New University of Michigan Tinnitus Discovery — Signal Timing

[DebInAustralia]

In the end, yes, we'll find out in due time when/if the device is approved. Hopefully such a date is not too far in the future.

I recently received this invite from the FDA to attend the following:

Please join us at the Regulatory Education for Industry (REdI) Annual 2024 Conference Wednesday May 29th and Thursday May 30th. This year's REdI Conference is FREE featuring both an in -person and online version. This year's Plenary Session is "Innovation in Medical Product Development" followed by separate session tracks on drugs, devices and biologics. To find more information about Redi, including information on how to register, please visit https://www.fda.gov/drugs/news-even...e-2024-innovation-medical-product-development

Attending will unlikely uncover information about the burning question around Dr. Shore's submission, but it might be helpful.

 

[Paulmanlike]

I was on the Lenire study like a hawk. However, I am a bit behind with the latest study with Dr. Shore. Apologies if this has been answered before.

I have just been reading through the second trial results, which look 'too good to be true. ' However, what was the percentage of responders out of the 49 active treatment subjects who showed clinically meaningful improvement? It only shows the whole, which I assume is the median. Are there any breakdowns of each subject?

 

[AfroSnowman]

I was on the Lenire study like a hawk. However, I am a bit behind with the latest study with Dr. Shore. Apologies if this has been answered before.

I have just been reading through the second trial results, which look 'too good to be true. ' However, what was the percentage of responders out of the 49 active treatment subjects who showed clinically meaningful improvement? It only shows the whole, which I assume is the median. Are there any breakdowns of each subject?

I wouldn't put money down on it, but I'm pretty sure that 60% had statistically meaningful improvement.

 

[Nick47]

what was the percentage of responders out of the 49 active treatment subjects who showed clinically meaningful improvement? It only shows the whole, which I assume is the median. Are there any breakdowns of each subject?

• Placebo group: 20% statistically significant improvement.
• Active group: 60% statistically significant improvement.

 

[RunningMan]

I was on the Lenire study like a hawk. However, I am a bit behind with the latest study with Dr. Shore. Apologies if this has been answered before.

I have just been reading through the second trial results, which look 'too good to be true. ' However, what was the percentage of responders out of the 49 active treatment subjects who showed clinically meaningful improvement? It only shows the whole, which I assume is the median. Are there any breakdowns of each subject?

It's not quite as good when you dig in.

The 65% includes only the per-protocol group receiving active treatment before the crossover, which was included in the analysis, with only 30 participants, after excluding 19 others. Some of those had worsened tinnitus or received no benefit, and they were not included in the analysis. Add back in those five excluded participants who got worse tinnitus or no benefit, and you're closer to 54% of 35 participants who received clinically meaningful improvement when receiving the active treatment. However, as mentioned, 25% could be a placebo effect, as that is what the control side of the study showed.

The other piece to consider is that the average reduction in tinnitus volume was only about 6 dB better than that of the placebo group.

 

[Paulmanlike]

Thanks to all those who responded to my question.

It all looks too familiar with other studies' results (I know they had a control group on this one), which materialized in disappointment in 'real world' cases. It always seems to be around 60% of respondents and slightly higher than placebo (I know it's more than double). Just like Lenire, ACRN, LLLT.

Sadly, I don't feel excited about it, although I will wait to see 'real world' testimonies on this site if it happens. I would be more excited if the placebo was lower and the activity was much higher.

I take it Auricle is still proceeding to commercialize this. We are waiting for FDA approval, which Dr. Shore cannot comment on.

@RunningMan, only 6 dB better than placebo is 'half as loud' according to the study? That bit seems to be pretty good, to be fair.

 

[RunningMan]

only 6 dB better than placebo is 'half as loud' according to the study? That bit seems to be pretty good, to be fair.

It's better than nothing. It takes about 3 dB just to be noticeable in direct comparisons, so it's better than that. -6 dB to -10 dB is generally considered half as loud.

There are some audio samples posted earlier in this thread in which someone can sample what that difference sounds like with a test tone.

→ Sample Tones

 

[Jim Vasilakis]

So, I see we have circled back to the skepticism era. I understand it; tinnitus can make everyone pessimistic and bitter. I just want to remind you most bimodal stimulation studies with electrical signals have reduced the tinnitus volume and annoyance in most participants. So, it's not just Dr. Shore and her device. A correctly made and calibrated bimodal device with correct signal timing WILL reduce the tinnitus volume in most people using it. That's the consensus based on at least five different studies.

It is unknown how much it will reduce it, but I have a good feeling that the more you use the device, the more it calms the cells.

 

[Kleiner]

The skepticism is mainly directed at Auricle's supposed inability to market this product effectively.

 

[Bhaveen]

So, I see we have circled back to the skepticism era. I understand it; tinnitus can make everyone pessimistic and bitter. I just want to remind you most bimodal stimulation studies with electrical signals have reduced the tinnitus volume and annoyance in most participants. So, it's not just Dr. Shore and her device. A correctly made and calibrated bimodal device with correct signal timing WILL reduce the tinnitus volume in most people using it. That's the consensus based on at least five different studies.

It is unknown how much it will reduce it, but I have a good feeling that the more you use the device, the more it calms the cells.

Thanks for this, Jim. I do check this thread when there are new posts, and reading the ones before yours dampened my spirits somewhat, but reading yours brought them back to a happy medium.

I have to admit, I have read so much about this treatment as being a "game changer," but some of the posts I read here make it sound no better than Lenire.

 

[Paulmanlike]

So, I see we have circled back to the skepticism era. I understand it; tinnitus can make everyone pessimistic and bitter. I just want to remind you most bimodal stimulation studies with electrical signals have reduced the tinnitus volume and annoyance in most participants. So, it's not just Dr. Shore and her device. A correctly made and calibrated bimodal device with correct signal timing WILL reduce the tinnitus volume in most people using it. That's the consensus based on at least five different studies.

It is unknown how much it will reduce it, but I have a good feeling that the more you use the device, the more it calms the cells.

You can find studies on all the previous treatments that have had positive results. However, these never translated to real-world experiences. There is nothing wrong with positivity, but there is also nothing wrong with healthy cautiousness.

 

[Cmspgran]

What are people's theories as to the mechanism behind those people whose tinnitus was made worse by Dr. Shore's device? Was it incorrect timing? Was the tone matched incorrectly? Were the electrodes placed incorrectly?

 

[Gb3]

Does anyone really care what some random on Tinnitus Talk says?

All we can do is wait and hope to hear about FDA approval.

 

[Pinhead]

What are people's theories as to the mechanism behind those people whose tinnitus was made worse by Dr. Shore's device? Was it incorrect timing? Was the tone matched incorrectly? Were the electrodes placed incorrectly?

According to Dr. Shore's Q&A, from what I can recall, she could only contribute one "worsening" to her device. Other factors were present in the other cases, and I'm not sure any of them were permanent worsenings, just spikes.

 

[Cmspgran]

According to Dr. Shore's Q&A, from what I can recall, she could only contribute one "worsening" to her device. Other factors were present in the other cases, and I'm not sure any of them were permanent worsenings, just spikes.

This is what I always thought, but if you refer back to @RunningMan's post, he states several who dropped out of the trial did so due to worsening.

 

[RunningMan]

You can find studies on all the previous treatments that have had positive results. However, these never translated to real-world experiences. There is nothing wrong with positivity, but there is also nothing wrong with healthy cautiousness.

That's right, and if you dig into the study, the numbers don't lie, regardless of the optimism or pessimism someone has for the device.

And as you mentioned, real-world experiences with Lenire turned out much worse than people were expecting. So while Dr. Shore's device study may have shown that 30% of participants truly benefited when accounting for those experiencing the placebo effect, as I mentioned earlier, for a modest decrease in tinnitus volume, real-world results are likely to come up short, so perhaps 10% to 20% will see a small improvement in tinnitus in the real world if we are lucky, and hopefully not as disappointing as Lenire. I'm hoping it's toward the higher end.

One concern is that the device may become less effective over the longer term (year or years) as your brain gets accustomed and habituates to its stimulus, thereby losing most of the early benefit.

 

[Watasha]

Does anyone really care what some random on Tinnitus Talk says?

All we can do is wait and hope to hear about FDA approval.

All of the needless back and forth could have been thousands of letters to our representatives in Congress.

 

[Utdmad89]

All of the needless back and forth could have been thousands of letters to our representatives in Congress.

How many did you send?

 

[RunningMan]

This is what I always thought, but if you refer back to @RunningMan's post, he states several who dropped out of the trial did so due to worsening.

Worse tinnitus or no benefit accounted for five that were excluded from the PP analysis of the active treatment group. Obviously, if you exclude some of those who didn't improve from the analysis, your percentage of those receiving clinically significant improvement is higher among the relatively small group.

 

[Nick47]

It's difficult not to hang all your hopes on this. However, there are reasons for optimism in the study results. It's just not going to be effective for a lot of people. This is why we must push for more and more treatments. I can see a future of treatment options and possibly an objective test circa 2028/29.

There will be different treatments for different patients, though.

 

[JeffToob]

All of the needless back and forth could have been thousands of letters to our representatives in Congress.

I appreciate the thread here. Where else can we better hash out our nerves, hopes, skepticism, and questions? I've read the thread from the start since joining Tinnitus Talk. @Hazel and @Markku have been in touch with Dr. Shore, and it's now at a standstill. The debates here would not really transfer to thousands of letters to anyone. We only care because we have it.

 

[Jim Vasilakis]

That's right, and if you dig into the study, the numbers don't lie, regardless of the optimism or pessimism someone has for the device.

And as you mentioned, real-world experiences with Lenire turned out much worse than people were expecting. So while Dr. Shore's device study may have shown that 30% of participants truly benefited when accounting for those experiencing the placebo effect, as I mentioned earlier, for a modest decrease in tinnitus volume, real-world results are likely to come up short, so perhaps 10% to 20% will see a small improvement in tinnitus in the real world if we are lucky, and hopefully not as disappointing as Lenire. I'm hoping it's toward the higher end.

One concern is that the device may become less effective over the longer term (year or years) as your brain gets accustomed and habituates to its stimulus, thereby losing most of the early benefit.

A placebo effect can't cut your tinnitus in half for months. That's not how it works.

 

[Watasha]

I appreciate the thread here. Where else can we better hash out our nerves, hopes, skepticism, and questions? I've read the thread from the start since joining Tinnitus Talk. @Hazel and @Markku have been in touch with Dr. Shore, and it's now at a standstill. The debates here would not really transfer to thousands of letters to anyone. We only care because we have it.

Don't get me wrong, I don't just appreciate the thread here, I LOVE it, as this thread and others have given me so much hope through the years. Tinnitus Talk is undoubtedly one of the best websites to obtain cutting-edge information on tinnitus research, support, etc. But at a certain point, beating a dead horse over mere speculation is, in my opinion, empty talk that is a waste of time and effort that could and should be spent elsewhere.

Sometimes, we like to think we as individuals can't make a difference, so we resign ourselves to chats on forums, but I don't look at it that way. Unfortunately, the tinnitus community has historically been well-known for its inability to mobilize, so I do get a little frustrated when I see mindless back and forth over some things that aren't controllable when we can all be doing something to move the needle, even if just a tiny bit.

 

[Paulmanlike]

Does anyone really care what some random on Tinnitus Talk says?

Who are you talking about?

 

[RunningMan]

A placebo effect can't cut your tinnitus in half for months. That's not how it works.

Actually, the placebo effect can be very strong. I've seen it much higher than 25% in some studies. Google it.

The active treatment and sham treatment was only six weeks (see graphic). And "half" is only a 6 dB reduction. I recommend you read the study if you don't believe I am relaying the study info accurately. Let me know if you find any inaccuracies.

And note, I'm hopeful and optimistic, so I truly hope it's higher than the 10% to 20% range that experiences clinically significant reduction after subtracting for placebo. But I recommend you keep your expectations in check. We've been down this road before with a previous product that people had such high hopes for.

 

[Gb3]

Who are you talking about?

99% of the posts on this thread.

 

[Jim Vasilakis]

Actually, the placebo effect can be very strong. I've seen it much higher than 25% in some studies. Google it.

The active treatment and sham treatment was only six weeks (see graphic). And "half" is only a 6 dB reduction. I recommend you read the study if you don't believe I am relaying the study info accurately. Let me know if you find any inaccuracies.

And note, I'm hopeful and optimistic, so I truly hope it's higher than the 10% to 20% range that experiences clinically significant reduction after subtracting for placebo. But I recommend you keep your expectations in check. We've been down this road before with a previous product that people had such high hopes for.

View attachment 56827

The placebo effect doesn't cut your tinnitus by 75% and 11 dB for almost two months. I'm not a tinnitus expert, but that I know. A decrease like that is physiological, not psychological. I don't think there has been a tinnitus sufferer who had the placebo effect for more than some days.

 

[Bhaveen]

Worse tinnitus or no benefit accounted for five that were excluded from the PP analysis of the active treatment group. Obviously, if you exclude some of those who didn't improve from the analysis, your percentage of those receiving clinically significant improvement is higher among the relatively small group.

View attachment 56825

Okay, so there were people who didn't receive the treatment but had their tinnitus worsen. Is this what the data says?

Is there anywhere we can see the results of the first trial in such detail? It seems like the first trial hasn't been mentioned much, but it seems more successful.

There's something I can't quite wrap my head around. If Lenire had a success rate in the high 80s percentile but no placebo, and we assume a 20 percent improvement for the placebo, that still leaves Lenire at the high 60s percentile for improvement, which is more than Auricle. Am I missing something here? This comparison doesn't seem to add up. I'd appreciate any insights you could provide. Thank you!

 

[Nick47]

If Lenire had a success rate in the high 80s percentile

Yes, 80% success as measured in what? What success? Measuring fucking what? 80% got a new job after Lenire? 80% reduced depression?

Look at the outcome measures!

 

[Paulmanlike]

The placebo effect doesn't cut your tinnitus by 75% and 11 dB for almost two months. I'm not a tinnitus expert, but that I know. A decrease like that is physiological, not psychological. I don't think there has been a tinnitus sufferer who had the placebo effect for more than some days.

You cannot say it's physiological without an objective measure I'm afraid, and there isn't one.