Frequency Therapeutics — Hearing Loss Regeneration

Discussion in 'Research News' started by RB2014, Dec 8, 2016.

    1. Kleiner

      Kleiner Member

      Tinnitus Since:
      08/2020
      Cause of Tinnitus:
      Sound trauma
      This is the problem:

      This single dose study didn't have a placebo control. But the results were no better than the placebos in Phase 2a.

      I repeat: 33% improvement to 10% or more is no better than placebo. They have no way of knowing if this improvement is due to the FX-322 or the placebo.

      These results are in the field of the placebo.
       
      • Agree Agree x 1
    2. ThomasRobert

      ThomasRobert Member Benefactor

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      You cannot take or compare anything from Phase 2a.

      Phase 2a does not have a verified baseline from anyone, so please stop considering Phase 2a with anything.

      Phase 2a is just a complete garbage. If you don't have verified baseline from either placebo or candidates who took the drug, then it's just zero value.

      As for the open label of moderate (not placebo-controlled) Phase 1, all the candidates know they are getting the drug so they have less bias/incentive to lie in hopes of getting it.

      So in this open label, they claim many got good results...
       
      • Agree Agree x 3
      • Like Like x 1
    3. Lucifer

      Lucifer Member Podcast Patron Benefactor Hall of Fame

      Location:
      Clown World
      Tinnitus Since:
      -
      Cause of Tinnitus:
      -
      If Phase 1 wasn’t a fluke and those patients did have improvements in audiograms and word scores, then I expect the Phase 2 repeat should be the same with only single dosing of FX-322.
       
      • Agree Agree x 2
    4. ThomasRobert

      ThomasRobert Member Benefactor

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      Yes, those patients had improvement in word scores only.

      With current formulation and delivery method no audiogram improvement was ever recorded till date.

      In future studies, Frequency Therapeutics wants to try multiple doses far away from each other to see if it provides better results in terms of word recognition and audiogram.
       
    5. incelitus
      Question it

      incelitus Member

      Tinnitus Since:
      2017
      Cause of Tinnitus:
      qtip gangbang/kurt cobain
      All that hope for this shit.

      What a f*cking disappointment.
       
      • Agree Agree x 5
      • Like Like x 1
    6. ThomasRobert

      ThomasRobert Member Benefactor

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      I feel not everyone is understanding what's happening, here is an example:

      Michael and Laura are desperate to get FX-322, so they both apply for the Phase 2a trials:

      1.JPG

      Michael in reality can hear 30 words out of 50, but as he is desperate, he fakes his initial screening to get into the trial by telling the doctor he can only hear 15 words out of 50.

      Laura in reality can hear 35 words out of 50, but tells the doctor she can only hear 20 out of 50:

      2.JPG

      The doctor is happy he found good candidates for the trial. He gives Michael the placebo, and Laura gets the drug (FX-322):

      3.JPG

      After the trial is completed, the doctor gets the results:

      4.JPG

      The doctor saw that Laura improved! She used to hear 20 words out of 50 and now after getting the drug, she can hear 35 words out of 50! The doctor is happy!

      Michael was never given the drug but also improved? Michael now hears 30 words out of 50.

      So what does the doctor do now?

      He basically just claims that Michael was a bias... and he is happy that Laura improved! :)

      Are you guys getting the point?

      Michael and Laura never improved, their real scores stayed the same the whole time.
       
      • Like x 2
      • Hug x 2
      • Agree x 1
      • Informative x 1
      • Creative x 1
    7. Exit

      Exit Member Benefactor

      Tinnitus Since:
      01/2020
      Cause of Tinnitus:
      Noise
      Thomas... are you okay...? :)

      I think you need a chill pill :D
       
      • Agree Agree x 2
      • Funny Funny x 1
    8. Piney

      Piney Member

      Tinnitus Since:
      March 2018
      Cause of Tinnitus:
      Shingles virus
      That’s an excellent example, but let me demonstrate why I complain about this criteria to get accepted into the trial.

      To enter the trial, you needed 4 or 8 words out of 20 or 30.

      This is a different scenario. You can’t fake the words unless you get extremely lucky. You have to repeat the word back, not just say you heard it.

      If I heard 1 word, I could’ve been given the drug or the placebo. If I heard 2 words next week (repeated back), you’d have your answer whether it does something or not with future testing in the following weeks.

      If I heard 0 words, it would be the same scenario, so it doesn’t make sense to have these limitations unless they feel there’s not enough hearing for the drug to do anything. I’d still be willing to give it a shot.

      Let me point that out again for those who complain patients falsified the trial, you have to repeat the word back and get the word correct to enter the trial.
       
      • Hug Hug x 1
    9. Willlly

      Willlly Member

      Tinnitus Since:
      03/2019
      Cause of Tinnitus:
      Noise Induced
      Ok, that's the pessimistic view. In reality Laura may have improved to now hear 40 words.

      But because Michael "improved" with placebo there is no statistically significant improvement with the drug.

      There is no point trying to read into the numbers because we don't know who was faking or not in both groups.

      The saving grace is that all groups that received the drug saw some benefit in their word scores. Imagine if there was no benefit from the drug but there was from placebo. In that case FX-322 would be dead.
       
      • Agree Agree x 1
      • Hug Hug x 1
    10. GlennS

      GlennS Member Podcast Patron Hall of Fame

      Tinnitus Since:
      1992
      Cause of Tinnitus:
      Loud music
      giphy.gif
       
      • Like Like x 1
    11. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      1-2019
      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools

      giphy.gif

      Screen Shot 2021-05-25 at 3.44.53 PM.png
       
      • Like Like x 2
      • Funny Funny x 1
    12. Zugzug

      Zugzug Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      Autoimmune hyperacusis from Sjogren's Syndrome
      Here's where I agree and disagree with you:

      I disagree with you that current evidence (2 successful single-dose studies, failed ARHL trial, and failed multi-dose trial) suggests that the drug surely does absolutely nothing at all for clarity. Obviously, I'm critical of the open-label study because it's not placebo controlled; I'm critical of the Phase 1/2 study because the treatment group had a huge advantage due to (by chance) being far less prone to the ceiling effect, as well as the fact that there weren't lead-in baseline WR scores, although the incentive was far less for that trial. Nonetheless, the evidence of the drug helping clarity at the single-dose level is unclear, but certainly not nothing.

      Where I agree with you is that the company is, in some ways, using the terrible Phase 2a trial design to gloss over the fact that multi-dose truly failed epically. Granted, they do admit that multi-dose failed and that four injections in weekly time intervals created a damaging environment. They do admit that it just didn't work.

      However, from my perspective, there is sort of a vibe of like:

      "Multi-dosing kind of failed, but we really messed up the trial. Can you believe that a patient in the placebo group said 'not sure' 22 times at the baseline and only 3 times at day 90?! How horrible! But ultimately it's our fault due to trial design and not accounting for this bias. Ah, it's all so confusing. Multi-dosing kind of failed, there were cheaters, but it's our fault."

      The multi-dosing simply failed. Actually, it's sort of fortunate that they made that mistake in the trial where the multi-dosing would have failed anyways because: (a) They can learn better for next time and (b) they get to muddy the waters a bit.

      With all of this being said, I definitely think there were real super responders in Phase 1/2 at the single dose level. This drug isn't dead -- we shouldn't give up on it. It's okay to admit that the drug needs a lot of work. But something is going on in vivo for some patients, which is a wonderful thing.
       
    13. Gb3

      Gb3 Member

      Tinnitus Since:
      12/19
      Cause of Tinnitus:
      Sshl
      @ThomasRobert, bruh you need to chill out. Have you ever done a word recognition test? You can’t just say you didn’t hear the word. I think it would be very easy to tell if someone was making the words up. There would be a lot of hesitation.
       
    14. ThomasRobert

      ThomasRobert Member Benefactor

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      Sorry to break it down for you but 10 dB Improvement is not an accurate measurement. 10 dB is not a tangible gap.

      30 dB and above can be considered as an improvement bearing in mind how these tests are being measured...
       
      • Like Like x 1
      • Winner Winner x 1
    15. ThomasRobert

      ThomasRobert Member Benefactor

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      Sorry but the Phase 1/2 was done before fixing the bias glitch, so we can consider this study as bias also...

      For me, the severe trial will give us a FINAL conclusion about this whole thing...
       
    16. ThomasRobert

      ThomasRobert Member Benefactor

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      You can just say not sure...

      OTC HIS Program: Word Recognition Testing
       
    17. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      1-2019
      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools
      Source?
       
    18. Tanni
      Provocative

      Tanni Member Benefactor

      Tinnitus Since:
      October 2017
      Cause of Tinnitus:
      ???
      It's easy to fake a word recognition test.

      And isn't that the basis for why many here think the trial failed? Because people faked the test to get in?

      The part I find confusing is: if you believe audiogram improvements are not necessary to demonstrate improvement in hearing, and WR tests can be faked, I'm not sure what measurement can be used to demonstrate drug effectiveness. Which means the trial will always either fail (because of audiograms) or be 'fake-able' (because of WR).
       
    19. Zugzug

      Zugzug Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      Autoimmune hyperacusis from Sjogren's Syndrome
      I wish this was the case (as it's obviously a no-brainer), but sadly, Frequency Therapeutics was dumb enough to let people refuse to guess. It's almost a joke how much they mismanaged the trial design.

      Evidence:

      upload_2021-7-8_15-23-50.png
       
      • Agree Agree x 1
    20. aorelia

      aorelia Member

      Tinnitus Since:
      2021
      Cause of Tinnitus:
      Headphones
      Hmm, so people believe FX-322 is a failure for people with little to no hearing loss and high frequency tinnitus?
       
    21. ThomasRobert

      ThomasRobert Member Benefactor

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      • Like Like x 1
    22. GlennS

      GlennS Member Podcast Patron Hall of Fame

      Tinnitus Since:
      1992
      Cause of Tinnitus:
      Loud music
      We need consistent and repeatable results, folks. It ain't there yet.
       
      • Agree Agree x 2
    23. EDDTEKK

      EDDTEKK Member

      Location:
      Belgium
      Tinnitus Since:
      1999
      Cause of Tinnitus:
      Infection
      Did the trials fail? Sorry, I didn’t read the whole thread.

      This thread was the highlight of Tinnitus Talk. FX-322 is yet another failure like Lenire?
       
      • Good Question Good Question x 1
    24. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      1-2019
      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools
      • Agree Agree x 1
      • Creative Creative x 1
    25. Zugzug

      Zugzug Member Podcast Patron Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      05/2019
      Cause of Tinnitus:
      Autoimmune hyperacusis from Sjogren's Syndrome
      Sadly, you are right that because there is no objective test for clarity, we have to resort to these subjective WR tests where we have to trust that the person is answering correctly. However, with this understood, a well-run trial will lean on the side of the "lesser of two evils." Let me explain.

      If you have a lead-in WR screen, they are basically taking your (documented in medical records) score from > 6 months ago, comparing it to your screening score, and confirming that they are pretty close. In other words, the person seems legit.

      Technically speaking, the person could still provide a dishonest screening score (intentionally screwing up a few words so that they score about the same as >6 months ago). However, the reason why this is not so bad is because the actual baseline data point will not have any incentive to be altered. Patients don't get kicked out once they're in. So for example, worst case scenario, Frequency Therapeutics would think they are recruiting someone with around 25/50 WR, but their true score is really like 30. They take the actual baseline test and score 30. It's not the ideal patient they wanted, but it's accurate. Then at follow-ups when they keep tracking the data, the person continues to lack incentive to take the tests dishonestly. It's the lesser of two evils.

      The alternative is what they did (much worse), which is to incentivize people to have low WR to get in and then use that same score as the baseline score. In other words, a legit data point was tainted by incentive.

      If in the next trial, they prioritize precision between scores from > 6 months ago and at screen, they should, at the very least, get accurate data, even if here and there they lose out on the ideal patient.

      With regards to outer hair cells and audiograms, they hired Jeffery Lichtenhan in order to use better audiometric tests. One of these tests is the OAE test, which is an objective measure of outer hair cell activity.

      They have plenty of information to put together a well-run Phase 2 repeat, but we may have to be prepared to be patient as they try to get this right.
       
      • Informative Informative x 1
      • Useful Useful x 1
    26. ThomasRobert

      ThomasRobert Member Benefactor

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      “Manual pure tone audiometry is considered to be the gold standard for the assessment of hearing thresholds and has been in consistent use for a long period of time. An increased legislative requirement to monitor and screen workers, and an increasing amount of legislation relating to hearing loss is putting greater reliance on this as a tool. There are a number of questions regarding the degree of accuracy of pure tone audiometry when undertaken in field conditions, particularly relating to the difference in conditions between laboratory calibration and clinical or industrial screening use.”

      “having a maximum deviation of around ±10 dB ... that there is a significant margin of error in audiometric screening.“

      https://www.noiseandhealth.org/arti...16;issue=72;spage=299;epage=305;aulast=Barlow
       
    27. Diesel

      Diesel Member Benefactor Ambassador Hall of Fame Advocate

      Tinnitus Since:
      1-2019
      Cause of Tinnitus:
      20+ Years of Live Music, Motorcycles, and Power Tools
      Now you're getting the hang of it.

      I'd like to quote your quote here.

      "There are a number of questions regarding the degree of accuracy of pure tone audiometry when undertaken in field conditions, particularly relating to the difference in conditions between laboratory calibration and clinical or industrial screening use."​

      Why again are we fixated on Audiograms here? It seems like Audiograms suck equally as much as Word Score. Maybe WIN is better only because it seems to test both IHC and OHC performance?
       
    28. UHPTS
      Wishful

      UHPTS Member

      Tinnitus Since:
      October 2019
      Cause of Tinnitus:
      Ear infection
      10 dB is about 1/6th of the volume slider on your computer. You can check for yourself what difference 10 dB makes.
       
      • Hug Hug x 1
    29. ThomasRobert

      ThomasRobert Member Benefactor

      Location:
      ME
      Tinnitus Since:
      06/2019
      Cause of Tinnitus:
      Ototoxic
      If you jump to the conclusion section, it will be scarier:

      “Even the median variation in sound pressure at the ear could contribute an error of 4 dB in hearing threshold values, which is sufficient to cause misdiagnosis on an audiogram. Where the degree of variation is at its highest, there is a potential error of 20 dB, which even in a single frequency band could lead to the misdiagnosis of a patient due to its contribution to the values used to categorize hearing loss.”​

      My point earlier was that the 10 dB improvement is not an accurate measurement. That's all.
       
      • Agree Agree x 1
    30. Piney

      Piney Member

      Tinnitus Since:
      March 2018
      Cause of Tinnitus:
      Shingles virus
      While you're in the booth, they purposely do not reveal how many words you need to enter the trial. You don't know if it's 1 or 50. How are you faking that to get in?
      Patients were not aware which ear was going to be treated: I'm deaf in one ear, what ear do I think I'm going to get the shot in? This is all rubbish.
       
Loading...

Share This Page