Lenire — Bimodal Stimulation Treatment by Neuromod

[Hazel]

Hmm.... 6%? How does this reconcile with Lim's interview which amounted to roughly 20% disimprovement?

I'm no expert, but my understanding is that the 20% constitutes those who scored the same or worse on the TFI/THI after treatment compared to before. It's in essence the counterpart of the 80% or so whom they claim "improved" (I'm highly critical of this claim, as you can read in my blog). That's something different than "adverse events" which is what you're referring to now.

An adverse event is more serious than scoring slightly worse on some questionnaire. I don't know the details of what constitutes an "adverse event" per se, but I think there are formal criteria for this, as well as what constitutes a mild/moderate/severe event. Hope that helps a little bit.

 

[tommyd87]

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Hmm.... 6%? How does this reconcile with Lim's interview which amounted to roughly 20% disimprovement?

View attachment 41141

Lenire definitely does sound underwhelming and also actually quite shady.

 

[UKBloke]

View attachment 41133

@Hazel just wrote an independent assessment outlining all the pros and cons of Lenire.

Please take a moment to read, comment, and share it where you can.

I think this is a very very fair summation.

 

[GlennS]

I'm no expert, but my understanding is that the 20% constitutes those who scored the same or worse on the TFI/THI after treatment compared to before. It's in essence the counterpart of the 80% or so whom they claim "improved" (I'm highly critical of this claim, as you can read in my blog). That's something different than "adverse events" which is what you're referring to now.

An adverse event is more serious than scoring slightly worse on some questionnaire. I don't know the details of what constitutes an "adverse event" per se, but I think there are formal criteria for this, as well as what constitutes a mild/moderate/severe event. Hope that helps a little bit.

Not trying to come down on you here but when I read this sort of lengthy qualification all I can think of is Bill Clinton saying (adopt Clinton impersonation voice here):

For those who say Lenire helped them, well, I can understand how they might express gratitude here for being lucky and disinterested in negative stats. For those waiting on the sidelines even 8% would make one feel like being invited to play Russian Roulette, let alone 20.

That being said, when I last asked whether Tinnitus Talk would reach out to Neuromod again, the response was that it wouldn't be worth the time. Maybe if you are putting time into following up via a blog post you might reconsider talking to Neuromod again and having them compare notes between their data and Tinnitus Talk's statistics.

 

[ajc]

I'd like Neuromod to reach out to all their patients who got worse and ask how they are now and then publish a detailed report.

Too much to ask?

David Stockdale did not pressure Hubert Lim enough.

 

[ThomasRobert]

Neuromod raises €10.5m for expansion
Fundraising to push commercialization and advance entry to US market oversubscribed

Link:
https://www.irishtimes.com/business...neuromod-raises-10-5m-for-expansion-1.4385927

 

[Hazel]

Not trying to come down on you here but when I read this sort of lengthy qualification all I can think of is Bill Clinton saying (adopt Clinton impersonation voice here):

To be clear, I wasn't defending Neuromod, just trying to help you understand the difference between the percentages. That's all.

I also don't get why the "lengthiness" of my explanation (I don't think it was lengthy at all) should make you suspicious; is there a relation between length of response and validity?

You said you don't mean to come down on me, but that's exactly what you're doing. I'll take counter-arguments any time, responding to the content of my comments. But that's not what you're doing; instead you're making a caricature of me with the Bill Clinton meme, which I don't appreciate.

That being said, when I last asked whether Tinnitus Talk would reach out to Neuromod again, the response was that it wouldn't be worth the time. Maybe if you are putting time into following up via a blog post you might reconsider talking to Neuromod again and having them compare notes between their data and Tinnitus Talk's statistics.

We'll consider it. We have a lot of other projects going on though and very limited time (remember we're doing this in our spare time, next to day jobs). I'm also worried that — having already done two interviews with Neuromod — interviewing them a third time would be giving them too much exposure compared to other companies or researchers who are working on treatments.

 

[UKBloke]

Have rewatched the Stockdale/Lim video and there's just a few points and thoughts I think are worth putting forward again (in no particular order).

There was an important discussion we all had some months ago regarding questions around the possibility that Lenire could cause lasting harm or "disimprovement". From my perspective the basis (and result) of that discussion really only boiled down to allowing a potential user to become informed enough as to be able to make a balanced risk-assessment on whether or not to purchase the device.

One point I would raise again in this context is that I consider the placebo effect can be so powerful that it may, in certain circumstances, still be a valid enough rationale for someone who is suffering badly with their tinnitus to take the plunge with Neuromod. In other words, if I were to purchease the device on the understanding that the worst I could expect would be placebo I still might be prepared to travel to Ireland.

The problem is of course that we're pretty certain now that this is not the case, placebo is not the worst we might expect. And this uncertainly is compounded terribly by the fact that it seems nigh on impossible to actually gauge a) what the percentage chance of the device causing us harm is, and b) if we were harmed, what kind of harm could we possibly be facing?

If we go by Hubert Lim's own language in the video my understanding only becomes more clouded. For example, he says these adverse events (whatever these adverse events may be of course) ""could" subside for "some" of those individuals". Or that, "early in the treatment we noticed "some" individuals had an increase but things "could" subside over time for "some" of these individuals". And "overall we were able to close out all of these "adverse" events.. except those we lost the follow up".

The fact that Hubert Lim is talking to the lead tinnitus charity in the UK (I can give David Stockdale a break in terms of grilling Lim further because he's the CEO with trustees etc), I would have expected him to have some hard stats to hand. But we don't see or hear of any. What we actually have is a very non-committal language, which is vexxing to say the least but (and I want to try and remain as fair and impartial as I can here because I hate "trial by Internet") crucial to those of us that have been closely following Neuromod because the lack of clarity has impeded our ability to make a decision.

On the upside it is clear we are going to get more data further down the line. Lim assures us that they try to be transparent, and that all, or at least much more, of the details will come out in the "proceeding study that we have for TENT-A2".

So where does that leave us? I've rarely felt as confused over a product as I have Lenire. I'm sure this is not something Neuromod would like to hear but in all fairness it's their own conduct - or perhaps better to say, "approach" - that has gotten us here.

I'm wondering whether an open letter endorsed by Tinnitus Talk to Hubert Lim, posted here, raising the various concerns and offering him an opportunity to reply might be appropriate? It's something I'd be willing to help organise and put together, although please be aware I'm not a stats person or anything like that.

The only other option I can see at this point is more waiting for this further detail out of TENT-A2, but as I say, I'm uncomfortable with this, actually for no other reason than they're already out there selling the device.

Sorry for the long post. It was all stream-of-conscious stuff that I wanted to get off my chest.

 

[tommyd87]

Neuromod raises €10.5m for expansion
Fundraising to push commercialization and advance entry to US market oversubscribed

Link:
https://www.irishtimes.com/business...neuromod-raises-10-5m-for-expansion-1.4385927

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This is going to take at least a year and as a result Lenire could be available in the US after Dr. Shore's device. I'd be very interested to see whether Lenire would stack up. Not to mention Neuromod would have to do a placebo control group too.

 

[BigNick]

Aren't adverse effects common place with a lot of medical treatments, be them tech based like Lenire or drugs?

I've taken four different antidepressants one of which gave me severe diarrhea and left me barely able to open my eyes, doesn't mean it's not helpful to others.

I also think the placebo can work both ways i.e. a tinnitus patient has a good tinnitus day and thinks Lenire is responsible, likewise another patient has a bad tinnitus day and blames Lenire.

One thing I'm convinced of is that bimodal stimulation modulates tinnitus in some patients, another is that the approach needs further work to improve outcomes.

The naysayers will continue to frown and shake their heads, that's the way some people think I'm afraid.

 

[F-u-T]

This is going to take at least a year and as a result Lenire could be available in the US after Dr. Shore's device. I'd be very interested to see whether Lenire would stack up. Not to mention Neuromod would have to do a placebo control group too.

I really don't think we will see a device from Dr. Shore anytime soon. My bet is 3-5 years until her device is available for purchase.

 

[ThomasRobert]

This is going to take at least a year and as a result Lenire could be available in the US after Dr. Shore's device. I'd be very interested to see whether Lenire would stack up. Not to mention Neuromod would have to do a placebo control group too.

I think this is a wake up call for Susan Snore...

 

[DaveFromChicago]

The Open Letter is an excellent idea, UK Bloke. In particular I would request his response regarding the seriously adverse effect that it had on one Tinnitus Talk participant, which arguably (according to his comments) contributed to his decision to commit suicide. Another lady on Tinnitus Talk reported that after it's application (was it 4 days?) excruciatingly inflamed her Trigeminal Nerve; I don't believe we ever heard from her again.

Regarding your legitimate theory about it's sheer potential placebo value, for me personally I already went through my baptism by fire with Desyncra, and have been shorn of any placebo susceptibility.

(Incidentally, three years after I finished with them they are no longer in business, and consigned to the trash heap of previous, numerous dud treatments).

Given their inconclusive commentary, I will be very surprised it they get FDA approval. My ENT Doctor has a sense of very strict scientific evaluation, and I will consider this only if he recommends it.

(I mean, does this thing work or not? Fess up with a plain, direct answer).

 

[tommyd87]

I think this is a wake up call for Susan Snore...

Dr. Shore is actually already ahead because she will get approval from the FDA first because this process is already being followed.

From what I understand, Lenire needs to go to the start and go through the whole process.

I'm positive that if, say, Otonomy's OTO-413 will have good results with tinnitus then there could be limited gain for Lenire in the US.

 

[UKBloke]

Aren't adverse effects common place with a lot of medical treatments, be them tech based like Lenire or drugs?

Undoubtedly. Whether it be diarrhea with antidepressants, nausea with aspirin, or drowsiness with anti-histamines, I think the potential side effects of these (and of course various tech) are very well acknowledged. That said I do think the situation changes if one of, or even the main side effect, is a potential worsening of the condition the system is meant to treat.

There's always going to be naysayers like you say, but there will also always be those who demand hard facts, and I'm definitely in that latter group, especially where tinnitus treatment is concerned. Probably comes with being a sufferer of thirty years.

 

[tommyd87]

The Open Letter is an excellent idea, UK Bloke. In particular I would request his response regarding the seriously adverse effect that it had on one Tinnitus Talk participant, which arguably (according to his comments) contributed to his decision to commit suicide. Another lady on Tinnitus Talk reported that after it's application (was it 4 days?) excruciatingly inflamed her Trigeminal Nerve; I don't believe we ever heard from her again.

Regarding your legitimate theory about it's sheer potential placebo value, for me personally I already went through my baptism by fire with Desyncra, and have been shorn of any placebo susceptibility.

(Incidentally, three years after I finished with them they are no longer in business, and consigned to the trash heap of previous, numerous dud treatments).

Given their inconclusive commentary, I will be very surprised it they get FDA approval. My ENT Doctor has a sense of very strict scientific evaluation, and I will consider this only if he recommends it.

(I mean, does this thing work or not? Fess up with a plain, direct answer).

I am thinking we are on the same page Dave, however I think that the interesting thing will be firstly whether Neuromod gets American approval from the FDA and secondly what the outcomes will be from when they have to actually do a placebo controlled trial.

A placebo controlled trial will probably be Lenire's downfall due to the fact that it is ultimately going to show how well the treatment works. Unlike pharmaceutical drug options (albeit being early in their clinical trials) which have to demonstrate that they don't have a placebo effect. Lenire, on the other hand, has happened to not do a placebo control group at all and even if they weren't required to do this it still has led to people having legitimate concerns over the treatment.

I reckon Lenire will be exposed when it is evaluated against the placebo.

Foremost I see Lenire as being a a somewhat effective treatment for some with tinnitus, however right now it doesn't achieve anywhere near as much as Neuromod claims it does. I also think before they can get FDA approval for Lenire in the US, they really need to make some significant improvements in its performance and those outcomes which it delivers, otherwise they will struggle to get that approval.

Essentially the best thing about it being taken through the FDA process is that the requirements are really very stringent which help stop any unsafe or dud products getting approved. As a result, I reckon that we can be quite assured that Lenire is legitimate if it passes the FDA process since it has to go through a whole heap of hurdles and requirements it didn't have to face in the Republic of Ireland.

Lenire seems to be quite similar to Hough Ear Institute in the way which we have seen them respond to certain requests for information and questions. Neuromod have been rather selective in the information they have willingly released, with both entities avoiding disclosing certain things and also actually only seemingly divulging the good things.

Thus while I could be wrong, I think that we'll see Lenire getting exposed and their product won't be anywhere as assistive or beneficial as Neuromod is claiming it to be.

 

[cjbhab]

Here's the thing, if they are using THI to determine improvement, it means absolutely nothing.

2 weeks ago I wanted to kill myself because my tinnitus in my right ear was so bad, it was the loudest it had ever been, I could hear it over everything for a whole week.

Last week, I had a full 7 days where I felt good, yes I had tinnitus, but it wasn't bothersome, I barely thought about it, I went about my business.

This week my left ear has a rattling noise in it that is infuriating me.

My THI changes literally by the week, for better or worse. It depends when you ask me to evaluate it.

 

[UKBloke]

Here's the thing, if they are using THI to determine improvement, it means absolutely nothing.

2 weeks ago I wanted to kill myself because my tinnitus in my right ear was so bad, it was the loudest it had ever been, I could hear it over everything for a whole week.

Last week, I had a full 7 days where I felt good, yes I had tinnitus, but it wasn't bothersome, I barely thought about it, I went about my business.

This week my left ear has a rattling noise in it that is infuriating me.

My THI changes literally by the week, for better or worse. It depends when you ask me to evaluate it.

Couldn't agree more. THI is a really odd one. I've just filled out a THI questionnaire and scored 48, which is moderate. Today, however, my tinnitus is off the charts; squealing in both ears, particularly shrill in the left ear. Went for a walk this afternoon and heard it outside, as is usual for me.

Today is a "bad" day. But THI says it's moderate (have been as honest as I can when filling in the form). By relying on THI I think science has skipped a stage. They need to go back a step and learn how to actually measure tinnitus loudness/perception properly. There has to be a tangible signal somewhere in the brain.

 

[GlennS]

If we go by Hubert Lim's own language in the video my understanding only becomes more clouded. For example, he says these adverse events (whatever these adverse events may be of course) ""could" subside for "some" of those individuals". Or that, "early in the treatment we noticed "some" individuals had an increase but things "could" subside over time for "some" of these individuals". And "overall we were able to close out all of these "adverse" events.. except those we lost the follow up".

I'm just sensing a lot of equivocation and statistical sleight-of-hand here.

People viscerally react to numbers. A risk-factor of less than 10% feels relatively safe. A risk-factor of 20% does not. But you have to know exactly what those numbers signify and whether certain people were being selectively filtered out of it due to a technicality.

By equivocating, Neuromod can always claim to be "transparent" and "honest" but they know damn well how laymen will react to certain numbers and terminology being thrown around (not the least of which--disimprovement, which is their own euphamism). Disimprovement sounds milder than worsening because it at least has the word "improvement" in it.

 

[tommyd87]

I'm just sensing a lot of equivocation and statistical sleight-of-hand here.

People viscerally react to numbers. A risk-factor of less than 10% feels relatively safe. A risk-factor of 20% does not. But you have to know exactly what those numbers signify and whether certain people were being selectively filtered out of it due to a technicality.

By equivocating, Neuromod can always claim to be "transparent" and "honest" but they know damn well how laymen will react to certain numbers and terminology being thrown around (not the least of which--disimprovement, which is their own euphamism). Disimprovement sounds milder than worsening because it at least has the word "improvement" in it.

I'm telling you Neuromod are mainly very good at marketing with what we are seeing them do and say about Lenire. It's seen with everything that they have done after release like the research article and the things that they have said about Lenire to try to make it seem like it is greater than it probably actually is.

If you have got any idea how to pull things apart you can clearly see what they're trying to actually do with this thing.

 

[UKBloke]

I am thinking we are on the same page Dave, however I think that the interesting thing will be firstly whether Neuromod gets American approval from the FDA and secondly what the outcomes will be from when they have to actually do a placebo controlled trial.

Do we have an idea how long that process could take? I'm presuming years?

 

[weab00]

Do we have an idea how long that process could take? I'm presuming years?

Never right. How would they be able to show significance with a placebo group?

 

[GlennS]

Never right. How would they be able to show significance with a placebo group?

Susan Shore managed to do it--somehow. Maybe move the electrode slightly so that it doesn't actually pass the signal down the trigeminal nerve--then weaken the signal so that it can still be felt, but barely?

 

[tommyd87]

Susan Shore managed to do it--somehow. Maybe move the electrode slightly so that it doesn't actually pass the signal down the trigeminal nerve--then weaken the signal so that it can still be felt, but barely?

I don't know, however with what Neuromod published about Lenire, I don't think that they have an understanding how to do this. Let alone do this in some way which shows that the device has no placebo effect.

 

[PeterPan]

Susan Shore managed to do it--somehow. Maybe move the electrode slightly so that it doesn't actually pass the signal down the trigeminal nerve--then weaken the signal so that it can still be felt, but barely?

I'm not sure if you even need to do anything like this. The placebo effect comes about due to participant's expectation that the treatment will work. I think the placebo effect is such a big factor with tinnitus because tinnitus is related to stress. If I have a strong expectation that I am going to have significant success with the treatment in the near future, then this is likely to reduce my stress, which will actually cause the treatment to be successful (at least for a while anyway) .

So, in the trial if you subject the participant to a battery of tests before and after treatment, pay a lot of attention to them, use a device that's obviously created for the purpose of treating tinnitus, use staff with medical qualifications, then you are likely to set this expectation. It probably doesn't matter that there is no tingling on the tongue (and staff could explain to the participant that the threshold is set so low that there will be no sensation; it would better if the staff used believed this as well). Tingling on the tongue would add to the overall effect, and would contribute to convincing the patient that they are getting the real deal, but it's probably not necessary.

The other way that you can try to reduce the placebo effect is to have several different treatment arms, and show that one arm is superior to another, and hence demonstrate a real effect. This is what Neuromod tried to do in their trial. But all 3 arms had the same results in THI reduction after 12 weeks (although they were different after 12 months, and participants with hyperacusis did experience a difference). This means that either:

a) There is something about the treatment (non-placebo) that causes it to be effective (the music played, the tongue stimulation etc) which is common to all 3 arms, or

b) The common thing for all 3 arms is the placebo effect.

I am leaning towards b).

 

[UKBloke]

(and staff could explain to the participant that the threshold is set so low that there will be no sensation; it would better if the staff used believed this as well)

Bingo. That would have been a rational way for them to double-blind a placebo arm. I think their main problem now the machine is out in the open, is that it's going to be practically impossible not to deliver some kind of sensation to the tongue-tip during any future trial.

 

[UKBloke]

Never right. How would they be able to show significance with a placebo group?

Off the top of my head the only way I can of is for them to fudge up some kind of fake tongue tip that looks and feels like the real thing but doesn't actually deliver any current. Perhaps some kind of high-frequency vibration instead.

 

[tommyd87]

I'm not sure if you even need to do anything like this. The placebo effect comes about due to participant's expectation that the treatment will work. I think the placebo effect is such a big factor with tinnitus because tinnitus is related to stress. If I have a strong expectation that I am going to have significant success with the treatment in the near future, then this is likely to reduce my stress, which will actually cause the treatment to be successful (at least for a while anyway) .

So, in the trial if you subject the participant to a battery of tests before and after treatment, pay a lot of attention to them, use a device that's obviously created for the purpose of treating tinnitus, use staff with medical qualifications, then you are likely to set this expectation. It probably doesn't matter that there is no tingling on the tongue (and staff could explain to the participant that the threshold is set so low that there will be no sensation; it would better if the staff used believed this as well). Tingling on the tongue would add to the overall effect, and would contribute to convincing the patient that they are getting the real deal, but it's probably not necessary.

The other way that you can try to reduce the placebo effect is to have several different treatment arms, and show that one arm is superior to another, and hence demonstrate a real effect. This is what Neuromod tried to do in their trial. But all 3 arms had the same results in THI reduction after 12 weeks (although they were different after 12 months, and participants with hyperacusis did experience a difference). This means that either:

a) There is something about the treatment (non-placebo) that causes it to be effective (the music played, the tongue stimulation etc) which is common to all 3 arms, or

b) The common thing for all 3 arms is the placebo effect.

I am leaning towards b).

I think that the placebo outcomes might be common too. I actually wonder whether Neuromod also discovered this and as a result this is the reason that they didn't test for placebo either.

 

[cjbhab]

I think that the placebo outcomes might be common too. I actually wonder whether Neuromod also discovered this and as a result this is the reason that they didn't test for placebo either.

I can't understand how somebody could possibly have the placebo effect and think their tinnitus is gone. LOL.

I'm the opposite, I don't believe anything will ever help me, so I don't think I could feel a placebo effect.

 

[AfroSnowman]

I can't understand how somebody could possibly have the placebo effect and think their tinnitus is gone. LOL.

I'm the opposite, I don't believe anything will ever help me, so I don't think I could feel a placebo effect.

99% of those who report improvement, don't report that their tinnitus is gone. Mostly just a bit less intense.