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Post by dictatorsaurus on Oct 23, 2016 11:16:25 GMT -5
Doctors and medical professionals put an expiration date on patients, especially older ones. Happened with my father. Dr's considered 200 to be normal for a man in his 70's with T2. The fact that such high number greatly accelerate the process of kidney and organ failure did not matter to them.
The experience with my father was heartbreaking and eye opening. It made me realize how badly diabetes is managed and how little Dr's know about this disease. And even worse, how little they care.
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Post by bwills on Oct 23, 2016 11:41:37 GMT -5
Doctors and medical professionals put an expiration date on patients, especially older ones. Happened with my father. Dr's considered 200 to be normal for a man in his 70's with T2. The fact that such high number greatly accelerate the process of kidney and organ failure did not matter to them. The experience with my father was heartbreaking and eye opening. It made me realize how badly diabetes is managed and how little Dr's know about this disease. And even worse, how little they care. Doctors don't consider "200 to be normal for a man in his 70's with T2." They simply weigh the risks of long term complications from hyperglycemia versus the risks of over-managing resulting in complications such as hypoglycemia possibly contributing to dementia and injury due to falls. Also, many older patients take multiple drugs that have their own side effects. Every new additional drug poses potential for interactions that produce even further complications. It comes down to risk versus benefits.
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Post by letitride on Oct 23, 2016 11:45:20 GMT -5
The more I read the more I become convinced Afrezza has everything to offer and the diabetic community has everything to lose. Its time to bring diabetic care out of the dark ages.
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Post by letitride on Oct 23, 2016 11:54:41 GMT -5
After consulting with a half dozen ER doctors the one thing they all agreed on was hypos were a huge problem. If Afrezza reduces that risk significantly as it has been claimed it seems a trial to prove it should be a priority.
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Post by radgray68 on Oct 23, 2016 13:55:45 GMT -5
After consulting with a half dozen ER doctors the one thing they all agreed on was hypos were a huge problem. If Afrezza reduces that risk significantly as it has been claimed it seems a trial to prove it should be a priority. To my satisfaction, lower hypos was demonstrated in the 171-175 trials. "You have to be trying to cause a hypo" - Al There was also a single patient anomaly that, to my recollection from a hated statistics class I took 25 years ago, results are reviewed both with and without outliers. Whatever, that's history, so I'm moving on from that FDA oversight. As unnecessary as I believe it to be given the statistical certainty proven in prior trials, if the FDA wants additional trials for a most favorable label, it should be of the smallest agreeable size and cost and be a fast-track guaranteed submission. Supposedly, consumer health is their priority. I agree with the poster up above here that the apathy seen in some instances by patients, doctors and the FDA is aggravating and sad. To to another poster from today, I'll help you with those lights.
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Post by agedhippie on Oct 23, 2016 22:01:56 GMT -5
After consulting with a half dozen ER doctors the one thing they all agreed on was hypos were a huge problem. If Afrezza reduces that risk significantly as it has been claimed it seems a trial to prove it should be a priority. To my satisfaction, lower hypos was demonstrated in the 171-175 trials. "You have to be trying to cause a hypo" - Al There was also a single patient anomaly that, to my recollection from a hated statistics class I took 25 years ago, results are reviewed both with and without outliers. Whatever, that's history, so I'm moving on from that FDA oversight. As unnecessary as I believe it to be given the statistical certainty proven in prior trials, if the FDA wants additional trials for a most favorable label, it should be of the smallest agreeable size and cost and be a fast-track guaranteed submission. Supposedly, consumer health is their priority. I agree with the poster up above here that the apathy seen in some instances by patients, doctors and the FDA is aggravating and sad. To to another poster from today, I'll help you with those lights. The same person cannot be responsible for the hypos in both 171 and 175. The 171 trial was Type 1 but the 175 trial was type 2 - different trial populations.
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Post by beardawg on Oct 25, 2016 6:58:57 GMT -5
To my satisfaction, lower hypos was demonstrated in the 171-175 trials. "You have to be trying to cause a hypo" - Al There was also a single patient anomaly that, to my recollection from a hated statistics class I took 25 years ago, results are reviewed both with and without outliers. Whatever, that's history, so I'm moving on from that FDA oversight. As unnecessary as I believe it to be given the statistical certainty proven in prior trials, if the FDA wants additional trials for a most favorable label, it should be of the smallest agreeable size and cost and be a fast-track guaranteed submission. Supposedly, consumer health is their priority. I agree with the poster up above here that the apathy seen in some instances by patients, doctors and the FDA is aggravating and sad. To to another poster from today, I'll help you with those lights. The same person cannot be responsible for the hypos in both 171 and 175. The 171 trial was Type 1 but the 175 trial was type 2 - different trial populations. I don't believe he said the same person was responsible for hypos in both trials. I took it to mean that those trials together show lower hypo rate. The only thing affecting the numbers was one patient, and it could be in any of the trials - because the trials' data together showed the results. One or two trials showing skewed data could affect the whole batch.
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Post by peppy on Oct 25, 2016 7:06:12 GMT -5
The more I read the more I become convinced Afrezza has everything to offer and the diabetic community has everything to lose. Its time to bring diabetic care out of the dark ages. The problem in a nut shell.
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Post by agedhippie on Oct 25, 2016 7:41:02 GMT -5
The same person cannot be responsible for the hypos in both 171 and 175. The 171 trial was Type 1 but the 175 trial was type 2 - different trial populations. I don't believe he said the same person was responsible for hypos in both trials. I took it to mean that those trials together show lower hypo rate. The only thing affecting the numbers was one patient, and it could be in any of the trials - because the trials' data together showed the results. One or two trials showing skewed data could affect the whole batch. Separate results are shown for 171 and 175 in the ADCOM filing. More generally you cannot combine the results in a paper into a single result because the trials have different parameters so they are not like for like.
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Post by derek2 on Oct 25, 2016 8:01:45 GMT -5
I don't believe he said the same person was responsible for hypos in both trials. I took it to mean that those trials together show lower hypo rate. The only thing affecting the numbers was one patient, and it could be in any of the trials - because the trials' data together showed the results. One or two trials showing skewed data could affect the whole batch. Separate results are shown for 171 and 175 in the ADCOM filing. More generally you cannot combine the results in a paper into a single result because the trials have different parameters so they are not like for like. Regardless, there were thousands of hypo events in each trial. It's mathematically imposdsible for one person to have accounted for half the hypos in either trial. Al may have been talking about severe hypos, which accounted for about 3% of all hypos. 60% of T2s, for example, reported at least one hypo event. This "Afrezza = no hypo" truism was disproven years ago.
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Post by peppy on Oct 25, 2016 8:22:53 GMT -5
Separate results are shown for 171 and 175 in the ADCOM filing. More generally you cannot combine the results in a paper into a single result because the trials have different parameters so they are not like for like. Regardless, there were thousands of hypo events in each trial. It's mathematically imposdsible for one person to have accounted for half the hypos in either trial. Al may have been talking about severe hypos, which accounted for about 3% of all hypos. 60% of T2s, for example, reported at least one hypo event. This "Afrezza = no hypo" truism was disproven years ago. ok, I'll run with that. How about, Afrezza, it is harder to get hypos. www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf
I have looked at a fair share of continuous glucose monitors. I want to say, I have seen afrezza with the basal these people are running,hit 60 to 70 line on the continuous glucose monitors. I have not seen a blood glucose level below that. for example, I have seen no 40's no 30's. big difference, severity of hypo. afrezza users have to reduce basal?
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Post by derek2 on Oct 25, 2016 8:57:29 GMT -5
Regardless, there were thousands of hypo events in each trial. It's mathematically imposdsible for one person to have accounted for half the hypos in either trial. Al may have been talking about severe hypos, which accounted for about 3% of all hypos. 60% of T2s, for example, reported at least one hypo event. This "Afrezza = no hypo" truism was disproven years ago. ok, I'll run with that. How about, Afrezza, it is harder to get hypos. www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf
I have looked at a fair share of continuous glucose monitors. I want to say, I have seen afrezza with the basal these people are running,hit 60 to 70 line on the continuous glucose monitors. I have not seen a blood glucose level below that. for example, I have seen no 40's no 30's. big difference, severity of hypo. afrezza users have to reduce basal?
Yes, I think that more accurately reflects the situation. I haven't seen any reliable data re: basal reduction. Social media accounts are all over the place: less, more, same.
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Post by brentie on Oct 25, 2016 9:09:44 GMT -5
The same person cannot be responsible for the hypos in both 171 and 175. The 171 trial was Type 1 but the 175 trial was type 2 - different trial populations. I don't believe he said the same person was responsible for hypos in both trials. I took it to mean that those trials together show lower hypo rate. The only thing affecting the numbers was one patient, and it could be in any of the trials - because the trials' data together showed the results. One or two trials showing skewed data could affect the whole batch. Here's what Al actually said.
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Post by derek2 on Oct 25, 2016 10:50:39 GMT -5
I don't believe he said the same person was responsible for hypos in both trials. I took it to mean that those trials together show lower hypo rate. The only thing affecting the numbers was one patient, and it could be in any of the trials - because the trials' data together showed the results. One or two trials showing skewed data could affect the whole batch. Here's what Al actually said. "There was one patient that had almost half of the hypoglycemic incidents" Simply not possible. 171 - number of subjects: 174 Number of Gen2 subjects with hypoglycemic events: 167 (96%) Number of events: 7919 Incidence per subject month: .48 175 - different metric quoted: Incidence Rate Analyses The exposure adjusted incidence of ‘any hypoglycemic’ event was 1.63 per subject year vs. 0.78 per subject year exposure, for Afrezza TI and placebo, respectively. To get an incidence per subject month for Gen 2: just divide by 12 = .135 Since the subject population is the same as 171, we can derive the number of hypos in the Gen2 arm of 175: = 7919 * (.135 / .48) = 2227 hypo events So it strains credulity to believe that in a 90-day study one patient either had 3960 hypos (study 171) or 1113 hypos (study 175) - that would be 44 hypos per day (171) or 12 hypos per day (175) when blood glucose was not even being measured that often.
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Post by compound26 on Oct 25, 2016 11:21:30 GMT -5
Here's what Al actually said. "There was one patient that had almost half of the hypoglycemic incidents" Simply not possible. 171 - number of subjects: 174 Number of Gen2 subjects with hypoglycemic events: 167 (96%) Number of events: 7919 Incidence per subject month: .48 175 - different metric quoted: Incidence Rate Analyses The exposure adjusted incidence of ‘any hypoglycemic’ event was 1.63 per subject year vs. 0.78 per subject year exposure, for Afrezza TI and placebo, respectively. To get an incidence per subject month for Gen 2: just divide by 12 = .135 Since the subject population is the same as 171, we can derive the number of hypos in the Gen2 arm of 175: = 7919 * (.135 / .48) = 2227 hypo events So it strains credulity to believe that in a 90-day study one patient either had 3960 hypos (study 171) or 1113 hypos (study 175) - that would be 44 hypos per day (171) or 12 hypos per day (175) when blood glucose was not even being measured that often. It is clearly established that Afrezza causes less hypos. That is discussed in detail in the FDA briefing document.
Afrezza has lower hypo events and incidences in every category as compared with RAAs. See pages 124-126 of the document (the version I looked has 248 pages as noted on the document itself). And when we are discussing hypo rate, we are mainly look at study 171 (the study for Type ones), i.e., a comparison with RAAs. www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM390864.pdfAs for what Al Mann was referring to, even though he did not specify, IMHO, he was referring to severe hypos events. For Afrezza (on Generation 2 device), there were only 65 severe hypo events (as compared to 7979 total hypo events). It is quite possible that one or two subjects accounted for a significant percentage of these severe hypo events. And if one looks at the severe hype events, which I believe is the most important to the PWDs, Afrezza ((on Generation 2 device, i.e. dreamboat) beats RAAs hands down.
Number of severe hypo events 65 vs 130 and event rate 8.05% vs 14.45%.
Hypo events with Glucose <= 36 mg/dl 94 vs 230 and event rate 11.64% vs 25.57%.
Too bad that FDA does not allow Mannkind to include less hypo in the label. FDA reviewer had the following comment reagrding this. (Reviewer’s comment: For the T1DM trial, conclusions regarding hypoglycemia are confounded by the difference in efficacy observed between the two study arms and are entirely consistent with the fact that Afrezza was demonstrated to be less effective than comparator. For the T2DM trial, the result of greater hypoglycemia risk vs. placebo is expected.) If this is FDA's reason or excuse for not allowing Mannkind to include less hypo in the label, I personally found it to be less than persuasive. This because the Afrezza trial was designed and approved by FDA to show non-inferior and the trial did show non-inferior. I.e., FDA is acknowledging that Afrezza is non-inferior to RAAs in terms of reducing A1Cs. If so, how can FDA ignore the significant reduction in hypo events and incidence rates? Other than BP influence embedded in the FDA review process, I personally cannot find any other explanation.
IMHO, the choice of words there "entirely consistent" clearly reflects FDA reviewer's bias. Afrezza is shown to be "non-interior" to RAAs (i.e., if less effectively, only marginally so, in terms of reducing A1Cs), why is this "entirely consistent" with Afrezza's significant reduction in hypo events and incidence rates (especially severe hypo events and incidence rates)?
Did the FDA reviewer cite any study backing up his/her conclusion or showing how he/she arrives with such "entirely consistent" conclusion? At least I did not find any!
(There is no reason to look at the hypo rates for study 172, as study 172 is Afrezza vs placebo. So that is insulin vs no-insulin. Afrezza is expected to have higher hypo rates in study 172. If you add insulin to the system, you are increasing the possibility for hypo events. The FDA briefing document made that clear.) Because of this, even though Al Mann did not specify, when he was speaking about Hypo events, IMHO, he must be referring to the 171 study, not the 172 study.
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