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Post by kc on Aug 19, 2015 18:16:41 GMT -5
Has anybody reviewed the changes on the UK NHS site as of August 19, 2015
Has anybody had a chance to look this over? Items Bold seem to have changed since I last looked at this site. ?
www.ukmi.nhs.uk/applications/ndo/record_view_open.asp?newDrugID=4631
Trial or other data
Aug 15: Results of PIII trial, published in Diabetes care, found that in patient with TIIDM and HbA1c levels over or equal to 7.5% but less than 10% despite metformin alone or two or more oral antidiabetics, add-on prandial Afrezza reduced HbA1c by -0.4% (95% CI -0.575 to -0.23%) compared to placebo (p<0.0001) [32].
19/08/2015 13:56:56
Seems some of the other language on the page has changed(BOLD) too. I wish that I had an old screen shot.
Category
BNF Category:
Short-acting insulins (06.01.01.01)
Pharmacology: Ultra rapid acting human insulin using Technosphere® drug delivery technology; Technosphere particles loaded with insulin change from powder to liquid upon contact with the neutral pH of the alveoli surface deepin the lung.
Epidemiology: In 2011 the UK prevalence of diabetes was 4.45% (about 2.9 million people). It is thought a further 850,000 are undiagnosed. The prevalence is projected to increase to 5 million people by 2025. About 90% of patients with diabetes have type 2 disease.
Indication: Type 1 and 2 diabetes mellitus
Method(s) of Administration
Inhalation
Company Information
Name: Sanofi
US Name: MannKind
Further Information
Anticipated commissioning route (England) CCG
High cost drug list? Awaiting Update
Tariff Likely Healthcare Resource Group included.
Implications Available only to registered users
Evidence Based Evaluations
FDA doc www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM390864.pdf
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Post by cyn on Aug 19, 2015 20:33:44 GMT -5
"in patient with TIIDM and HbA1c levels over or equal to 7.5% but less than 10% despite metformin alone or two or more oral antidiabetics, add-on prandial Afrezza reduced HbA1c by -0.4% (95% CI -0.575 to -0.23%) compared to placebo (p<0.0001)"
kc, On page 6 of the "Evidenced Based Evaluation" FDA doc (referenced in your NDO find), it reads .... "In general, every percentage point drop in HbA1c blood test results (e.g., from 8.0% to 7.0%) can reduce the risk of microvascular complications (eye, kidney, and nerve diseases) by 40%"
Now, just a thought ... If a drop of 8.0% to 7.0% (equating to an overall 0.125% reduction) in HbA1c corresponds to a 40% risk reduction in microvascular complications, then what would a 0.4% reduction in HbA1c (as cited above) equate to risk reduction in microvascular complications? Guesses anyone??? I come up with 128% ... (0.4 divided by 0.125) multiplied by 40%
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Post by xoxoxoxo on Aug 19, 2015 21:48:17 GMT -5
Your math is a bit off. if 1% HbA1c drop means 40% reduction, then a .4% drop which isn't as significant as 1% would mean the calculation would be 40% * .4 or a 16% drop instead of 128%.
Think about it, if the drop was half as much, you'd expect the benefit to be half as much.
Source: math
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Post by tayl5 on Aug 20, 2015 1:39:11 GMT -5
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Post by xoxoxoxo on Aug 20, 2015 6:38:13 GMT -5
The main reason Afrezza didn't drop HbA1c much during the trials was the stupid way the study was designed. They had to take Afrezza way before the meal and weren't allowed to take correction doses after the meal. Most people have reported they take Afrezza right as they start eating instead of 20 minutes early because of how quickly it works. Remember the studies were designed to prove non-inferiority, not show how much better Afrezza is than the RAAs. |
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Post by gestan on Aug 20, 2015 7:56:23 GMT -5
The main reason Afrezza didn't drop HbA1c much during the trials was the stupid way the study was designed. They had to take Afrezza way before the meal and weren't allowed to take correction doses after the meal. Most people have reported they take Afrezza right as they start eating instead of 20 minutes early because of how quickly it works. Remember the studies were designed to prove non-inferiority, not show how much better Afrezza is than the RAAs. Ahh... nice point. I did not realize this myself until now. Thanks. |
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Post by cyn on Aug 20, 2015 11:13:06 GMT -5
Thanks xoxo. Definitely hosed that calculation!  Yes, agree with your calculation that if a 1% HbA1c drop means a 40% risk reduction in microvascular complications … then a .4% drop in HbA1c equates to a 16% risk reduction (40% * .4). With respect to the trial results, I agree that a -0.4% and -0.8% reduction in HbA1c in both placebo and controlled groups; respectively, is still pretty darn good considering the restrictive manner in which the trial was designed. Now that Afrezza has acquired FDA approval, you’d think that Mnkd-Sanofi would be chomping at the bit to initiate post-approval trials designed to prove superiority. What better way to promote and back your product but by aggressively investing the needed resources to prove superiority now … not later. |
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Post by tayl5 on Aug 21, 2015 3:07:08 GMT -5
Thanks xoxo. Definitely hosed that calculation! Yes, agree with your calculation that if a 1% HbA1c drop means a 40% risk reduction in microvascular complications … then a .4% drop in HbA1c equates to a 16% risk reduction (40% * .4). With respect to the trial results, I agree that a -0.4% and -0.8% reduction in HbA1c in both placebo and controlled groups; respectively, is still pretty darn good considering the restrictive manner in which the trial was designed. Now that Afrezza has acquired FDA approval, you’d think that Mnkd-Sanofi would be chomping at the bit to initiate post-approval trials designed to prove superiority. What better way to promote and back your product but by aggressively investing the needed resources to prove superiority now … not later. Cyn, your calculation assumes a linear relationship between HbA1c and risk reduction. I don't know what the relationship actually looks like but I would expect that the higher the HbA1c starting point, the greater the risk reduction. For example, taking someone from 8.6 to 8.2 might have a bigger benefit than taking someone from 7.2 to 6.8. |
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Post by agedhippie on Aug 21, 2015 5:22:01 GMT -5
Cyn, your calculation assumes a linear relationship between HbA1c and risk reduction. I don't know what the relationship actually looks like but I would expect that the higher the HbA1c starting point, the greater the risk reduction. For example, taking someone from 8.6 to 8.2 might have a bigger benefit than taking someone from 7.2 to 6.8. It is linear in that for every 1% drop the risk halves. However most of the risk curves are almost flat by the time you reach the mid 6 region as half almost nothing is still almost nothing. It matters at the higher end where a 1% drop from an HbA1c of 14, which would give you serious risks, halves those risks and that is definitely significant. |
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Post by tayl5 on Aug 22, 2015 5:44:21 GMT -5
Cyn, your calculation assumes a linear relationship between HbA1c and risk reduction. I don't know what the relationship actually looks like but I would expect that the higher the HbA1c starting point, the greater the risk reduction. For example, taking someone from 8.6 to 8.2 might have a bigger benefit than taking someone from 7.2 to 6.8. It is linear in that for every 1% drop the risk halves. However most of the risk curves are almost flat by the time you reach the mid 6 region as half almost nothing is still almost nothing. It matters at the higher end where a 1% drop from an HbA1c of 14, which would give you serious risks, halves those risks and that is definitely significant. Here area few curves that I took from the web. The first is from a trial called The Diabetes Control and Complications Trial (DCCT) published in 2004 (http://www.medscape.com/viewarticle/470738) and the second from a study published in 2000 (http://www.ncbi.nlm.nih.gov/pubmed/10938048). It's probably an oversimplification to think of only one curve since the specific complication, age, time before treatment, etc. are all factors, but it looks like the relationship between HbA1c and relative risk is exponential, while similar data expressed as the complications per 1000 patient-years is linear. A close look at both curves suggests there is significant risk reduction associated with lowering HbA1c from 7 to 6. Or to put it another way, if you could, why wouldn't you?   |
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Yes, agree with your calculation that if a 1% HbA1c drop means a 40% risk reduction in microvascular complications … then a .4% drop in HbA1c equates to a 16% risk reduction (40% * .4). 
