JAMA article

[savzak]

@calhasan209: $MNKD long but the recent #Afrezza article in #jama @jama_current is interesting. What are your thoughts regarding? t.co/FzswKuvN3J

t.co/FzswKuvN3J

Nate's Notes response:

@natesnotes: @calhasan209 @jama_current I have not read the whole article... from which studies is the "only modestly effective..." claim derived? Thx!

[oscarlonzo]

The JAMA article is simply a reprint of this:

medical letter

One thing it mentions is that "Approval of Afrezza was based on 2 unpublished clinical studies..." Why were they not published? Publishing would make them more accessible to clinicians for review.

[blindhog1]

I saw only a portion of this article mentioned on twitter this evening. I looked it up on JAMA but could only get the first page. Thanks for the whole paper. Basically this is what we have known for the last year but what caught my attention was the Conclusion.

    "CONCLUSION — Afrezza, the only inhaled formulation of insulin currently available in the US, appears to be only modestly effective in reducing HbA1c. Cough is a common side effect and the long-term pulmonary safety of inhaling insulin is unknown."

Since we're currently getting feedback from multiple users, I think it is fair to say that the results from Afrezza is much much more than "only modestly effective" and the pulmonary issue is why we are looking at the labeling. Users have stated that the first few doses have caused a cough but that is only initial (probably the same as a non-smoker trying their first cigarettes).

[esstan2001]

Jun 16, 2015 3:56:44 GMT -5 blindhog1 said:

I saw only a portion of this article mentioned on twitter this evening. I looked it up on JAMA but could only get the first page. Thanks for the whole paper. Basically this is what we have known for the last year but what caught my attention was the Conclusion.

    "CONCLUSION — Afrezza, the only inhaled formulation of insulin currently available in the US, appears to be only modestly effective in reducing HbA1c. Cough is a common side effect and the long-term pulmonary safety of inhaling insulin is unknown."

Since we're currently getting feedback from multiple users, I think it is fair to say that the results from Afrezza is much much more than "only modestly effective" and the pulmonary issue is why we are looking at the labeling. Users have stated that the first few doses have caused a cough but that is only initial (probably the same as a non-smoker trying their first cigarettes).

The conclusion over generalizes. As stated, It should have been qualified with,

...only modestly effective in reducing HbA1c when restricted to the titration and dosing regimen specified under the FDA trials that were designed to demonstrate non-inferiority.

Then note the exceptional anecdotal data being consistently presented via social media, and mention how this warrants further investigation. 

That's what I'd do.    :-)

[suebeeee1]

Jun 16, 2015 6:45:46 GMT -5 esstan2001 said:

Jun 16, 2015 3:56:44 GMT -5 blindhog1 said:

Yeah....while that is what you would do, JAMA is a medical journal, not a blog.  They sort through hundreds of thousands of bits of information each year.  All they have to go by are the trials that were done under very specific standards to show "non-inferiority" only.  Many, many substance have failed in trials where they had previously had tons of anecdotal information.

And, they have the delightful packaging brought to us by the FDA.  So much for being given latitude in their response.

I would just ignore JAMA for now, until a published paper can come out showing how Afrezza works to battle diabetes instead of merely controling it

[Chris-C]

Jun 16, 2015 0:02:07 GMT -5 oscarlonzo said:

The JAMA article is simply a reprint of this:

medical letter

One thing it mentions is that "Approval of Afrezza was based on 2 unpublished clinical studies..." Why were they not published? Publishing would make them more accessible to clinicians for review.

It is important to keep in mind the nature of The Medical Letter. This publication is fundamentally a subscription based professional newsletter that summarizes drug information in a concise, readable style to make it easier for practicing physicians to keep abreast of pharmaceutical developments relevant to practice.

For new drugs, it simply takes information off the FDA website. In the Medical Letter issue "reviewing" Afrezza, it did the same. So neither JAMA or The Medical Letter had access to evidence other than the trials reviewed by the FDA in its approval process. Much has been made by shorts who point to the very conservative conclusions based on non-inferiority studies done according to negotiated FDA study protocols. This is perhaps another reason why initiation of the dosing study by Sanofi is important.

As I pointed out in another post several months ago, The Medical Letter perhaps is given greater importance than it deserves from a scientific standpoint. It is not published by a scientific organization, nor does it fund or conduct studies, and it does not have a staff of scientists. It claims to do comparative reviews that are evaluated by a panel of experts who agree on the conclusions of the articles it provides. The number of experts consulted, their credentials, and the specific process used in achieving consensus not described in detail.

The publishing organization itself is set up as a tax exempt non-profit 501c3 to provide continuing medical education to physicians and others in the health care industry. You can review its Form 990, a required and detailed IRS filing that lists the principals and employees of the organization and its budget. A little sleuthing shows that the primary content editor of the medical letter is a non practicing pharmacist with unknown scientific experience, a clinical doctorate in pharmacy, and three years of clinical practice at Sloan Kettering. She is assisted by other PharmD's. Much of the editorial work involves reading scientific publications and publicly available material from the FDA, synthesizing it, forming an independent and conservative conclusion, and having that conclusion reviewed by one or more clinical experts.

Characterizing or citing The Medical Letter as a scientific source may go beyond what is justified, since it is fundamentally a continuing medical education newsletter, fashioned on the model of Consumer's Report.  Its primary value is that it is objective and independent, so its reviews are intended to avoid influence by the pharmaceutical industry.

[lynn]

Take this FWIW but I wanted to share about the convo I had with our Intensivist today at the Hospital where I work . Mind you , it was during the middle of rounds , it was a busy day ( in fact, I was pulled to a different unit right after )so I didn't get to follow up .

Another Nurse was talking about her Diabetic patient so I seized the opportunity to bring up Afrezza . His reply was ( from my memory ) . "Yeah I've heard about it , I read about it in JAMA, it isn't available yet & there were 4 cases of Cancer " . My reply , it has been available in the States since Feb, early adopters are lowering their A1C's and experiencing non diabetic blood sugars for the first time in their lives . I also told him a bit about the trials (2 cancer pts were ex smokers) ect .

He DIDN'T even know it was available . The other Nurse standing next me had her interest piqued & said WOW . He then said " We'll wait about 8 years , we'll let Europe have it first , bc there were those cancer cases . He didn't seem to register anything else that I said (& I like this Doc ) . I wish I had the chance to speak to him longer . My question would have been who is "We"? . Is it Kaiser ? Or your personal opinion . But unfortunately I didn't get the chance .

So , just sharing what I heard today . It doesn't shake my confidence at all ! But I did gain some insight . The leaders like Dr.Bode ect need to be convinced ( as they are starting to already ) & will be even more so as more A1C results start rolling in . Then, these leaders will shift the thoughts of those that are more close minded . And it won't take 8 years

Lynn

[Chris-C]

Slow steady increases in awareness are needed. People resisted phones. cars and airplanes when they were first introduced, and despite the impatience many here feel - unless it is mentioned on CSI or a reality show- awareness will take some time to develop among providers and the public. Mr Mann commented in his 2014 interview that attitudes about Exubera would exist but would be overcome.