New University of Michigan Tinnitus Discovery — Signal Timing

I have 12 years experience working in the medical device industry. I deal with regulatory bodies as the FDA and BSI every other month. The company I work for design and create implantable devices which are scrutinised far more than non-implantable devices such as Dr. Susan Shore's.

I can give a brief overview of the process and answer any further questions (if I'm able to that people may have).

Generally, upon submission for regulatory approval with the FDA, a 6 month clock starts. The FDA normally review all the data, studies, reports etc within 2-4 weeks and will send back a list of questions to you. At this point, the 6 month clock pauses. You have 2 weeks to respond to their questions and/or provide the necessary missing data.

When you go back to them, the clock starts again. If they are not satisfied, they may either come back to you or perform an in-person audit. During the audit, they can and do ask to see any data/reports etc they like. This can range from study data to technical drawings of the device. If you cannot provide these, you get a deficiency letter and have 14 days to provide the FDA with a thorough plan of how you intend to fix the issue(s). If the issue is huge, the submission is rejected and you can re-submit once you have carried out the necessary work they have asked for. On the other hand, if they are happy, your submission application may get expedited. But more often than not, the FDA use every minute of that 6 months they allow themselves.

Once you receive approval, you are in a position to immediately begin manufacturing and/or shipping of your device.

Each country has its own regulatory body like the FDA. Generally, the FDA are the worst to deal with (i.e. they ask to see some obscure stuff). If you gain FDA approval, you're almost guaranteed worldwide approval (although Japan are also notoriously difficult).

If you're an American based company, it's a lot easier to get FDA approval, so that should go in our favour with this device.

As this is a non-implantable, non-pharmaceutical, non life-sustaining device, I seriously cannot see any issues with FDA approval. There is no way the submission will take 2 years as per other posts.

 

The only reason Lenire is taking over 2 years for device approval from the FDA is because they are practicing shit science. They geared their trial for investor approval, not for FDA approval, by not including a placebo.

Dr. Shore is an honest scientist who is basing her approach on what she calls 'basic science'. I believe she will be a lot more meticulous and conscientious in her approach to information gathering than Neuromod was.

Device approval by the FDA can take place anywhere from 3 to 8 months, and it's very infrequent that it takes longer than that. Maybe this is optimistic of me, but I think with Dr. Shore's methods it will sail through the FDA approval process. One of the biggest stop gaps for progress is that she is insisting on publishing her work before pursuing FDA approval or commercialization because that is what she views as required of her as a "reputable scientist".

She submitted her reports to be published in the scientific journals around December 5th and she estimates it will take up to six months for the results to be published.

 

I agree with @dj_newark that Lenire seems to be taking forever partially because of COVID-19 slowing the review process down and the fact that Lenire seems less than effective. I feel the FDA is doing its job and protecting us from placebos and scams.

And, it is annoying to have to wait for Dr. Shore's work to go through the peer review process. Hopefully, the editor of the journal is doing their job and pinging the reviewers for their reviews. And, hopefully, the reviewers are diligently doing their reviews and not just sitting on their review requests.

I'd love to see her research get accepted to the journal on the first try, but even for someone as accomplished as her, I worry she'll have to go through at least one round of review and re-submit. Her reviewers are likely going to have questions for her. The reviewers asking questions is good for science and good for quality, but time ticking away as there is a back and forth between her and the reviewers sucks for us.

I just hope once it is accepted by the journal, she starts moving her process along. The date between acceptance and publication can differ by many months. Acceptance is the seal of approval, there is no need to wait for her to wait in the publication queue to release the information to the world.

Finally, could she have submitted to the journal and the FDA at the same time? Is there something in the medical sciences that prohibits having one's work reviewed by an academic journal and the FDA at the same time? Other than looking for feedback from their peers, is there any reason one would go academic review --> FDA review in order rather than concurrently?

*As always, I'm guessing off of my experience in the social sciences, I don't know the nuance of how the medical sciences work. And, I have a bit of faith that she is a good scientist and honest, so I'm assuming her research is solid and will pass the review process, but who knows what the editor and reviewers will think of her research.

 

I don't think she will need to submit anything. It's 20 years of research and this device was also tested years ago at the University of McMaster in Canada so it's well known and tried, with support of other schools to back her research up.

 

Please don't spread misinformation. Ignorance isn't an excuse. She 100% has to go through the normal processes, and she has already stated herself that her work is going to be peer reviewed by an academic publication and her team will be applying for FDA approval. This is how science and medical interventions work. You don't get a free pass if you've worked on something for 20 years.

 

@2noist, please.

Once it's done been tested by MC MASTER (in Canada), don't nobody else need to be testing it for approval.

 

Spelling error. I was supposed to say re-submit anything... Calm down...

 

So is this the real thing? A working treatment for the majority of tinnitus sufferers? Are we confident that this will help? Of course, no one knows for sure right now. But this is different, right?

I’m in desperate need of a real perspective.

 

So far it seems so, because Phase 2 was even better than Phase 1. I have never seen anything like that in the past. Things like OTO-313 and OTO-413 died in Phase 2.

Dr. Shore can now go for FDA approval after the successful Phase 2 and, since this is a device, it makes the process a lot quicker in comparison to a medication. I think in 24 months we will see this device in the market.

 

It's the first time I've ever known a treatment go through two well controlled double blind human studies with clinically significant results in tinnitus volume reduction. It won't work for everyone, in the way that, for instance Clonazepam, doesn't reduce the volume for everyone. What's important is that we had basic significant findings in research and a working treatment is coming to market out of that science.

For too long attempts at developing treatments have often been carried out like 'a fishing expedition'.

 

Do you think Dr. Shore's device will also help conditions like Visual Snow, which, in theory, come from a similar (or close) place where tinnitus is originated?

 

I'm expecting to see the publication of Dr. Shore within the coming weeks if this was submitted early December. Making the assumption that 1. there are plenty of peer reviewers wanting to peer review this one, and 2. that it will be published without revisions. Submission early December should mean we are almost there.

 

If this only helps for somatic tinnitus, then what good does it do for people that don't have that?

I can move my jaw and hear a different tinnitus signal and when I stretch the same thing happens, but it doesn't modulate the noise I hear in my ears. I mean, the sound when I move my jaw takes over, but it doesn't seem to change anything. Dr. Shore says they're going to test on different types of tinnitus, but I am only cautiously optimistic about this.

 

At the moment it isn't fully known.

My tinnitus is the same as yours, not really considered to be somatic although I can do those same 'different tinnitus signals' through stretching or opening mouth wide etc... but it's not the same.

Dr. Shore has obviously seen better results for those with somatic tinnitus than without, otherwise it wouldn't have been a condition to apply for the clinical trials. She won't, I doubt, come forward with any conclusions or answers for non-somatic at the moment. Perhaps closer to launch but I doubt any information will be published at this time as not to take away from the maximum benefits she would like to show for publication and approval.

Whether it will do nothing or something for non-somatic sufferers still remains to be seen.

We have our fingers crossed.

 

I believe that is somatic tinnitus as far as Dr. Shore's study is concerned.

 

@InNeedOfHelp, that's very unrealistic to expect it published in a few weeks. It was submitted 2nd week of December and after this it will be peer reviewed, then published. She said in her own words it can take up to 6 months. At the very earliest I would think middle of March, however April/May is more likely.

 

I don't want to be rude, but as someone who has published papers, I can tell you that you have no idea what you are talking about.

 

Well that’s a relief then.

 

When you publish crappy papers, it takes 5 years to publish yes (that's a joke )

Renowned scientists on groundbreaking research will have faster peer review, that's a fact.

Previous papers from Dr. Shore took 3 months from pre-print on Biorxiv to peer review. Besides, earlier papers were also released pre-print.

• Publication date: 11 August, 2022
• Peer reviewed release: 11 November, 2022

We are 1.5 months in. Another 1.5 months is technically another few weeks of wait.

That's the maximum timeline I'd say. It's simple, she does not want to overpromise and that makes sense.

Remember, she also said in her own words she would have the results peer reviewed before sharing them, and me and others stated that it would make zero sense to wait for a peer review of the results.

The same as it makes zero sense to wait for a peer review before submitting to FDA which again is a very unlikely scenario.

 

Dr. Shore estimates that publication of her work could take "up to 6 months". It could be more, it could be less, but that's about what I'm expecting.

 

She had to pick a specified demographic for the applied research part of her studies, this limited the variables in trials. Additionally her pick probably came from the fact that somatic tinnitus patients would be the most likely super responders. There is no reason as of yet to say this will not be effective for other types of tinnitus, because to my understanding all tinnitus is generated in the DCN; Dr. Shore obviously will not claim something that is not tested and been proven to be scientific theory due to her risking her academic integrity. Running around claiming that you solved the tinnitus problem, "once and for all, my paper here proves it!" would look rather foolish if it did not shake out of the metaphorical bag quite right.

I would hold my breath, and just try the device when it comes out. I would say you should respond to the treatment by what you typed. The most important thing I think, is the science being developed here. If this device works for somatic tinnitus as well as they claim, that means there is a possibility we will not have to reinvent the wheel; simply refining the product we already have may garner rapid success and be able to treat a wider demographic of patients.

Tinnitus Talk Podcast's latest episode touched upon cochlear stimulation. It has become rather obvious that tinnitus can be modulated via electrical stimulation seemingly regardless of its "type" as long as the stimulation matches the right frequency, etc.

 

Then, as someone who has experience in publishing papers, share your viewpoint about the timeline?

 

Answers below:

There are never a "plenty of peer reviewers wanting to peer review." Actually, I don't think nobody would voluntarily peer review a paper. It is a very ungrateful activity where reviewers are not paid, but are imposed extremely tight deadlines and conditions.

This is so stupid I can't believe I really need to explain it. In short: Not only are there always revisions, but there are usually several rounds of revisions.

This is even more stupid. Time until publication depends on the journal you submitted the paper to, the journal's editor, how fast they are finding reviewers, how fast reviewers accept or decline the invitation to review, the deadline the editor sets, if reviewers actually abide by the deadline, how many revisions they ask for, the editor's feedback...

 

It seems you need some serious training on writing papers if all of this keeps happening to you. Best of luck!

 

Anything else to contribute other than an ad hominem fallacy?

 

Calm down everyone. @InNeedOfHelp is just optimistic. Why not? Let’s hope it will be published as soon as possible. The world is waiting for it!

 

Not sure if this was ever posted, but the patent for Dr. Shore's device is co-registered by Seth Koehler.

https://patents.google.com/patent/US9682232B2/en?inventor=Seth+KOEHLER

Seth Koehler is Associate Director of Decibel Therapeutics, which is a biotech company. It doesn't seem to be in scope of Decibel Therapeutics ,but I wonder if they will be involved in this.

 

What caught my eye is this part here:

"The method of claim 6, wherein the sound comprises a tone, a narrowband noise, a broadband noise, a harmonic complex, or a combination thereof."​

This maybe means that the device can output all kinds of sound for the auditory stimulation and be able to help patients with other sounds than just tonal tinnitus - broadband noise, hissing, hum, cicadas etc etc.

 

Seth Koehler from Decibel Therapeutics worked for the Michigan University: "research into the role of the somatosensory system in tinnitus“ for almost 6 years (from 2007 to 2013). So he was part of the team I guess.

 

@EDDTEKK, yes, I did a search on him. There's a whole team in the Shore Lab and he was part of it. I noticed he has been at Decibel Therapeutics for over 4 years in an executive role.