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Post by agedhippie on Jul 11, 2024 16:06:49 GMT -5
... MNKD needs to figure out what they are going to do with those in the study who are not properly dosing. Why are they not properly dosing? Can they be put in a separate category so we only count those that properly dosed? With the CGMs they could not hide the fact they were not following dosing protocol. We heard it from some of the presenters. If their numbers can be removed from the overall A1c average - afrezza wins and will be superior. I say we will have to wait until after October to see how Mike and team addresses this. Trials are trials, you don't get to cherry pick just the results you want. Compliance, especially second doses, has always been a problem for Afrezza and we saw that clearly in STAT-1 trial results. While it is possible in subsequent papers to split out the compliant and non-compliant members (as in the STAT-1 paper) but you cannot do that in the trial itself because you would never get the protocol approved. The trial is meant to mirror real life and real patients so you are stuck with what you have. |
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Post by sayhey24 on Jul 11, 2024 16:25:22 GMT -5
... MNKD needs to figure out what they are going to do with those in the study who are not properly dosing. Why are they not properly dosing? Can they be put in a separate category so we only count those that properly dosed? With the CGMs they could not hide the fact they were not following dosing protocol. We heard it from some of the presenters. If their numbers can be removed from the overall A1c average - afrezza wins and will be superior. I say we will have to wait until after October to see how Mike and team addresses this. Trials are trials, you don't get to cherry pick just the results you want. Compliance, especially second doses, has always been a problem for Afrezza and we saw that clearly in STAT-1 trial results. While it is possible in subsequent papers to split out the compliant and non-compliant members (as in the STAT-1 paper) but you cannot do that in the trial itself because you would never get the protocol approved. The trial is meant to mirror real life and real patients so you are stuck with what you have. If they are not following the study protocol I would think you could not count their numbers. The were non-compliant. Before CGM reports it was not possible but now we know when they dosed and when they did not. What we don't know is why they did not follow protocol. We do know we have some presenters saying these people did not follow protocol. Adding results of people who for whatever reason intentionally did not follow the protocol would be improperly representing the study. Removing their numbers would make all the sense in the world. Since widespread CGM adoption, I have never really heard of anyone complaining about follow-up dosing afrezza. I have never heard it to be a problem. I have heard many people saying they were never told to follow-up dose. In Stat-1 afrezza kicked ass with post prandial results but dosing before bed was not part of the protocol. |
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Post by ktim on Jul 11, 2024 17:49:35 GMT -5
sayhey24 Think a bit about what you are proposing. Let's say there is a drug on the market that requires one to inject it every hour on the hour for best efficacy. A new drug is developed that allows one to take a pill once in the morning. Unless this is a deadly disease, the drug requiring an hourly injection is going to have compliance problems. People in their real lives are undoubtedly going to skip or inadvertently miss doses... or simply not time them exactly right (oops, I should have injected this 20 min ago). Should it be tracked and anyone missing or mistiming a dose thrown out of a head to head study, or should the new drug be able to claim superiority partly on the fact that in real life people will be far more likely to dose it properly. If protocols were to throw out those missing an hourly injection, the new drug, that in the real world might produce better outcomes, could be labeled "non inferior" and thus not covered by insurance. Properly designed trials should inform patients about the best way of using each drug, but the results are going to be based on how the participants actually use the product. As aged states, nothing prevents data to be split out and published to help doctors best utilize a drug... e.g. for Afrezza a doctor might want to emphasize that follow up doses are really important for best results, and perhaps even deciding Afrezza isn't suitable for a patient that then says that's too much of a hassle and they are unlikely to regularly do follow up dosing. But for things like determining whether a drug is safe and effective, it's important to look at how large groups of real people (none of whom are flawless) use the product at home without having a compliance officer looking over their shoulder... unless of course having compliance tracked and intervened is part of the proposed drug usage protocol, but then the FDA would need to include such tracking and intervention in the prescription requirements.
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Post by prcgorman2 on Jul 11, 2024 17:58:12 GMT -5
From what I’ve read, compliance is a huge problem but it isn’t unique to Afrezza or diabetes.
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Post by agedhippie on Jul 11, 2024 19:22:18 GMT -5
From what I’ve read, compliance is a huge problem but it isn’t unique to Afrezza or diabetes. Compliance is a problem with every drugs. Sometime listen to doctors complaining about patients and blood pressure drugs... |
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Post by agedhippie on Jul 11, 2024 19:43:40 GMT -5
If they are not following the study protocol I would think you could not count their numbers. The were non-compliant. Before CGM reports it was not possible but now we know when they dosed and when they did not. What we don't know is why they did not follow protocol. We do know we have some presenters saying these people did not follow protocol. Adding results of people who for whatever reason intentionally did not follow the protocol would be improperly representing the study. Removing their numbers would make all the sense in the world. Since widespread CGM adoption, I have never really heard of anyone complaining about follow-up dosing afrezza. I have never heard it to be a problem. I have heard many people saying they were never told to follow-up dose. In Stat-1 afrezza kicked ass with post prandial results but dosing before bed was not part of the protocol. They do follow protocol, they don't follow it perfectly. Notice that the panel were in no way surprised that there was variability in how well people followed protocol. You can complain about this as much as you want, but when the results came out everyone will be in it and those will be the results the endos care about. If nobody is complaining about follow up dosing with Afrezza there shouldn't be a problem, and yet here we are.... Everyone will have been told to take follow up doses, they even tell RAA users to take follow up doses, likewise insulin at bed time (which I do every day). The fact that so few people do is a compliance problem, not ignorance. |
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Post by sayhey24 on Jul 12, 2024 7:52:48 GMT -5
If they are not following the study protocol I would think you could not count their numbers. The were non-compliant. Before CGM reports it was not possible but now we know when they dosed and when they did not. What we don't know is why they did not follow protocol. We do know we have some presenters saying these people did not follow protocol. Adding results of people who for whatever reason intentionally did not follow the protocol would be improperly representing the study. Removing their numbers would make all the sense in the world. Since widespread CGM adoption, I have never really heard of anyone complaining about follow-up dosing afrezza. I have never heard it to be a problem. I have heard many people saying they were never told to follow-up dose. In Stat-1 afrezza kicked ass with post prandial results but dosing before bed was not part of the protocol. They do follow protocol, they don't follow it perfectly. Notice that the panel were in no way surprised that there was variability in how well people followed protocol. You can complain about this as much as you want, but when the results came out everyone will be in it and those will be the results the endos care about. If nobody is complaining about follow up dosing with Afrezza there shouldn't be a problem, and yet here we are.... Everyone will have been told to take follow up doses, they even tell RAA users to take follow up doses, likewise insulin at bed time (which I do every day). The fact that so few people do is a compliance problem, not ignorance. No - they are not following the protocol. If dosing before bed is a protocol requirement and they are not doing it - they are non-compliant. Why they are not doing it Mike needs to get his people to nail down and figure out a plan. In in old days pre-CGM we would not have know. Now we do. There is no hiding from CGM numbers and afrezza dosing on the CGM. |
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Post by prcgorman2 on Jul 12, 2024 7:54:53 GMT -5
A plan to make people remember better or feel like doing something they don’t feel like doing? Pay them!
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Post by sayhey24 on Jul 12, 2024 8:00:10 GMT -5
sayhey24 Think a bit about what you are proposing. Let's say there is a drug on the market that requires one to inject it every hour on the hour for best efficacy. A new drug is developed that allows one to take a pill once in the morning. Unless this is a deadly disease, the drug requiring an hourly injection is going to have compliance problems. People in their real lives are undoubtedly going to skip or inadvertently miss doses... or simply not time them exactly right (oops, I should have injected this 20 min ago). Should it be tracked and anyone missing or mistiming a dose thrown out of a head to head study, or should the new drug be able to claim superiority partly on the fact that in real life people will be far more likely to dose it properly. If protocols were to throw out those missing an hourly injection, the new drug, that in the real world might produce better outcomes, could be labeled "non inferior" and thus not covered by insurance. Properly designed trials should inform patients about the best way of using each drug, but the results are going to be based on how the participants actually use the product. As aged states, nothing prevents data to be split out and published to help doctors best utilize a drug... e.g. for Afrezza a doctor might want to emphasize that follow up doses are really important for best results, and perhaps even deciding Afrezza isn't suitable for a patient that then says that's too much of a hassle and they are unlikely to regularly do follow up dosing. But for things like determining whether a drug is safe and effective, it's important to look at how large groups of real people (none of whom are flawless) use the product at home without having a compliance officer looking over their shoulder... unless of course having compliance tracked and intervened is part of the proposed drug usage protocol, but then the FDA would need to include such tracking and intervention in the prescription requirements. This is a study with a specific protocol. One of the requirements was dosing before bed. Some people are not doing that which significantly changes their A1c. In daily life it is what it is but this study is to determine if when using a specific protocol afrezza is as good/better than MDI/AID. What we see is when the protocol is followed afrezza wins and wins by a lot. When we add in people not following a major step in the protocol afrezza average down to non-inferior. Do you see the difference? A major step is not being followed. For the study result we need superiority an need to throw out the numbers of non-compliant participants. What would the AID results look like if these PWDs turned their AID off before going to bed? That is what is effectively being done by not afrezza dosing. Before the CGM reports we would have had no idea this was being done. |
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Post by sayhey24 on Jul 12, 2024 8:02:17 GMT -5
A plan to make people remember better or feel like doing something they don’t feel like doing? Pay them! I would not be surprised if they were not already getting paid to not dose before bed and not by MNKD. Do you think BP wants afrezza to show superiority? |
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Post by agedhippie on Jul 12, 2024 8:30:23 GMT -5
A plan to make people remember better or feel like doing something they don’t feel like doing? Pay them! Some trials you get paid to participate, I don't know if this is one. All of them you get free supplies for the trial so insulin, CGMs, etc. are covered for free. |
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Post by agedhippie on Jul 12, 2024 8:39:49 GMT -5
... In daily life it is what it is but this study is to determine if when using a specific protocol afrezza is as good/better than MDI/AID. What we see is when the protocol is followed afrezza wins and wins by a lot. When we add in people not following a major step in the protocol afrezza average down to non-inferior. ... Welcome to the world of clinical trials. You might not like it but this is how trials are run and the results will be based on this and not an idealized world. |
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Post by sayhey24 on Jul 12, 2024 9:18:50 GMT -5
... In daily life it is what it is but this study is to determine if when using a specific protocol afrezza is as good/better than MDI/AID. What we see is when the protocol is followed afrezza wins and wins by a lot. When we add in people not following a major step in the protocol afrezza average down to non-inferior. ... Welcome to the world of clinical trials. You might not like it but this is how trials are run and the results will be based on this and not an idealized world. Yes, I hear you. But, that is the way it use to be. Its the best we could do in the past. In fact I think 5 or so years ago I suggested CGMs should be used during these trials and you told me thats not the way these trials are run. You see things change over time and we can improve on past practice. We can now show proof positive these people were non-compliant. Before CGMs there would have been no way to tell. What if the doctors at the testing center told the AID people to turn off their AID at bedtime? How should we handle this? Do you see what you are saying? We should just accept this as the world of clinical trials? |
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Post by hellodolly on Jul 12, 2024 9:25:55 GMT -5
A plan to make people remember better or feel like doing something they don’t feel like doing? Pay them!
Do you think BP wants afrezza to show superiority? I know HIPPA would apply here but, you suspect BP got to the clinicians, too. If so, they would have to divulge patient names, addresses, telephone numbers, etc. and bank records would exist for payments, and so much more incriminating evidence. Call me skeptical but, I'm "skeptical" that BP, directly or indirectly, could/would influence enough patients, or practitioners in such a large trial (without tipping off some questionable conduct that rubbed someone wrong) in so far they wouldn't blow the lid off this? |
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Post by uvula on Jul 12, 2024 9:48:45 GMT -5
Sayhey, when you say "But, that is the way it use to be" you are ignoring the reality that THIS IS STILL THE WAY IT IS. It doesn't matter how we feel or how it should be.
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