New University of Michigan Tinnitus Discovery — Signal Timing

[Daphne91]

Well said, @Pixelito! Also, it's important to understand that a "randomised, double blinded crossover study," as this was, is pretty much the most rigorous/solid type of study you can conduct. It's right up there. I had to get my dad who's a doctor to explain what each of those terms means haha, but now I get it!

 

[Nick47]

And for others, it reduced their ringing. When the device is used in real-world applications for longer periods than the limited testing in clinical trials, there is every reason to believe the percentages of success are going to increase exponentially.

I believe when all is said and done, the number of people who receive absolutely no benefits from the device is going to be a very small minority.

I agree with some of your commentaries; however, beyond the clinically significant improvers, we don't know if the rest had any improvement. There has been no individual participant data shared.

And, we can't assume, even though rationale may suggest, that longer use will give more reduction.

 

[RunningMan]

Well said, @Pixelito! Also, it's important to understand that a "randomised, double blinded crossover study," as this was, is pretty much the most rigorous/solid type of study you can conduct. It's right up there. I had to get my dad who's a doctor to explain what each of those terms means haha, but now I get it!

It would have been better to have a complete effective crossover study.

Unfortunately, because of what happened during the study, the crossover was thrown out for analysis of the second trial.

Dr. Shore explained this in the Q&A:

What we saw was that the treatment after 6 weeks was so long lasting that we did not see recovery. In fact, we saw a continued treatment effect up to 12 weeks (and beyond). For that reason the crossover did not work for the second study. This is called a "crossover effect" and it means that the second treatment period was biased by the first period. When that happens, it is not statistically valid to analyze the second half of the study. That is why we focused our analysis only on the first period.

The first half of the study looks promising, even factoring in a certain percentage of placebo effect.

 

[Lipshitz]

If there was a lot of confidence in Dr. Shore's device being able to help a lot of people, why isn't it available yet? Anything that had a very good chance of helping the majority of people to some degree, wouldn't be delayed for as long as her device has been.

Maybe Dr. Shore doesn't want to look like a scammer after the device hits the market and there is a lot of failure to it.

 

[Nick47]

Am I being really thick here?

I can see that those treated first had sustained improvement that lasted well into the washout and control period. However, there is still no explanation for why those who got control first did not improve after washout with the treatment.

Can anyone explain?

 

[IYIiKe]

If there was a lot of confidence in Dr. Shore's device being able to help a lot of people, why isn't it available yet? Anything that had a very good chance of helping the majority A people to some degree, wouldn't be delayed for as long as her device has been.

Maybe Dr. Shore doesn't want to look like a scammer after the device hits the market and there is a lot of failure to it.

I hate to break it to folks but you're looking at possibly 1.5 years for FDA approval if Lenire is any comparison.

Additionally, Dr. Shore isn't in charge of marketing and rollout. This will likely be phased out to audiologists and I'm betting treatment will require multiple trips to an audiologist so we can all be milked.

There is a lot that goes into device production and rollout.

There is precedent for Fast Track FDA approval but I doubt that Dr. Shore's device qualifies.

 

[Jammer]

If there was a lot of confidence in Dr. Shore's device being able to help a lot of people, why isn't it available yet? Anything that had a very good chance of helping the majority of people to some degree, wouldn't be delayed for as long as her device has been.

Maybe Dr. Shore doesn't want to look like a scammer after the device hits the market and there is a lot of failure to it.

Maybe it failed to meet the endpoints of the study? Just a guess.

 

[Fields]

I hate to break it to folks but you're looking at possibly 1.5 years for FDA approval if Lenire is any comparison.

Additionally, Dr. Shore isn't in charge of marketing and rollout. This will likely be phased out to audiologists and I'm betting treatment will require multiple trips to an audiologist so we can all be milked.

There is a lot that goes into device production and rollout.

There is precedent for Fast Track FDA approval but I doubt that Dr. Shore's device qualifies.

As previously discussed, Lenire's approval is likely to speed things up for Auricle:

The FDA has concluded that the Lenire device should be classified into Class II. This order, therefore, classifies the Lenire, and substantially equivalent devices of this generic type, into Class II under the generic name combined acoustic and electrical external stimulation device for the relief of tinnitus.

As such, it is hypothesized that Auricle can take a shortcut by submitting their device as a 510(k) in the form of a substantially equivalent device.

 

[Joey72]

If there was a lot of confidence in Dr. Shore's device being able to help a lot of people, why isn't it available yet? Anything that had a very good chance of helping the majority of people to some degree, wouldn't be delayed for as long as her device has been.

Maybe Dr. Shore doesn't want to look like a scammer after the device hits the market and there is a lot of failure to it.

Maybe the medical community doesn't give a shit about us? That's the impression I get from the ones I have dealt with.

 

[AfroSnowman]

I hate to break it to folks but you're looking at possibly 1.5 years for FDA approval if Lenire is any comparison.

Additionally, Dr. Shore isn't in charge of marketing and rollout. This will likely be phased out to audiologists and I'm betting treatment will require multiple trips to an audiologist so we can all be milked.

There is a lot that goes into device production and rollout.

There is precedent for Fast Track FDA approval but I doubt that Dr. Shore's device qualifies.

The delay for Lenire was because the FDA made them go do another clinical study before approval.

Shore's study is way more robust, US based, and created with the idea of FDA approval process in mind. I know nothing about nothing, but I'd be pretty surprised if they made her go through another clinical study before approval.

 

[gameover]

View attachment 56481

Am I being really thick here?

I can see that those treated first had sustained improvement that lasted well into the washout and control period. However, there is still no explanation for why those who got control first did not improve after washout with the treatment.

Can anyone explain?

Good question. Could it be that control/placebo (i.e. sound only) did something bad to brain that prevented real treatment (bimodal stimulation) from working effectively?

 

[RunningMan]

Good question. Could it be that control/placebo (i.e. sound only) did something bad to brain that prevented real treatment (bimodal stimulation) from working effectively?

And it's also odd that the two extra weeks made such a big difference from the first trial, where there was quick recovery:

 

[UKBloke]

Am I being really thick here?

Nope, you're not being thick. I was baffled by that chart the moment I saw it. Seeing it again only compounds that.

The control in Treatment 1 appears to be driven by placebo, but if the sham had zero therapeutic effect, then after the washout/crossover period, I would (under ideal conditions) have expected the dB/SL of those now receiving the proper treatment to notch down to around -5 dB by about week 16. Meandering off in the way it does is bizarre.

FWIW, I'm currently not only discounting the washout and crossover (something UMich have openly stated they've already done), I'm also discounting the control arm of Treatment 1 until I can make sense of that transition. What we have left is still encouraging I believe, even if expectations feel like they're shifting a bit.

 

[Fightthearmy]

Is it the case that around this time next month (end of Q1) we should be able to check the FDA's open database to see if the device has been submitted for approval?

This will not be submitted in Q1. Be sure to ask your dad to explain to you "marketing", "public relations", "hype", "spin".

 

[Jonno02]

Nope, you're not being thick. I was baffled by that chart the moment I saw it. Seeing it again only compounds that.

The control in Treatment 1 appears to be driven by placebo, but if the sham had zero therapeutic effect, then after the washout/crossover period, I would (under ideal conditions) have expected the dB/SL of those now receiving the proper treatment to notch down to around -5 dB by about week 16. Meandering off in the way it does is bizarre.

FWIW, I'm currently not only discounting the washout and crossover (something UMich have openly stated they've already done), I'm also discounting the control arm of Treatment 1 until I can make sense of that transition. What we have left is still encouraging I believe, even if expectations feel like they're shifting a bit.

Treatment 1 in Study 2 and Group 1 and 2 in Study 1 all agree. It looks like Treatment 2 in Study 2 are the outlier here with how little effect the active treatment seemed to have.

That's what still gives me hope.

 

[Nick47]

Treatment 1 in Study 2 and Group 1 and 2 in Study 1 all agree. It looks like Treatment 2 in Study 2 are the outlier here with how little effect the active treatment seemed to have.

That's what still gives me hope.

I agree we need to look at the overall picture for both studies. It's just that Dr. Shore never addressed this anomaly in the Q&A despite lots of us picking this up from the published study. We are talking 40-50 participants who had placebo, then a washout, and didn't improve in the treatment phase vs. 40-50 who improved (as a mean) if they had the treatment first.

 

[UKBloke]

It's just that Dr. Shore never addressed this anomaly in the Q&A despite lots of us picking this up from the published study.

It appears there was essentially two issues:

• Control in T1/S2 seems to adversely affect T2/S2
• Active T1/S2 seems to affect Control of T2/S2 after washout

I wonder whether there's a bit of manouevering going on. By only focussing on one of those issues, i.e. the effects of the active T1 lingering into control T2, could it be the team conveniently avoid having to discuss the strange control situation with the FDA?

Well, that's the cynic is me talking but like @Jonno02 has pointed out the helicopter view still looks hopeful regardless of what's going on behind the scenes.

 

[Daphne91]

This will not be submitted in Q1. Be sure to ask your dad to explain to you "marketing", "public relations", "hype", "spin".

Lol. Just going off what's stated at the end of this announcement from UMich where it was developed.

 

[Jonno02]

By only focussing on one of those issues, i.e. the effects of the active T1 lingering into control T2, could it be the team conveniently avoid having to discuss the strange control situation with the FDA?

 

[Fightthearmy]

Lol. Just going off what's stated at the end of this announcement from UMich where it was developed.

Yes, we are all aware of this announcement.

 

[Pixelito]

And, we can't assume, even though rationale may suggest, that longer use will give more reduction.

True, but isn't this assumption based directly on Dr. Shore's study?

More than 60% of participants reported significantly reduced tinnitus symptoms after the six weeks of active treatment, but not control treatment. This is consistent with an earlier study by Shore's team, which showed that the longer participants received active treatment, the greater the reduction in their tinnitus symptoms.

 

[ErikaS]

Lol. Just going off what's stated at the end of this announcement from UMich where it was developed.

I see you and your hope, @Daphne91. It's what keeps a lot of us going, even when it's minimal. Keep bringing that energy, no matter what someone's response is

 

[RunningMan]

More than 60% of participants reported significantly reduced tinnitus symptoms after the six weeks of active treatment, but not control treatment.

It was actually 53% of the full group of 99 participants, and that's before discounting that 20% of the placebo/control group had clinically significant reduction. So, subtracting for placebo/control, that gives you about 33% of the entire group that had clinically significant reduction in tinnitus as a result of the active bimodal treatment.

 

[AnthonyMcDonald]

It was actually 53% of the full group of 99 participants, and that's before discounting that 20% of the placebo/control group had clinically significant reduction. So, subtracting for placebo/control, that gives you about 33% of the entire group that had clinically significant reduction in tinnitus as a result of the active bimodal treatment.

You're introducing statistical bias by including the people who didn't follow protocol to a tee. We have to keep in mind most of the 99 were "normies" (many of them boomers, most likely) who probably didn't follow instructions perfectly, went to concerts, listened to headphones, didn't use the device in a controlled/silent environment.

 

[2noist]

You're introducing statistical bias by including the people who didn't follow protocol to a tee. We have to keep in mind most of the 99 were "normies" (many of them boomers, most likely) who probably didn't follow instructions perfectly, went to concerts, listened to headphones, didn't use the device in a controlled/silent environment.

The majority of them probably did follow instructions to a tee. Being given a chance at reducing your tinnitus by following protocol, I bet it's more likely you follow instructions than not.

I think you are trying to sugarcoat things by accusing trial participants of not following protocol, which you have no proof of (except for that one participant that Dr. Shore mentioned, I believe...)

 

[Jonno02]

It was actually 53% of the full group of 99 participants, and that's before discounting that 20% of the placebo/control group had clinically significant reduction. So, subtracting for placebo/control, that gives you about 33% of the entire group that had clinically significant reduction in tinnitus as a result of the active bimodal treatment.

33% success rate for a gen 1 device is still huge.

I don't think anybody here is expecting this to be a golden bullet. But if it works for 33% of people, not only does it show tinnitus is treatable, but there's a somewhat simple pathway that maybe needs further development to get that 33% up.

Tinnitus will no longer be a completely elusive beast that's exclusively 'treated' by talking about your feelings.

 

[AnthonyMcDonald]

Being given a chance at reducing your tinnitus by following protocol, I bet it's more likely you follow instructions than not.

I highly doubt that, considering 26 participants withdrew from the trial after being enrolled.

I think you are trying to sugarcoat things by accusing trial participants of not following protocol, which you have no proof of

You're joking, right? No offense, but have you even read the trial? Dr. Shore clearly states the existence of the per protocol (PP) population, who were the group supposedly following instruction to a tee (consisting of a total of 56 participants (30 + 26 = 56).

Based on this information, do you really think most of the people in the trial sat in sound isolation chambers at the same time every day to use the device? I highly doubt it. Not to mention, the "one participant" you mentioned worsened from going to a concert (seriously?).

The participants were obviously not as responsible as you give them credit to be. People lie about brushing their teeth to their dentists - what makes you think these trial participants are saints?

 

[Nick47]

So, subtracting for placebo/control, that gives you about 33% of the entire group that had clinically significant reduction in tinnitus as a result of the active bimodal treatment.

I think we have to look at all the data, including Phase 1. Put together and looking at the placebo like you said, it suggests somewhere between 30-40% are going to find this treatment very useful.

When you consider the tinnitus patient population worldwide, that's a lot of patients treated.

 

[Muggumbo]

You're introducing statistical bias by including the people who didn't follow protocol to a tee. We have to keep in mind most of the 99 were "normies" (many of them boomers, most likely) who probably didn't follow instructions perfectly, went to concerts, listened to headphones, didn't use the device in a controlled/silent environment.

Another thing we can be pretty sure of is that the 30-minute daily use was most likely so the study could be completed since most participants probably wouldn't be trusted to use it longer. If 2 additional weeks increased the effectiveness, then imagine what doubling the usage time to an hour or more would do.

 

[RunningMan]

You're introducing statistical bias by including the people who didn't follow protocol to a tee. We have to keep in mind most of the 99 were "normies" (many of them boomers, most likely) who probably didn't follow instructions perfectly, went to concerts, listened to headphones, didn't use the device in a controlled/silent environment.

The Per Protocol group excluded anyone whose tinnitus got worse and for other reasons, which makes the results of the Per Protocol look better and introduced statistical bias there. See diagram below:

However, if we look at the Per Protocol results only, 25% of the control/placebo group had clinically significant improvement, so if you subtract that 25% from the 65% of those receiving significant improvement from the active bimodal treatment, there's a net 40% who receive a real improvement from the active treatment.

So, perhaps somewhere between 33% to 40% will most likely receive a real non-placebo improvement due to bimodal treatment. Of course, the study was also restrictive in who they would let participate, so you would expect a lower success rate for the general public where many won't meet the same criteria that the study required.

33% success rate for a gen 1 device is still huge.

I don't think anybody here is expecting this to be a golden bullet. But if it works for 33% of people, not only does it show tinnitus is treatable, but there's a somewhat simple pathway that maybe needs further development to get that 33% up.

Tinnitus will no longer be a completely elusive beast that's exclusively 'treated' by talking about your feelings.

33% receiving a noticeable decrease in tinnitus is definitely a good thing for those people who will benefit, but my post was in the response to the "over 60%" post, which seems overly optimistic based on the full study results (prior to crossover) for the participants who met the qualifications to participate.

I think we have to look at all the data, including Phase 1. Put together and looking at the placebo like you said, it suggests somewhere between 30-40% are going to find this treatment very useful.

When you consider the tinnitus patient population worldwide, that's a lot of patients treated.

Yes, that range seems like a very reasonable expectation.