I've been in contact with Autifony and here is what they've told me so far:
(if anybody here has any good questions or worthwhile suggestions for Autifony, I'll be glad to forward and could act as official TT liason to Autifony )
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We do certainly wish to put subjects on study who are bothered by their tinnitus. Were they not to be bothered by it we don't believe they would enroll in the study when they see all the time they would have to commit, and neither would we anticipate significant change on the TFI score - the primary endpoint!
Key point is that we have no prior knowledge of CNS drug interactions (except the laboratory tests that we have carried out) and any subject taking "heavyweight" CNS drugs will be excluded; they may become more sedated or fatigued. If they maybe need a low dose of, for example, a tricyclic at night would be OK but subjects who need significant antidepressants will not be OK for this first study. Obviously if they are not bothered by it then they will not fulfill the TFI entry criteria. Later on when we have more experience of CNS drug interactions then we hope that things will open up for a wider range of co-medications as well as other CNS pathologies.
We believe that the key to getting an answer in this study is to manage out heterogeneity. We shall be doing this in a variety of ways including stratifying for various parameters on study entry and balancing these across drug and placebo. One stratification variable is the severity of the tinnitus as measured by the TFI. All the experts, as well as the statistician, advised that we should NOT include all severeties of tinnitus but should instead have two (arbitrary) levels, mild to moderate (TFI 24-35) and moderate to severe (36-68). This we have done. They likened this to testing, for example, an antihypertensive where it is usual to start with less severe disease and work up as we build the knowledge, confirm the dosage levels etc etc.
- the second answer is that the experts advised that subject experiencing tinnitus severity >68 on the TFI score are almost "always" using something else to cope with their disturbed lives - usually antidepressants along with various pieces of equipment. This would likely render them subject to exclusion criteria. I realise that this is not totally categoric but we decided to draw the line as in the heterogeneity argument above.
I hope this seems clear even though it is a pragmatic way forward in an area of ignorance over exactly how best to test the medication. We did consider only mild, or only moderate tinnitus, only age-related, only noise-induced etc etc and we let the experts guide us here. We shall next year be looking at working up a study, for example with the military, evaluating 063 in noise-induced tinnitus with virtually no hearing loss but severe tinnitus…..again all under careful consideration. We are also talking next month with the the two largest VA centres in the US about possible work with them.
I value all your interest as well as feedback and ideas!
Many thanks and regards.
(if anybody here has any good questions or worthwhile suggestions for Autifony, I'll be glad to forward and could act as official TT liason to Autifony )
____
We do certainly wish to put subjects on study who are bothered by their tinnitus. Were they not to be bothered by it we don't believe they would enroll in the study when they see all the time they would have to commit, and neither would we anticipate significant change on the TFI score - the primary endpoint!
Key point is that we have no prior knowledge of CNS drug interactions (except the laboratory tests that we have carried out) and any subject taking "heavyweight" CNS drugs will be excluded; they may become more sedated or fatigued. If they maybe need a low dose of, for example, a tricyclic at night would be OK but subjects who need significant antidepressants will not be OK for this first study. Obviously if they are not bothered by it then they will not fulfill the TFI entry criteria. Later on when we have more experience of CNS drug interactions then we hope that things will open up for a wider range of co-medications as well as other CNS pathologies.
We believe that the key to getting an answer in this study is to manage out heterogeneity. We shall be doing this in a variety of ways including stratifying for various parameters on study entry and balancing these across drug and placebo. One stratification variable is the severity of the tinnitus as measured by the TFI. All the experts, as well as the statistician, advised that we should NOT include all severeties of tinnitus but should instead have two (arbitrary) levels, mild to moderate (TFI 24-35) and moderate to severe (36-68). This we have done. They likened this to testing, for example, an antihypertensive where it is usual to start with less severe disease and work up as we build the knowledge, confirm the dosage levels etc etc.
- the second answer is that the experts advised that subject experiencing tinnitus severity >68 on the TFI score are almost "always" using something else to cope with their disturbed lives - usually antidepressants along with various pieces of equipment. This would likely render them subject to exclusion criteria. I realise that this is not totally categoric but we decided to draw the line as in the heterogeneity argument above.
I hope this seems clear even though it is a pragmatic way forward in an area of ignorance over exactly how best to test the medication. We did consider only mild, or only moderate tinnitus, only age-related, only noise-induced etc etc and we let the experts guide us here. We shall next year be looking at working up a study, for example with the military, evaluating 063 in noise-induced tinnitus with virtually no hearing loss but severe tinnitus…..again all under careful consideration. We are also talking next month with the the two largest VA centres in the US about possible work with them.
I value all your interest as well as feedback and ideas!
Many thanks and regards.
x 1000000000000000000000000000 doesn't even begin to express my ffrustration
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