New University of Michigan Tinnitus Discovery — Signal Timing

[AfroSnowman]

Just doing a search for Susan Shore in the news and came up with an audio program from Australia originally broadcast in August 2021. Susan Shore is on it briefly. She had an interesting comment about how she was potentially thinking about how the treatment may be used:

"Susan Shore: So the idea is that if we do six weeks, now maybe it will take two weeks to return to baseline. So in that case, the worst case scenario, then people have to do it on the weekends. Maybe they do it every day for six weeks and then thereafter they tune it out."​

Looks like she is describing getting it under control with constant use, then just using minimally to keep it under control. That would be awesome.

 

[Tomas80]

Please, I'm completely confused. I don't understand what's going on at all. The study results will be in a scientific journal first, then the FDA process starts? Or do they occur at the same time?

I would also like to know what you think - would the CEO of Auricle say that the device is ready for the market if they had poor results?

 

[Bambam0]

Please, I'm completely confused. I don't understand what's going on at all. The study results will be in a scientific journal first, then the FDA process starts? Or do they occur at the same time?

As I understand it, once the study is unblinded, they will work on these two things concurrently. Sounds like they're already working with the FDA.

 

[AfroSnowman]

I would also like to know what you think - would the CEO of Auricle say that the device is ready for the market if they had poor results?

I think that, as a result of blinding, no one should have advance information about results. My general impression from the University of Michigan page about it, various interviews, and reported emails is that they have set up the infrastructure to move aggressively towards the market when they get FDA approval.

 

[GlennS]

they have set up the infrastructure to move aggressively towards the market when they get FDA approval.

Or IF.

The story of so many treatments in development resemble this:

I'm not happy about Lenire either, but at least it entered the market.

 

[ploughna]

It's the difference between the world of academia and commerce - completely different motivations and measures of success. Papers published, peer recognition, etc vs. $$$.

It seems time is rarely a consideration for academics. Unless you count 'within one's lifetime', and even then...

 

[InNeedOfHelp]

Let me clarify some of the FDA work and process here of medical devices:

First, the almost market ready video was an investors pitch - not meant for end users. After 20 years of research, the remaining 3 years is 'almost ready'. That makes completely sense. This was no open publication from Auricle but a pitch given at a fundraiser to attract investors. This is purely meant to show that significant research is already done long ago and that investors do not have to wait decades for return of investment.

Second, they have an investor onboard, that is what Jon Pearson CEO of Auricle said. An investor is not a charity. They want return on investment, meaning moving to market sooner then later. An investor will absolutely not wait for a peer reviewed publication before any FDA submission. They want to be first to market. If we are lucky, big pharma is on board (Abbott Labs and others e.g., already have neuromodulation devices).

Third, FDA does not require any peer review or publication at all. The FDA makes decision based on the data provided and the questionnaires filled in. Since I assume a Pre-Submission to the FDA was already done (maybe someone can clarify If this was confirmed by Jon Pearson?), Auricle knows which information/datasets have to be handed over. Preparing the FDA submission is a lengthy process - the regulatory filing is very strict and an extensive bookwork of papers, data etc.

Fourth, FDA has to approve the device. As this is a non-invasive device I assume it will be a Class II device (Class III are invasive devices such as pacemakers, implants, defibrillators and life-or-death devices). A Class II device is usually submitted through the 510K application

Approval of a Class II device takes around 180 days. I did not see any FDA Fast Track for Auricle. With Fast Track it can be limited to three months. However, there is a big hurdle - there are no similar devices submitted to the FDA as to date. One of the criteria of requesting a 510k approval is:

Submitters must compare their device to one or more similar legally marketed devices and make and support their substantial equivalence claims.

Because of this, the 510K procedure cannot be followed and a De Novo Classification procedure has to be started, more information on the process can be found here:

https://www.fda.gov/medical-devices...ect-submission/de-novo-classification-request

The FDA has to approve a request within 150 days (5 months). There could be some back and forth in discussion where Auricle has to provide additional information. Auricle has up to 180 days to clarify open matters.

This means, in total, the maximum submission length is around 11 months in the worst case scenario.

Once approved, the device can be found here in the De Novo database:

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm

Fifth, no production would take place before any FDA approval. Production will cost millions - no investor will back that up unless the device is approved.

Summing up, my best scenario would be an FDA submission at the end of this year (takes 5-6 months to prepare the submission file, an FDA approval summer 2023 (7 months to approve including some back and forth) and wires around our necks at the end of 2023 on the first select amount of locations/clinics. Full enrollment/distribution later in 2024.

I expect the paper to appear in the summer of 2023. There is no open database to look for De Novo submissions. I assume the investor comes forward once submitted. This will create traction and will increase the stockprice/capital if the investor is on the stock exchange market.

 

[DaveFromChicago]

"The treatment promised by Shore,
Was delayed all the More and More,
But when finally Done,
The Heat from the Sun,
Fried the Earth to its Very Core."

Note: Within 50 million years the Sun will expand and burn the Earth out of existence.

 

[Chinmoku]

Let me clarify some of the FDA work and process here of medical devices:

First, the almost market ready video was an investors pitch - not meant for end users. After 20 years of research, the remaining 3 years is 'almost ready'. That makes completely sense. This was no open publication from Auricle but a pitch given at a fundraiser to attract investors. This is purely meant to show that significant research is already done long ago and that investors do not have to wait decades for return of investment.

Second, they have an investor onboard, that is what Jon Pearson CEO of Auricle said. An investor is not a charity. They want return on investment, meaning moving to market sooner then later. An investor will absolutely not wait for a peer reviewed publication before any FDA submission. They want to be first to market. If we are lucky, big pharma is on board (Abbott Labs and others e.g., already have neuromodulation devices).

Third, FDA does not require any peer review or publication at all. The FDA makes decision based on the data provided and the questionnaires filled in. Since I assume a Pre-Submission to the FDA was already done (maybe someone can clarify If this was confirmed by Jon Pearson?), Auricle knows which information/datasets have to be handed over. Preparing the FDA submission is a lengthy process - the regulatory filing is very strict and an extensive bookwork of papers, data etc.

Fourth, FDA has to approve the device. As this is a non-invasive device I assume it will be a Class II device (Class III are invasive devices such as pacemakers, implants, defibrillators and life-or-death devices). A Class II device is usually submitted through the 510K application

Approval of a Class II device takes around 180 days. I did not see any FDA Fast Track for Auricle. With Fast Track it can be limited to three months. However, there is a big hurdle - there are no similar devices submitted to the FDA as to date. One of the criteria of requesting a 510k approval is:

Submitters must compare their device to one or more similar legally marketed devices and make and support their substantial equivalence claims.

Because of this, the 510K procedure cannot be followed and a De Novo Classification procedure has to be started, more information on the process can be found here:

https://www.fda.gov/medical-devices...ect-submission/de-novo-classification-request

The FDA has to approve a request within 150 days (5 months). There could be some back and forth in discussion where Auricle has to provide additional information. Auricle has up to 180 days to clarify open matters.

This means, in total, the maximum submission length is around 11 months in the worst case scenario.

Once approved, the device can be found here in the De Novo database:

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm

Fifth, no production would take place before any FDA approval. Production will cost millions - no investor will back that up unless the device is approved.

Summing up, my best scenario would be an FDA submission at the end of this year (takes 5-6 months to prepare the submission file, an FDA approval summer 2023 (7 months to approve including some back and forth) and wires around our necks at the end of 2023 on the first select amount of locations/clinics. Full enrollment/distribution later in 2024.

I expect the paper to appear in the summer of 2023. There is no open database to look for De Novo submissions. I assume the investor comes forward once submitted. This will create traction and will increase the stockprice/capital if the investor is on the stock exchange market.

I'm on the fence on whether it's Class 2 or 3. It stimulates nerves through electrodes, which can lead to serious problems if done wrong, but it is non-invasive. DeSyncra, as I mentioned earlier in the thread, was approved specifically for tinnitus and was Class 2, but was pure sound therapy, no electrodes, much simpler than Auricle (and quite ineffective). From some slides I saw but cannot recall precisely I would have imagined Class 3. Anyway, given the lack of effective devices, they might have conceded the Fast Track at least.

For the rest, I insist their communication is very poor and uninformative (Pearson's email up here and their press release) but this is what we have to work with. A few people will be lost. Veterans will suffer longer. Nothing we can do.

 

[Padraigh Griffin]

It's Class 2 as it's non-invasive. That is my two cents without reading anything about it. I thought the talk on here was that it was always a Class 2 medical device. Something like Neuralink is a Class 3. Big step up there in comparison to this.

Also, Lenire had no trouble getting EU approval. It was very smooth. That would suggest Class 2 is correct.

 

[Chinmoku]

"The treatment promised by Shore,
Was delayed all the More and More,
But when finally Done,
The Heat from the Sun,
Fried the Earth to its Very Core."

Note: Within 50 million years the Sun will expand and burn the Earth out of existence.

I think it will take much longer (billion) for the sun to go red, but yeah.

This is turning into a fantasy that would make Ursula Le Guin proud. Tinnitus treatment on the farthest shore of Earthsea. We may have to talk to dragons there to have some precise information.

 

[Chinmoku]

It's the difference between the world of academia and commerce - completely different motivations and measures of success. Papers published, peer recognition, etc vs. $$$.

It seems time is rarely a consideration for academics. Unless you count 'within one's lifetime', and even then...

This is changing though. For example, in the UK every 5-7 years there is an assessment by the government for every academic department. They check quality of publications but more and more value is given to industry impact. This also determines funding. If the US followed the same route, Uni of Michigan would benefit from Auricle coming out sooner rather than later.

 

[Tomas80]

Let me clarify some of the FDA work and process here of medical devices:

First, the almost market ready video was an investors pitch - not meant for end users. After 20 years of research, the remaining 3 years is 'almost ready'. That makes completely sense. This was no open publication from Auricle but a pitch given at a fundraiser to attract investors. This is purely meant to show that significant research is already done long ago and that investors do not have to wait decades for return of investment.

Second, they have an investor onboard, that is what Jon Pearson CEO of Auricle said. An investor is not a charity. They want return on investment, meaning moving to market sooner then later. An investor will absolutely not wait for a peer reviewed publication before any FDA submission. They want to be first to market. If we are lucky, big pharma is on board (Abbott Labs and others e.g., already have neuromodulation devices).

Third, FDA does not require any peer review or publication at all. The FDA makes decision based on the data provided and the questionnaires filled in. Since I assume a Pre-Submission to the FDA was already done (maybe someone can clarify If this was confirmed by Jon Pearson?), Auricle knows which information/datasets have to be handed over. Preparing the FDA submission is a lengthy process - the regulatory filing is very strict and an extensive bookwork of papers, data etc.

Fourth, FDA has to approve the device. As this is a non-invasive device I assume it will be a Class II device (Class III are invasive devices such as pacemakers, implants, defibrillators and life-or-death devices). A Class II device is usually submitted through the 510K application

Approval of a Class II device takes around 180 days. I did not see any FDA Fast Track for Auricle. With Fast Track it can be limited to three months. However, there is a big hurdle - there are no similar devices submitted to the FDA as to date. One of the criteria of requesting a 510k approval is:

Submitters must compare their device to one or more similar legally marketed devices and make and support their substantial equivalence claims.

Because of this, the 510K procedure cannot be followed and a De Novo Classification procedure has to be started, more information on the process can be found here:

https://www.fda.gov/medical-devices...ect-submission/de-novo-classification-request

The FDA has to approve a request within 150 days (5 months). There could be some back and forth in discussion where Auricle has to provide additional information. Auricle has up to 180 days to clarify open matters.

This means, in total, the maximum submission length is around 11 months in the worst case scenario.

Once approved, the device can be found here in the De Novo database:

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm

Fifth, no production would take place before any FDA approval. Production will cost millions - no investor will back that up unless the device is approved.

Summing up, my best scenario would be an FDA submission at the end of this year (takes 5-6 months to prepare the submission file, an FDA approval summer 2023 (7 months to approve including some back and forth) and wires around our necks at the end of 2023 on the first select amount of locations/clinics. Full enrollment/distribution later in 2024.

I expect the paper to appear in the summer of 2023. There is no open database to look for De Novo submissions. I assume the investor comes forward once submitted. This will create traction and will increase the stockprice/capital if the investor is on the stock exchange market.

And what's the plan for Europe? When can we expect it to be available here?

 

[UKBloke]

When Tinnitus Talk interviewed Susan Shore (in Taipei) she said a couple of things that resonated with me.



One was a comment about her commitment to producing a treatment that is rooted in basic science. The other was an observation that in seek of a cure other researchers/developers in this space had often participated in 'fishing expeditions'.

The other night when I learned of Bryan Pollard's passing I went back and listened to the Tinnitus Talk Podcast he did with @Hazel.



What really impressed me about Bryan (and it's something I think is often missing in tinnitus/hyperacusis research) was his undertaking to approach hyperacusis research as an engineering problem.

My own experience with engineering (albeit many years ago) taught me that engineering doesn't do fishing expeditions. It also doesn't (and quite frankly couldn't) solve a problem it can't identify. Susan Shore's stated commitment to basic science and her unwillingness to fish for a cure (which let's face it always requires unnecessary risk of horrible side-effects for the patient) suggests to me that there's something of the engineer in her and her approach, which I think is a good thing.

I personally, have always believed that tinnitus (perhaps all human maladies quite honestly) is essentially an engineering problem. So for those basic remarks Susan Shore made, I have to give her the benefit of the doubt.

 

[IntotheBlue03]

Hi all,

Just checking in on the consensus of what we will see when the study is unblinded. Are any of you not expecting to see the results until the peer review?

@AfroSnowman, @InNeedOfHelp, @Chinmoku, @Bambam0, @Padraigh Griffin?

Sorry I'm not able to do a better job of following posts with this visual nightmare I am dealing with. Nystagmus and tinnitus are twins of the same evil.

 

[Chinmoku]

Hi all,

Just checking in on the consensus of what we will see when the study is unblinded. Are any of you not expecting to see the results until the peer review?

@AfroSnowman, @InNeedOfHelp, @Chinmoku, @Bambam0, @Padraigh Griffin?

Sorry I'm not able to do a better job of following posts with this visual nightmare I am dealing with. Nystagmus and tinnitus are twins of the same evil.

Sorry you are still suffering with your eyes too, @IntotheBlue03.

It seems there will be a parallel process of data submission to the FDA and of paper/peer review submission. I don't know if they will publish a pre-print with the trial results but this might violate FDA rules. I gave up understanding the Byzantine rules governing FDA and early trial data disclosure. I think we will know either when FDA has completed their review or when the journal version becomes available unless, as would happen in a world with a minimum of sense, they publish a pre-print first.

 

[InNeedOfHelp]

And what's the plan for Europe? When can we expect it to be available here?

There is no EMA approval needed, only CE. CE is a matter of weeks (even pencils are CE).

It depends on the willingness of Auricle. I'm quite sure devices will find our way before any European launch through import from audiologists and researchers (such as Prof. Dirk de Ridder). Based on what I see on the statements of Jon Pearson, it will take another year at least for Europe to have a full scale launch. Don't worry. We do not have to wait that long, I'm convinced.

 

[GlennS]

time is rarely a consideration for academics. Unless you count 'within one's lifetime', and even then...

Given Susan Shore's age, she might think of picking up the pace or at least finding an heir apparent.

 

[GlennS]

It stimulates nerves through electrodes, which can lead to serious problems if done wrong, but it is non-invasive.

I agree with that. Not to engage in FUD, but the regulatory agencies are really naive about the harm this class of device could potentially do. I would hope the FDA is more on the ball than Europe where this is concerned.

 

[SunshineSoul]

The ENT I met last week stated because this involves the tongue it won't really do anything about the actual tinnitus; just merely our reactions to tinnitus. I think he has it wrong (and proves just how absolutely excruciatingly difficult it is to find a single decent ENT)... or is he right?

Either way, the fact that every ENT I've met all know about this device, and one seemed pretty optimistic about it, is at least encouraging.

 

[kingsfan]

The ENT I met last week stated because this involves the tongue it won't really do anything about the actual tinnitus; just merely our reactions to tinnitus. I think he has it wrong (and proves just how absolutely excruciatingly difficult it is to find a single decent ENT)... or is he right?

Either way, the fact that every ENT I've met all know about this device, and one seemed pretty optimistic about it, is at least encouraging.

I'm pretty sure the electrodes attach to the neck. I think your ENT may be confused with Lenire.

 

[InNeedOfHelp]

Just read that part of the strategy was a pre-submission to the FDA. Which is good news and may cut off some months.

 

[dj_newark]

Just read that part of the strategy was a pre-submission to the FDA. Which is good news and may cut off some months.

The ENT I met last week stated because this involves the tongue it won't really do anything about the actual tinnitus; just merely our reactions to tinnitus. I think he has it wrong (and proves just how absolutely excruciatingly difficult it is to find a single decent ENT)... or is he right?

Either way, the fact that every ENT I've met all know about this device, and one seemed pretty optimistic about it, is at least encouraging.

The Michigan device attaches to the cheek or neck. It does not attach to the tongue. Your ENT is confusing the Lenire device with the Michigan device. He's not emotionally or intellectually invested enough in tinnitus to know the difference. That's probably because he doesn't have it or has a very mild case of it himself. Our condition is very difficult to relate to for the normals. Hence it generates no empathy or caring on their part.

 

[Warchop]

Bimodal stimulation does work. I think the problem is that as bimodal stimulation is making changes in the brain, the brain is also undergoing changes. The research seems to indicate that two identical sequences can have two different outcomes on two different people.

Sequence one:

0 ms: shock start
1 ms: shock stop
5 ms: tone start
55 ms: tone stop
150 ms: sequence restarts

Sequence two:

0 ms: tone start
5 ms: shock start
6 ms: shock stop
50 ms: tone stop
150 ms: sequence restarts

Sequence one, I believe, based on research, induces expression in those with noise damage, and potentiation in those with noise-damaged hearing systems. Sequence two is just the opposite.

When people go use Lenire, I believe they have a 30-day period, and then they go back in and the device is adjusted.

After 2 years of using a "DIY bimodal stimulation" device I have had success with my left side, but the right side is out-of-balance.

The issue I think with the bimodal devices is that there is a lack of brain imaging. I believe if you look at a normal versus abnormal brain under an MRI, you can tell distinct differences.

Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI

If bimodal works, you should see a tinnitus brain slowly starting to quiet down under imagery, which means you should be able to design a home device that reads brain activities in the regions identified to cause tinnitus:

These Guys Are Creating a Brain Scanner You Can Print Out at Home

It's gotta be tough getting something through FDA approval that works on some, but not others. The brain is plastic and because it is changing, the researchers who have developed these devices, are going to have continued difficulty getting FDA approval. I think these companies shot themselves in the foot by not including brain-imaging early on, because, with real-time brain imagery, you can tell what is happening in the brain, and with an intelligent enough program, adjustments can be made to effectively fine-tune the brain. Also, the bimodal devices might excite things before they make them quieter, and people using Lenire have reported new tones being induced... so a lot of stuff going on, and without imagery, I don't see how these can be effective unless the user becomes the "imager" and can self-adjust the device as they go based on how they feel things are working... not sure that FDA would approve of patients making adjustments to their own therapy.

 

[AfroSnowman]

It's gotta be tough getting something through FDA approval that works on some, but not others.

I don't know much about FDA approval really, but my understanding of treatments in general is that nothing works for everyone, so as long as it can be shown to be safe and effective for some, I have to imagine that it won't be a barrier to approval.

 

[lolkas]

This whole idea with modulating neurons in auditory cortex makes a lot of sense and it is great to hear that Dr. Shore has engineer-like approach to this. She does emphasize that this isn't like "let's just try and see if it works", rather she definitely figured out how to influence auditory cortex in a way that it balances things out which in return "cancels" out tinnitus. Almost like noise-cancelling headphones (in the way), but instead of noise it is an electrical signal over skin/nerves. If it really does what they claim, and we can calm our tinnitus to a point where it is substantially quieter, then this will provide a decent relief to vast majority of population around the world whom is affected by this terrible misalignment. While it isn't a fix for hearing restoration, and it won't do anything to make hearing aspect better, at least it will allow people who suffer to find moments of peace, which in turn would make it way easier to wait for actual fix that all of these companies are working on.

I also expect that once this device makes it out there - a lot of other companies will try to make a "clone", therefore I also understand that an investor whom is going to be spending their money on device development is going to limit Dr. Susan in her publications about how this works until the device is in production and sales have started. Understandably all and any engineered devices can be reverse-engineered and copied, so I expect them wanting having time advantage.

 

[Chinmoku]

Bimodal stimulation does work. I think the problem is that as bimodal stimulation is making changes in the brain, the brain is also undergoing changes. The research seems to indicate that two identical sequences can have two different outcomes on two different people.

Sequence one:

0 ms: shock start
1 ms: shock stop
5 ms: tone start
55 ms: tone stop
150 ms: sequence restarts

Sequence two:

0 ms: tone start
5 ms: shock start
6 ms: shock stop
50 ms: tone stop
150 ms: sequence restarts

Sequence one, I believe, based on research, induces expression in those with noise damage, and potentiation in those with noise-damaged hearing systems. Sequence two is just the opposite.

When people go use Lenire, I believe they have a 30-day period, and then they go back in and the device is adjusted.

After 2 years of using a "DIY bimodal stimulation" device I have had success with my left side, but the right side is out-of-balance.

The issue I think with the bimodal devices is that there is a lack of brain imaging. I believe if you look at a normal versus abnormal brain under an MRI, you can tell distinct differences.
[...]

Seeing how thorough Susan Shore is, I would be surprised if she left out something this fundamental. On the other hand, Hubert Lim did base his bimodal approach in Minnesota on brain scans too, so I think you might be onto something here.

 

[F-u-T]

I also expect that once this device makes it out there - a lot of other companies will try to make a "clone", therefore I also understand that an investor whom is going to be spending their money on device development is going to limit Dr. Susan in her publications about how this works until the device is in production and sales have started. Understandably all and any engineered devices can be reverse-engineered and copied, so I expect them wanting having time advantage.

Susan Shore has a bunch of patents in place to hopefully prevent this scenario being a hold up.

 

[Greg Sacramento]

Still think, in completing trial - their judging data for a 513(g), a "request for classification." You can argue for a Class II or III classification from the FDA. The same is not allowed with a pre-submission. The advantage of a 513(g) is that you can go into the De Novo submission with an agreed-upon classification.

Complete Guide to Bringing a Medical Device to Market

De Novo Pathway: Explaining the Process for Medical Device Companies

I don't think patents would be an issue at this point. It's common to share patents.

 

[AfroSnowman]

Is it July yet? This is taking forever.