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Post by mnholdem on Jan 13, 2018 14:49:40 GMT -5
If I recall correctly, mango touched on a big part of the answer last year when he posted the names of several physicians who are paid $millions by BP for research paper publication. In this industry that's what it seems to take in order to have Afrezza make it into the major medical journals. Frankly, MannKind hasn't be able to invest the multiple $millions that global pharmaceutical companies pay to these researchers and KOLs. Incidently, many of the doctors who are responsible for publishing the ADA Diabetes Standards of Care have been recipients of these $millions and are not likely to bite the hand that feeds, IMO.
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Post by agedhippie on Jan 13, 2018 15:22:39 GMT -5
Merck aquired SmartCells, Inc. in 2010 to pursue a "smart insulin" or glucose-responsive insulin and they completed a three part clinical trial back in 2016 that involved only 74 participants. No study results have been published since the trial's completion. It obviously was a flunk. Others have developed adhesive "micro-needle" patches that have over 100 needles on them that are suppose to be responsive to blood glucose levels, one in particular uses glucose-sensing enzymes. On the other hand, we have Afrezza which is non-invasive and mimics the endogenous secretion of prandial insulin like that of a healthy, non-diabetic pancreas and restores the first-phase insulin response that is loss in PWD, which also in turn restores glucose homeostasis. Can't get any better than that my friend. 😉 And there you have it Mango! It can't get any better than that! So why is it that BP and the rest of the medical community still fail to see the obvious and apparent benefits of Afrezza? Afrezza should be what every Endo and Diabetic are talking about. And here we sit, under .50 pre split. A brutal beating! Why is it that BP and the rest of the medical community still fail to see the obvious and apparent benefits of Afrezza? The simple answer is that there is no trial data to support those assertions and for that reason the reps cannot use them. If there was trial data then the claims could be reflected on the label, the reps could use it, and doctors would listen.
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Post by mango on Jan 13, 2018 16:24:43 GMT -5
And there you have it Mango! It can't get any better than that! So why is it that BP and the rest of the medical community still fail to see the obvious and apparent benefits of Afrezza? Afrezza should be what every Endo and Diabetic are talking about. And here we sit, under .50 pre split. A brutal beating! Why is it that BP and the rest of the medical community still fail to see the obvious and apparent benefits of Afrezza? The simple answer is that there is no trial data to support those assertions and for that reason the reps cannot use them. If there was trial data then the claims could be reflected on the label, the reps could use it, and doctors would listen. Are you implying that Endocrinologists only get their medication information from pharmaceutical reps and do not do any independent research and/or reading of their own? If they did, then they too would know these things. A clinical trial does not have to be conducted for one to know that Afrezza mimics the first-phase insulin response. The first-phase insulin response and Afrezza's kinetics are both well published and the fact that Afrezza does indeed mimic the endogenous first-phase insulin response is also published. Peak serum insulin concentration is reached in less than 15 minutes with Afrezza, and that is what the natural physiologic time requirement is in order for the first-phase response to successfully occur. A clinical trial for these is not warranted. The facts are already there and published.
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Post by dreamboatcruise on Jan 13, 2018 17:11:47 GMT -5
Merck aquired SmartCells, Inc. in 2010 to pursue a "smart insulin" or glucose-responsive insulin and they completed a three part clinical trial back in 2016 that involved only 74 participants. No study results have been published since the trial's completion. It obviously was a flunk. Others have developed adhesive "micro-needle" patches that have over 100 needles on them that are suppose to be responsive to blood glucose levels, one in particular uses glucose-sensing enzymes. On the other hand, we have Afrezza which is non-invasive and mimics the endogenous secretion of prandial insulin like that of a healthy, non-diabetic pancreas and restores the first-phase insulin response that is loss in PWD, which also in turn restores glucose homeostasis. Can't get any better than that my friend. 😉 And there you have it Mango! It can't get any better than that! So why is it that BP and the rest of the medical community still fail to see the obvious and apparent benefits of Afrezza? Afrezza should be what every Endo and Diabetic are talking about. And here we sit, under .50 pre split. A brutal beating! Simple... need clinical trial data showing the benefits.
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Post by agedhippie on Jan 13, 2018 18:08:37 GMT -5
Why is it that BP and the rest of the medical community still fail to see the obvious and apparent benefits of Afrezza? The simple answer is that there is no trial data to support those assertions and for that reason the reps cannot use them. If there was trial data then the claims could be reflected on the label, the reps could use it, and doctors would listen. Are you implying that Endocrinologists only get their medication information from pharmaceutical reps and do not do any independent research and/or reading of their own? If they did, then they too would know these things. A clinical trial does not have to be conducted for one to know that Afrezza mimics the first-phase insulin response. The first-phase insulin response and Afrezza's kinetics are both well published and the fact that Afrezza does indeed mimic the endogenous first-phase insulin response is also published. Peak serum insulin concentration is reached in less than 15 minutes with Afrezza, and that is what the natural physiologic time requirement is in order for the first-phase response to successfully occur. A clinical trial for these is not warranted. The facts are already there and published. Do doctors largely get their medical information from reps? Exclusively - no, are they a source - yes. If they aren't we are wasting a lot of money having a sales force. Do they read articles on their own - the ones I know do. Then we get to the assertions you are making. If you want to be taken seriously then you need to have data to back the assertions that is gathered in a clear and transparent way. That is the whole reason for trials, and why the standards of care assign such weight to them. Does Afrezza mimic the first phase response? Superficially it looks like it, but does it really is a question you need scientific evidence to support and a hunch is not good enough. Does the fact that peak serum levels are reached in less than 15 minutes provide a sufficient copy of the first phase response or are there other components beyond the simple release of insulin? Again - trial data to show that Afrezza really does mimic the full first phase response. If you don't produce the data then don't be surprised when assertions are ignored.
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Post by peppy on Jan 13, 2018 18:13:33 GMT -5
Are you implying that Endocrinologists only get their medication information from pharmaceutical reps and do not do any independent research and/or reading of their own? If they did, then they too would know these things. A clinical trial does not have to be conducted for one to know that Afrezza mimics the first-phase insulin response. The first-phase insulin response and Afrezza's kinetics are both well published and the fact that Afrezza does indeed mimic the endogenous first-phase insulin response is also published. Peak serum insulin concentration is reached in less than 15 minutes with Afrezza, and that is what the natural physiologic time requirement is in order for the first-phase response to successfully occur. A clinical trial for these is not warranted. The facts are already there and published. Do doctors largely get their medical information from reps? Exclusively - no, are they a source - yes. If they aren't we are wasting a lot of money having a sales force. Do they read articles on their own - the ones I know do. Then we get to the assertions you are making. If you want to be taken seriously then you need to have data to back the assertions that is gathered in a clear and transparent way. That is the whole reason for trials, and why the standards of care assign such weight to them. Does Afrezza mimic the first phase response? Superficially it looks like it, but does it really is a question you need scientific evidence to support and a hunch is not good enough. Does the fact that peak serum levels are reached in less than 15 minutes provide a sufficient copy of the first phase response or are there other components beyond the simple release of insulin? Again - trial data to show that Afrezza really does mimic the full first phase response. quote: you need to have data to back the assertions that is gathered in a clear and transparent way. reply: there has been continuous glucose monitor data for years. pretty transparent. Afrezza keep your glucose from going up in the first place.
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Post by agedhippie on Jan 13, 2018 18:34:58 GMT -5
Do doctors largely get their medical information from reps? Exclusively - no, are they a source - yes. If they aren't we are wasting a lot of money having a sales force. Do they read articles on their own - the ones I know do. Then we get to the assertions you are making. If you want to be taken seriously then you need to have data to back the assertions that is gathered in a clear and transparent way. That is the whole reason for trials, and why the standards of care assign such weight to them. Does Afrezza mimic the first phase response? Superficially it looks like it, but does it really is a question you need scientific evidence to support and a hunch is not good enough. Does the fact that peak serum levels are reached in less than 15 minutes provide a sufficient copy of the first phase response or are there other components beyond the simple release of insulin? Again - trial data to show that Afrezza really does mimic the full first phase response. quote: you need to have data to back the assertions that is gathered in a clear and transparent way. reply: there has been continuous glucose monitor data for years. pretty transparent. Afrezza keep your glucose from going up in the first place. The counter-argument is that the group is self-selected. There are no CGM posts from the drop outs, and no control arm. This is why the time in range study is important - it's a small group but it is more representative. That study has the potential to change the label, but CGM posts from a few people on Twitter will never do that. Trial data is what moves this forwards.
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Post by peppy on Jan 13, 2018 18:47:14 GMT -5
quote: you need to have data to back the assertions that is gathered in a clear and transparent way. reply: there has been continuous glucose monitor data for years. pretty transparent. Afrezza keep your glucose from going up in the first place. The counter-argument is that the group is self-selected. There are no CGM posts from the drop outs, and no control arm. This is why the time in range study is important - it's a small group but it is more representative. That study has the potential to change the label, but CGM posts from a few people on Twitter will never do that. Trial data is what moves this forwards. that is right. This is America. counter argument. self selected group, got it. there is one self selected group on Afrezza, who loves it , another self selected group has continuous glucose monitors showing good/superior glucose control. DO NOT EXTRAPOLATE> We live in a one size fits all.
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Post by agedhippie on Jan 13, 2018 19:10:09 GMT -5
The counter-argument is that the group is self-selected. There are no CGM posts from the drop outs, and no control arm. This is why the time in range study is important - it's a small group but it is more representative. That study has the potential to change the label, but CGM posts from a few people on Twitter will never do that. Trial data is what moves this forwards. that is right. This is America. counter argument. self selected group, got it. there is one self selected group on Afrezza, who loves it , another self selected group has continuous glucose monitors showing good/superior glucose control. DO NOT EXTRAPOLATE> We live in a one size fits all. Sorry - that is all a bit of a rant so you may want to stop now. If I had my way anyone who wanted it could have it. I am not in favor of diabetics having their treatment options restricted unless the treatment is actively dangerous and I want there to be as many options as possible. I would never go on a low fat / high carb diet because I think it's unhealthy but I would never criticize those who do. On the drug side Actos seems to work but I have always avoided it however there are people who swear by it and have no side effects - I don't think it should be withdrawn. As far as I am concerned if people have made an informed decision, even if I think it is wrong (cinnamon? really?) I think they should be able to do it. Trial data is good because it filters out biases and takes a decent stab at getting to an impartial question. Yes you can bend trials by framing the question, but that influence is front and center in the filing. That's the reason the Standard of Care gives such high weight to trial data. The insurer just cares about their profit, can I get a similar if inferior response for less. This is not just a problem for Mannkind, look at DVAX (another sterling investment of mine, I should really stay away from this sector) who have a superior Hep B vaccine which requires 2 rather than 3 doses and is hugely more effective with diabetics (Type 1 is a high risk class) that the FDA stalled. It's approved now, but the company reached the stage where the market effectively viewed the vaccine as dead and valued the company on their other products alone.
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Post by mnholdem on Jan 13, 2018 20:20:35 GMT -5
Remarks by Scott Gottlieb, M.D. Commissioner of Food and Drugs Examining the Impact of Real-World Evidence on Medical Product Development―Workshop One: IncentivesNational Academy of Sciences Washington, DC September 19, 2017 Excerpt :
To enable greater adoption of RWE in clinical and regulatory decisions, we’ll need to work with the healthcare system to change the way clinical information is collected. Ideally, we’d like to have a system where providers have the right incentives to enter clinically relevant information into EMRs at the point of care. But a lot of the incentives force data to be structured in ways that are geared to billing. Clinically relevant information that can tell us what’s happening to patients often remains in an unstructured notes. We’re unable to learn as much as we could about a product’s profile when that information isn’t accessible. We also need to find a better way to collect information directly from patients, because an EMR and claims data is really the patient’s perspective filtered via the provider. FDA also needs to do its part to advance the use of RWE. I recognize that FDA isn’t always clear about our approach to RWE in regulatory decisions. So how innovators incorporate these concepts into medical product development is also likely to falter. Knowing this, FDA is taking steps to provide more clarity. Last month, we issued final guidance on the use of RWE in the development of devices. Since early 2015 alone, we’ve approved or cleared more than eight new medical devices and expanded the use of more than six technologies based on evidence derived from RWD. This includes drug-eluting stents, transcatheter heart valves, and technologies for spinal cord stimulation and esophageal atresia, as well as in IVDs. In these cases, we’re using robust evidence that was generated in less time and at a lower cost than in the past, in some cases saving one to two years of development time. Increasingly, medical device makers are also meeting their post-market study requirements by leveraging real world data sources. These approaches allow for more rapid data collection. It increases the likelihood that the evidence will be generated, because it’s already being gathered as a part of routine clinical practice. We’re now working on policies to support the use of RWE in the approval of new indications for already marketed drugs. This may be especially relevant in settings like rare diseases or other unmet medical needs, where it can be hard to enroll patients in clinical trials. We’re also expanding policies to enable the use of RWE to support post-approval drug study requirements.
Link: www.fda.gov/NewsEvents/Speeches/ucm576519.htm
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Post by mango on Jan 13, 2018 22:02:28 GMT -5
Are you implying that Endocrinologists only get their medication information from pharmaceutical reps and do not do any independent research and/or reading of their own? If they did, then they too would know these things. A clinical trial does not have to be conducted for one to know that Afrezza mimics the first-phase insulin response. The first-phase insulin response and Afrezza's kinetics are both well published and the fact that Afrezza does indeed mimic the endogenous first-phase insulin response is also published. Peak serum insulin concentration is reached in less than 15 minutes with Afrezza, and that is what the natural physiologic time requirement is in order for the first-phase response to successfully occur. A clinical trial for these is not warranted. The facts are already there and published. Do doctors largely get their medical information from reps? Exclusively - no, are they a source - yes. If they aren't we are wasting a lot of money having a sales force. Do they read articles on their own - the ones I know do. Then we get to the assertions you are making. If you want to be taken seriously then you need to have data to back the assertions that is gathered in a clear and transparent way. That is the whole reason for trials, and why the standards of care assign such weight to them. Does Afrezza mimic the first phase response? Superficially it looks like it, but does it really is a question you need scientific evidence to support and a hunch is not good enough. Does the fact that peak serum levels are reached in less than 15 minutes provide a sufficient copy of the first phase response or are there other components beyond the simple release of insulin? Again - trial data to show that Afrezza really does mimic the full first phase response. If you don't produce the data then don't be surprised when assertions are ignored. Here we have a clinical study and the Textbook of Diabetes 5th Edition that say exacly what has already been scientifically proven. Afrezza is able to stop blood glucose levels from rising after use because it reaches peak serum insulin concentration in ~ 12 minutes which is required for the first-phase insulin response. It mimics exactly what the first-phase response does—blunts the rise of blood glucose by signaling to the liver to temporarily stop production of glucose. To you it is superficial, but sciences shows us it indeed does fully mimic the first-phase insulin response. Clinical Results of an Automated Artificial Pancreas Using Technosphere Inhaled Insulin to Mimic First-Phase Insulin SecretionThe addition of an ultra-rapid insulin at meal time allows for superior post- prandial control. Using this hybrid semiautomated approach has several advantages. First the patient would have to do only a rough estimation of the CHO content. The controller will take care of any remaining insulin requirement. Second, the use of TI mimics first phase secretion of insulin with a fast-peak and rapid clearance, which results in lower post- prandial peaks and less late postprandial hypoglycemia. Third, its use also results in both lower insulin delivery and glucose concentration variability.This study was designed to demonstrate a proof of concept that giving a small, consistent bolus of ultra-rapid insulin that provides a first phase meal correction could improve the postprandial glucose profile as compared to fully automated closed-loop control with very minimal user intervention or need to count CHOs and enter estimation to the closed-loop system.journals.sagepub.com/doi/pdf/10.1177/1932296815582061• The Texbook of Diabetes, 5th Edition
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Post by dreamboatcruise on Jan 13, 2018 23:16:29 GMT -5
Are you implying that Endocrinologists only get their medication information from pharmaceutical reps and do not do any independent research and/or reading of their own? If they did, then they too would know these things. A clinical trial does not have to be conducted for one to know that Afrezza mimics the first-phase insulin response. The first-phase insulin response and Afrezza's kinetics are both well published and the fact that Afrezza does indeed mimic the endogenous first-phase insulin response is also published. Peak serum insulin concentration is reached in less than 15 minutes with Afrezza, and that is what the natural physiologic time requirement is in order for the first-phase response to successfully occur. A clinical trial for these is not warranted. The facts are already there and published. Do doctors largely get their medical information from reps? Exclusively - no, are they a source - yes. If they aren't we are wasting a lot of money having a sales force. Do they read articles on their own - the ones I know do. Then we get to the assertions you are making. If you want to be taken seriously then you need to have data to back the assertions that is gathered in a clear and transparent way. That is the whole reason for trials, and why the standards of care assign such weight to them. Does Afrezza mimic the first phase response? Superficially it looks like it, but does it really is a question you need scientific evidence to support and a hunch is not good enough. Does the fact that peak serum levels are reached in less than 15 minutes provide a sufficient copy of the first phase response or are there other components beyond the simple release of insulin? Again - trial data to show that Afrezza really does mimic the full first phase response. If you don't produce the data then don't be surprised when assertions are ignored. Not to mention, the pancreas releases insulin into the portal vein which goes directly into the liver. The concentration of insulin is much higher going into the liver than occurs with a comparable amount of insulin entering the general circulation and then going to the liver. Of course if there is still some active beta cells, exogenous insulin would only need act as an adjunct not a full replacement. I agree that many doctors primarily want to see real world trial results vs logical arguments for why something should be beneficial. Tons of new drugs have theoretical mechanisms of beneficial action which don't actually pan out in vivo.
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Post by sportsrancho on Jan 14, 2018 9:27:11 GMT -5
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Post by agedhippie on Jan 14, 2018 10:32:19 GMT -5
That's an interesting paper. It's looking at the design of the CV Outcomes Trials that the FDA mandates now and discussing if they make any sort of sense at all. The conclusion seems to be that the trials are heavily weighted to people who already have CVD, and are not typical of the patient group. Also that the sheer cost of the trials means that some pharmas just abandon the market.
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Post by sayhey24 on Jan 14, 2018 10:56:55 GMT -5
Are you implying that Endocrinologists only get their medication information from pharmaceutical reps and do not do any independent research and/or reading of their own? If they did, then they too would know these things. A clinical trial does not have to be conducted for one to know that Afrezza mimics the first-phase insulin response. The first-phase insulin response and Afrezza's kinetics are both well published and the fact that Afrezza does indeed mimic the endogenous first-phase insulin response is also published. Peak serum insulin concentration is reached in less than 15 minutes with Afrezza, and that is what the natural physiologic time requirement is in order for the first-phase response to successfully occur. A clinical trial for these is not warranted. The facts are already there and published. Do doctors largely get their medical information from reps? Exclusively - no, are they a source - yes. If they aren't we are wasting a lot of money having a sales force. Do they read articles on their own - the ones I know do. Then we get to the assertions you are making. If you want to be taken seriously then you need to have data to back the assertions that is gathered in a clear and transparent way. That is the whole reason for trials, and why the standards of care assign such weight to them. Does Afrezza mimic the first phase response? Superficially it looks like it, but does it really is a question you need scientific evidence to support and a hunch is not good enough. Does the fact that peak serum levels are reached in less than 15 minutes provide a sufficient copy of the first phase response or are there other components beyond the simple release of insulin? Again - trial data to show that Afrezza really does mimic the full first phase response. If you don't produce the data then don't be surprised when assertions are ignored. In the world of engineering we do not have "trials". We built prototypes and we model. The reason for this is we can measure and develop algorithms and have predictive results. Sometimes things are overlooked but in hind-sight can be explained. Take the Tacoma Narrows Bridge which collapsed due to an aeroelastic flutter. We can exactly model why this happened. The world of medicine has traditionally been an art. We give people something and then we sit back and we see what happens. We call these trials. The great news is in some areas we can apply engineering to medicine. For years we have had EKGs and now we have CGMS. With CGMs we can apply engineering directly to diabetes. Richard Bernstein the engineer knew years ago diabetes was an engineering flow control problem. He did the best he could using the three tools he had to address the problem; point in time meter; old school insulin; food. Did he start by having huge studies? No, he measured his own BG. Then his family's, then others. What he understood is engineering can be applied directly in diabetes. The need for huge "studies" with the use of afrezza is mostly OBE(overtaken by events). When you say "Does Afrezza mimic the first phase response? Superficially it looks like it" that is an absurd statement. Post meal BG can be measured and the effect afrezza and the healthy pancreas have on it is not up for debate nor is it "Superficially". Its reality. Insulin reduces BG levels. Banting and Best showed that 96 years ago. We have known for a very long time that once you get the insulin in the blood, it works. The problem has always been getting it into the blood. If you are now arguing there is some other "magic" fluid the pancreas is releasing which is having the direct impact on lowering BG that insulin has I would suggest you are in "afrezza denial". Will there be other studies, you bet. We need to keep feeding the academic beast. What will these studies say - "afrezza seems to work amazingly well, BUT we need more studies". One thing about studies is you always need another study. Does afrezza mimic first phase pancreatic release, absolutely because you can get a lot of insulin into the blood fast and predictable. In fact, it can mimic second and fasting release if taken in smaller more frequent puffs because all the pancreas does with insulin is get it into the blood fast and this is exactly what afrezza does. If someone was willing to take a puff every few minutes afrezza really would be the artificial pancreas for insulin delivery.
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