you understand different aspects of the research,
14:36
different aspects of work-life balance.
14:40
I, too, have been just absolutely incredibly lucky
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with the mentorship teams that have
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kind of become my village, for lack of a better word,
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and just to be able to go to people
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and kind of ask questions.
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And then finding mentorship outside of academia.
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There's different groups and I know we're gonna talk
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about this a little bit later with the clinical trials PI.
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You can find different PIs for different areas
15:08
of research that you want.
15:09
And finding those people that you're able to kind of go to
15:11
that are at different universities
15:14
or in different spaces in life.
15:16
There's another one IMPACT-AD
15:18
where Elizabeth and I actually got to meet,
15:21
and you're able to surround yourself
15:23
with other researchers either at your stage
15:25
or a little bit above or a little bit below.
15:27
And it's amazing just being able to chat with people
15:30
and have those ideas kind of spur off of one one another,
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and really just learn from each other
15:36
and make the science and the research space
15:39
just keep evolving and keep getting better.
15:42
- I think that's excellent advice.
15:44
- I have to throw out there that Inga's father,
15:47
is another world renowned clinical trialist
15:48
at the University of Rochester.
15:50
- I'm in his office.
15:53
- He's one of my mentors for my,
15:54
I have a career development award through the NIH,
15:57
and he is one of my mentors.
15:58
So he's one of those people
15:59
that I call every other month of like,
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what am I doing, are you sure I can do this?
16:03
Fantastic, so I just wanted to plug in here for him as well.
16:07
- It's a beautiful small world.
16:08
We all like each other.
16:09
We all, like, want learn and grow from each other.
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And I think that's one of the best things, Elisa,
16:15
and I feel like I'm talking over everyone, though.
16:18
- Yeah, I mean, great notes about a mentoring network.
16:20
I think that's excellent advice.
16:22
Elisa, I'm really interested to hear
16:24
how you came into this field.
16:25
- Yeah, so my path is a little bit different
16:28
because in Brazil it's really hard to do clinical trials.
16:31
That's true because of the rigour,
16:34
because the ethical approval is very long.
16:40
Sometimes can take two years
16:43
to have an ethical approval here.
16:45
So I started, like, trying to understand why illiteracy
16:50
was a risk factor.
16:53
So I was looking into the MRI,
16:56
so to correlate MRI with memory
16:59
and to see if there is a correlation
17:02
between illiteracy and poor memory.
17:05
So I found a lot of evidence that,
17:09
yes, they had poor memory, they had poor brain connections,
17:13
but everybody was asking me, what do you know?
17:18
It's interesting that they have poor memory, but what else?
17:21
Do you know if you do something,
17:23
can you do something about it?
17:25
And I think all of you talked a little bit about,
17:29
we want to improve patients and people's lives,
17:33
so there is no point of discovering something
17:36
and then you cannot, like, put that into practise
17:41
to improve their lives.
17:42
So that's how I entered this world,
17:46
a little bit afraid to be honest because I was,
17:48
oh, my God, I'm going to do a clinical trial.
17:50
When I was like writing clinical trial, I was like,
17:54
I'm not sure if I'm doing a clinical trial.
17:56
But anyway, so I had incredible support from mentors.
18:01
My mentor here in Brazil.
18:02
He led a lot of clinical trials here,
18:06
medicine, behavioural intervention.
18:08
So he had a lot of experience, he helped.
18:11
And I had like the Global Brain Health Institute training
18:15
that some of you may know.
18:16
It was a wonderful experience
18:20
and I learned a lot about leadership, team management,
18:25
some things that are really important
18:27
in running a clinical trial, respect, community,
18:31
like, involvement with the community.
18:33
And also I had the IMPACT-AD training,
18:37
and I think it was,
18:39
I did the clinical trial before
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and when I did the IMPACT-AD training, I was like,
18:43
oh, my God, I should, I made a lot of mistakes.
18:47
And they say, no, it's okay.
18:48
I say, okay, you know, so the papers, they're like,
18:52
you know, there's this, this, this and that, I'm so sorry.
18:55
But anyways, I learned a lot,
18:58
and I entered this word to actually to show,
19:03
so to prove and to bring this to public policy
19:09
because some schools here in Brazil,
19:12
they were about to close for adult literacy training
19:17
because the government said,
19:18
ah, you know, they don't do anything.
19:20
They just go there, don't learn.
19:23
And I was trying to show that they learn,
19:27
their brains get better,
19:29
so you should invest in this approach here.
19:33
So that's how and I agree with our field,
19:35
like, mentorship is incredible important.
19:37
And I had like, and I think I have to say about women here
19:42
because I had a male mentor, he's amazing,
19:48
but he doesn't understand the woman stuff, you know?
19:51
You said being a mom, and one of my mentors,
19:54
she had three children, and I was like,
19:56
okay, if she can do it, I can do it.
19:59
So I also had two children, three I think is too much,
20:02
but I had two.
20:03
And like, she helped me with managing career,
20:07
as Elizabeth said, career and being a clinician
20:12
and also the clinical trials did the research part.
20:15
And funding is a very important, so my first, first trial,
20:19
pilot trial was from the Alzheimer's Association,
20:23
so the grant.
20:24
So I think you should go there and find grants.
20:29
To start you need to do a pilot, right?
20:31
A small pilot, few people, feasibility,
20:34
and then you go over into larger one.
20:40
- Thank you so much.
20:41
I mean, I really wanna point out,
20:43
A, that all of us to some extent experienced
20:47
or talked about some imposter syndrome entering this space.
20:50
And I think that's for a lot of reasons.
20:52
But we also talked about some
20:53
of the tools we have relied on
20:54
or benefited from in order to overcome that.
20:57
I wanna shift the conversation a little bit to a new topic,
21:00
which somewhat relates to imposter syndrome.
21:03
I think coming into the trial space,
21:05
there was so much emphasis on medicines
21:08
or pharmacology as the true trials,
21:11
yet each of you works on interventions
21:12
that are so far beyond that and incredibly important
21:15
and translational and affecting policy, you know?
21:19
So I'd love to hear a little more about that.
21:21
Elizabeth, could you tell us more about your multisensory
21:24
and home environment work
21:25
and how applying trial methodology has shaped that?
21:29
- Absolutely, thank you for that question.
21:32
If we think about,
21:34
at least within the United States landscape,
21:36
insurance and Medicare and Medicaid pay
21:39
for interventions that are evidence-based.
21:41
Evidence-based really boils down to the gold standard
21:45
of clinical trial methodology.
21:47
If we as clinicians have anecdotal interventions
21:50
and programmes and things that we see
21:51
are working in the field,
21:53
but that don't necessarily have that gold standard
21:55
to back it up from an evidence-based standpoint,
21:58
then we can't change policy.
21:59
We can't show up and say, these are what we need to do
22:02
because here's the evidence.
22:03
You can't deny facts, right?
22:05
So thinking about how do we take this concept of,
22:10
we each have these ideas
22:11
and we wanna change and improve care,
22:13
but we have to do it within a space of evidence-based care
22:17
that boils down to clinical trial methodology.
22:20
But a lot of our professions may not be,
22:22
you know, in developing and designing clinical trials
22:25
at the level of medicine.
22:26
So how do we boil that down?
22:28
There's actually several different models
22:30
that have really been integrated
22:32
into how I've developed my interventions
22:34
and how I use the environment that NIH has a stage model
22:39
of behavioural intervention development.
22:41
So it talks about the stage zero of like the basic,
22:44
understand your mechanisms
22:45
that are influencing what you're gonna measure.
22:48
Stage one is then looking at the pilot and the feasibility.
22:51
Stage two is similar to,
22:53
like, a phase two clinical trial of a medicine,
22:55
which you're looking at the efficacy.
22:57
In ideal situations, can you actually show a difference
23:01
because of your intervention?
23:02
The third is looking at the effectiveness.
23:04
Then we're moving into implementation and sustainability,
23:07
and really looking at this full circle of,
23:10
how do we create a manualized intervention
23:12
regardless of if it's how people sleep
23:15
and prepare to sleep or how they exercise
23:18
or how they design their home environment.
23:21
It's about creating a manual,
23:22
a protocol that you can measure.
23:25
And if you need to tailor it here, there, do that,
23:27
but put that in your measures and your rigour
23:29
so that you can replicate it over and over.
23:31
So going back to the question of,
23:33
specifically, how does multisensory
23:36
and home environment come into play?
23:38
I mentioned earlier this idea of assessments.
23:41
So let's understand the personal preferences
23:44
and the personal processing ability
23:46
or capacity of that individual's brain.
23:49
For example, we had an individual
23:50
who was refusing to take showers
23:53
and we did the adult sensory profile with him,
23:55
and we found out that he had tactile defensiveness.
23:58
He didn't wanna be touched, especially in his feet.
24:01
He didn't wanna be touched in his feet.
24:03
So we talked to the occupational therapist,
24:05
talked to the wife and said,
24:06
"Have you ever heard or considered using water shoes,
24:09
those little non-skid shoes that people wear
24:11
to the beach or whatever?"
24:13
And she left and said,
24:14
"We used to go to the lake every summer
24:16
and he would never take his shoes off.
24:17
He always had water shoes on
24:19
and we still had four pair in the closet."
24:21
So the OT said, "Well, why don't you put him in the next
24:24
to the shower to create an environment
24:26
that's prepared for him with the tools that he needs?"
24:29
The man independently put on his water shoes,
24:31
got in the shower, gave himself a shower and got out
24:33
without any behavioural problems or resistance.
24:36
He could still independently give himself a shower.
24:39
He couldn't communicate the need
24:41
that he didn't want his feet wet or touched,
24:43
and he didn't have the resources anymore,
24:45
the capacity to go ahead and independently create,
24:49
seek out the shoes or, you know, set up that environment
24:51
in a way that's prepared for what his specific needs are.
24:54
So creating an environment,
24:56
or home using these sensory elements,
24:58
or really thinking about these individual needs,
25:01
figuring out how do we make it fit?
25:03
And then training the caregivers
25:04
to really be the tool to implement these spaces.
25:07
Because, like Inga mentioned earlier, everybody is different
25:11
and every care situation is different.
25:13
We don't have manuals on how to raise children,
25:16
we don't have manuals on how to help support people
25:18
through the terminal process of dementia,
25:21
but we can find these little ingredients
25:23
that will make things a little bit easier
25:24
and a little bit smoother as we go.
25:26
- That's amazing and thank you for sharing that story.
25:29
And I think it, another aspect that I really love
25:33
to bring up is involving participants from the beginning
25:37
because of stories just like this
25:39
where we don't know what's happening
25:42
in every single situation or every single family.
25:45
And there's so many things
25:47
that people have already figured out
25:48
that can then help another family or another person.
25:51
And so, involving people who are living with dementia
25:55
or their care partners or their clinicians
25:57
who maybe have insight into what might work,
26:00
what might not work from the beginning
26:02
just to see is this something
26:04
that people would actually respond to
26:06
or that they would like,
26:07
or are we delivering it in a way that is helpful
26:10
or is it actually more of a burden?
26:12
And I think that's a really important aspect
26:14
of kind of methodology and trial design
26:17
and having a community advisory board.
26:19
Because in the end, we're trying to do good on our patients,
26:23
we're trying to do good for people,
26:25
and we're trying to make these interventions really work
26:28
and work be accessible.
26:30
And I think involving people from the get go
26:33
and having stories like the one you just told
26:35
is so important because we wouldn't know that
26:38
if we didn't have that story attached to everything.
26:41
And I just, that was absolutely beautiful,
26:43
so thank you so much for sharing that, I think, so.
26:45
- Yeah, thank you for your comments.
26:46
I will say there's one other element to that too,
26:49
of when we're putting people in clinical research,
26:51
it's kind of hard.
26:52
It's hard to do things, it's hard to track your behaviours,
26:55
it's hard to learn something new.
26:57
And so making sure that we're compensating
26:59
and supporting caregivers,
27:01
but in the very beginning of this journey that I've been on,
27:03
I had, you know, social support teams tell me
27:06
they weren't gonna refer people to my clinical trial
27:09
because I was asking them to do too much,
27:10
that it was gonna be too burdensome
27:11
on people that were already burdened.
27:14
Thankfully, we talked through it,
27:16
and we did end up getting full enrollment for the trial,
27:18
but we tracked caregiver burden.
27:20
And what we found is that burden didn't get worse.
27:23
It actually improved, people felt better.
27:25
And we know that from other evidence as well,
27:27
that when we give caregivers the tools
27:29
and the techniques to provide the care
27:31
and teach them how to kind of understand this process,
27:34
their burden doesn't go away completely,
27:36
it's hard to care for people, but it gets better.
27:39
It's not as stressful, it's not as strenuous,
27:41
and they can be able to prepare and adapt,
27:44
and live this life the best they can with the tools
27:48
that they need with less stress and higher satisfaction.
27:53
- I really appreciate the attention
27:55
to patient-oriented and community-oriented work
27:57
and how you're integrating that into your trials.
27:59
I think this is a great point to bring Elisa in
28:02
given all of the work that you've been doing,
28:04
I'm sure community partnership is such a massive part.
28:07
Would you tell us more about that
28:08
and maybe other methodological considerations
28:11
that come up in your trials?
28:13
- Yeah, sure, so I am a neurologist
28:16
and I decided to work with literacy training.
28:19
So first challenge was how to deliver literacy.
28:23
So I had to engage with a educator, a teacher, a pedagogue,
28:29
and she's specialised in adult education.
28:32
And I showed her, I didn't do this first part
28:38
of community engagement the first time.
28:41
So I showed her my protocol and it was like,
28:44
oh, in, like, very small letters,
28:47
and not in capital letters.
28:49
And she said, the participants will never do that.
28:51
It's impossible, they are literate.
28:54
And I said, oh, no, I never realised.
28:58
So I had to spend a time with her developing the protocol.
29:02
And then I spent a time with the teachers,
29:05
the teachers in the room, the teaching room,
29:07
to ask them what would work the assessments,
29:12
like, the outcomes that would be important
29:15
for them and for the students.
29:17
And then I also, like Elizabeth,
29:20
spent, like, almost one year developing the protocol
29:23
because it was from the beginning
29:25
my initial protocol was totally wrong.
29:27
And at the same time,
29:29
I needed to have hazards and tools
29:32
that were already published in the literature.
29:36
And that was already another challenge
29:40
because it is in Portuguese, it has to be in Portuguese
29:43
because it's in Brazil, they speak Portuguese,
29:46
they won't say anything in English.
29:48
And there was not a lot of literature out there,
29:53
and instruments that were validated some things.
29:58
So we had to develop a lot of instruments.
30:01
And the teacher I engaged with the leader,
30:05
she developed a protocol to teach adults
30:10
and she published because of the child.
30:12
So we had this,
30:15
like, this care of publishing things
30:18
that we used so people could understand
30:23
and our trial could be reliable
30:25
and with the rigorous that it's needed.
30:28
But I'm also have to say
30:30
that I am very touched about Elizabeth story.
30:33
As a neurologist who takes care of people with dementia,
30:37
I see this a lot.
30:38
And sometimes really hard during the consultation
30:41
to understand this, you know, at this small details.
30:46
But it has a lot of difference.
30:47
And the easy part is to give a pill, right?
30:52
So to just like run a clinical trial for pills for,
30:56
you know, behavioural problems.
30:58
But you see, you have like this very interesting
31:02
and multisensory intervention that it's safe
31:06
and it makes a lot of difference.
31:10
- You know, as you were talking, I had this thought,
31:11
if it's okay, I'll just throw it out there.
31:13
We talk about health disparities a lot, right?
31:16
And the differences that people have with access to care
31:18
and all the things that lead in to health disparities.
31:22
But as you're talking, Elisa, there's this element of,
31:25
I don't know if we would call it disparities,
31:27
but disparities in trial readiness for clinicians
31:32
and researchers across the world.
31:34
We have different levels of accessibility,
31:36
like validated tools and assessments in English
31:40
that you have to overcome those hurdles.
31:42
Or I can get an IRB passed in two to three weeks
31:45
compared to two years, right?
31:47
So there's these elements that really facilitate
31:51
and allow kind of changes the landscape of how easy it is.
31:55
Everything is hard, behavioural trials are hard, period,
31:58
but I feel like there's so many different elements
32:02
that make it even more hard based
32:03
on the environment that you're in.
32:05
So kudos to you for being able to overcome so many barriers
32:09
and that push and that will to just keep going.
32:13
But I think it ties into, you know,
32:15
early career researchers across the world
32:17
and how do you get started, but I guess making sure
32:20
that we're identifying the resources
32:22
and maybe we need to start writing up
32:24
and talking about the barriers
32:26
to becoming a clinical trialist
32:27
just at that really basic level.
32:30
- Yeah, and I've absolutely gone through
32:31
so many different challenges
32:33
and just the resilience it takes
32:35
to keep going and to have this idea and say,
32:37
this is so worthwhile and we need this.
32:40
And to keep that moving.
32:42
I think that's absolutely beautiful.
32:44
- Yeah, that's true for early careers,
32:45
especially in non-US based or non-Europe, let's say.
32:49
I know Europe is also challenging,
32:52
so easy some places, right?
32:54
But so non-US or non-Europe based,
32:58
we face a lot of challenges.
32:59
So language and the preparedness of the participants too.
33:04
There is some misconception about participating in a try-on,
33:09
saying, ah, you are going to be a,
33:11
I forgot the name in English, a pig man, no.
33:14
- A guinea pig. - A guinea pig, that's it.
33:20
I don't want to be a guinea pig.
33:21
And it is really hard to get their trust
33:25
because they were, like, they were excluded from life
33:29
from the beginning of their life.
33:32
So for 50 years they don't know how to read and write.
33:35
So everything, they had to ask people,
33:38
they are very ashamed of that to say that they don't read.
33:43
So in the school they assume that,
33:46
but if you go to the community and you show,
33:48
for example, a prescription, a doctor's prescription,
33:51
and sometimes the participant say,
33:53
or the patient looks at the prescription,
33:56
and they say, do you know how to read?
33:58
And the person says no.
34:00
And it's really, so this person to engage this person,
34:03
the clinical trial is really hard to go to the MRI
34:06
and to do this, you know, paper, pencil test.
34:09
So this is disparity that we have to face.
34:11
But I said I didn't want to give up
34:15
because I wanted to give this step,
34:18
so other people can come to and give this a step,
34:22
but it's really a challenge.
34:24
But I think everyone in the early career world,
34:28
especially in the non-US and non-Europe,
34:30
don't give up, go for it, you're going to do it.
34:33
- So even just talking about an IRB being passed
34:37
in two or three weeks versus two years,
34:39
and sometimes it's up, you know,
34:41
depending on the trial it's a little bit longer.
34:44
Early career researchers trying
34:45
to break into the clinical trial space.
34:47
Clinical trials take a long time.
34:50
And I think that's a huge barrier
34:52
when you're just starting to get into it.
34:54
When your early career you have
34:55
to look at the promotions committee
34:58
and how am I going to get that next job?
35:00
Because a clinical trial won't generate any data
35:03
for papers for several years.
35:05
And I think that's a big thing that kind of,
35:09
if you have a great mentor,
35:10
they can talk about that early on.
35:12
I'm extremely fortunate.
35:13
I have, (indistinct) has, you know, kind of taught me
35:18
from my very early stages of career to,
35:21
hey, you have to have different streams of research.
35:23
You have to have, you know, papers that you're putting out
35:26
so that you can show that you're growing as a researcher.
35:29
So, so you can show expertise so that you can show
35:31
kind of that there is this progression.
35:33
And I think, Elisa, you talked about that,
35:36
that you needed certain and certain aspects
35:39
of your trial kind of taken care of
35:41
before you could go to the clinical trial.
35:43
And then you can build your clinical trial,
35:45
but it almost has to be on the side.
35:47
So a clinical researcher, especially early career,
35:50
has to wear two hats.
35:52
You have to be progressing in your field
35:54
on some other stream so that you can show
35:58
that you are moving forward and learning those skills.
36:01
But then you also have to be working
36:02
on that trial in the background
36:04
because you know it's going to take 2, 3, 7 years
36:08
for you to then get that data
36:10
and put that data out there and analyse it.
36:12
And I think that it's a barrier we kind of forget about
36:16
because time just keeps moving.
36:19
- I really appreciate you bringing this up
36:21
and we sort of have gone to
36:23
what I was gonna ask about next,
36:25
which is you're all involved in ISTAART
36:27
and we all share that we are IMPACT-AD alums,
36:31
shout out to IMPACT-AD, amazing programme.
36:34
These all seem like great ways to get people skilled,
36:37
ready to conduct trials,
36:39
but you're also giving some fantastic advice
36:41
about other practical steps that people might take
36:44
or considerations for starting
36:47
as an early career researcher in this.
36:49
I will just add for myself,
36:51
I think a massive challenge to overcome
36:54
was just understanding all the regulatory pieces of trials.
36:58
That could have been a year or two of my career alone,
37:02
just getting up to speed on
37:03
all of the different regulatory bodies,
37:06
the differences between needing
37:07
an independent safety officer versus a,
37:10
you know, a safety monitoring board.
37:12
What your institutional regulations might look like
37:14
versus things at the funding level.
37:17
So that was really overwhelming for me and I did find,
37:19
you know, taking specific coursework on that
37:22
was incredibly helpful.
37:24
From your own perspectives,
37:26
any other tidbits of advice beyond
37:28
what you've already talked about for early career listeners
37:31
who wanna enter clinical trials?
37:33
Maybe we can start with you, Elisa.
37:35
- Yeah, sure, I think we should talk about ISTAART
37:39
because I began my career at ISTAART.
37:43
So I was at reserve and resilience
37:46
professional interest area, the PIA,
37:51
and I was like doing the programme chair
37:54
and then communications chair, so I got involved.
37:58
And as a early career researcher from other country,
38:01
from Brazil, this involvement with the leadership there,
38:05
like in the United States, in Europe,
38:06
was very important and I participated
38:09
in the meetings and the webinars.
38:12
They are very helpful, the clinical trials PIA,
38:14
they have a lot of webinars teaching this kind of basic,
38:18
and I think to engage in this opportunities,
38:22
to engage in the PIA, in this case,
38:25
the clinical trials PIA, is really helpful.
38:28
Other opportunity I engaged that it was really important
38:31
was the Mentors Breakfast
38:35
and also the AWARE PIA.
38:37
So we are all women here again.
38:40
And there is this AWARE PIA at ISTAART,
38:43
they have this breakfast,
38:46
and you go there and you, like, listen,
38:48
you join with the, some,
38:50
you know, women that it's a researcher, very famous,
38:55
or, you know, consolidating the field,
38:57
and you can talk a little bit about these challenges
39:00
that you don't have opportunity to ask,
39:05
like in the talk or something like that.
39:07
And it's really important to not only
39:09
to understand the science,
39:10
but also what do you need to do the science properly.
39:15
So I think that engage these communities
39:19
and go for and show up and don't be afraid
39:23
of getting risks that, for clinical trial,
39:27
it's a risk for from the beginning.
39:30
But believe, you know,
39:35
in what we're doing, with the rigorous of the science.
39:39
- Awesome.
39:40
Elizabeth, what about you?
39:42
- Yeah, I think I have two thoughts that really stand out.
39:45
The first is this idea of knowing your why
39:49
because things get really, really, really hard.
39:52
And then like we mentioned earlier,
39:53
we have lots of internal challenges and thought processes
39:57
that can slow us down or stop us.
39:59
So, if you really think about and you embody your why,
40:03
that will help you overcome the barriers
40:05
and the challenges and the days
40:06
where you have to stay up till one o'clock in the morning
40:08
to get a grant submission in or whatever it might be.
40:11
My other thought to that is tied in,
40:14
but it's this idea of seeing failure outside
40:17
of your own identity.
40:19
That failure is actually learning,
40:21
and we call them growing pains
40:23
because it literally is painful to grow,
40:25
but we don't learn and grow without that level of failure
40:29
because I know those tests that you failed or whatever,
40:31
that paper that got rejected, whatever it might be,
40:33
some of those might be standing out the most in your memory,
40:37
but then you learn and you grow above that and beyond that.
40:40
So not having those rejections and the failures,
40:44
whatever you might call that,
40:46
it's not tied to your identity and who you are.
40:48
You are sound, you're smart, you're brilliant
40:50
and doing great things in the world
40:53
to make an impact for people who need it the most.
40:56
But it really lies into our ability to be resilient
40:59
and overcome those hard times, to stay focused on our why,
41:03
to help us carry through,
41:05
to be able to celebrate all the wins,
41:06
and the great opportunities to connect to people.
41:10
To go into people's houses and sit on their couch
41:12
and talk about how their quilting is going, you know?
41:15
Those are the elements,
41:16
the humanistic side of why we do what we do.
41:20
- Incredible advice, I am officially asking you
41:23
to be a PIA mentor at this point.
41:26
Inga, let's end with you.
41:29
- It's a tough act to follow, that was beautiful.
41:32
And I agree everything that's been said so far.
41:34
So I think what I can add
41:36
is just also making sure that you're trying
41:41
and putting yourself out there and asking for,
41:44
it's not the easiest thing to email someone or cold email,
41:48
but the field is just such a lovely place
41:49
where people are really excited to mentor,
41:52
they're excited to help.
41:53
And so, I think if there's any kind of hesitation of,
41:57
I'm not sure, or imposter syndrome,
42:00
I know we talked a little bit about that,
42:01
just jumping over it, it takes 30 seconds of courage
42:05
and just like build it up and hit send and see what happens.
42:09
And so, I think it's getting yourself
42:13
a little bit of experience, even if it's,
42:15
you know, collecting data or analysing the data with a team.
42:19
Those little aspects of experience kind of build over time
42:22
and they compound and then you're gonna build
42:24
that confidence and start feeling more and more ready,
42:27
and then joining these different programmes.
42:29
Really, I think those, the different programmes in ISTAART,
42:33
so IMPACT-AD, ISTAART, all these things,
42:36
those are like the catalyst
42:37
to really bring you to the next level,
42:40
especially in this field.
42:41
And it's just a really collaborative,
42:42
beautiful environment.
42:45
- Fantastic advice.
42:46
(upbeat music)
42:52
So we are almost out of time.
42:54
Before we finish, I'd like to end on something
42:56
a little bit fun.
42:57
I'm gonna ask that in the interest of time,
42:58
you keep your answers to just the research question,
43:02
but if you could run a trial on absolutely anything at all,
43:06
no matter how unrealistic, somewhat whimsical or silly,
43:09
what would you test?
43:10
So this could be the effect
43:11
of your favourite snack on productivity,
43:14
whether dogs and meetings improve team morale,
43:17
or just anything that makes you smile.
43:18
So one research question,
43:20
and Inga I'm putting you on the spot first.
43:25
- Well, I am a huge fan of dogs,
43:27
so actually that one really resonated with me.
43:29
And honestly, I would love to see how dogs
43:31
just kind of impact people's ability
43:35
to live their best kind of life, you know?
43:39
So I know we're keeping it short.
43:41
- Awesome, fellow dog lover here.
43:43
Elizabeth. - Yeah, I'm a music nut.
43:46
And we know that the music you like
43:48
from the ages of 15 to 25 is the music you're gonna like
43:51
for the rest of your life, right?
43:52
So we can see that those genre are generational.
43:55
So I listened to hardcore rap when I was 16.
43:58
My grandpa is not gonna have the same response to that.
44:01
If I could do a research question or a trial,
44:03
it would really be to look at the functional MRI
44:05
and the imaging and the neurochemical release
44:08
of listening to your favourite song
44:10
from that generational era.
44:12
And what does that do in your brain
44:14
and how does that correlate to behavioural response?
44:16
- The elder emo and me loves that answer so much.
44:21
And last, but at least,
44:22
Elisa, what's your research question?
44:24
- Oh, my god, that's a tough one.
44:26
I would say that the question the teachers ask me,
44:30
why some people don't learn?
44:32
So my research question was,
44:35
the best teaching strategy for adults
44:40
who are difficult learners, let's say.
44:43
And using this functional MRI
44:45
to understand their brains while they are learning.
44:48
- Fantastic, well, thank you all so much,
44:51
Elizabeth, Inga, and Elisa for joining me today,
44:54
and to all of you for listening.
44:57
As ever, you can find more information,
44:59
links to resources and details on our website
45:02
at DementiaResearcher.nihr.ac.uk.
45:07
Do also check out our community app
45:09
where we continue these conversations
45:11
and share news, events, blogs, and podcasts.
45:14
This has been an amazing discussion.
45:16
I feel like you've all shared incredible information,
45:19
both as early career researchers
45:21
and those getting fantastic trials
45:22
off the ground and finished in some cases.
45:25
We heard about your dedication
45:27
to patient-oriented and community-oriented outcomes,
45:30
your ability to balance the rigour of trials
45:32
with things like more tailored,
45:35
individualised interventions.
45:37
We heard about mentoring networks
45:38
and how you might build them.
45:39
But I think what I'm taking away
45:41
is just this idea of all of you taking chances
45:43
and putting yourselves out there, taking those opportunities
45:46
that are in front of you to learn,
45:47
but also to, you know, really grow in your own skillset.
45:51
So, so appreciative of your willingness to share that advice
45:55
and that wisdom with all of us.
45:57
I am Annalise Rahman-Filipiak,
45:59
you have been listening to the Dementia Researcher podcast.
46:03
Bye. - Thank you.
46:05
- Thank you so much. - Thank you, bye.
46:09
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46:10
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46:13
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46:15
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46:18
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46:22
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