|
|
Post by babaoriley on Aug 28, 2015 12:50:29 GMT -5
mn, I'm pretty sure the FDA was guided by a series of letters from Marty S. in determining the non-inferiority standard.  |
|
|
|
Post by mssciguy on Aug 28, 2015 13:07:53 GMT -5
mn, I'm pretty sure the FDA was guided by a series of letters from Marty S. in determining the non-inferiority standard. Shrek is a self-serving _______ . That said, I can tell you from my years in pharma that FDA works with them and imposes requirements (as an example) to insure that supplies of insulin will be available at all times even if some national emergency occurred (little known post-911 fact and not at all cheap). So there is skepticism about new kids on the block and we can't forget that the (former?) FDA administrator's husband is a hedge fund guy. Yeah all kinds of politics. The older I get the more I look back and go, "wow -- I really didn't have any clue how things really happen" and once you've been in govt you know for sure. |
|
|
|
Post by dreamboatcruise on Aug 28, 2015 17:12:48 GMT -5
I do not understand the issue of follow up doses being a problem in trial design? There are very simple and elegant ways around this and there is absolutely no reason for needing (or even wanting) follow up prandial injections. This is, to me at least, a non issue and has nothing to do with why a superiority trail can't or isn't being done. My interpretation of the discussion of placebo injections was that what would be considered ideal is a double blind study where each patient is given both inhaled and injected with one being placebo and the other not and neither patient nor doctor knowing who is on which. Maybe if the baseline is assuming that currently RAA injections are simply used once per meal without correction then you could have a protocol whereby a trial subject injected 20 minutes before a meal, inhaled at the start of a meal and then tested an hour after meal and only dosed a correction with inhaled (which might or might not be placebo). It just seems complicated to have this sort of double blind with each participant having to follow a regime consisting of the union of what would be best for two different forms of prandial insulin. Seems like compliance might be a problem. Though I'm sure your knowledge of how these trials are designed is far better than mine. I easily could be way off base. |
|
|
|
Post by mssciguy on Aug 28, 2015 17:27:17 GMT -5
I do not understand the issue of follow up doses being a problem in trial design? There are very simple and elegant ways around this and there is absolutely no reason for needing (or even wanting) follow up prandial injections. This is, to me at least, a non issue and has nothing to do with why a superiority trail can't or isn't being done. My interpretation of the discussion of placebo injections was that what would be considered ideal is a double blind study where each patient is given both inhaled and injected with one being placebo and the other not and neither patient nor doctor knowing who is on which. Maybe if the baseline is assuming that currently RAA injections are simply used once per meal without correction then you could have a protocol whereby a trial subject injected 20 minutes before a meal, inhaled at the start of a meal and then tested an hour after meal and only dosed a correction with inhaled (which might or might not be placebo). It just seems complicated to have this sort of double blind with each participant having to follow a regime consisting of the union of what would be best for two different forms of prandial insulin. Seems like compliance might be a problem. Though I'm sure your knowledge of how these trials are designed is far better than mine. I easily could be way off base. Placebo controls do not make as much sense with something having such a measurable outcome as insulin.... Placebo outcomes do make sense, however, in neuroscience, where a placebo can cure depression almost as well as an antidepressant in 50% of cases. Insulin regulation is not subject to placebo effect, I am almost 100% sure of that but would love discussion otherwise. Pharma is a dirty business. Afrezza is one of the most sensible medications to hit the market in decades.... Col. Eli Lilly would have loved it, but the current Lilly has it's head in Wall Street's _______ If you don't know the story of Col. Lilly, he's a very admirable guy, kind of an Al Mann--- but things have changed over the centuries. |
|
|
|
Post by dreamboatcruise on Aug 28, 2015 17:38:00 GMT -5
mssciguy... the placebo in this case is simply used to make the study double blind since they are different routes of administration. All patients would have one or the other insulin if the study was just to explore superiority of Afrezza over traditional RAA. The placebo effect isn't what they'd be looking for... and I think you're right that a placebo control arm for insulin has never found the placebo effect to work in reducing A1c. Placebos are good for some things. Depression as you mentioned and surprisingly, back pain.
|
|
|
|
Post by mssciguy on Aug 28, 2015 17:53:39 GMT -5
mssciguy... the placebo in this case is simply used to make the study double blind since they are different routes of administration. All patients would have one or the other insulin if the study was just to explore superiority of Afrezza over traditional RAA. The placebo effect isn't what they'd be looking for... and I think you're right that a placebo control arm for insulin has never found the placebo effect to work in reducing A1c. Placebos are good for some things. Depression as you mentioned and surprisingly, back pain. Agree completely, but it's a whole different field of medicine or psychology even, when we can be told we are taking a placebo and still get a placebo effect... endlessly fascinating. And in regards to back pain, as someone who foolishly ran several dozen marathons, the best way I can find to avoid pain is to be really engaged with some activity that is promising... amazing but that is how the brain works and we don't understand it at all... sorry to go off topic but for sure, this same kind of reasoning could be applied to control of food intake for diabetics for example |
|
|
|
Post by jpg on Aug 28, 2015 22:32:18 GMT -5
This is, to me at least, a non issue and has nothing to do with why a superiority trail can't or isn't being done. My interpretation of the discussion of placebo injections was that what would be considered ideal is a double blind study where each patient is given both inhaled and injected with one being placebo and the other not and neither patient nor doctor knowing who is on which. Maybe if the baseline is assuming that currently RAA injections are simply used once per meal without correction then you could have a protocol whereby a trial subject injected 20 minutes before a meal, inhaled at the start of a meal and then tested an hour after meal and only dosed a correction with inhaled (which might or might not be placebo). It just seems complicated to have this sort of double blind with each participant having to follow a regime consisting of the union of what would be best for two different forms of prandial insulin. Seems like compliance might be a problem. First off I think we need to convince diabetic experts (patients and physicians) and not necessarily the FDA so a best practice comparison might be better than a weirdly crafted FDA directed trial. I think I understand what you are saying. Having a perfectly blind study is always a good thing but comparing therapies in ways that they aren't or rarely ever used (routine or frequent 2nd dose of sc insulin (and blinded on top of that)) could be unethical (i.e. dangerous). Best practices in Afrezza vs best practices in sc prandial use would be the only study needed and probably the only study possible. Complex double blinding using a central decision process could work but again as you stated would be challenging. At a certain point jumping through hoops for the FDAs blessing makes less sense than convincing patents and patient advocate groups? |
|
|
|
Post by harryx1 on Aug 29, 2015 9:01:12 GMT -5
|
|
Deleted
Deleted Member
Posts: 0
|
Post by Deleted on Aug 29, 2015 12:38:42 GMT -5
|
|
