Reflections on Tinnitus Research 2018

(gentle music) – Basically what we're doing is, it's kind of a brief chat. It's nothing, expressing any
other opinions than ours. – Absolutely. – Talking about TRI (Tinnitus Research
Initiative) Conference and about research, the state of research. How things can move forward and such. – Yeah, yeah and just to
be clear, like Steve said, I think this is just really, we're just looking to
shoot the breeze a bit about what's out there,
what our thoughts are on the latest research, 'cause both Steve and I have attended the main tinnitus conferences this year. And just really hopefully
introduce some new ideas as well, and just give our own takes
on where the field's at at the moment.

– Yeah, so I guess let's start with TRI. – Yeah. – It was a while ago. – March I think. – Aye, yeah. (laughing) And for clarity, it's now November. – Yeah. – Well only just.
– Yeah. – Coming into December. So I have the memory of a goldfish, so I kind of remember bits of it, and it's the standout bits, I guess. You've probably got a
lot better memory than I have. – Mm. Well, we'll see. Yeah, I mean, overall I
thought the conference was quite neatly done because
there was a lot of new people giving keynotes, which
was really exciting.

– Yeah.
– It wasn't the, it wasn't the same old crowd really, the sort of people you'd expect and that gave the conference a nice feel. I think, it did make you
think that there were sort of emerging researchers that
had something new to say and that was really positive. – Yeah. Yeah yeah, I thought that as well. I think there were some of
the usual suspects there. – Were still there.
– Yeah. Which is good, I guess, because
you wanna see the people who've been in the
field for a lot of years actually keeping their knowledge up to date and mixing with the people who are brand new in the field as well. – Yeah. So, I mean, from that, I mean you said the things you remember, the bits that really stand
out for you, what were they? – I guess, for me, Will Sedley stood out above everything else, 'cause
his research is just like "wow!" I was just saying you
sit back and just think that's great that, and
it kind of resonates.

I won't pretend that I understood
more than probably about 25% of it but– – Yeah, yeah absolutely. I mean I've known Will for
a while so I kind of knew what he was presenting,
but, at the same time, it's always good to have
that wash over you again and just try and see new elements of it and I think out of the new crop, first of all it's great to
see a neuroscientist involved, – Yeah.
– because that's, that's not every day that
you've got that type of level of scientist that's
interested in tinnitus.

But as well, yeah, he's
really kind of starting to push the boundaries and
he's presenting a very new and novel idea for what tinnitus might be and what the model is and I
think that's refreshing to see because whilst we still don't have that one agreed upon model, actually
Will's makes a lot of sense because he's looking to tie a
lot of different ones together almost as well.
– Yeah, aye.

Yeah and I think the
thing for me, and all, you kind of, you look at
the idea of prediction model and it kind of, the neurophysiological
model makes sense. It's like yeah, you hear it (tinnitus)
you go, ah, what the hell's that and
then you kind of process it in such a way, but it doesn't explain why you continue to hear it. It doesn't explain why, when
you tackle the reaction, it (tinnitus) stays. It's kind of like, it throws
a lot of things out there but it doesn't answer all the questions. Whereas the prediction model,
taking it to a brain level, it's like "ah yeah." So that's the cognitive
process is happening behind which would explain why
I feel as though, I consider myself habituated, but I can't get rid of the bloody noise. It's got louder over the
years. So you think, well, if I'm habituated and I've learned to deal
with the reaction, why? And the prediction model
kind of explains that to me and it just, it really resonates. And afterwards,
I was just kind of like thinking of different ways that you can try and interrupt tinnitus and
what can you do to treat it.

How can you actually deal with
it in the prediction model? And, for me, it kind of
opened my eyes quite a lot. – Yeah and I think the
exciting thing is, now, how Will's using that. So obviously it's still
a theoretical model. He needs to prove it. But also looking at how he
might be able to develop an objective model,
or an objective measure, based on that is really
interesting as well. So I think, for me, Will Sedley's research is very much a sort of: watch this space and see where he takes it next. But he's certainly a
very exciting researcher and one that is great to have
in the field at the moment.

– Oh aye, definitely. – I think one of the other
interesting areas for me was the research that
Sarah Michiels presented on somatic tinnitus.
– Yes, yeah. – Because, especially in the UK, somatic tinnitus isn't really
given a high level of attention. It's not something that they
have a separate treatment or management protocol for, which was what Sarah was presenting. And that was really interesting because then we're introducing the idea of potentially another sub-type of tinnitus based on that as well, which I thought was interesting to see.

And looking at the approaches
and what Sarah was using around physiotherapy to address
that was really interesting. – Yeah I really like Sarah's
research as well because, from a selfish point of view, I've got a big somatic element to mine. From a jaw injury that I
had on a construction site many years ago. And it kind of all fits in a bit and the great thing is, as well, she was able to use some
of the research that we did at Tinnitus Hub.
And following on from that, we have actually got an
upcoming research project looking at the, now we've actually got the measures of somatic tinnitus, to actually ask people do they
have any of these identifiers and then trying to kind of profile it in the patient population.

And, like you say, it's an emerging area. And you talk to anybody with tinnitus and they've always got tension problems. There's always something in the neck or something in the jaw,
or something there. Even if it's not somatic
tinnitus there's, so often, you look and think there's
got to be a somatic component to it and if you can treat
the somatic component then yeah, you can help a lot of people. It might not be a cure,
but it could be for some. – Yeah. – But it's gonna really help, 'cause if I knew how to
treat my somatic component. I did, actually, exhange a couple of
emails with Sarah recently. I was asking her about Botox. – Okay. – Saying could you actually Botox? And, as she quite rightly pointed out, you have to get the dosage about right, because if you do it in the jaw people lose the ability to eat and speak.

So that's a little bit of a dilemma.
– It's not without risk. – Yeah exactly, aye. I was like, well what
about, sort of, for me, I know it comes from the
shoulder blade as well and up the neck. And she said, again, people won't be able to hold their head up if you get it (the dosage) too heavy. So there's a real balance to
be had from that perspective of the somatic tinnitus, yeah.

– Yeah. Yeah and so, yeah for me
that was, like I said, interesting because it's just not an area that's really considered
outside of some areas of Europe. I think, really, so yeah, it
was good to see and, again, I hope Sarah stays involved
in the research field really and looks at how to develop that work. Because, like you say, it
could be a real potential to look at as a sub-type. And there's all sorts
of different approaches beyond physiotherapy as
well, that might help there, which is exciting I think. – Oh absolutely, aye. – Yeah, and then another big one, for me, was Hubert Lim's talk, where he started to almost
lay the ground, if you like, for the Neuromod device that
we know is up and coming. So he was talking about how
using bimodal stimulation, which really has an impact on
tinnitus, and set up the talk, the industry talk, that
Neuromod gave later on in the conference as well. So, again, that was really
enlightening really. – Yeah. I think, and that in
parallel to sort of the…

Unfortunately Susan Shore couldn't make it, but a couple of her
students or collaborators, I don't what they were actually, but they explained, again,
their model and their thing and it was quite, yeah. That side of it really grabbed
us as well because it's, again, it's new emerging research isn't it? And it's something which,
again, makes perfect sense in the sort of the Neuromod, as they've been presenting recently, the idea of "priming" the brain. The idea of sort of saying okay, well here we've got this sound which may or may not
help people or whatever, but then if you prime the
brain you get in there and kind of push the
right buttons inside there that you actually make
the brain listen to it and make it pay attention and
then increase the efficacy of the treatment.

– Yeah, and it's really
interesting, I think, you've got two groups coming up with very similar ways to look at that. Both with slightly different protocols 'cause they're looking at that, both using sound as a
sensory input, of course, but then looking at a slightly
different nerve stimulation to get that sort of bypassing
the auditory pathways or to get the auditory
pathways more active. But yeah, really interesting to watch how those two emerge, really,
and almost compete, I guess, to see who can get it out there and which one has the best efficacy. It'll be really exciting to see. – Well the competition to get it out there looks like it's quite. – It's a little one-sided.
– Yeah yeah yeah. – But yeah, nonetheless, I think, yeah, it'll be really interesting to see what Susan Shore's team does next and
where that work goes as well. And hopefully hear it presented as well, because I think that is
a challenge at the moment. You can read the papers but, for me it's, seeing it presented, you
really get a much better idea, and the context of it
is interesting as well.

– Well the presentation they
did at TRI I thought was quite, it kind of made it like
wow, this is pretty cool and they showed some really good results. But, of course, they can't go into detail. It's still work in progress. It's still things that are being analyzed. So it was kind of, it was a window into it, and I think the session
that they had as well, it was cut a little bit shorter.
So it was, well I say that, I think they just had so
much information to present it was impossible to
fit it in to a session.

It was, you just wanted
to kind of almost have half a day on that. – Yeah it was frustrating
'cause that is a really big emerging area, and you thought, let's really understand this
a little bit more than we did. So that was interesting I think. And also, another, one
of the smaller talks, was on a drug that may provide
a residual inhibition as well for tinnitus, which I thought was a really interesting concept. And it's frustrating
because it had been shown in an animal model, I think, but the team that was presenting
really didn't have the clinical expertise to look
at how to translate that into a clinical model or run an RCT
(randomized controlled trial). But, again, it was another
interesting insight that you think: well that's got potential.

If you're gonna even find
a drug that does do that residual inhibition, A) what's the model that's making that happen? Because that's something
worth further exploration. And of course B) it at least
has the potential to give temporary respite as well. So, again, that was an
interesting talk as well that I thought was just
another one of those that's happening, that I
certainly had no awareness of and it was good to find out more about. – And I think that kind of
leads on to thinking about, as well, the lack of presence from pharma. – Yeah, yeah. – Which was quite striking
because you kind of, you really want the
pharmaceuticals to be involved and to be there and
interested in the whole thing. It's not to say that they're not, but, it's the biggest tinnitus
conference pretty much.

– Yeah.
– I'm sure our American brothers and sisters might
disagree with that, but… – Yeah. No and I think, you know, it's sold the Tinnitus Research Initiative as an international tinnitus conference, and I think it should be
looking to have that input from pharma and yeah, at the moment, there are a few niche
players, if you like, or some of the players that
are really involved in tinnitus that were there.

But yeah, overall, it wasn't
really clear and, of course, can't remember if it was
Auris or the other one, were meant to be there, but
withdrew their presentation 'cause they withdrew the drug on the day. Was it Autifony or
Auris, I can't remember. It was one of those two. So there are involvement there, but yeah, the big players aren't there,
and I think that points to some of the other frustrations
with TRI at the moment is that a lot of the
trials that are presented are quite small-scale. You don't see the big trials. You don't really see RCTs
that frequently in tinnitus.

And also, that kind of
leads to that model of what I said about
residual inhibition, that there's no real
translational research happening that often where you're looking at, okay, so we've done this and now
how do we get it to market? and how do we do it as rapidly? Which is why you see
something like Neuromod and it's quite refreshing, 'cause they really have
that focus on the market. But then the disadvantage of that is that they may well be
bringing something out before you've got the published research to demonstrate efficacy. So you've always got that sort
of push and pull, I think, with the research. – Yeah, and then that's from
the patient perspective. We all want things to
come out straight away. But equally, we don't
want them to come out without proper research. It means that there's a
constant sort of balance between the two and, I mean,
I think the first launch, for example, of Neuromod was too soon. And then they've come back
and they've done the research but then, of course, you can't win because people are complaining
it's not on the market.

– Yeah, why isn't it there? – Yeah.
– Yeah. – So you kind of, you've
got that balance to find all the time and it's really hard. I don't envy them at all. – No, no, not at all. And I think we saw some of the challenges 'cause both you and I
sat in the Q&A panel, you were on the panel, and one
of the questions put out was: How do we engage with pharma? And what do pharma want
from the tinnitus world? I think that was a little bit
concerning to hear, really, from TRI, because, from my perspective, I think there's been
quite a lot of discussion, especially from some of the
pharmaceutical companies who've had drugs that have failed, about what needs to happen
for them to engage more and what needs to happen for them to really start to invest
in tinnitus research.

So I think we know some of that. And it was a little
bit concerning, really, that the type of research that we
know they (pharma) want to be able to then move on wasn't really present. So when I'm talking about that, Action on Hearing Loss had
an excellent conference, the Translational Hearing Research Summit a couple of weeks after TRI, I think, and they had engagement
from pharma worldwide. And it wasn't just on tinnitus, it was on hearing much more broadly, but a couple of the big tinnitus
trials presented and, actually what was interesting from that wasn't just what's coming, but
just learning those lessons and, for the first time, a
few of the drugs companies who've had trials were
really talking about: Why did it go wrong?
And what needs to change? And the messages were coming
out loud and clear really.

One was around animal modeling. So there was a big belief that actually, maybe for tinnitus, the
animal models aren't ideal because all of the drugs
that went to human trials showed great success in an animal model. So actually is there
something we can do there to either improve the animal modeling or should we be looking
at humanizing the model? Which was an interesting thought. Can we use human tissue,
somehow, in that basic science to look at improving it? And so that was a really interesting point one of the presenters made. But then they were also looking at, well: Can we develop that
objective measure? Which, as you know, is something
I've been banging on about for years. – Yeah well, me as well. And you kind of, you're
in that position of if you haven't got an objective measure, how do you know? What
questionnaire do you use? And I think another thing,
at your conference recently, BTA conference, David Baguley
said in his talk about that: If the questionnaires
are just asking you "How terrible is your
tinnitus? How bad is it?" These very sort of negative
and leading things.

Are they really the best measures? 'Cause the best, almost like you would say from a patient perspective, the best measure is: Do you feel better? Is your tinnitus quieter? And it's that personal
thing but, of course, it's not clinically validated. – No and I think that's one of the skews. So a lot of the questionnaires
that are out there now have been developed for
use in research but, yeah, they don't necessarily help
because they don't give you that outcome, and actually I was
talking to one of the researchers who really does a lot of
work with the questionnaires and said, actually,
given the questionnaires that we've got out there at the moment, if we did cure tinnitus would
it show on a questionnaire as zero or would you actually
still score something? – Yeah.
– And, yeah, the belief was you'd probably still score something just because of how some
of it's phrased, like you said,
– Yeah.

– almost that "how awful
is your tinnitus?" stuff. And yeah, so, actually that
need for an objective measure, it's really refreshing to hear
pharma say the same thing: that until we have that way to check if tinnitus is present or
not, without, like you say, someone filling in a questionnaire, then it's tough to see how you'd move on with some of the drugs research. I think, personally, anyway,
and like I said before this is just personal opinions.

And so, yeah, something I
really want to push for more is, yeah, how we get that research to see if an objective measure is possible? And, I mean, I realize not
everyone might know what we mean by objective measure. So an objective measure
in tinnitus might be: You could do a blood test that shows if tinnitus is present or not. You may be able to do a brain scan. So an fMRI scan or an MRI scan that shows if it's there or not. There's different tools we could use to objectively say, "yes tinnitus
is present" or "no it's not." – Yeah.
– And I think that should be a real focus of
research over the next sort of period of time, as well
as looking to improve the subjective measures
we have, but to do that.

And the other area that
pharma identified as challenges to doing future research,
was around sub-typing as well. So a little bit like we said
about somatic tinnitus earlier. Is there a way that we can
better sub-type tinnitus? And actually, in a few of the
trials that were presented at TRI, we saw people starting
to play with their data to see if they could
develop sub-typing as well. – Yeah, and you do wonder,
as well, in the trials, are they gathering enough information to actually sub-type it? We do have some standard measures, some standard questionnaires.

I think one thing, as well, you think is: Is there a value to adding
additional questions like as in the masking level? I know we've got minimum masking levels, but actually asking a
person: "Well, how is it now, if you're in this social
situation or in that situation, do you still hear it?" And kind of trying to gauge different ways of actually measuring the
tinnitus in the person. But again, taking it back to the personal. But the sub-typing, there's so many things that you can look at. It took me probably about seven years before I actually realized
I had two more causes to add to the original
diagnosis of a sort of slight hearing loss. You can pick up these things and it wouldn't necessarily get
picked up in a questionnaire or in an interview.

You'd have to be quite in depth, you'd have to really interview somebody and ask a lot of questions
to try and understand if there'd been an acoustic
trauma at some point or a jaw trauma or a neck trauma because people don't necessarily, if they're filling out a
questionnaire they're just going "no, that's never happened, no." But if you drill into it
you'll find out, well, "oh yeah five years ago I
had this ear infection." "Yeah but that's got nothing to do with it 'cause I didn't get tinnitus at the time." And all these things
that could've actually played their part in it. That's where it starts getting
very expensive as well. – And the cause of tinnitus
might only be one way to sub-type, and it might
not be the ideal way. I mean that's the challenge. You could, of course, do like you say. You could look at sub-type by cause or you could look at sub-type by severity. Or there's lots of different
ways that you could sub-type.

And it's almost the challenge
is, where do you start? And how do you start? 'Cause obviously, as soon
as you start sub-typing then trials get more expensive 'cause you need more groups
of patients for each one. And the reason I think
it's so important is when you see some of the data presented you often see the charts and they'll show individual patients and
you'll see some absolutely fly and just, their tinnitus
scores just go off the charts and improve dramatically. You see others that go nowhere and you see some that get worse. And so, you know, if you
could figure out, well, that group who have really improved with this particular treatment, can we figure out what, are
there any characteristics that are the same? And likewise, are there any
characteristics for the group that have got worse, and could
we start to understand that a little bit better? And I think
we're seeing that emerging but I certainly don't
think it's there yet. – No and if you can pick out those things there's nothing to say that actually, for a reasonable amount of people, there isn't an actual cure right now.

You might be able to hit
with three, four, five different strategies
and knock the tinnitus in so many different ways that
you can actually kill it off. Kill it off. – That's one way to put it, yeah. – Aye, but yeah, so we
don't have that at all. And, again, the limitations
of a clinical trial: They are testing one thing. – Yeah. – And if they test more than one thing it throws so many variables into the mix that it's very difficult to measure, so it's a kind of Catch 22. You can't step beyond
it, you could do it as a complete experiment, but you're
not really gonna get anybody standing behind it because a lot of money will be involved,
a lot of variables involved and the outcomes are just, who knows? – Yeah, yeah. So, I mean, we're talking a lot about, here, about the challenges to
pharma and engaging with it but the other side of the coin, as well, is that they are engaged,
possibly not as well as they should be through
groups like the TRI, but there are pharmaceutical
companies out there and therapeutic companies
that are looking at tinnitus.

And what really surprised me at the Action on Hearing Loss Conference, was just speaking to some
of them outside of tinnitus and just in hearing loss generally, they understand where the field's at and they are keeping an active
watch on what's happening. And I think, at the moment, it might almost be opportunist in terms of they find a drug that through
serendipity seems to be curing someone's tinnitus as well, rather than really
looking for the formula, because we don't have those biomarkers and those targets at the moment.

So a lot of it is
opportunist, if you like, but yeah, they're definitely involved, they understand the
potential of the market, if I'm gonna put it in
those terms, as well, and the potential of
how big the market is, especially in the US – It's huge if you can get it right. The cynic in me always thinks
that it would end up being a sort of pill that they could sell because if they find something
that just knocks it out straight away they're not
gonna make so much money out of it. But that's the cynic. But I haven't read a lot about big pharma. – Yeah, well actually, yeah. Well I talked about that with someone who was representing
big pharma at the time and what they said was,
that is the case in terms of if you've got someone on a drug for life then obviously there's
benefits to a drug company.

But actually, that's really
really expensive for them to trial because you've gotta
do long term safety profiles on it which are incredibly expensive. So actually, if they did have a drug that obliterated tinnitus then
actually that may well be more cost efficient for them because you don't have to go through
all that safety profiling for the drug, to prove its
long term safety as well. – That's quite interesting that. – Yeah so it's a
different angle on it that I'd certainly not thought of. – No and I think, again,
it shows that, I think, pharma don't necessarily
engage 'cause things like that are really useful to
the community as a whole to actually get an understanding of it and it feels like pharma just don't have that level of engagement. They're kind of locked away in
an ivory tower, if you like. You don't really see or
hear an awful lot from them. – Yeah, I think some of
that's true in terms of they don't necessarily engage
at this level but it's, in a way, whilst it's
exciting for the community to understand and have that access, it's tough to see what's in it
for the company a little bit because they obviously have a compound that they're trying to protect and they'll want to do
trials on at some point.

Until they're at a stage
where they're almost at that sort of late phase
three, phase four trials it's hard to see why, what's
in it for them really, to really have that level of publicity. – Yeah. – But talking about
that, I mean like I said, we've said some of the negatives but there are some really
exciting things happening with pharma as well and I think it's worth highlighting them a little bit. So one I learned about at TRIH, the Action on Hearing Loss
Conference, was Otonomy. So they're a US based
drugs company, I think. They've done a lot of
work around many years and they've got a drugs compound that they're looking to
do trials in the US on in early 2019 as well.

So that's really exciting. I think it'll be interesting
to see what comes of that. I don't know a lot about it. I'm sure there's a strand on the
forum (Tinnitus Talk) about it. – Yeah.
– But, yeah, it's hard to quite understand
what's happening with that. But, again, that looks exciting. – Well it is, and it's got,
crossing over into the, unfortunately, tinnitus didn't
win the Frontiers Project which was a shame, but it was won by, it was a balance disorder,
which was quite interesting because it kind of seemed
to be suggesting about novel intervention, about
actually finding a way to cure balance disorders.

So whereas it was a big
disappointment because there was a lot of effort, a
lot of community effort put in to getting the altmetrics and actually disseminating the research, it's quite nice to actually
have something which is related and you would like to
think there'd be some translational research from
that area into tinnitus as well. Especially with drug development because if you target in that area then… – Yeah so, and like I said, Otonomy's one. Pragma Therapeutics are
looking very seriously at the moment, both a drug
that may suppress tinnitus, so stop people acquiring
it in the first place, and also looking at sort of
other therapeutic compounds as well, so it'll be interesting
what they come with next.

And, of course, the team at Pittsburgh
(Pittsburgh Hearing Research Center) now have a drug as well,
that they've now got Department of Defense funding
for to start the animal trials and the animal works. So, again, I think that'll
be exciting to watch where that goes. I'm not sure we'll hear much about it the next couple of years but, yeah, hopefully they'll be publishing
towards the end of that and their animal work. – Again, with the DoD being involved, you'd like to think it'll be fast-tracked. That it's not something which
is gonna sit around and have years and years and years. In the spirit of the size of the problem facing the veterans community, you hope that this is
gonna be pushed forward and it's something that
they can actually, yeah, it gets out there within
a couple of years.

– Yeah well, at the moment,
it looks like they've got a three year grant to do animal work. From what I can figure
out it's phase one trials. Assuming that's successful, then, they'll need a phase two
trial and three and four. So it's something that
it's hard to fast-track. Drug development does
take eight to 10 years. And actually that's something else that pharma was saying to us, was well, what we need to understand is
take the drugs work out of it, what will the tinnitus treatment and tinnitus management world look like, not now but in about a decade? 'Cause that's what you're looking at for some of the drug development work from pre-clinical to going out.

It may well be different
for the Pittsburgh team 'cause obviously that's a drug that has been on the market previously and has been modified so
I don't fully understand what they need to do. If they're just looking at
safety profiles for that and getting a more enhanced
safety profile for that drug or if they're doing
something much different. But yeah, it may well be faster but a lot of the work is around
just trying to understand that type of process of where we are in terms of how long a drug
takes to run through a pipeline. – Yeah 'cause, again,
you look at therapies which you wouldn't think would be curative and, again, look at it. Something like Neuromod. A company like that, a private company, can move quite fast. – Yeah. – And the drug development,
if they're thinking, well hang on, if they're doing that and if bimodal stimulation, for example, turns out to be this
amazing thing that you can, you're all of a sudden,
you're gonna have the, you had the transcutaneal [..]
which didn't quite… A few people tried to
do that as sort of self…

A homemade version of it, and
it didn't quite do anything. But when these things start to come out, people start experimenting
and think, well, if you can do it like that I wonder if I can access the brain by stimulating this nerve? I wonder if I can use this
piece of $20 or $30 kit to do this at home?
And you kind of get all that experimentation
and if it does prove to be what we hope it could be,
with the bimodal stimulation, or even in combination with
other therapies, then yeah, in 10 years' time it could be
a vastly transformed field.

– Yeah, absolutely, and it's hard to say 'cause obviously we've been
here a little bit in the past with things like acoustic neuromodulation, which had a huge impact on
the tinnitus community and – Yeah massive.
– When it came out the amount of questions we
had on our helpline about it, what it was, 'cause people
just latched on to it. And so you do see these
products come out and launch and it'll be really
interesting to see if Neuromod and the bimodal stimulation people can get the papers and
the research evidence to back up the product really.

But yeah, obviously the
product development pipeline, for something like that, is
shorter than it is for a drug, just for safety reasons, really. – Yeah and, again from, this
was something that was posted on the forum, probably
about four years ago now, and it was from PiHKAL
(a book) by Alexander Shulgin. And it was, what was it, MDPEA. Of course he tried, he tried
loads of compounds on himself and measured the effects
and in this it said, I think it was 200
milligrams: "Nothing happened and after 20 minutes my
tinnitus disappeared." And you're like "oh," but
you can't just jump in and research MDPEA. It's not scheduled, however, apparently, you can take a blocker, which would make it psychoactive. So as soon as you try to do anything on it it would become scheduled.
But you kind of think to yourself: It's a shame that with an audio treatment, you can just go out
there and say to somebody: "What's that like?" However trying to synthesize a drug which potentially could be illegal, you'd probably do it
in China and import it and then God knows what
you're getting into.

And then you end up with this thing which is really interesting, which you wanna see somebody research, becomes years of research and
safety profile and phase one and the millions will just
stack up and stack up. Whereas what you really
want, which I don't advocate, is a hundred or a couple of
hundred of Alexander Shulgins, just trying it out. – There are drugs that we
do know work for tinnitus. Lidocaine, we know suppresses
tinnitus, temporarily, until the lidocaine wears off. So we do know there are
drugs out there that work but the safety profile
on lidocaine just means you can't do that and also, you're not gonna go and get it injected.

Lidocaine's the type, the anesthetic you have given at dentists. So it's nothing that
you can take regularly and it's got a real safety issue anyway. So there are drugs out there
that we know have an effect on tinnitus but the real
challenge is how you develop that in a way that can have
something more long-lasting and ideally something that's oral rather than needs to be injected as well. So there are drugs out there
and compounds out there that we know work. It's then how you make them safe or how you find a
different way to deliver it that's gonna be efficacious
really, as well.

– And, again, the Trobalt thing. All of a sudden it was this miracle thing but the safety profile's horrific. It was withdrawn from the market. But it was, it's not something that you could continue to take. I think there was, anecdotally, it did actually wear down the
effect, over time, anyway. But yeah, and, again, that's
what's being researched at present. They're looking at a
modified version of it, acting on the potassium channels. But it's really interesting stuff but, if it's not safe then– – Yeah, No absolutely.
– Yeah. – Yeah so, and in terms of
what's coming up next year, I mean are you aware of
anything that's exciting you. What are you expecting to see
in 2019 in terms of research? – I have to say I'm an audio
geek anyway so anything, that's where the bimodal
stuff really grabs me. I know we've already covered it obviously, but anything like that, but I'm, there's nothing particularly coming up but I have noticed more that
people are interested in, bimodal is an interesting, more than one way of approaching it.

I'm kind of hoping that that
follows into the future that people start looking at
two ways or three ways and combinations of treatments
that actually could have much greater efficacy than when
you just do it by yourself. – Yeah. Yeah, no I agree. I think it'll be really exciting
to see Neuromod published, which I think we've certainly
got to expect next year. I'm not sure what Susan Shore's
timeline is at the moment, whether anything's coming out
from that center but, again, you'd hope to see, because I
know there is a trial going on so you hope you'd see
some results from that fairly soon.
– Yeah. – Another paper that's come
out that I'm still trying to get my head around is
one by Fatima Husain, which looks at using fMRI to try and see if you
can predict tinnitus.

And it looks like she might
have found a way to do that so might have found a potential
objective measure but, yeah, I don't understand the
paper well enough at the moment. But, again, I think it'll be
interesting to see what comes 'cause, again, she presented
something interesting around that at TRI. And we should see some trials kick off. It feels like there's been
a bit of a dip, I think, in tinnitus work but I think
with the Pittsburgh team, and with Otonomy, you
will see some pharma work start again and sort of re-emerge. That'll be positive to see. And I'd really hope that we'd start to see some papers emerge as
well from the PhD groups. Both the ESIT group and
also the TIN-ACT group. I mean ESIT are a little
bit further ahead but some of that research could
be really informative as well.

So I think it feels like
we should start to see quite a bit emerge over the
next sort of year or two. And alongside that, I know
we're focusing on cure and rightly so, but there'll
be a lot of research around management as well with the
publication of a number of Cochrane reviews which helps give us that high level of evidence as well. So it'll be good to have that out there and have that real pinnacle, if you like, of the research at the
systematic review level. And, again, that'll give
the basis and the argument for future research to happen as well. So where it does say
more research is needed then the scientists, if you
like, have got the justification and the cause for that. – Yeah, yeah and I think with
the stuff that you've been pushing recently, as
well, with the cure map, the cure roadmap as well,
and kind of highlighting that a lot of the management techniques are pretty much researched. Everything's in there.

There's still an importance to them, because there's a sort of
attitude and I totally get it, of well, we want a cure. Why are we interested in something that might help manage (tinnitus)
or might help this? I think they're still
really important because you've got to understand
the things that you can do to help you, and for some people they actually will help a hell of a lot. They'll get really good results and but, the thing, the feeling, and
I totally get it as well, is that "Oh if you've got
all this management technique why bother researching a cure?" You want people to research the cure. You don't want them to think:
"Ah well it's all right. People are happy enough." – Yeah, and I don't
think that's happening. What we've discussed around some
of the pharma investment that's going on, shows that
people still want a cure. And one of the reasons we did
the economic paper a while ago was to try and show that
there's a market there, that there is management
available that works for some, but not for everyone, and
actually this is sort of the cost and this is the benefit, if
you like, that people get in a sort of, in a measure that the
NHS (UK National Health Service) accepts.

So we got that but actually
what that does do then is say, okay, so if you can
develop a drug that works and delivers a better outcome, then actually you're gonna
smash through the targets, we're saying, in terms of what
we can deliver at the moment. And I think the other thing
with the management research is that it can inform the cure-based
research as well 'cause, like you say, management research,
look at CBT (cognitive behavioral therapy). There's a lot of papers on it. But you can then go back
through those papers and maybe going back through those is one way to start to sub-type,
because all of a sudden you've got big numbers of
people in a lot of trials, then maybe you can use it.

So I wouldn't necessarily see it all as either competing or separate in terms of the cure research and
the management research. They both inform each
other and often you see people and teams working across both. So it's not just that one happens
in isolation to the other. I think they do inform
each other quite a bit. – And I think the other
thing as well, with that, is that the management
techniques that we've got, we often talk about, we
often wait for 30% of people. It's that combination, again. If you've got a treatment which has got a reasonable efficacy,
combining it with something which is already proven and validated is a management technique.

Finding that right
technique for the individual and then combining the two is gonna have much greater effects. – And I think that's what you see a lot. When bimodal stimulation is
on the market, for instance, I'd be surprised if there's
not a psycho-education type of component to that. So you are actually using something that you know has some efficacy,
as well as the new device. So you do see those blended approaches. Even if you do have
something that becomes that, something that you can
manage tinnitus with much more effectively than you
can with the standard stuff, I think it'll still blend with
those existing things that we know are out there as well.

– Oh I think it will 'cause no matter, especially when you're
in the early stages, I would say the first
maybe year, two years. I don't know how long it
was really with me but in that early stage where things spook you and you're tense, you're up high, reactions are just like: "Oh God, I can't believe I've been to this place, I've damaged my ears again." "I've made a mess of things." "The tinnitus is gonna get worse." All these things that
play through your head. Actually learning to
manage those reactions, probably are gonna be a
really big part for people in the early stages, who
are getting treatment, which otherwise would help but
they could throw themselves out of it by kind of falling
into those thought patterns. – Yeah, 'cause you know,
I think you're right. How do you engage constructively
with the treatment if you're still in that sort of cycle? I think there is a bit of, you
still need that, like I say, psycho-education, almost, about
what is it and what's going on, to almost help do it
and that does form an active part of treatment,
I think, for a lot of things.

So yeah, whilst, let's say
we've got that happening, I don't see it as that link. and I know the BTA takes criticism 'cause we've supported CBT trials. But yeah, at the same time, they do inform other stuff as well so it's not they happen in isolation. They get presented.
And one of the reasons we have is because both the trials we have have been decent, high level, RCTs.

And that's something that's
lacking in the field is that real research rigor at times. 'Cause you do see so many studies done on small numbers of people,
protocols tweaked a little bit, and they do the same study almost, again, on a similar cohort, and you
just, you do need that rigor. That's sometimes not
always present, I think. – But, again, leading on to something else that was presented at TRI
is on the COMiT'ID and that development of
the outcome measures.

So we're actually, everybody's singing
from the same hymn sheet and we're not getting trials that say "well we've done this, we've
done this" and you're kind of… It's as if you're trying to
do a Cochrane review. You're trying to combine, say, 300 trials and they've all got these
hugely different measures. They've done things in
different ways and it's just, and I understand that, how
confusing it is and yeah, it's a desperate thing
to have these measures through COMIT'ID.

I was part of the panels. I went just round the
corner from where I live, which was very handy, to
the actual discussion day. And it was good and I won't
say that I agreed 100% with the things that came out of it but that was the whole
point of the process. It was consensus and everybody, from this huge number of
people that started off, hundreds that started off, it gets whittled down to the measures that we feel are important, as patients.

And then clinicians felt were
important as professionals. And it was really good
to actually get these outcome measures 'cause
if you ask any patient what do they want, they want it, loudness. That's it. It's loudness. There is nothing else that matters. Which always becomes
very difficult because you get told with a lot of therapies that loudness doesn't matter. Well ask any person and it
does, that's the primary, so loudness was always gonna be there. And I don't recall fully the
measures that we came out with. But it was quite a satisfying
process […] great. So moving forward, now I
don't know how well people will adhere to it, but I guess
there's the danger of not being considered high
quality research if you don't. – And I think it's, the
questionnaires are still some way off, because although
they've got the domains for drugs trials, sound trials,
and psychological approaches they still then need to
develop a questionnaire to measure the domains
that they've come up with.

And I think it was tinnitus intrusiveness that was the one across all
three (domains) that was seen as critical. And I know tinnitus loudness was included in the drugs trial domain
because the theory is that if you develop a drug you want to obliterate the tinnitus. – Yeah. – Whereas psychological approaches
aren't necessarily about reducing the sound, but
reducing reaction to sounds. So we're looking at slightly
different things and, yeah, it'll be interesting to see where they go. I know the Nottingham team
have put in applications to develop a questionnaire
on one of the domains, I think it might be sound. Not sure though. So they are looking at how
to take that work on now and it'll be interesting
to see but, again, questionnaire development takes time 'cause you got to develop a questionnaire, you've got to validate it.
And it's, again, sadly, years of work and that's
why everyone was so hopeful that the TFI (Tinnitus Functional Index)
would be the savior, if you like, for subjective measures and tinnitus.

And whilst it's probably
the best that's out there, I think most people agree on that, sadly in a UK population
study it kind of had issues. So that's a bit of a challenge and, yeah, one reason why COMiT'ID
is now out there I think. – Yeah. Well, again, I'm quite
interested in the questionnaires and research and understanding more about the sort of populations. Yeah, so and I think before
I got involved with that I had zero appreciation for
how long it actually takes to get these things validated. You just think well, for
what we could do tomorrow with what we do at Tinnitus Hub. Right, got a questionnaire, yeah. We'll get it written,
we'll get it out there. Three weeks later it's out there and it's gathering things in. But of course we can do what we want. You try and base it but then, of course, you get them and you try and base it on already validated measures.

You try and kind of, oh we'll use that from that questionnaire. We'll use that from that questionnaire. And try and kind of make sure
you're using the same scales and you're measuring the same things. But it's very difficult because a lot of the things you want
to measure and you wanna ask, there's no validated measures for them. – No and I think as soon as you do sort of cherry-pick like that, the
measure that you then create hasn't been validated. – Yeah. – So you run into
different troubles as well. – Yeah.
– But, yeah, and I agree 'cause obviously the BTA
does a lot of surveys. We do a lot of work as
well in similar ways. And yeah, it's that challenge
because as soon as you present at something like TRI they
want to see that you've used an outcome measure that's accepted. The story I always look back at is, I do a lot of work, sort
of training audiologists every now and then and one of the ways, one of the papers I use to train them is a paper on laser therapy.

Basically I ask them: "Well,
what does this paper show you?" And actually, if you
read it at face value, it shows you that lasers are great. They work really well. But then you can ask, okay: So have they used validated outcome measures? No, they've designed
their own Likert scale. It's just stuff like that and actually, once you start to look at it, the reasons you need those
validated measures is if you don't then it's easy to say that something's clinically measured and works clinically, whereas
actually, you dive down and the validated outcome
measures haven't been used. You look at where it's published. You look at the methodologies
and that's where you start to really understand a little bit more about how much weight you give to
that piece of research, I think. – Yeah and I think,
again, that's something that you don't appreciate
until you actually get into it.

It was, I think the first
book that I read, Bad Science, and that kind of, I
read that cover to cover in no time at all, and it was
just like a massive eyeopener. You're like "Whoa!". And then you kind of, you
go back to the sort of kitchen table discussions, if you like, and you've got them
going: "Ah well, you know, tomatoes are good for you this week and then bad for you next week." It's like, no.

They're misreporting the trials, they're misreporting the outcome. They've cherry-picked one tiny little bit to create a story and you're
kind of trying to explain it to your parents and they're just like: "Oh they change their mind all the time." It's like well yeah,
that's what science is. – Yeah.
– It moves on all the time but, yeah, anything that you say about the measures. – And I think that's one
of the key things because the other thing that's
gonna come up soon is practice guidance on tinnitus through NICE
(Nat. Inst. for Health and Care Excellence). And I think that's, I saw the
hearing loss practice guidance presented recently, and
Kevin Munro from Manchester presented it, who's a fantastic
professor, based there.

And he sort of gave a really
good example of using that, that actually the reason
we have guidance is because science changes and your knowledge
changes so, like you say, one thing that you thought was efficacious almost might be disproven
three years later. So you have practice
guidance, you update it to reflect what the science
tells you at the time. All they ever are is a snapshot. But you just continue
doing it so, like you say, you get to eat two tomatoes one week and avoid tomatoes the next. – Yeah.
– And you try and get the consistency and then try and get what science is telling you at the moment 'cause, of course, you hope
it moves on in that frame and it does tell you something different further down the line. – So coming back to the economics
of tinnitus and the work that you've done on
it, or the BTA have done on it, and you've published.
Is that published now? – Yes absolutely, yeah.
– It is. It took a while.
– Yeah yeah. The publication was a challenge but now we've got it out there now.

And there's also accompanying paper to it which looks at the sort of patient flow through the NHS as well. – So on that, you've looked at
what the cost is to the NHS. Is it the cost of the
patient going through this? So what's the hope of the outcome of that? Is that to convince the NHS that it's worth treating tinnitus? – Yeah. I mean the absolute headline
for us, through that paper, is that actually tinnitus management, as it stands at the
moment, is cost effective, using the benchmarks that NICE accepts and the NHS accepts.

So looking at cost of per quality, so per quality-adjusted
life year (QALY). So that assumes that you get a
small incremental improvement in your quality of life
for a number of years, based on getting successful
tinnitus management (treatment). It assumes that not everyone gets that. It assumes, I think we put
about 20% of people at each step, so it's quite a conservative improvement. If that happens, then actually,
yeah, the headline is that tinnitus management,
as it currently stands within the UK, is cost effective.

So that was our primary aim. Not to demonstrate that,
but just to understand if it is or not. We published all the
papers and we published the Excel spreadsheets we
used to calculate that as well, or the health economist
used to calculate that. So, again, we've made them available so that commercial companies,
pharma, can play with them, can put in their own treatments, and put in their own
cost of that to the NHS, and put in what they believe
is the efficacy of it, and see if their treatment comes out as more or less cost
effective than what exists. What we did show is that,
actually, if you go to your GP and your ENT, and you're
discharged at that point, that's not cost effective. And a lot of people seem to have that. So you have two diagnostic interventions but no actual management
or no sort of input in a way of how to manage it,
no basic psycho-education.

So that was very costly
but actually, yeah, GP to ENT to audiologist,
or even for the few people who get to psychology at the end, that whole pathway through
four different levels is cost effective as well. So that was positive and
we averaged the cost, it's been a while since
I've read the paper now, but the average cost per
patient is just over 700 pounds to the NHS, which includes
things like hearing aids which you can argue is not
just to treat the tinnitus. It's to treat underlying
hearing loss as well. The majority of the cost, in that, is doing the diagnostic tests. So we estimated that 50%
of people with tinnitus will have an MRI scan and that is the biggest
cost element of that, of the whole pathway, is the MRI scan and the ENT appointment. So actually, a lot of the
cost is in the diagnostic and looking at underlying pathology. But yeah, once you get beyond that, it's not that expensive
in terms of what's there at the moment, but also we're saying it's not that efficacious either.

So there is room to improve it if people come up with
better ways to manage it or better ways to
obviously cure it as well. Especially if it's a pill
and you can deliver that at GP level, it's
incredibly cost effective. So yeah, so there's real benefits
in what we've done there. What we also came up with
was a cost to society. So we estimated that
tinnitus costs UK PLC over two billion pounds a
year in lost time at work, in people retiring early,
in relationship breakdown, in loss of sleep and general
loss of productivity. So there's a huge underlying
cost to the UK as well that's actually a bigger
cost than the cost to the NHS of successful treatment,
as it stands at the moment. And some unsuccessful treatment. So actually, again, if we can show that there's a better treatment
out there, you can show that actually the saving to
UK PLC is gonna be quite impressive as well
and will make a difference. All of our figures, you can criticize and say they're conservative, because we don't take into account the impact on carers or loved ones or people around that person.

– What about comorbidities as well? 'Cause you've got, say,
stress, anxiety, depression, I would say are the
most common comorbidities that you would be going and getting concurrent treatment for. And the first big piece of research
that we (Tinnitus Hub) did was around asking people about that, and I don't know the figures
off the top of my head. There's a significant amount
of people who, we asked them: "Did you have this before
tinnitus? Did you have it after?" And yeah, stress, anxiety, depression. Not everybody, but there's a
significant amount of people reported that, reported
panic attacks, and you think then you've got another GP visit.

You've got drug treatment,
you've got whatever it is that they actually have to treat you with. And then how many visits to,
some people will visit A&E or they'll go through the system again and there's a lot of associated costs. – Yeah, and we included that in the two billion societal cost, so
we included it in there but our modeling wasn't
sophisticated enough to look at those additional costs
to the NHS in terms of mistreated or untreated tinnitus, or tinnitus that wasn't
successfully treated. So, yeah, we didn't include
it in the cost to the NHS but we did include it
in the societal costs.

You know, again, we've
been really honest about what that paper is. It's the start of a conversation really. It's done based on expert
opinion in terms of, we had a group of people
around a table who looked at what normal treatment looks
like and we used costs that were available to
us, and then we also did a patient survey as well. So it's certainly not high level evidence but it does give you those benchmarks and based on what else is out there, it's a pretty robust study in terms of what else we've got looking
at the cost of tinnitus. There's a study in Holland
and there's one in the US, as well, that we used as comparators and we're not far off
what they came to either.

– Yeah. Again, making that business case for it is another thing which the NHS, 'cause we're relatively unique aren't we with having the NHS in this country, but outside of that the
private health care's gonna be even more interested in the
fact of like, all right, well I'm not gonna spend
this pot later when I can spend this pot now and treat people upfront.

So I guess it's a broader perspective of trying to actually, and
once you start bringing the cost into it then you
can kind of think, all right, well let's look at what
treatments there are. And if they start looking
at what treatments there are it brings more people at the marketplace and it's kind of that
knock on effect isn't it? – Yeah, yeah absolutely, and like I said, the intention of the piece of
research was to understand if what's out there at the
moment is cost effective. But the other thing it does is, we're disseminating
that and made sure that all the pharma companies
who were involved in tinnitus research are aware
of that paper as well, because it is a big sort of green light.

It says: go fetch. – Yeah.
– Here's the size of the market. Here's what you'd need to do
to make your drug efficacious. And really trying to give
pharma the tools they need to make the economic case, in
an independent way as well, because pharma can go do their
own cost analysis, of course, but the challenge is that
if they then use that for evidence to go to
NICE, it's not independent. So they actually need that
independent work out there. So, again, it's not cure
research, in its purest sense, but it does help give
pharma that playing field, if you like, to say, right,
well here's something else. Here's another tool that
helps us understand the market and what we need to do to get there or… Neuromod or anyone else. Again, that's what we've looked to do with the cure map as well, is just try and plot where research is, so people can have that
overview and understand where we're at and also
what the challenges are in a way that just establishes that.

So everything that we're
trying to do at the moment is provide tools that we've been
told industry and pharma want to be able to look at tinnitus
research more seriously. – Yeah, and I think for me, as
well, just touching on that, it's good to see BTA
moving in that direction. And like you say, you've
had plenty of criticism in the past about "Oh you're funding this or you're funding that." I mean you don't really have
a big funding pot do you? – No.
– In terms of… – No exactly, I mean
the money we do put in isn't gonna support a phase
two clinical drugs trial. We're just not at that
level and what we do do is some of the basic science
that might get there and then, like I say, a lot of
the management research, which I fully understand, I
accept, gets criticism, but, at the same time, if we
can make a difference to people's lives in a couple
of years through doing that whilst also, hopefully, helping pharma to get the right tools to do it then we'll look at that.

And we are moving a
little bit more towards the curative side of it as well, and trying to challenge
research to get there. But yeah, at the same time, in the past we've certainly looked at how we could make a difference with, with what we have available. – Yeah, from looking at it, it's great. You've got the cure map and
where does it go from here? Is it kind of like, trying
to bring people in? 'Cause I guess the only way you can do it, unless all of a sudden people develop shallower pockets and longer arms, and start giving
reasonable amounts of money to actually support tinnitus research, which is massively under-supported. Let's say your budget's kind of like, it's never gonna make an impact. I guess the whole thing is
to try and encourage funders and donors and research
partners and kind of, like you say, making that case
and then just say: right, look, here you go.
– Yeah.

There are strategies
going to move to look at how we can work on projects
that we think are important but then, like you say,
approach those bigger funders to see if they'll invest
in those projects as well. So doing things like the
cure map, the economic paper… We'll have a paper out,
hopefully early next year which kind of covers a lot of the ground that we discussed here
actually in terms of some of the challenges that are out there. We really hope that
that just builds a case that we can go to some of the
bigger funders and say: "Look, here you are, consider
investing in tinnitus research." "Here's a portfolio of where we're at and this is what would make
a meaningful difference." So what we're looking to do,
as a charity, from here really is look at how we can
start to support research that systematically gets us to a cure. So we're not, obviously, gonna stop, or we're not gonna influence people who are already doing that, that research, in terms
of looking for a cure, but actually: What can we do
to help better understand if there is an objective measure? What can we do to help sub-type tinnitus? What can we do to really
answer some of those fundamental questions that
might help us understand if cures are already out there? Or to really give pharma
those tools that help them invest more in the future as well.

– Yeah, 'cause you look at the average, and I'm quoting in dollars,
but I think is it phase one trial's about a million dollars. – I'd imagine it's about that. – Yeah. – Pittsburgh have got is it… – Yeah.
– Is it 1.2 million for that? I can't remember exactly.
– Yeah I think they, I think their original
budget was a million but now 1.2. And that for a phase
one, just a safety trial.

– Yeah.
– I mean that's just way outside the reach of what you can lay your hands on. So I guess it's trying to
lay groundwork for that, so these people can
actually say: "Oh great, well, we might be able to fast-track." Or: "We know we've got a
market," or "we know we can, we know we can spend that
money with greater confidence." – Absolutely. So ideally they know
there's a market there so they don't have to do
the initial market research which saves them a few months.

So there's things like
that that I think we can do that helps those audiences and
it's about making sure, then, they know that's available.
And the more we can do that, hopefully, the more it just
looks like tinnitus is a field that's professionalizing
in terms of research and is worth investing in as well. – Yeah. Yeah absolutely. Well I think that's grand. Thank you very much for coming along and hopefully that's been useful
for the people watching and thanks very much. – Yeah and I guess there'll
be a strand on this somewhere and I'm happy to engage
in it to a level as well and answer any questions that come up. – Excellent, thank you. Cheers.
– Pleasure, thank you Steve. (gentle music).

You May Also Like