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Post by akemp3000 on Jun 5, 2018 18:24:45 GMT -5
The good news is that HbA1c will soon be in the dustbin of history thanks to TIR and the new CGMs. No one is going to care what their three-month average BG was in the past when compared to current knowledge or TIR. Unfortunately, such paradigm shifts can't happen quickly because the entire healthcare industry has been based on A1c for standards of care, approval of procedures, drug trials, medicines, medical reimbursements and more. Fortunately, better technology and science will replace antiquated science. Timing is the question and that seems to be accelerating. It sounds like Dr. Kendall and the new Scientific Advisory Board are about to step on the gas.
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Post by tomson1355 on Jun 5, 2018 18:38:07 GMT -5
Absolute terms, the terms prior to the %. Absolute terms show the numerator and denominator. SHOW YOUR WORK>www.youtube.com/watch?v=rcHQElKhWFcH Gilbert Welch - The Two Most Misleading Numbers in Medicine Love you. Here you go The starting HbA1c is 7.98% for Afrezza and 7.88% for Novolog. Over the 24 weeks of the trial the Afrezza HbA1c dropped by 0.21% to 7.77% and the Novolog dropped by 0.40% to 7.48%. That make 0.21/7.98 = 0.0263 or 2.63% drop vs. 0.40/7.88 = 0.0508 or 5.08%. The confusion is because HbA1c is measured in percentage of Hb so everything is measured in percentages, both the HbA1c change, and the amount of change. Thanks, AH, for the clarification. I stand corrected. In my defense I would say that to state that something drops by 0.21% means only one thing. If I were writing that sentence, I would say it dropped by 0.21 units or points. Because, as you point out, the drop is actually 2.63% and not 0.21%.
For instance, if, say, a lending rate dropped from 10% to 5%, it would be incorrect to say it dropped by 5%, even though the measurement is expressed in %. It would be correct to say that it dropped by 50%, or by 5 percentage points.
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Post by mango on Jun 5, 2018 18:49:45 GMT -5
So .21% and .40% do not equal .0021 and .0040 ? Just axin That in your avatar 😆
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Post by dreamboatcruise on Jun 5, 2018 18:50:02 GMT -5
Here you go The starting HbA1c is 7.98% for Afrezza and 7.88% for Novolog. Over the 24 weeks of the trial the Afrezza HbA1c dropped by 0.21% to 7.77% and the Novolog dropped by 0.40% to 7.48%. That make 0.21/7.98 = 0.0263 or 2.63% drop vs. 0.40/7.88 = 0.0508 or 5.08%. The confusion is because HbA1c is measured in percentage of Hb so everything is measured in percentages, both the HbA1c change, and the amount of change. good work. Afrezza. 7.98% - 7.77% = .21 Hba1c which is measured in %. Novolog 7.88% - 7.48% = .40 hbA1c which is measured in %. That is the absolute change aged. statistics, mathematics whatever is applied, the % above is the absolute change. so .21 % of 7.98% = 2.63% is what you are calculating. and .40% of a smaller number 7.88% = 5.08%. These calculations are made to baffle. let's see what the absolute change is this go around over 4 weeks. I think this exchange demonstrates why in finance a change in interest rate is referred to as basis points. If applied to A1c you'd say it changed by 21 basis points rather than the somewhat open to confusion 0.21%.
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Post by sayhey24 on Jun 5, 2018 19:02:04 GMT -5
Mango - awesome work, congratulations on moving the ball forward.
I will say I am having a real hard time following the discussion with Aged. My understanding of the poster is it was put together from the lost studies and to answer another discussion, yes there have been studies done in the past with TI and CGMS.
The goal of the 171 study was not to show improved A1c over Novolog. It was to show non-inferiority, nothing more and nothing less. In fact one doctor who aggressively dosed afrezza was accused by the FDA of "Cheating", her words not mine because his afrezza A1c numbers blew away Novolog. The FDA rep wanted to know why this same doctor did not aggressively dose the RAA and he told her "I would have killed my patients", his words not mine.
The goal of the STAT was improved TIR. In a couple of weeks it should be shown afrezza is the clear winner. Will it show an improvement in A1c? Maybe but TIR and A1c are apples and oranges. This study was designed to show the efficacy of TI for PPBG, PPGE, and time-in-range. The goal of a meal time anti-glycemic and RAA is to get the PWD back to their baseline asap not reduce A1c. In theory, the heavy lifting of reducing A1c would then be done by adjusting the basal in a T1. In a T2 the assumption is the pancreas still has enough "juice" during fasting to maintain the baseline. In reality the RAA's and all other anti-glycemics except afrezza don't do the job. They do not mimic first phase release to get the PWD back to baseline like a non-diabetic.
Will the STAT show reduced hypos? Maybe a little but unless there was an attempt to aggressively dose which is not in the study description I wouldn't be expecting much. As, the good doctor said at the Adcom to the FDA - aggressively dosing the RAA could be life threatening and I will add is not going to make the RAA work any faster. The study design was to keep the RAA user at their current dosage which in theory would not be causing "too many" hypos.
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Post by dreamboatcruise on Jun 5, 2018 19:42:49 GMT -5
Mango - awesome work, congratulations on moving the ball forward. I will say I am having a real hard time following the discussion with Aged. My understanding of the poster is it was put together from the lost studies and to answer another discussion, yes there have been studies done in the past with TI and CGMS.
Is it 162 you're talking about? That one does mention CGM to measure BG excursions and variability, but on FDA site it says that analysis was not done due to early termination of the trial. I guess we'll not know what's up with that hypo poster until the ADA session. There are multiple possibilities and we have been given no info from management about where the data came from or what sort of "adjusted" analysis might have been applied.
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Post by sayhey24 on Jun 5, 2018 20:16:10 GMT -5
DBC - here is a public one but I am expecting Dr. Kendall to be releasing info on Al's studies soon.
The CGM used was the Dexcom G4â„¢ Platinum (Dexcom Inc, San Diego, CA).
Results
The median percentage time in range (70-180 mg/dl, YSI BG) during the 5-hour postprandial period with the use of TI was 81.6% (IQ range 72.5-85%, Breakfast 75%, Dinner 93.3%) as compared to percentage time in range without the use of TI 60.0% (IQ range 50.8-75.8%, breakfast 61.6%, dinner 56.6%, P = .059). The median percentage time in range 80-140 mg/dl during the entire study period was 67.5% (IQ range 48.5-73.1%) as compared to percentage time in range without the use of TI of 55.2% (IQ range 52.0-60.1%, P = .032).
Those are pretty GREAT results considering afrezza was up against the AP.
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Post by brotherm1 on Jun 5, 2018 20:42:15 GMT -5
Absolute terms, the terms prior to the %. Absolute terms show the numerator and denominator. SHOW YOUR WORK>www.youtube.com/watch?v=rcHQElKhWFcH Gilbert Welch - The Two Most Misleading Numbers in Medicine Love you. Here you go The starting HbA1c is 7.98% for Afrezza and 7.88% for Novolog. Over the 24 weeks of the trial the Afrezza HbA1c dropped by 0.21% to 7.77% and the Novolog dropped by 0.40% to 7.48%. That make 0.21/7.98 = 0.0263 or 2.63% drop vs. 0.40/7.88 = 0.0508 or 5.08%. The confusion is because HbA1c is measured in percentage of Hb so everything is measured in percentages, both the HbA1c change, and the amount of change. Hmmm. Twisted math. That probably explains why doctor bills are so high and always outpace inflation in general. Trump should require passing grades in math for med students.
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Post by dreamboatcruise on Jun 5, 2018 20:47:24 GMT -5
DBC - here is a public one but I am expecting Dr. Kendall to be releasing info on Al's studies soon.
The CGM used was the Dexcom G4â„¢ Platinum (Dexcom Inc, San Diego, CA).
Results
The median percentage time in range (70-180 mg/dl, YSI BG) during the 5-hour postprandial period with the use of TI was 81.6% (IQ range 72.5-85%, Breakfast 75%, Dinner 93.3%) as compared to percentage time in range without the use of TI 60.0% (IQ range 50.8-75.8%, breakfast 61.6%, dinner 56.6%, P = .059). The median percentage time in range 80-140 mg/dl during the entire study period was 67.5% (IQ range 48.5-73.1%) as compared to percentage time in range without the use of TI of 55.2% (IQ range 52.0-60.1%, P = .032).
Those are pretty GREAT results considering afrezza was up against the AP.
Well yeah, I should have thought of the artificial pancreas study. Of course that had CGM... silly me. That's probably the one I was racking my brains to remember. It was blinded CGM as I remember. I don't think they'll be any other use of CGMs with TI other than this and 162. Most of the MNKD trials were before CGMs where widely available and considered accurate enough to be meaningful in clinical trials.
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Post by mango on Jun 5, 2018 20:54:49 GMT -5
Mango - awesome work, congratulations on moving the ball forward. I will say I am having a real hard time following the discussion with Aged. My understanding of the poster is it was put together from the lost studies and to answer another discussion, yes there have been studies done in the past with TI and CGMS.
Is it 162 you're talking about? That one does mention CGM to measure BG excursions and variability, but on FDA site it says that analysis was not done due to early termination of the trial. I guess we'll not know what's up with that hypo poster until the ADA session. There are multiple possibilities and we have been given no info from management about where the data came from or what sort of "adjusted" analysis might have been applied.
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Post by dreamboatcruise on Jun 5, 2018 21:03:57 GMT -5
mango... those are old presentations, correct?
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Post by mango on Jun 5, 2018 21:49:05 GMT -5
Yeah, thought it might be a clue
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Post by mytakeonit on Jun 5, 2018 22:22:41 GMT -5
The biggest clue is the date in the right bottom corner.
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Post by peppy on Jun 5, 2018 23:54:09 GMT -5
The Gen2 arm of the trial was non-inferior to Insulin Aspart in terms of change in HbA1c over the treatment period (-0.21 % vs -0.4%).Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month)Afrezza patients lost weight while Aspart patients gained weightFewer patients in the Afrezza arm achieved treatment goals of HbA1c < 7% or 6.5% compared to Aspart, this difference was statistically significant
Read more: mnkd.proboards.com/thread/49/red-acre-mnkd-8-18#ixzz5HcLx8faQ===================================================================== mango the above post by you part of the gold necklace? you are digging up the old work? heh ==================================================================== Recommendations - A reasonable A1C goal for many nonpregnant adults is ,7% (53 mmol/mol). A - Providers might reasonably suggest more stringent A1C goals (such as ,6.5% [48 mmol/mol]) for se- lected individual patients if this can be achieved without significant hypoglycemia or other adverse ef- fects of treatment (i.e., polyphar- macy). Appropriate patients might include those with short duration of diabetes, type 2 diabetes treated with lifestyle or metformin only, long life expectancy, or no signifi- cant cardiovascular disease. C - Less stringent A1C goals (such as ,8% [64 mmol/mol]) may be ap- propriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascu- lar or macrovascular complications, extensive comorbid conditions, or long-standing diabetes in whom the goal is difficult to achieve de- spite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin. B diabetesed.net/wp-content/uploads/2017/12/2018-ADA-Standards-of-Care.pdf
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Post by peppy on Jun 6, 2018 0:19:17 GMT -5
Here you go The starting HbA1c is 7.98% for Afrezza and 7.88% for Novolog. Over the 24 weeks of the trial the Afrezza HbA1c dropped by 0.21% to 7.77% and the Novolog dropped by 0.40% to 7.48%. That make 0.21/7.98 = 0.0263 or 2.63% drop vs. 0.40/7.88 = 0.0508 or 5.08%. The confusion is because HbA1c is measured in percentage of Hb so everything is measured in percentages, both the HbA1c change, and the amount of change. good work. Afrezza. 7.98% - 7.77% = .21 Hba1c which is measured in %. Novolog 7.88% - 7.48% = .40 hbA1c which is measured in %. Mango at work, interesting point. My take on the 0.21 vs 0.4% thing is first of all who was studied? This trial wasn't as if we were looking at insulin naive patients. And this is essential to keep in mind. They were already taking something. Why would they improve in the rapid acting group by 0.4%? That was the sophisticated protocols and monitoring/ titration by experts. Read more: mnkd.proboards.com/thread/49/red-acre-mnkd-8-18#ixzz5HcRfyCKjThe Gen2 arm of the trial was non-inferior to Insulin Aspart in terms of change in HbA1c over the treatment period (-0.21 % vs -0.4%). Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month)Afrezza patients lost weight while Aspart patients gained weight Fewer patients in the Afrezza arm achieved treatment goals of HbA1c < 7% or 6.5% compared to Aspart, this difference was statistically significant Read more: mnkd.proboards.com/thread/49/red-acre-mnkd-8-18#ixzz5HcLx8faQThis looks more clinically significant: Afrezza patients had fewer hypos than Aspart users (9.8 per subject-month vs 13.97 per subject-month)
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