New University of Michigan Tinnitus Discovery — Signal Timing

[Karen1979]

My biggest humdinger is the final cohort size. Originally it was posted as 400. Due to COVID-19, this was understandably not practical.

However, at 99 we still have a moderate size group to reduce the chances of a fluke/anomaly type situation. Small cohorts can provide false and misleading results, just think of Otonomy and Frequency Therapeutics. This is why many treatments fail at Phase 2 and Phase 3 as the bigger the cohort, the less chance the result was just by chance.

Now if I am right (if I'm wrong tell me), the data was collected from 56 participants as 37 discontinued or were unable to complete. It talks about ITT and PP, with ITT defined as intention to treat and PP as per-protocol. 56 were included in the PP analysis.

@Karen1979, in terms of NHS approval and the difficulties with them requiring level A-C evidence, they are looking at one trial of 20 patients and another trial of 56 patients. They will conclude that, due to the small and moderate cohorts, a larger trial is required.

For the device to become an "integrated care pathway," a part of NICE guidelines etc, yes, I believe a larger trial will be required. However (puts optimistic hat on), if it proves to be beneficial in the real world, funding can be requested if a case is made.

On an individual basis, there may be situations where a clinician believes that their patient's clinical situation is so different to other patients with the same condition that they should have their treatment paid for when other patients would not. In such cases, NHS clinicians can ask NHS England, on behalf of a patient, to fund a treatment which would not usually be provided by NHS England for that patient. This request is called an Individual Funding Request.

(Source)

I know this seems long-winded but it may be the way.

If this happened and the patient "borrowed" the device for treatment and then returned it, then in theory it is a way to have the device in a service. This would be a slow way for the device to get integrated. However, once it's in, then from there the case is built to get additional funding and so on.

In my service, I pleaded a case for a costly device and was agreed to the funding (£600). I now can use this device across services. This will come down to individual services and funding structure. We also get a lot of donations to our service which allows us to buy things we need, a "defibrillator" as an example, and this could be the same for audiologists/ENTs.

If this works, "WE JUST NEED TO STOMP OUR FEET A LOT!"

 

[AnthonyMcDonald]

For the device to become an "integrated care pathway," a part of NICE guidelines etc, yes, I believe a larger trial will be required. However (puts optimistic hat on), if it proves to be beneficial in the real world, funding can be requested if a case is made.

(Source)

I know this seems long-winded but it may be the way.

If this happened and the patient "borrowed" the device for treatment and then returned it, then in theory it is a way to have the device in a service. This would be a slow way for the device to get integrated. However, once it's in, then from there the case is built to get additional funding and so on.

In my service, I pleaded a case for a costly device and was agreed to the funding (£600). I now can use this device across services. This will come down to individual services and funding structure. We also get a lot of donations to our service which allows us to buy things we need, a "defibrillator" as an example, and this could be the same for audiologists/ENTs.

If this works, "WE JUST NEED TO STOMP OUR FEET A LOT!"

Of course while money is an issue for some, I think I would prefer buying it and using it for 500 weeks and seeing what happens.

 

[Karen1979]

Of course while money is an issue for some, I think I would prefer buying it and using it for 500 weeks and seeing what happens.

Agreed.

But my post was in response to NHS approval and eventual part of its treatment plans.

 

[Nick47]

For those that want to see the graphs showing loudness, TFI, THI and study design/dropouts, I recommend clicking the PDF at the top of the study, which is a better format for some. Otherwise you need to click through the illustration links.

 

[eagerUser]

I hate to see the word placebo!

If your tinnitus is lowered, why do you care if it it's from the placebo effect or from the real treatment? What are you looking for? A lower tinnitus or something not placebo?

I believe the fact that 25% of participants had their tinnitus lowered from placebo is a good thing because then we already have a second treatment called placebo that has a 25% chance of success.

I know that you are damn anxious to know if the device works or not but I would like to express that it has two super features: one is the treatment itself, the other is placebo.

No room for negativity now. Only if it fails can you ping me and tell me to fuck off!

Best wishes.

 

[Karen1979]

I hate to see the word placebo!

If your tinnitus is lowered, why do you care if it it's from the placebo effect or from the real treatment? What are you looking for? A lower tinnitus or something not placebo?

I believe the fact that 25% of participants had their tinnitus lowered from placebo is a good thing because then we already have a second treatment called placebo that has a 25% chance of success.

I know that you are damn anxious to know if the device works or not but I would like to express that it has two super features: one is the treatment itself, the other is placebo.

No room for negativity now. Only if it fails can you ping me and tell me to fuck off!

Best wishes.

I love this post.

And when the device gets approval and they tinker with the protocol and do further exploratory studies, I believe they can improve the 65% significantly.

 

[chinup]

Nothing mentioned on hyperacusis doesn't mean the device doesn't improve it. It may work or may not work on hyperacusis but there is a good chance it does. We'll see once the device is out!

I just don't see how blasting artificial noise directly into your ears would improve noxacusis. It seems like the exact opposite of what we have learned to do with this condition.

When I play tones the same pitch of my tinnitus tones, the tinnitus momentarily subsides. So with tinnitus there is at least some sort of mechanism at play for which Dr. Shore's device makes sense based on my experience. I just don't see that same angle with hyperacusis, and definitely not with noxacusis.

Hopefully I'm wrong and the bimodality is the game-changing element. If anyone can try to explain why this would potentially help hyperacusis, I'm all ears.

 

[DimLeb]

This thread has a 10 year anniversary in a few days, on 20 June. Lol.

 

[RunningMan]

I hate to see the word placebo!

If your tinnitus is lowered, why do you care if it it's from the placebo effect or from the real treatment? What are you looking for? A lower tinnitus or something not placebo?

That depends. Placebo effects are usually not as strong and don't last as long. Previously reported positive experiences of other products and supplements mentioned in the past on this forum may have been due initially to the placebo effect, when it was later reported it's not working after-all. I do remain optimistic of what this product's actual effectiveness will be.

I believe the fact that 25% of participants had their tinnitus lowered from placebo is a good thing because then we already have a second treatment called placebo that has a 25% chance of success.

The 65% figure of the active treatment group results would be cumulative of the ones who actually benefited from active treatment and ones who benefited from the placebo effect. I made an error in my previous post. The active treatment group was 40% points higher than the control group, not 45%.

 

[ErikaS]

I hate to see the word placebo!

If your tinnitus is lowered, why do you care if it it's from the placebo effect or from the real treatment? What are you looking for? A lower tinnitus or something not placebo?

I believe the fact that 25% of participants had their tinnitus lowered from placebo is a good thing because then we already have a second treatment called placebo that has a 25% chance of success.

I know that you are damn anxious to know if the device works or not but I would like to express that it has two super features: one is the treatment itself, the other is placebo.

No room for negativity now. Only if it fails can you ping me and tell me to fuck off!

Best wishes.

Love this post and you, @eagerUser! This evil condition and all its even more debilitating counterparts naturally fill us with freaking negativity every freaking day. I personally cry at least every other day and legitimately fear my future, so if there is SOMETHING that someone as experienced and esteemed as Dr. Susan Shore invented after 20 YEARS of comprehensive research that could POTENTIALLY help many, we NEED to allow our brains to think "things COULD/CAN get better". As many said, this device will only catapult improved versions/tweaks and interventions alike.

 

[ChrisBoyMonkey]

I know I've been helped by Lenire, but I get it might not help everyone, whereas this is kind of what we've all been waiting for. If you've been thinking of getting Lenire, I recommend holding out for this instead. Hoping we'll all be sleeping without any noise soon.

 

[Fightthearmy]

For those that want to see the graphs showing loudness, TFI, THI and study design/dropouts, I recommend clicking the PDF at the top of the study, which is a better format for some. Otherwise you need to click through the illustration links.

The "supplemental content" leaf is a vast resource of all sorts of tables, before anyone asks more questions about participants. For instance:

Not entirely sure we haven't seen before the following, but we might learn more in Supplement 2: Trial Protocol and Statistical Analysis (last updated in February 2022), for instance, reiterating what we've heard before about the FDA approval:

A pre-submission has been reviewed already by the FDA and they were in agreement that this device would be de novo, non-significant risk.

In addition: FDA and the IRB consider our device class 2 de novo, thus we do not require an IDE to run the clinical trial, stage 2.

View attachment 54971

That's not her in the black harlequin suit, that's a dentist from Lake City, MI, with the same name.

 

[AnthonyMcDonald]

View attachment 54981

Not gonna lie, all those Susan Shore devices in one picture really makes my heart skip a beat

 

[Damocles]

That's not her in the black harlequin suit, that's a dentist from Lake City, MI, with the same name.

Yes. The team needed a dentist, because they're going to be knocking the teeth out of tinnitus.

Disclaimer: Doctor Susan Shore is not actually in any of the "harlequin suits".

 

[SarahMLFlemmer]

Yes. The team needed a dentist, because they're going to be knocking the teeth out of tinnitus.

Disclaimer: Doctor Susan Shore is not actually in any of the "harlequin suits".

Front left.

 

[JRC1]

I applaud what Dr. Shore and her team are accomplishing.

Question - the TFI and dB reduction seem highly correlated. But there seems to not be high correlation with the THI results. Can anyone offer an explanation for this?

 

[in_LA]

Yes. The team needed a dentist, because they're going to be knocking the teeth out of tinnitus.

Disclaimer: Doctor Susan Shore is not actually in any of the "harlequin suits".

Do you think Dr. Shore's device could help with palinacousis in some way? It seems palinacousis is related to tinnitus and hyperacusis?

 

[AnthonyMcDonald]

I applaud what Dr. Shore and her team are accomplishing.

Question - the TFI and dB reduction seem highly correlated. But there seems to not be high correlation with the THI results. Can anyone offer an explanation for this?

The discrepancy could be due to the different aspects of tinnitus that the TFI and THI evaluate. The TFI is more detailed/comprehensive, it assesses a broad spectrum of tinnitus-related issues, and the THI mostly focuses on the functional and emotional impacts. Basically the subjective nature of the questionnaires could have potentially led to variability in the responses.

 

[@dam]

I applaud what Dr. Shore and her team are accomplishing.

Question - the TFI and dB reduction seem highly correlated. But there seems to not be high correlation with the THI results. Can anyone offer an explanation for this?

The TFI and THI tests look extremely subjective.

• TFI (PDF)
• THI (PDF)

The TFI looks a lot more rigorous than the THI. If I had to do both tests everyday, they would vary so much, despite my tinnitus being the same volume. We crucially need an objective way to measure tinnitus, I guess dB reduction is the next best thing.

 

[PeterPan]

Here are some observations and queries:

1) The total number of participants who completed the study according to protocol (the "PP" group) was 56, which represents quite a high drop-out/non-compliance rate (originally 99 participants). The sample size is not that large.

2) In numerous parts of the paper, there is reference to an average 14.1 dB loudness reduction for the PP group at week 12 for group 1 (e.g., in the "Results" section). But the graphs e.g., Fig 3b only shows a 11 dB reduction. Anyone know why this is the case? 11 dB means the tinnitus was about 28% as loud, while 14.1 dB represent about 20%. In either case, it's quite impressive.

3) There were also changes in loudness (about 5 dB) and TFI (about 8 points) in the control in group 1 at week 12. A 5 dB reduction means the tinnitus was about 56% as loud. The paper proposes a scientific reason for this in the discussion section.

4) The paper states "In the pilot and the present studies, all participants reported quickly habituating to the electrical stimulus, which was close to threshold, making the stimulus difficult to detect. Participants stated that they could not tell whether they were receiving the control or active treatment". This statement appears contradictory (how can you habituate to the stimulus if you can't detect it?) and anecdotal (is there a more scientific way of assessing the degree to which participants could detect the stimulus?).

5) In contrast to the original study, the tinnitus reduction appears to be ongoing after the treatment.

6) When determining the efficacy of a treatment, the paper compares the TFI, THI, loudness statistics with the baseline rather than the control. Wouldn't it make more sense to compare to the control? Maybe that wasn't statistically significant?

7) According to the paper, "Given the large carry-over effect due to the longevity of the response, only period 1 was further analyzed per the standard procedure". The results from period 2 seems to be quite a bit different than period 1. I interpret the below graph to mean that the group that experienced the treatment in weeks 1-6 did much better than the group that experienced the treatment in weeks 13-18 (and I don't see that there should be any particular reason for this but I believe that the paper says it is due to the significant carry-over effect?). The paper focuses its attention mostly on the first group.

 

[DimLeb]

I thought I'd test out how big the reductions in dB really are. I used a sine tone at 500 Hz and with an equaliser I lowered its volume from 0 dB (max), to -6 dB and to -10 dB, as mentioned in the study. I'm attaching both the images of the equaliser with the reductions and the audio files for anyone to compare. Be careful to set your volume low to avoid any damage whatsoever and don't change the volume while comparing.

Yes, the dB scale is logarithmic and blah blah, but I think the difference is certainly noticeable, but not THAT BIG. This device is the best thing we can have right now, but I hope they improve it even further.

The software I used is FL Studio (music production DAW).

 

[PeterPan]

Yes, the dB scale is logarithmic and blah blah, but I think the difference is certainly noticeable, but not THAT BIG. This device is the best thing we can have right now, but I hope they improve it even further.

Thanks for that, very helpful. Personally, I think it is quite a reduction.

If I set my speakers so that the 0 dB matches my tinnitus loudness (something that is not easily done with precision), and then listen to the -10 dB file (or perhaps it should be -14 dB, refer to my post above) file, I can hardly hear it (although I am having a quiet day today).

 

[Nick47]

1) The total number of participants who completed the study according to protocol (the "PP" group) was 56, which represents quite a high drop-out/non-compliance rate (originally 99 participants). The sample size is not that large.

A very good analysis! My original count was not quite right but I did notice that a large proportion did not complete all aspects of the study.

Looking again, of the 99 finally enrolled, 43 did not follow the protocols in some way. They were marked in the ITT group. The actual study size was 56, although the ITT were included separately. Whilst the results are promising, it definitely reduces the quality of the study as we have a smaller sample size.

According to the paper, "Given the large carry-over effect due to the longevity of the response, only period 1 was further analyzed per the standard procedure". The results from period 2 seems to be quite a bit different than period 1. I interpret the below graph to mean that the group that experienced the treatment in weeks 1-6 did much better than the group that experienced the treatment in weeks 13-18 (and I don't see that there should be any particular reason for this but I believe that the paper says it is due to the significant carry-over effect?). The paper focuses its attention mostly on the first group.

Yes, I had to look a few times at this to wonder what the heck was going on here. It shows that the group that had placebo first did not benefit from the treatment after the washout. A really bizarre finding and I'm surprised no one else has brought this up as contentious?

Overall it's in the general direction of something positive, however I do think we need to run a more critical eye over things, rather than running off to get a Susan Shore tattoo.

This certainly isn't a Frequency Therapeutics type scenario as it's clearly showing responders, but we should keep things in check and not only see what we want to see.

 

[DaveFromChicago]

There is only One Important Question:

Will Auricle finally place @Michael Leigh (and everything he recommends and stands for) in The Dustbin of History?

 

[RunningMan]

I thought I'd test out how big the reductions in dB really are. I used a sine tone at 500 Hz and with an equaliser I lowered its volume from 0 dB (max), to -6 dB and to -10 dB, as mentioned in the study.

Yes, the dB scale is logarithmic and blah blah, but I think the difference is certainly noticeable, but not THAT BIG.

Yes, I posted pretty much the same thing from the testing of those dB reduction levels that I did a few posts back in this thread. I was testing at 6 kHz. As I mentioned then, I don't think it would be life changing for me at those reductions, but the actual reduction for anyone in particular could be greater than that with continued treatment.

I just did some sampling of tones at these different dB levels. It's noticeable, but it's not nearly as much of a reduction as I would have hoped and probably wouldn't be much of a difference maker for me at only 6 to 10 dB reduction. I can get a lot larger reduction on a very short term basis using tones to cause residual inhibition. Of course yes, that's very short term.

 

[DimLeb]

Thanks for that, very helpful. Personally, I think it is quite a reduction.

If I set my speakers so that the 0 dB matches my tinnitus loudness (something that is not easily done with precision), and then listen to the -10 dB file (or perhaps it should be -14 dB, refer to my post above) file, I can hardly hear it (although I am having a quiet day today).

Yeah, it is certainly a difference that would mean the world to many people. And it's literally 1000 times better than what we currently have to objectively reduce the tinnitus volume, meaning nothing at all. And well, it only gets better and better if someone responds with a 14 dB reduction.

Yes, I posted pretty much the same thing from the testing of those dB reduction levels that I did a few posts back in this thread. I was testing at 6 kHz. As I mentioned then, I don't think it would be life changing for me at those reductions, but the actual reduction for anyone in particular could be greater than that with continued treatment.

Ahh, I must have missed your post. Anyway yeah, it's not as huge a difference as one would have hoped for. But it also matters what the frequency of the tinnitus is. We are more sensitive to high frequencies, especially to those high mids (3-6 kHz), so a 10 dB reduction there would not be as life-changing as the same reduction to, say, 1 kHz tinnitus. I don't know.

Or maybe, it would make an ultra high 15 kHz tinnitus non existent, because those tend to seem very loud, even though they are objectively at low dBs, but pierce through everything because not many sounds in everyday life are that high. So yeah, it's all very subjective, but it's actually amazing that something finally works.

 

[Jim Vasilakis]

Is there a guarantee that the only reduction will be that of 12 dB?

The trial participants only used the device for a month and then stopped. What if we use it for two months straight?

 

[Jonno02]

Is there a guarantee that the only reduction will be that of 12 dB?

The trial participants only used the device for a month and then stopped. What if we use it for two months straight?

No.

There is a lot of speculation on here the decrease will continue with prolonged use.

 

[ErikaS]

Yes, I had to look a few times at this to wonder what the heck was going on here. It shows that the group that had placebo first did not benefit from the treatment after the washout. A really bizarre finding and I'm surprised no one else has brought this up as contentious?

This is very bizzare and not a finding you want to see, and again thank you @PeterPan and @Nick47 for bringing this to attention. I struggle to understand how/why this would be the case, because what you'd expect, and want, given group 1's response, is that there would be a notable effect/benefit once the control group got the actual treatment following washout from placebo.

 

[chinup]

I thought I'd test out how big the reductions in dB really are. I used a sine tone at 500 Hz and with an equaliser I lowered its volume from 0 dB (max), to -6 dB and to -10 dB, as mentioned in the study. I'm attaching both the images of the equaliser with the reductions and the audio files for anyone to compare. Be careful to set your volume low to avoid any damage whatsoever and don't change the volume while comparing.

Yes, the dB scale is logarithmic and blah blah, but I think the difference is certainly noticeable, but not THAT BIG. This device is the best thing we can have right now, but I hope they improve it even further.

The software I used is FL Studio (music production DAW).

I appreciate the effort here but this is the equivalent of tearing your ACL, going to physical therapy once, and saying that you feel a little bit better but your knee is still pretty wrecked.

We just don't know what happens if you use the device for 12 months rather than 1 month, or for 3 hours a day instead of 30 minutes. There's too much of a possibility that the reductions will compound with further treatment to draw any conclusions about the total reduction possible based on one round of treatment.