New University of Michigan Tinnitus Discovery — Signal Timing

[RunningMan]

Is there a difference between being cautiously optimistic and questioning every response given by Dr. Shore. If she has said it's possible, she must have her reasons to believe it's possible... of course, I don't expect miracles.

You are reading more into that than what she actually said. Regardless of her belief, she would be expected to say it's "possible" that there "may" be further reduction in tinnitus rather than saying it's "likely" because the study did not test beyond that. So, without any data to refute it, she says it's possible. But we really should stick to what the study shows rather than speculating.

This is important because thousands of people who suffer from this condition rely on what they read on this forum, so let's get back on the right track.

My reference to the reduction being 10.9 dB for the PP group through week 12 rather than 6 dB was definitely positive. That's a better improvement on average. 6 dB to 10 dB is generally considered half as loud. Dr. Shore mentioned the 6 dB figure.

Out of the 7 study participants who discontinued participation and whose tinnitus worsened, 4 were first in the control treatment group and 3 were first in the active treatment group. I'm not sure how how many weeks of the auditory-only or active treatment they received before dropping out.

Right. In any case, the data for those people was not included in the PP group analysis that showed the 10.9 dB reduction in volume of tinnitus. There were only 30 people in that first active group in the final PP group analysis. The ones who received the control treatment first didn't perform so well when they were provided the active treatment and were not included in the PP group analysis, either. I know there were some concerns about the results of the second half of the study, and Dr. Shore addressed that in the Q&A.

And anyway, Dr. Shore's device represents a revolution in any case.

If truly 15% of the world's population suffers from tinnitus (1.2 billion out of 8 billion), and of those, 70% have somatic tinnitus (840,000,000), and 53% of them are "cured" (445,200,000), how can one complain about such results in the face of nearly half a billion treatable people?

I wouldn't say that 53% were "cured". They received "treatment" that showed a clinically meaningful reduction in the TFI scores at week 6. It didn't eliminate the tinnitus, and they will likely need continued treatment, as Phase 1 trial did show tinnitus to worsen after stopping active treatment, although it didn't immediately do so in this Phase 2 trial.

All of this excluding the fact that:

• Improvements are possible even for those with non-somatic tinnitus.
• Further improvements are possible after the 12th week.

If they weren't confirmed through testing, we shouldn't speculate that they are facts. We can remain hopeful, of course.

I know many of us may think, "I'm probably part of that 47% that doesn't improve, so it's better to keep expectations low," but let's try to be positive.

It's not just about whether you are among those that will see improvement but whether that improvement is meaningful to you. It's going to vary from person to person. Keep expectations in check with what the study shows if you want to avoid a possible big disappointment. You can still be "positive" in your thinking that that you will be among the 53% that have meaningful reduction or that your tinnitus volume reduction will be at least average compared to the PP group's 10.9 dB.

The study had some requirements that excluded some people from being able to participate, so if those people had participated, such as people with significant hearing loss, the results would have been expected to be lower. So when we are looking at the world population of tinnitus sufferers, keep that in mind as well.

 

[Anuar Lukios]

You are reading more into that than what she actually said. Regardless of her belief, she would be expected to say it's "possible" that there "may" be further reduction in tinnitus rather than saying it's "likely" because the study did not test beyond that. So, without any data to refute it, she says it's possible. But we really should stick to what the study shows rather than speculating.

My reference to the reduction being 10.9 dB for the PP group through week 12 rather than 6 dB was definitely positive. That's a better improvement on average. 6 dB to 10 dB is generally considered half as loud. Dr. Shore mentioned the 6 dB figure.

Right. In any case, the data for those people was not included in the PP group analysis that showed the 10.9 dB reduction in volume of tinnitus. There were only 30 people in that first active group in the final PP group analysis. The ones who received the control treatment first didn't perform so well when they were provided the active treatment and were not included in the PP group analysis, either. I know there were some concerns about the results of the second half of the study, and Dr. Shore addressed that in the Q&A.

I wouldn't say that 53% were "cured". They received "treatment" that showed a clinically meaningful reduction in the TFI scores at week 6. It didn't eliminate the tinnitus, and they will likely need continued treatment, as Phase 1 trial did show tinnitus to worsen after stopping active treatment, although it didn't immediately do so in this Phase 2 trial.

If they weren't confirmed through testing, we shouldn't speculate that they are facts. We can remain hopeful, of course.

It's not just about whether you are among those that will see improvement but whether that improvement is meaningful to you. It's going to vary from person to person. Keep expectations in check with what the study shows if you want to avoid a possible big disappointment. You can still be "positive" in your thinking that that you will be among the 53% that have meaningful reduction or that your tinnitus volume reduction will be at least average compared to the PP group's 10.9 dB.

The study had some requirements that excluded some people from being able to participate, so if those people had participated, such as people with significant hearing loss, the results would have been expected to be lower. So when we are looking at the world population of tinnitus sufferers, keep that in mind as well.

I'm only relying on the hypotheses of an expert, not reading more into what she has actually said, and I don't expect miracles.

I specified why some people worsened because there was alarmism on certain pages.

I used the term "cured" in quotes because I couldn't find a suitable term at that moment... you know, "cured" serves exactly for that among many other things.

I don't understand... are you here to put everyone in a bad mood and engage in unnecessary disputes, trying to find flaws in every bit of information released by Dr. Shore? My tinnitus is so mild that I only hear it with a background noise below 23 dB (practically, my own breath is louder than my tinnitus), and there's no damage to my hearing or ears. I could simply mind my own business, but it bothers me to constantly read negative things.

Let's talk about how research and treatments could change in the coming years thanks to the discoveries made by Dr. Shore... that's certainly more useful.

 

[Nick47]

I think I remember reading something in the animal study that they treated their tinnitus at the 8 kHz range, but it did nothing for their tinnitus outside of 8 kHz. If this is the case, I'd imagine that you could continue working with the audiologist to figure out the correct frequencies if the results aren't good at first.

This is the most common tinnitus frequency. To be exact, I think it was 8037 Hz for most people.

 

[nomorenoise]

I read that the device only goes up to 12 kHz. I wonder how this will affect people whose tinnitus pitch is higher than that?

 

[Fightthearmy]

This is the most common tinnitus frequency. To be exact, I think it was 8037 Hz for most people.

Fun fact: Homer Simpson's tinnitus is 764 Hz. He also has a second tone, around 11000 Hz, which is somewhat lower than mine. My second-most annoying one clocks at a mere 100 Hz.

 

[ErikaS]

I read that the device only goes up to 12 kHz. I wonder how this will affect people whose tinnitus pitch is higher than that?

Do you remember where you read that? My highest tone sits somewhere between 15-16 kHz and I know I'm not alone in "something above 12 kHz" so I hope that's not the case. However, I am also in the camp of it doesn't have to match the tinnitus sound perfectly to gain improvement, just like @linearb shared what he experienced in the clinical trial.

 

[SarahMLFlemmer]

I have a quick question: if you can't be positive, why are you trying to make others feel negative? How does it help to be cautiously optimistic?

And why?

After all, it's not Dr. Shore's fault that the person attended a (rock?) concert.

People get hurt by unmet expectations. I would consider myself realist

...Your optimism is truly contagious though, so please, keep that up!

 

[nomorenoise]

Do you remember where you read that? My highest tone sits somewhere between 15-16 kHz and I know I'm not alone in "something above 12 kHz" so I hope that's not the case. However, I am also in the camp of it doesn't have to match the tinnitus sound perfectly to gain improvement, just like @linearb shared what he experienced in the clinical trial.

As a high frequency sufferer (15-16 kHz) I also reached out to the clinician regarding the pitch matching of their device which, while maybe listed in one of their publications, I wasn't able to easily locate. He advised that the maximum frequency was in the 12 kHz range but again, since the target of the device is the DCN, still feels the device will be beneficial regardless of exact pitch matching.

 

[Jonno02]

I read that the device only goes up to 12 kHz. I wonder how this will affect people whose tinnitus pitch is higher than that?

As per the patent, it appears to cover up to 24 kHz.

Sound levels were adjusted to account for the system response using a programmable attenuator (PA5, TDT, Alachula, Fla.) to deliver calibrated levels (dB SPL) at frequencies from 200 Hz to 24 kHz.

 

[eagerUser]

People get hurt by unmet expectations. I would consider myself realist

...Your optimism is truly contagious though, so please, keep that up!

IMHO, people get hurt anyway, whether by unmet expectations or by tinnitus but positivity gives you enough motivation to continue for the time being. Let's call it realistically optimistic which means we are gonna see a miraculous device soon

 

[Stayinghopeful]

I'd assume most older people would have a lot of hearing loss in those extended ranges.

I wonder if it would work for all of us with extended frequency hearing loss over 40 dB and tones around 13 kHz.

 

[DeanD]

I don't understand... are you here to put everyone in a bad mood and engage in unnecessary disputes, trying to find flaws in every bit of information released by Dr. Shore? My tinnitus is so mild that I only hear it with a background noise below 23 dB (practically, my own breath is louder than my tinnitus), and there's no damage to my hearing or ears. I could simply mind my own business, but it bothers me to constantly read negative things.

Perhaps you have answered your on question. I would imagine your mild case is pretty unique to most in this thread.

I can't hear my breathing because of the volume of my tinnitus - I can't always hear people's voices because of the volume level of my tinnitus. When you start hitting that level (and hopefully you never do) you will perhaps understand the absolute desperation, fear and negativity and sheer frustration of people here.

My tinnitus was like yours for 44 years, I never even knew this place existed, I wouldn't have understood the place where the negativity is coming from either - until now.

I want to remain hopeful even though I am almost ruled out of the Auricle device on two counts, and I hope this is a major breakthrough that sees larger companies want to have a buy in to tinnitus treatments, but when you live in the way most on here do - you will understand where negativity slips in.

 

[Nick47]

I want to remain hopeful even though I am almost ruled out of the Auricle device on two counts, and I hope this is a major breakthrough that sees larger companies want to have a buy in to tinnitus treatments, but when you live in the way most on here do - you will understand where negativity slips in.

Why are you ruled out?

 

[Anuar Lukios]

Perhaps you have answered your on question. I would imagine your mild case is pretty unique to most in this thread.

I can't hear my breathing because of the volume of my tinnitus - I can't always hear people's voices because of the volume level of my tinnitus. When you start hitting that level (and hopefully you never do) you will perhaps understand the absolute desperation, fear and negativity and sheer frustration of people here.

My tinnitus was like yours for 44 years, I never even knew this place existed, I wouldn't have understood the place where the negativity is coming from either - until now.

I want to remain hopeful even though I am almost ruled out of the Auricle device on two counts, and I hope this is a major breakthrough that sees larger companies want to have a buy in to tinnitus treatments, but when you live in the way most on here do - you will understand where negativity slips in.

Having mild or moderate tinnitus does not make my thoughts any less important than someone who has severe tinnitus.

The point is that talking about negative things, circulating pessimism, criticizing research, denying science, downplaying the results of one of the most important research studies is of no use.

Let's close the thread then, or rather call Dr. Shore directly and tell her "look, your PhD is useless, your research was a waste of time and the device won't help almost anyone because strangers on a forum say so."

 

[2noist]

Having mild or moderate tinnitus does not make my thoughts any less important than someone who has severe tinnitus.

The point is that talking about negative things, circulating pessimism, criticizing research, denying science, downplaying the results of one of the most important research studies is of no use.

Let's close the thread then, or rather call Dr. Shore directly and tell her "look, your PhD is useless, your research was a waste of time and the device won't help almost anyone because strangers on a forum say so."

Stop the nonsense. You are asking people to drop critical thinking and become blind sheep.

In the world of science, there have been more promising developments (than this device) that ended up being relatively ineffective in the real world.

 

[DeanD]

Having mild or moderate tinnitus does not make my thoughts any less important than someone who has severe tinnitus.

The point is that talking about negative things, circulating pessimism, criticizing research, denying science, downplaying the results of one of the most important research studies is of no use.

Let's close the thread then, or rather call Dr. Shore directly and tell her "look, your PhD is useless, your research was a waste of time and the device won't help almost anyone because strangers on a forum say so."

Nothing to do with your thoughts - it was the attitude of not understanding why people were in a state of negativity over some of the results when deep diving in. But equally someone who is severe is just as entitled to have their thoughts too.

Whether anyone up-plays or down-plays the results, it makes no difference in the real world. No one else is reading this. People on here are suffering enough to be entitled to an opinion. Everything on here is an opinion, some will be good, some will be bad. If you don't like the negativity - and that negativity exists in the real world - don't read it.

No idea what the point of that statement was. Why phone Dr. Shore? - No idea what you're talking about.

Why are you ruled out?

Firstly, because none of my tinnitus is somatic, so although that doesn't completely rule me out - it isn't shown to work for non-somatic type (yet).

Secondly, because I have bad hearing. Already down to 70 dB at 8 kHz in one ear, and down to 50 dB at 8 kHz in the other - but gradually getting worse. By the time it comes out I could have passed the 50 dB threshold required for the device to work - unless I misunderstood this part.

 

[Nick47]

The point is that talking about negative things, circulating pessimism, criticizing research, denying science, downplaying the results of one of the most important research studies is of no use.

I agree with positivity. However, many on these forums have seen good looking research and treatments fail. Given the nonsense from Lenire and Frequency Therapeutics, it is our job to critically evaluate what is before us. No one has criticised Dr. Shore's science, however we may critique her study and findings.

 

[Anuar Lukios]

Secondly, because I have bad hearing. Already down to 70 dB at 8 kHz in one ear, and down to 50 dB at 8 kHz in the other - but gradually getting worse. By the time it comes out I could have passed the 50 dB threshold required for the device to work - unless I misunderstood this part.

Yes, unfortunately in the Q&A she answered that severe hearing loss would preclude use of the device, but she also said that the sound could be effective as long as one ear can hear it.

I hope for you that it won't get any worse until the device comes out.

A stupid question:

Could hearing aids be useful in your case?

I ask because in a response she said:

We excluded subjects who had used a hearing aid in the 6 months preceding trial enrollment so that any potential treatment impact would be eliminated. But there is no reason why hearing aid use would be a contra-indication provided that the patient's hearing loss threshold is within our prescribed range.

 

[eagerUser]

I'd assume most older people would have a lot of hearing loss in those extended ranges.

I wonder if it would work for all of us with extended frequency hearing loss over 40 dB and tones around 13 kHz.

I would say, according to science, almost everyone over the age of 20 has some sort of hearing loss in the extended ranges. So, Dr.Shore has definitely taken this fact into account when her team was developing the device. Just my 2 cents.

 

[DeanD]

Yes, unfortunately in the Q&A she answered that severe hearing loss would preclude use of the device, but she also said that the sound could be effective as long as one ear can hear it.

I hope for you that it won't get any worse until the device comes out.

A stupid question:

Could hearing aids be useful in your case?

I ask because in a response she said:

Thank you - I appreciate that.

Ahh so you are saying that wearing hearing aids whilst using the device may boost hearing enough to hear the prescribed 50 dB or better range? I hadn't seen that, but that is an interesting way to look at it - thanks.

 

[RunningMan]

I'm only relying on the hypotheses of an expert, not reading more into what she has actually said, and I don't expect miracles.

You are still reading more into it than what she said. My point that it was NOT a hypothesis or even a speculation from Dr. Shore that she thinks tinnitus reduction will continue if treatment is continued longer. She simply stated that "it's possible" without any indication of how likely she thinks it is. She goes by the science, and since she didn't test it, she doesn't know. So I think her response is valid. If the question had been worded as "is it possible the tinnitus volume reduction plateaus if treatment is extended longer than in the study?", then her previous response can apply there, as well. It's possible. So, I'm focusing on the study and what the actual results are, not something that may or may not be true and was never tested or even stated as likely by Dr. Shore.

I don't understand... are you here to put everyone in a bad mood and engage in unnecessary disputes, trying to find flaws in every bit of information released by Dr. Shore?

Bad mood? I never engaged in any unnecessary disputes - not sure what you're talking. And extracting data from the study and posting detail about it to this thread as myself and others have done is not "finding flaws in every bit of information released by Dr. Shore." It's simply pointing out and drawing attention to specific info from the study, which is what this thread is about.

I'm optimistic that this will work for about half the people for a clinically significant reduction in tinnitus, as shown in the study, but that's just my opinion.

Let's talk about how research and treatments could change in the coming years thanks to the discoveries made by Dr. Shore... that's certainly more useful.

I don't see how speculating about the uncertain future beyond this product is going to be more useful than discussing the current device and study that this thread is specifically for. We still need to see how successful this device is in the real world for chronic severe tinnitus sufferers. That could already be 2 or 3 years before it's widely available in the U.S.

Thank you - I appreciate that.

Ahh so you are saying that wearing hearing aids whilst using the device may boost hearing enough to hear the prescribed 50 dB or better range? I hadn't seen that, but that is an interesting way to look at it - thanks.

The device will have settings to increase the volume for the patient. I don't think she meant you would wear hearing aids while actually using the device, but you could wear hearing aids at other times and still use the device without the hearing aid if your hearing was in the hearing loss threshold for the device. Since timing is important for this device, I wonder if a hearing aid while using the device could even mess up the timing due to the delay in audio to the electrical stimulation.

 

[Anuar Lukios]

You are still reading more into it than what she said. My point that it was NOT a hypothesis or even a speculation from Dr. Shore that she thinks tinnitus reduction will continue if treatment is continued longer. She simply stated that "it's possible" without any indication of how likely she thinks it is. She goes by the science, and since she didn't test it, she doesn't know. So I think her response is valid. If the question had been worded as "is it possible the tinnitus volume reduction plateaus if treatment is extended longer than in the study?", then her previous response can apply there, as well. It's possible. So, I'm focusing on the study and what the actual results are, not something that may or may not be true and was never tested or even stated as likely by Dr. Shore.

Bad mood? I never engaged in any unnecessary disputes - not sure what you're talking. And extracting data from the study and posting detail about it to this thread as myself and others have done is not "finding flaws in every bit of information released by Dr. Shore." It's simply pointing out and drawing attention to specific info from the study, which is what this thread is about.

I'm optimistic that this will work for about half the people for a clinically significant reduction in tinnitus, as shown in the study, but that's just my opinion.

I don't see how speculating about the uncertain future beyond this product is going to be more useful than discussing the current device and study that this thread is specifically for. We still need to see how successful this device is in the real world for chronic severe tinnitus sufferers. That could already be 2 or 3 years before it's widely available in the U.S.

The device will have settings to increase the volume for the patient. I don't think she meant you would wear hearing aids while actually using the device, but you could wear hearing aids at other times and still use the device without the hearing aid if your hearing was in the hearing loss threshold for the device. Since timing is important for this device, I wonder if a hearing aid while using the device could even mess up the timing due to the delay in audio to the electrical stimulation.

Useless controversy in which among other things you don't even understand what I'm saying, the discussion was already over this morning and you're still continuing?

I just said that, for now, I rely on what the doctor says without obviously expecting great things and I try to be a little optimistic.

I never said we shouldn't question what the doctor says.

There is way and way of criticizing and there is someone (I don't want to name names) on several pages who always complains about the same things, going so far as to say that a 6 dB reduction is little or useless.

Brother, that last part was ironic. Do you take everything literally? I was just saying that sometimes it is more useful to say "By hitting the DCN, perhaps in the future we will get rid of tinnitus" rather than repeating every time "6 dB is too little, it will never come out or it will take at least 5 years."

 

[RunningMan]

Stop the nonsense. You are asking people to drop critical thinking and become blind sheep.

In the world of science, there have been more promising developments (than this device) that ended up being relatively ineffective in the real world.

Very well said!

Useless controversy in which among other things you don't even understand what I'm saying, the discussion was already over this morning and you're still continuing?

I just said that, for now, I rely on what the doctor says without obviously expecting great things and I try to be a little optimistic.

I never said we shouldn't question what the doctor says.

The discussion was not over this morning. I had not responded to your previous reply to me, which was misinformation about what I was saying or doing. Are you suggesting I can't address that? I understand what you were saying, but you were not understanding me, and you were misinterpreting what Dr. Shore was stating, so I clarified her words, which were quite clear to me all along. Simple as that.

You can be optimistic without misrepresenting what she said or what I have said. I did not question what Dr. Shore said. I agree with her that it's possible. I hope it's true, but I'm not going to factor that in when I say the study showed 10.9 dB reduction in tinnitus. As I said, it's best to stick to the facts of what the study shows and not read into her comments just because it's "possible".

There is way and way of criticizing and there is someone (I don't want to name names) on several pages who always complains about the same things, going so far as to say that a 6 dB reduction is little or useless.

Well, no point in being upset about that because the average reduction is more than 6 dB, and that is sometimes considered a drop to half the perceived volume, including by Dr. Shore. I think there were some audio files posted earlier that demonstrate that difference. Although it's not a lot for my severe tinnitus, the study did show better results on average - 10.9 dB for the PP group.

Brother, that last part was ironic. Do you take everything literally? I was just saying that sometimes it is more useful to say "By hitting the DCN, perhaps in the future we will get rid of tinnitus" rather than repeating every time "6 dB is too little, it will never come out or it will take at least 5 years."

What is ironic about it? Science should be literal. You can speculate about the unknown if you want and misinterpret Dr. Shore's comments (and mine) in your own mind if you want, but the study speaks pretty well for itself, which is what I have focused on. The reduction on average is actually more than 6 dB from baseline, as I've stated in some recent posts. And I never said it will take 5 years to come out. After a lot of discussion in this thread, I'm thinking 2 to 3 years for wide scale availability in the U.S., but hopefully sooner.

It's ironic, your original reply to me was to the post that I stated the reduction is 10.9 dB rather than 6 dB as someone stated prior to me, yet you are still harping about 6 dB. It seems you should have just let my positive statement stand as it was correct all along without the speculation of what hasn't been tested yet.

Hopefully we are clear on the matter now. Have a nice day.

 

[slc]

Just reviewing the Shore Q&A on the subject of the degree hearing loss. It strikes me that both severity and range of the loss will be key. According to Dr. Shore, in answer to "What if you have bilateral severe to profound hearing loss in the same frequency as your tinnitus? Will it impact the treatment?"

She responded:

At present, bilateral severe to profound hearing loss would preclude use of the device as the signal needs to be heard to be effective. The study only included up to moderate hearing loss.

There are unknowns about outcomes for folks with profound loss who, for example, would be able hear the treatment sound perhaps if the decibel level were increased -- as folks with profound loss were not in the study. Also, Dr. Shore referred to a spectrum of sound. What might the results be for a person who only heard a portion of that spectrum?

Just thoughts to ponder rather than assume that profound hearing loss would automatically rule out any benefit from Auricle.

 

[SarahMLFlemmer]

In the world of science, there have been more promising developments (than this device) that ended up being relatively ineffective in the real world.

Or worse.

 

[Jeggie3]

Jeez I didn't think my response would contribute to such a tussle. I have a PhD in Neuroscience and work in the psychiatric disease drug discovery field so I have a little experience in both writing and reading the preclinical and clinical CNS therapeutic literature. Based on my reading of the manuscript, there's a lot to be highly optimistic about. I mean if I saw data like these from my clinical colleagues I would be overjoyed. The science going back to the animal mode data is extremely sound and the results surprisingly strong. In fact, finding a way to induce long term depression in humans in a circuit of such clinical significance is quite remarkable. (One minor critique is the error bars are SEM with n = around 50 so the spread could be greater than it looks, and it would be nice to see the individual data plotted to see just how variable they are.)

Certainly, Dr. Shore has to keep her public enthusiasm limited in the face of FDA consideration, so it's understandable she can't speculate about better results with longer treatment time. But if I saw those data, privately I would be hypothesizing like crazy about that. So coming from someone who is typically very skeptical about a lot of published science, I stand by these data being extremely encouraging.

Anyways, my two cents and hopefully nobody fights anymore. Though disagreement and debate is always ok of course.

 

[Nick47]

and it would be nice to see the individual data plotted to see just how variable they are.)

This is something I was asking about much earlier in the thread. Academics can actually request this data.

 

[Jeggie3]

This is something I was asking about much earlier in the thread. Academics can actually request this data.

For sure — Anybody can ask the journal for access to the raw data and authors should comply. Though at this point I'm not sure I'd want to bother the authors since they have an important job of commercialization that I'd rather them not get distracted from...

 

[RunningMan]

Jeez I didn't think my response would contribute to such a tussle. I have a PhD in Neuroscience and work in the psychiatric disease drug discovery field so I have a little experience in both writing and reading the preclinical and clinical CNS therapeutic literature. Based on my reading of the manuscript, there's a lot to be highly optimistic about. I mean if I saw data like these from my clinical colleagues I would be overjoyed. The science going back to the animal mode data is extremely sound and the results surprisingly strong. In fact, finding a way to induce long term depression in humans in a circuit of such clinical significance is quite remarkable. (One minor critique is the error bars are SEM with n = around 50 so the spread could be greater than it looks, and it would be nice to see the individual data plotted to see just how variable they are.).

Hello. Your response did not contribute to the tussle, so no worries. Speculation on further reduction had already been mentioned in response to my earlier post as well as multiple times earlier in the thread.

It makes sense to be optimistic - I am as well. But what did you think of the tinnitus loudness reduction data from the second half of the study, after week 12? This caused concern when the study was published, and Dr. Shore didn't include this in the analysis, which she also mentioned in the Q&A, due to the tinnitus not reverting quickly to baseline during the washout period vs. the first trial (on right below) that used a shorter 4 week time frame for active treatment and washout before changing the groups who were receiving the active vs. control treatment.

 

[Jeggie3]

Hello. Your response did not contribute to the tussle, so no worries. Speculation on further reduction had already been mentioned in response to my earlier post as well as multiple times earlier in the thread.

It makes sense to be optimistic - I am as well. But what did you think of the tinnitus loudness reduction data from the second half of the study, after week 12? This caused concern when the study was published, and Dr. Shore didn't include this in the analysis, which she also mentioned in the Q&A, due to the tinnitus not reverting quickly to baseline during the washout period vs. the first trial (on right below) that used a shorter 4 week time frame for active treatment and washout before changing the groups who were receiving the active vs. control treatment.

View attachment 56084

Good question.

Looking at the left figure, I'm assuming the concern is well maybe the first response in the bisensory condition is a fluke since there's no response beyond sham treatment in the group that got sham first.

And yes, ideally, I would want to see that.

However, the positive spin on it is this is some kind of "order effect" where the initial sham treatment somehow interfered with the bisensory treatment that came afterwards through some unknown mechanism. (Insert handwavey explanation as to why that maybe -- maybe receiving the noise alone for a while alters the network to make it unable to respond when the e-stimulation is added and makes it more resistant to the plasticity paradigm?). This order effect seems to results in a "carryover effect" that does indeed invalidate the second half of the study from an analysis perspective.

But in the real world, nobody will receive 6 weeks of sham followed by 6 weeks washout before the therapeutic stimulation when this device is finally available, and so I remain optimistic that the protocol will work in naive patients when provided with the therapeutic bisensory stimulation.

A question I have is if there's any methodology differences between the pilot and phase 2 studies that would explain why it returned to baseline in the pilot beyond the two additional weeks of treatment. Was the protocol precisely the same or did they refine it in between? Maybe I'll go dig into the methods. Okay the methods are not great and rather barebones, so not much to go on.