009, 117, 171 & 175 Trial Results

[opc]

Aug 19, 2013 15:08:52 GMT -5 johnnicholas14 said:

Opc: please read the FDA Guidance on Non Inferiority. 0.24 is not the data point of interest, it's 0.40, the upper confidence bound. That number equals the margin the FDA suggested for the study. Consult the guidance.

John,

Confidence Intervals speak to the reliability of the data.  IOW, if we were to replicate the trial multiple times we are 95% sure the results would fall within the range (in this case) of .08 to .40.  But you can't just ignore the results.

In a nutshell, you are stating (in 009) because Afrezza's upper CI ( .40) was equal to the FDA margin (.40) therefore non-inferiority was not attained. But, the result, the difference, was .24 and within the CI.  We will have to agree to disagree. 

I would also add that throughout the FDA NI Guidance doc:

1) they repeatedly draw a distinction when the upper CI EXCEEDS M1. In our case we were equal to or less. The fact that MMRM produced a CI upper band less than .4 (.38 to be exact) would also be to our favor  

2) M1 (FDA's margin; in this case .40) is a pre-trail assumption, and p. 8 states, "Note that the clinically acceptable margin could be relaxed if the test drug were shown to have some important advantage (e.g., on safety or on a secondary endpoint)". 

I believe the latter point might apply to us.


btw-Where are you finding the FDA suggested margin? Are you getting that only from the 009 PR or elsewhere?

[johnnicholas14]

I believe the common practice for HbA1c reduction is to be within a margin of 0.40%. For sure MNKD mgmt has cited this number in previous NI trials. For example Robert Baughman cited 0.40 in the recent discussion of the data.

However, this number may change when the study concludes. It can be smaller, but not larger than 0.40%

HTH

jn

[opc]

wasn't doubting you. i had also read that in PR's. just wanted to know the genesis of the .40. thanks.

[mannmade]

A rare find... Just saw below on Yahoo Message Board.

finance.yahoo.com/mbview/threadview/?&bn=0243242e-59fb-3abc-8d27-962c7bf26a1d&tid=1376958617844-d92da4bf-2463-4c6d-9bfd-d09163dee16e&tls=la%2Cd%2C13%2C3

Interesting article explaining why A1C isn't a great marker for glycemic control.
Why is hemoglobin A1c unreliable?

While this sounds good in theory, the reality is not so black and white. The main problem is that there is actually a wide variation in how long red blood cells survive in different people. This study, for example, shows that red blood cells live longer than average at normal blood sugars. Researchers found that the lifetime of hemoglobin cells of diabetics turned over in as few as 81 days, while they lived as long as 146 days in non-diabetics.

This proves that the assumption that everyone’s red blood cells live for three months is false, and that hemoglobin A1c can’t be relied upon as a blood sugar marker. In a person with normal blood sugar, hemoglobin will be around for a lot longer, which means it will accumulate more sugar. This will drive up the A1c test result – but it doesn’t mean that person had too much sugar in their blood. It just means their hemoglobin lived longer and thus accumulated more sugar. The result is that people with normal blood sugar often test with unexpectedly high A1c levels.

This confused me early in my practice. I was testing blood sugar in three different ways for all new patients: fasting blood glucose, post-meal blood sugar (with a glucometer) and A1c. And I was surprised to see people with completely normal fasting and post-meal blood sugars, and A1c levels of 5.4%.

In fact this is not abnormal, when we understand that people with normal blood sugar often have longer-lived red blood cells – which gives those cells time to accumulate more sugar.

On the other hand, if someone is diabetic, their red blood cells live shorter lives than non-diabetics. This means diabetics and those with high blood sugar will test with falsely low A1c levels. And we already know that fasting blood glucose is the least sensitive marker for predicting future diabetes and heart disease. This is a serious problem, because fasting blood glucose and hemoglobin A1c are almost always the only tests doctors run to screen fo Less

[MnkdMainer (MM)]

I cannot pass up the opportunity to give my kudos to OPC. I've not posted prior to doing so on this board. I believe in calling a spade a spade, and I don't let my feathers get ruffled when someone disagrees with me. If I can't take the heat, I stay away from the fire. That said, I'm enjoying the warmth.

[MnkdMainer (MM)]

Liane, I respect you as I do OPC. I appreciate Spiro's frank comment, which is rationally based on the perception of the witness. I don't think there's any disrespect there. No ad hominems, just frank comments, which, again, are rationally based.

Needless to say, I share Spiro's observation to John, which is worth reiterating, "If you believe your interpretation of studies 009 and 171 are correct, it makes no sense for you to be long MNKD."

[BD]

Since OPC deleted all of his content from the original post in this thread, the thread becomes rather useless. I am locking it.

Additionally, OPC has elected to not be a participant of this board rather than to abide by the rules. Therefore, his account has been disabled.