1/2019 NACNR – Development of novel, biophysically designed fluids for swallowing disorders

1/2019 NACNR – Development of novel, biophysically designed fluids for swallowing disorders


[music playing]>>JoAnne Robbins:
Thanks come from me, as I said, to Dr. Cashion and to Dr. Evon Brown
[phonetic sp], on behalf of Zachary Pats
[phonetic sp], thank you very much
for having us here to speak with you. And we thank
Dr.[inaudible] for all of his leadership
over the past few years with our SBIR
and we feel very fortunate as we bring something
out of the university after my 30 years
there to the patient. The question is,
how do you get your research out of the laboratory,
into the patient’s hand? It s a huge question
for many of us. The pharmaceutical companies
have it down but other areas don’t. So, this SBIR program
was sent from heaven as far as I’m concerned. The first slide in my talk
about developing biophysically designed beverages,
is really about my gratefulness to the broader
federal government. Funny time to be saying
that, isn’t it? [laughter] But, you can see
there’s a ladder of funding in the federal government, and even within the NIH
for career. And I was told this
when I was in graduate school, “You know JoAnne, you can fund
your whole career with this ladder.” And, as it turns out,
when I look back, that’s exactly what I’ve been
fortunate enough to do. And I do have —
I did have a T-32. I just — the name with Kirsten
down the hallway, and it should be at the bottom
there under 1984. It was my first grant,
it was my post-doc, and I’ve been very lucky. And I tell my students
and MPs and fellows that this is available, because many people
don’t realize it. In 1997, you can see,
it was a randomized control trial, clinical trial, and I’ll be talking about that
about midway through the career. So, I’m just pointing
that out for you now that we built a base
for a number of years and the clinical trial was,
we thought, ready to go, and then what ensued after that. So, the challenge, I tell many
students and colleagues who might need to hear it,
but not many do, that it’s important
to have a career question from my point of view, a big question to answer,
if you like doing research, and I like doing
clinical research. And so that career question,
that big question, can be parsed
into five-year pieces; smaller,
but still important questions that can be answered by funding, which usually is three to
five years as we move along. My big career question had to do
with oropharyngeal swallowing problems, because as
I entered the medical world back as a speech pathologist, nobody was dealing
with swallowing problems, specifically oropharyngeal
swallowing problems. And so, the system —
thank you, was being bypassed and g-tubes were being put in
the stomachs of the patients. And, while I was
helping patients who couldn’t communicate
or talk so well, I noticed many of those same
people could not swallow well. And, unfortunately either were
not getting what they needed, or getting a g-tube
in their stomach, which was unacceptable to me, being somebody
who might be someday, in that particular
situation. So, necessity is the mother
of invention. Plato told us
that a long time ago, and Frank Zappa repeated it
in the ’60s to remind us, so it still holds true. [laughter] And it is, necessity leads
to innovation, and that s what happened, and is
still happening in dysphagia, or swallowing problems.
The world as you know, is facing a situation
without precedent, we soon will have more older
people than we have children, and more people at extreme
old age than ever before. Nothing new to you, but population aging
is a powerful demographic. And this is happening, not just
here in the U.S. nationally, but globally. So, we need to really address
as we, many of us,
approach aging, some of us are retiring
and that s a sign sometimes. But dysphagia is a population
health issue that is age related in that
there are 18 million adults with swallowing problems
just in this country, there are millions more
children, just in this country. Harder to track because
they don t have Medicare, they have Medicaid. But you can see that
this is a growing concern. Let me now do something
a little more entertaining and show you a video
fluoroscopic swallow study, many of you may be familiar
with these. But to understand
swallowing anatomy, physiology, and its interaction
with what we put in the system, the stimuli, which is food
or beverage, we use radiography, particularly x-ray,
moving x-rays, fluoroscopy. And we need
a radiopaque contrast because the head and neck
tissues inside are soft, they’re soft tissues,
hard tissue, like bone, images well, soft tissue,
like tongue, doesn’t image well. Barium is
the radiopaque contrast that outlines soft
tissue structures. So, this is a young person
swallowing a thin liquid, barium.
It’s — can we go back? It’s about the thickness
of water, but its radiopaque. Notice, and hold it up,
how clean and fast that was. You swallow a teaspoon of water
in a half a second, less than half a second.
So, swallowing’s very quick, and in that time
we want to see it go down as it did for her,
into the GI tract, which posterior through the
pharynx into the esophagus. We don t want to see it go
anteriorly, under the epiglottis,
into the airway. That’s going to be
a concern for aspiration, which leads to pneumonia. So, if everybody got
a good glimpse of how fast and quick normal is, let’s move on now
to this left side. And this lady had a stroke
the day before I met her. [inaudible commentary] Ah, good sound. So, you heard the response
to the aspiration which outlined her anterior
and posterior trachea. And she did not cough, so she’s
what we call a silent aspirator, which is a real threat to the
professionals in the hospital, to her, to her family,
et cetera. Because she doesn’t know,
nobody knows she’s aspirating which is why this method
is so important. So, what am I going to do
as the clinician, and I was, we never want
somebody to aspirate twice because of us as clinicians.
And so, we thickened the liquid. Nutritionists have been talking
about thickened liquids for many years,
and we thickened the barium and gave it to her
on her next swallow. Gone, no aspiration, and we repeat that
to make sure it’s not just luck. So, thickened liquid was thought
to be a good thing to reduce aspiration, and maybe go as far
as to reduce pneumonias, but that’s a big leap. But thickening liquid
for this stroke patient worked for the 24 or 48
that she was being rushed off to MRIs,
all sorts of tests that are done when you’re in the hospital
before a speech pathologist or swallowing clinician
could really work with her. And keep her safe,
which is what we do initially for some of the many patients
that we see. So, the causes and effects
of dysphagia are numerous. I want to mention,
you saw stroke patients, there are hundreds
of neurogenic etiologies for swallowing problems. I’m not going to get into them
because of time limitations, head and neck cancer,
many etiologies. The biggest one that’s growing
is sarcopenia, and we’ll talk about that
in a little while. But I bet some of you
have sarcopenia and sometimes cough
on a thin liquid when you don’t mean to, to the point
that you might even be a little embarrassed
at a restaurant, particularly if you’re
talking and drinking. Okay, I see a few smiles,
maybe that means you do, maybe that means you don’t,
at any rate, the clinically significant
problem is aspiration, but there’s also malnutrition,
decreased rehab potential, increased length
of hospital stays, and as I said, pneumonia, if we don’t treat dysphagia
adequately and effectively. Of course,
then hospitalizations, as you know cost lots of money, and bounce backs,
coming back into the hospital within 30 days after discharge,
have targeted pneumonia. That’s probably because
you cannot fix pneumonia with — you cannot fix dysphagia, which is the cause
of so many pneumonias, just with antibiotics. You can treat the pneumonia,
but it will come back, and antibiotics again will be given
if dysphagia etiology targets aren’t the direction
of intervention. So, we have to really
get good at diagnosing and treating dysphagia. All right, so what I’d like
to point out here is that bariums that we used for swallowing diagnosis,
for many years, were just taken off the shelf
in the radiology suite, and they were designed
for upper GIs, lower GIs, certainly nothing
about oropharyngeal swallowing. There was a lack
of standardization, maybe even my own hospital, I worked the VA which is
attached to the UW hospital, I worked in both, and they were using
different bariums for their swallowing problems, let alone what Vanderbilt was
using where I had been before. On and on, and we wanted
to do a clinical trial. How can you do
a clinical trial when you don’t even have
standardization of your methods? And so, the first year of our
NIH funded clinical trial, fondly called Protocol 201
by the NIH, was inventing, innovating,
making standardized bariums. And we used
the nutritionists’ labels largely based in viscosity
of thin barium, nectar thick,
and honey thick. But we had data,
we had standards, we knew that nectar
thick was 300 centipoise. We knew that honey
thick was 2000 centipoise, which is a viscosity measure. And we invented that
and we found a partner, a big company, one of the two barium
companies at the time, called E-Z-EM,
now Bracco Diagnostics, and were still — we had become the standard
of practice in this country. So, I have that patent,
the UW has that patent, and it’s a very proud thing, and I hope some of you
are working, knowing that you can do that. We can make contributions
we didn’t dream of along the way until you get there
and it hits you in the face, and you realize it’s necessity,
the mother of innovation. So, we — this clinical trial, once we realized the first year
had to be inventing bariums, lasted 10 years
instead of the funded five. We didn’t get
a whole lot more money, so it was no-cost extensions, thank you NIH
I am none the less thrilled. And Jerry Logaman [phonetic sp] was the P.I. and I was
the person who ran the trial, and there was a big name
for me that was fancy but I don’t remember
what it was. So, as we went along,
we realized, of course
if you have the bariums that you’re diagnosing
swallowing problems, and saying a person
can swallow this, let’s say they aspirate on the
nectar barium but not the honey, then what are you going
to give them to drink? Because what we wanted to test was does drinking thickened
liquids diminish pneumonia as an outcome or does a simple
chin-tuck diminish pneumonia as an outcome, and I suggest any of you
with sarcopenia tuck your chin if you’re choking
on thin liquids, it works like a charm. So, we really wanted
to test that and we have to then also create the beverages
to match the liquids because if you give someone
who aspirates on nectar fluids, they aspirate
on nectar barium, they’re going to aspirate
on their drinks, on their beverages. So, you have to match fluids
to the diagnostics to eliminate aspiration which became another part
of this trial, but really based on outcomes. We had to learn —
well we needed it for the trial, but we needed something really
hardwired based on our outcomes. We had to match our beverages
to our bariums afterwards. What we found,
with another funded study, this was by the USDA — and I think we are
the only people, the only lab
that was ever funded in swallowing by the USDA. We had learned that thicker,
as you saw with our stroke lady, is not always safer for beverages
for people with dysphagia, they get pneumonia,
some people with thicker, really thick beverages,
get pneumonia. We had starch base
in our clinical trial, and starch base is hard
to cough out, we hypothesize. So, we wanted to create
beverages, of course, then that will
diminish aspiration and then had to do
a lot of research on what are our best thickeners.
And what else besides viscosity is important to make
swallowing better. And we actually looked
at 30 thickeners with starch and kinds
of starch being one group, but we looked at gums
and other thickeners as well, and when I say
looked at, studied, but I only had 20 minutes here
before Eric comes up, so that would take up — talking about 20 thickeners
would take up my 20 minutes. So, I’m going to keep
moving here. We needed to do a rheology
research for beverages. This is a rheometer,
a Brook– no it’s not, a rheometer
would be thousands, tens of thousands of dollars
more expensive, this is a viscometer. A Brookfield viscometer
that we borrowed to study the beverages
in a very discrete way. And we studied,
in addition to viscosity, and found that other
parameters of rheology, like yield stress,
like flow rate, et cetera, are important parameters
for swallowing. May make the bolus
move slower so the muscles
have time to kick in, especially in people who have,
for instance, a neurogenic issue,
et cetera. But we started to form —
reform a team, I must say
the NIH has been kind, I was told by some friends here
that my grants would come in and it would, ugh,
damn, there’s Robinn’s again with that huge multidisciplinary
group we have to fund. This was 20 years ago,
we had radiologists, we had nutritionists,
we had speech pathologists, engineers, et cetera,
and it’s only gotten bigger. So, as this came about,
Rich Hartal [phonetic sp] one of the finest
food scientists who studied chocolate
his whole career and opened up his brain
to study dysphagia with me. Because he had the viscometer
on campus that I found and was kind enough to borrow it
[sic], became part of our group along with a sensory scientist
named Zeta Vickers at Minnesota. Reach out, I think that’s
important to tell our students and our post-docs et cetera; reach out,
there are smart people, not right in the walls
where you are. At any rate, let’s just talk for
one more minute about sarcopenia because my lab in Madison
was the first lab to define sarcopenia
in the head and neck muscles. So, this fellow has sarcopenia
in his quadriceps. You’re seeing
the diminished muscle mass, and with that goes
diminished strength. And as we age, as you age,
as I age, we are becoming sarcopenic,
most of us, not all of us, but some of us,
it’s healthy aging. So, we defined it and we knew
that it is prevalent, the NIH had two seminars on it
in the Journal of Gerontology put out two journals documenting
seminars of the workshop. And we decided we needed protein
in our beverages as well because maybe we could kill
two birds with one stone. And if we have thick beverages
to not be aspirated, to build nutrition,
we also could put in protein and maybe build muscle mass or
affect it in some positive way. Being from Wisconsin,
we have lots of cows, so whey protein became
the protein of choice. Proteins taste horrible,
so this took quite a while, recently, and this was the SBIR,
what shall we call it, magic that we are
so grateful for. To really get those proteins in,
to make acceptable beverages that the patients
will adhere to drinking. If you don’t have adherence,
you have nothing, correct? We all know that. I was thrilled to see
that Jerry’s head of, or doing palliative care,
because one of the things we do is help people choose
how to die. Are you going to drink
beverages, thin beverages, I mean, it s a huge area
and growing. Doctor Miller, I’m sorry. I’ve known Jerry
for so many years. And I think I may have used
way beyond my time, and want to turn over to Eric,
but I need to say that it’s been such a pleasure doing
clinical research as a career, that I hope some of you
are doing it and go home at night
feeling lifted by it. Both parts of it come together
and we can make it better. So, thank you the NIH
and other agencies and all scientists
and nursing is so important. Education is so important, not that nursing’s
the one to do it, but we need to educate
about dysphagia because most people,
those who even get it, don’t even know
how to talk about it. They don’t know what it is,
they’re surprised by it, and education
is huge as a need. So, thank you so much
for letting me share with you all of the wonderfulness of what
I’ve been doing for a while. And Eric has only
made it better, being the CEO
of Swallow Solutions, helping us get this invention or set of inventions
to the patients. Eric Horler –>>Eric Horler: Okay — [applause]>>JoAnne Robbins: — will tell
you about the solutions. No pun intended.
Solutions.>>Eric Horler: So, now I think
I have six minutes. So, we’ve all come — climbed
the mountain with JoAnne, and all of the science
and the research, the clinical work
that got to the solution, which you can see
on the screen here. Biophysically designed beverages
for people with dysphagia that create matched standards
for diagnosis and treatment
and address sarcopenia. What I’m going to talk about
is that unless you can figure out how to
get your product into the hands, or in this case the mouths,
of your patients, it doesn’t matter and it’s not going to make any
different for the population. And so, that’s where
commercialization comes in. There’s a lot of
different things that got into
commercializing any product. So, you need to understand
your market, you need to figure out
how you’re going to actually take your product
and get it out to the market. How are you going to sell it, how are you going to
distribute it. How are you going
to manufacture it, you know, are you going to do
everything yourself or are you going to partner, and of course,
underlying all of this, can you even make money?
Because if you can’t make money, again, it’s not going to matter
how innovative your product is. Being as how I only have
six minutes, there’s no way I’m going to
try to address all of that, rather what I’m going to do is I’m going to give you
an example of just
a tiny piece of it, as kind of a case study
of how commercialization figured into what we did
at Swallow Solutions. And the two points
I want to make, so I want to echo
what Oggy [phonetic sp] said about the importance
of commercialization. How do you learn
about commercialization? You talk to customers. The only thing I’m going
to challenge a little bit is this idea that commercialization
is phase three. Commercialization needs
to start way before that. Commercialization needs to start
at the very beginning, or you need to be thinking
about commercialization at the very beginning, or you’re going to get
to the end of the road and you’re going
to have something that you can’t
commercialize. So, I’m going to talk a little
bit about how we went about gathering
the information we needed to make sure that we would have
a commercially viable product. Commercialization,
just like science, needs to be data driven
and it needs to be rigorous. So, we started way back
in that phase one in that SBIR doing interviews,
doing qualitative research. We followed that up
with quantitative research so that we could get statistics on what the market
was looking for, what the market valued
when it says value prop. That means value proposition, basically that just
is business speak for what do people care about,
what are people willing to buy. And then, as we went through the
process of doing development, and all of this
was in parallel to our SBIR, we were gathering more
and more and more data and making course corrections
in the product as we went. So, just again,
using as an example, some of the things
that we learned from those first two boxes, so the very early research
that we did, back in parallel
to our phase one. What you have on the right-hand
side of this slide is an influencer map,
we’ll call an influencer map. So, in the center
you’ve got the person who’s the decision maker
on the purchase of your product. The size of the circles
indicates how much influence any given individual
has on the purchase and the arrows show
you have that influence works. So, we learned some really
interesting things, which are shown
in this graph, when we got out and
started doing market research. One of the things we learned, notice where the patient
is on this map? The patient is really far
from the purchase decision. The patient has essentially
zero influence on the purchase decision
for this kind of a product. Whether that’s right or that’s
wrong, that’s important to know if you’re going to try
to commercialize it. Also really interesting to us
was that the speech pathologist, the qualified clinician
who understands the science that JoAnne was
just talking about, also has very limited influence
on the purchase. That’s a challenge,
that was something that we had to figure out how are
we going to address that? I mean, if you look
at the graph, state regulators
have more influence on this purchase decision
than the speech pathologist. Dieticians, on the other hand, have a higher level
of influence. And then, ultimately with
our quantitative research, we were able to go out and test which of the different
value proposition, which of the different potential
benefits of the product, resonate more
with different groups. And on the far-right hand
side of this slide, you’ll see where
we have force-ranked what the market felt, relative to the strength
of the influencers, were the most important
value propositions. And what really floated
to the top was protein. So, JoAnne said, “By putting protein
in these beverages, we could kill two birds
with one stone.” Commercialization told us, if you don’t kill both of those
birds with that single stone, then you don’t have a stone. We learned this,
during our phase one, we were very focused
on rheology. We adjusted as we moved
into our phase two and said we need to not lose
any focus on rheology, but we’ve got to do it
with protein. And one of the things we
discovered was getting protein in a beverage
at the correct thickness, that tastes okay, you notice
sensory, number three here, was a tremendous
technical challenge. It took us a year and a half
,with some really, really brilliant
food scientists, to solve that problem. But all of that we learned,
from talking to the market, was what we needed to do. So, in the end,
this is what we developed. We developed a line
of thickened beverages, based upon scientific research. Safe for individuals
with mild to severe dysphagia, matched to
the diagnostic standards so that you no longer
have the safety risk that came from that mismatch.
That were all appropriate as both a primary source
of hydration and protein, we learned from the market
exactly how much protein they needed to have
and that’s — I’m out of time
to talk about all of that. All the things we need
to and along the way we actually did manage
to generate some new intellectual property. If we had not done
early commercialization work, and just continued on the path
that we started on, we would’ve ended up
with a product that ultimately would have been
extremely difficult to sell to the people who are actually
going to be purchasing it, and that means
the patients never get it. I’d be happy — I think I did its JoAnne
in about seven minutes.>>JoAnne Robbins: I knew
you could Eric.>>Eric Horler: I would of
course love to talk about all those
other commercialization topics, every single item in that box,
if I go back a couple slides, I’m stealing time.
Every single item in that box is a separate
Swallow Solutions story. You know, distribution,
manufacturing, all of that, every piece of that
is really important, but unfortunately,
we’re out of time. Thank you very much again
for inviting both of us, echo everything JoAnne said, this is really
a wonderful honor for us, so thank you Oggy
and thank you to the council. [applause]>>Female Speaker: Are there
any pressing questions at this point? You may want to just
hit your microphone.>>Female Speaker: Hi, I wonder
if — has this been used for like,
patients who’ve had tubes — feeding tubes for a long time,
is there any potential like, they’re not using their mouths
or you know?>>JoAnne Robbins: I’m not sure
I understand, but people who had —
do I have to hit this button?>>Male Speaker: No,
no, it’s on.>>JoAnne Robbins: But people
who have had gastronomy tubes have been weaned from them
and used these beverages as they’ve progressed
in their swallowing mastery.>>Female Speaker: Thank you –>>JoAnne Robbins: Then –>>Female Speaker: — yes
you’ve answered my question, thank you.>>JoAnne Robbins: Yeah
we’re proud of that. I got to tell you,
I used to say, I’d come home and I’d say, “There’s nothing like getting
a million-dollar NIH grant.” Instead of that,
you know what it is? It’s, “There is nothing like
getting somebody off a g-tube.” Right? That is the truth.
Anyway, yeah.>>Shirley Moore: So,
I hear a lot of — I guess I’m going to challenge
that “there’s nothing like” –>>JoAnne Robbins: Yes>>Shirley Moore: — I hear
a lot of sweat equity along the way>>JoAnne Robbins: Yeah.>>Shirley Moore: And so, I’m just wondering,
with your patent, are you making money?
Is the university making money? You know, other than
the altruistic “Oh, I did good?” I mean, we’re nurses,
we do good every day –>>JoAnne Robbins: Right –>>Shirley Moore:
— with the patients>>JoAnne Robbins: and speech
pathologists have that.>>Shirley Moore: I’m just
wondering about the journey and the work and –>>JoAnne Robbins: Yeah.>>Shirley Moore: Kind of
that bigger pack –>>JoAnne Robbins: Yeah.>>Shirley Moore: How do we
sell this to young people, you know, this sweat equity part
and the hours that are put in.>>JoAnne Robbins: It’s funny
because some of my post-docs were just together
and they said to me, “How did you get the passion?”
The first patent I mentioned where the barium solutions
came out of our lab, when we’re funded
by the federal government at the University of Wisconsin,
were faculty member [sic]. The Wisconsin Alumni
Research Foundation is kind of a partner
of the university, but it’s not the university,
and it — you have to bring your patents
through WARF as it’s called. And WARF has —
if the patent is issued, if we’re lucky enough, you know,
WARF has the patent attorneys. They work with you very closely, and if we’re lucky enough
to have a patent issued, WARF has a formula by which
the royalties are distributed. So, yes, the inventor or the
inventors, one of my patents I had seven or eight
of my students on with me, and so they got checks
when it was being used then. I’m sure they didn’t know where
the checks were coming from, because they’d been out
of school for a long time. But it’s — I think it’s fair
what was done with the patents and having that formula. My department also
is in that formula, and the department
gets part of that. So, I was the first tenured PHD
woman in the medical department, the biggest department
in the medical school, and I don t know if they used
that patent money in my department or what, but for a long time
they gave it to me. Now, this tenured position
is part of the faculty going forward.
So, while I retire, my best mentee
will be assistant professor, which is so exciting to me, it s a new program
in the medical school, not in communicative disorders
or some other school. Did I answer adequately, and
if not, I’m happy to talk later.>>Female Speaker: Maybe one
quick follow up question or finishing question and then
we’ll go to the next speaker.>>Female Speaker: To further
answer Shirley’s question and build
on what you’ve said. It varies by
the university, so it’s really important
if any of us –>>JoAnne Robbins: Yes.>>Female Speaker: — do this
that you clearly read the rules
of your university because some universities
are more generous than others.>>JoAnne Robbins: Yes.>>Female Speaker: So, at Penn
when I did it, I started out
at 51 percent owner and the university
was 49 percent. And then, as investors
come in you get diluted.>>JoAnne Robbins: Are you
talking about your patent?>>Female Speaker: No, about
starting a business.>>JoAnne Robbins: And I was
just talking about the patent, so I’m sorry –>>Female Speaker: Yeah –>>JoAnne Robbins: —
so maybe I misunderstood.>>Female Speaker: — it sounds
very similar, because it is a formula –>>JoAnne Robbins:
[affirmative]>>Female Speaker: —
and so the royalties flow to the department
and to the inventor, yeah. So, we had an invention,
so it’s a similar thing. But anyway I learned during that
process that other universities will take something
like 20 percent and the rest goes
to the inventors, you know, and Penn’s was 49 percent,
so it varies by university. And so, you know, that split of
when royalties come in, where all the royalties go,
and finally they get to you, it really varies,
it really varies.>>JoAnne Robbins: Yeah,
and what was nice is I was on the conflict
of interest committee of the whole school —
university. The rotation was
for three years, they kept me on for five years
I think because we had, I had generated five
or six patents. They wanted to make sure
I got it, you know,
I understood these rules, because they also are —
they change.>>Male Speaker: Yeah.>>JoAnne Robbins: Yeah.
So, I’m with you Shirley, I hope that we all are strong
and don’t settle for less than counterparts
in other professions and of other genders
are receiving.>>Shirley Moore: I just wonder if we should be
counseling young people when they apply
to a university, if they think
this is in their future, to be asking about
that formula at application. Because, the difference between
20 percent and 50 percent is quite a bit. And I’m not sure we do
that very systematically because we haven’t been
thinking of that — kind of a future —
in the future.>>JoAnne Robbins: Right,
my first — my last post-doc
who I just mentioned, will be going on
as faculty member, the first thing I did
when she came into my lab was I made her
a WARF ambassador. So, an ambassador
to the Wisconsin Alumni Research Foundation, so she would learn all of this
as she did her funded research, hand in hand.
Thank you. [music playing]

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