[Mick]

I liked the old world, in which we could trust the FDA. Yeah, we had the occasional FDA mistake, and there was a whole industry of experts making money on how to influence the FDA. But we've never had serious reason to worry whether or not the FDA is operating with a political agenda. Sad to see this.

Me too. I would alter this to say that the FDA always did operate with a political agenda, but that agenda was mostly to do the best job possible and to not screw up. Sometimes there were behind the scenes back and forth on policy related questions but not political pressure on specific approvals. The problem we have today is that Trump wants to take credit for approvals, so he needs more of them, even if the treatment doesn't actually work. To what extent the FDA will be affected by this desire remains to be seen, but the idea that the president will weigh in on a decisions publicly is an abomination, IMHO.

I also believe it is singularly inappropriate for any employee of the FDA to ever, under any circumstances, tweet about their work. Given how formal the review process is, and how rigid the FDA is regarding document submission, the idea that somebody there would opine casually in public is just absurd. Getting the FDA to answer a direct question in your pre-IND meeting is hard enough, and then it might be OK for somebody to tweet about whatever they feel like? Yet we have this https://twitter.com/stevefda/status/1298...24452?s=21

I do however think the Convalescent Plasma EUA was appropriate. It is an emergency use measure, and that use will be monitored. It isn't an approval. The standards are lower and I think it met them (but in fairness I can't know that). I also think that the EUA will be rescinded as soon as an approved monoclonal antibody treatment is available, if not before.

This reminds me of an example from the accounting profession.  Years ago, each of the Big Five accounting firms (Arthur Andersen, Deloitte & Touche, Ernst & Young, KPMG and PricewaterhouseCoopers) had an internal Technical Standards Board (TSB), basically a group of lawyer/accountants who would opine as to whether specific audit/accounting treatments were legitimate or not when approached by audit partners in the field.  At four of those five firms, the TSB's pronunciations were law.  Period.  Full stop.  At one of those firms, the TSB's pronouncements were advisory -- the auditor in the field could override the TSB's decision.

Anyone want to guess which of the Big Five had that last scenario?  I'll give you a hint...it's why the Big Five is now the Big Four...

Trump overrides the FDA at our peril, not his. He's (again) playing with fire. I'm not an anti-vaxxer, not by a long stretch. Heck, my puppy won't have all of her vaccinations for six more weeks, and parvo's mortality rate for dogs makes COVID's human mortality rate look like a case of the sniffles, so I will continue to walk her around in a stroller for a month and a half. But I don't know that I'm going to trust the first vaccine that comes out...

[Mick]

I liked the old world, in which we could trust the FDA. Yeah, we had the occasional FDA mistake, and there was a whole industry of experts making money on how to influence the FDA. But we've never had serious reason to worry whether or not the FDA is operating with a political agenda. Sad to see this.

Me too. I would alter this to say that the FDA always did operate with a political agenda, but that agenda was mostly to do the best job possible and to not screw up. Sometimes there were behind the scenes back and forth on policy related questions but not political pressure on specific approvals. The problem we have today is that Trump wants to take credit for approvals, so he needs more of them, even if the treatment doesn't actually work. To what extent the FDA will be affected by this desire remains to be seen, but the idea that the president will weigh in on a decisions publicly is an abomination, IMHO.

I also believe it is singularly inappropriate for any employee of the FDA to ever, under any circumstances, tweet about their work. Given how formal the review process is, and how rigid the FDA is regarding document submission, the idea that somebody there would opine casually in public is just absurd. Getting the FDA to answer a direct question in your pre-IND meeting is hard enough, and then it might be OK for somebody to tweet about whatever they feel like? Yet we have this https://twitter.com/stevefda/status/1298...24452?s=21

I do however think the Convalescent Plasma EUA was appropriate. It is an emergency use measure, and that use will be monitored. It isn't an approval. The standards are lower and I think it met them (but in fairness I can't know that). I also think that the EUA will be rescinded as soon as an approved monoclonal antibody treatment is available, if not before.

This reminds me of an example from the accounting profession.  Years ago, each of the Big Five accounting firms (Arthur Andersen, Deloitte & Touche, Ernst & Young, KPMG and PricewaterhouseCoopers) had an internal Technical Standards Board (TSB), basically a group of lawyer/accountants who would opine as to whether specific audit/accounting treatments were legitimate or not when approached by audit partners in the field.  At four of those five firms, the TSB's pronunciations were law.  Period.  Full stop.  At one of those firms, the TSB's pronouncements were advisory -- the auditor in the field could override the TSB's decision.

Anyone want to guess which of the Big Five had that last scenario?  I'll give you a hint...it's why the Big Five is now the Big Four...

Trump overrides the FDA at our peril, not his. He's (again) playing with fire. I'm not an anti-vaxxer, not by a long stretch. Heck, my puppy won't have all of her vaccinations for six more weeks, and parvo's mortality rate for dogs makes COVID's human mortality rate look like a case of the sniffles, so I will continue to walk her around in a stroller for a month and a half. But I don't know that I'm going to trust the first vaccine that comes out...

[dabigv13]

The new FDA spokesperson was previously from "One America News Network", so she's well steeped in far right propaganda and conspiracy theories.

Again, very typical and normal for the FDA!

Roger Sollenberger (@SollenbergerRC) Tweeted:
wow how weird https://t.co/dEV4l5MMBG 

[tweet]https://twitter.com/SollenbergerRC/status/1298342653604573184?s=20[/tweet]

[dabigv13]

The new FDA spokesperson was previously from "One America News Network", so she's well steeped in far right propaganda and conspiracy theories.

Again, very typical and normal for the FDA!

Roger Sollenberger (@SollenbergerRC) Tweeted:
wow how weird https://t.co/dEV4l5MMBG 

[tweet]https://twitter.com/SollenbergerRC/status/1298342653604573184?s=20[/tweet]

[BostonCard]

Getting the FDA to answer a direct question in your pre-IND meeting is hard enough...

They'll answer; it's just that it will take 60 days to set up the meeting and the answer you are likely to get is "it will be an issue for review"

BC

[BostonCard]

Getting the FDA to answer a direct question in your pre-IND meeting is hard enough...

They'll answer; it's just that it will take 60 days to set up the meeting and the answer you are likely to get is "it will be an issue for review"

BC

[Goose]

Getting the FDA to answer a direct question in your pre-IND meeting is hard enough...

They'll answer; it's just that it will take 60 days to set up the meeting and the answer you are likely to get is "it will be an issue for review"

BC

Yep. Given these facts, it makes tweeting out anything at all about anything at all hard to justify IMHO.

Right now, the FDA is (attempting to) expanding like mad in the Cell and Gene Therapy area because they are inundated by various filings. The number of "quality" hires they can make is small, partly because they don't pay very well and partly due to the nature of the work. Those "good" hires they make are mostly short-timers who want it on their resume when they apply for a much better job in industry in 18 months. This expansion has also resulted in the usual musical chairs. Just what we don't need in the middle of an epidemic.

[Goose]

Getting the FDA to answer a direct question in your pre-IND meeting is hard enough...

They'll answer; it's just that it will take 60 days to set up the meeting and the answer you are likely to get is "it will be an issue for review"

BC

Yep. Given these facts, it makes tweeting out anything at all about anything at all hard to justify IMHO.

Right now, the FDA is (attempting to) expanding like mad in the Cell and Gene Therapy area because they are inundated by various filings. The number of "quality" hires they can make is small, partly because they don't pay very well and partly due to the nature of the work. Those "good" hires they make are mostly short-timers who want it on their resume when they apply for a much better job in industry in 18 months. This expansion has also resulted in the usual musical chairs. Just what we don't need in the middle of an epidemic.

[BostonCard]

I don't have an issue with him clarifying his testimony. I didn't think it was such a big deal; it struck me as an honest mistake, but I was happy to see him clarify.

I do think Twitter is the wrong forum for him to delve into the more substantive issues like uner what conditions an EUA would be revoked.

BC

[BostonCard]

I don't have an issue with him clarifying his testimony. I didn't think it was such a big deal; it struck me as an honest mistake, but I was happy to see him clarify.

I do think Twitter is the wrong forum for him to delve into the more substantive issues like uner what conditions an EUA would be revoked.

BC

[Goose]

I don't have an issue with him clarifying his testimony.  I didn't think it was such a big deal; it struck me as an honest mistake, but I was happy to see him clarify.

I do think Twitter is the wrong forum for him to delve into the more substantive issues like uner what conditions an EUA would be revoked.

BC

I agree it was a good idea for him to clarify his testimony, but wouldn't it have been better if he had released a statement through the FDA official channels? Tweeting something like this sends the message that social media is an appropriate channel for important FDA information to flow to the public. It also seems to set a precedent that other FDA folks can chime in if they want to do so without coordinating their messages through official channels. Both things seem like a very bad ideas to me.

[Goose]

I don't have an issue with him clarifying his testimony.  I didn't think it was such a big deal; it struck me as an honest mistake, but I was happy to see him clarify.

I do think Twitter is the wrong forum for him to delve into the more substantive issues like uner what conditions an EUA would be revoked.

BC

I agree it was a good idea for him to clarify his testimony, but wouldn't it have been better if he had released a statement through the FDA official channels? Tweeting something like this sends the message that social media is an appropriate channel for important FDA information to flow to the public. It also seems to set a precedent that other FDA folks can chime in if they want to do so without coordinating their messages through official channels. Both things seem like a very bad ideas to me.

[BostonCard]

Agree with Gottlieb here:

[tweet]https://twitter.com/ScottGottliebMD/status/1297850201403789312[/tweet]

The whole thread is a pretty good back and forth.

BC

[BostonCard]

Agree with Gottlieb here:

[tweet]https://twitter.com/ScottGottliebMD/status/1297850201403789312[/tweet]

The whole thread is a pretty good back and forth.

BC

[BostonCard]

Some thoughts on convalescent plasma:

https://blogs.sciencemag.org/pipeline/ar...e-politics

First, the medical aspects: in my view, for what that’s worth, convalescent plasma is likely to be at least somewhat helpful to hospitalized coronavirus patients. I think that its safety profile is likely to be good as well, and I really have no problem with it being used.

As Goose has noted, this is a stopgap measure until monoclonal antibodies (or cocktails) make it through clinical trials.

All of these considerations are taken care of by dosing monoclonal antibodies instead of the isolated antibody fractions, and as mAbs become more available, I would expect convalescent plasma to become less widely used. There are costs and production aspects to rolling out mAbs, but biologically, they are the perfected version of what convalescent plasma is trying to achieve.

The piece makes a very good point about the scientific drawbacks of being too lose with emergency use authorizations.

The problem is that we still haven’t generated any controlled clinical data on how useful it is. The Mayo-led data that were talked about during yesterday’s press conference had no control group, making that key question impossible to really answer. This shows the perverse danger of being too free with emergency use. If you just turn everyone loose on a bunch of therapies, they will be used under all sorts of conditions and the chances of getting a useful read on any of them go down. Look at our current situation: we have data on over 35,000 patients who have received convalescent plasma, but we still don’t have a good comparison to not receiving it. It shouldn’t have happened this way.

I think I've made this point before, and Mayo holds a lot of the blame here.  But also, the IND shouldn't have been a blank check to enroll thousands of patients in an uncontrolled study.  Maybe you get a couple hundred uncontrolled patients, and then the FDA should have said that it is time to move to a randomized, controlled study.

Finally, that leads us to the political aspect of this, damn it all. Yesterday’s press conference was announced the night before by the White House as concerning “a major therapeutic breakthrough”. The president and his allies echoed this language, with phrases like “historic breakthrough”, “a truly historic announcement”, and so on. It wasn’t. Convalescent plasma has been used for many decades in other infectious diseases, and it was tried very early on in the first countries affected by the coronavirus. Announcing an Emergency Use Authorization this late in the game for it in the US is, as I tried to convey in the above paragraph, closer to being something that we should be vaguely ashamed about.

And... yikes!

Commissioner Hahn’s and Sec. Azar’s obsequious statements yesterday (and the mangling of the statistics to make everything look rosier) were terrible to see. And the FDA’s own web site announcement includes the phrase “Another Achievement in Administration’s Fight Against Pandemic” in the headline, which is a first, to the best of my knowledge, since the FDA is not supposed to be tied to any particular presidential administration and is not supposed to be shining anyone’s shoes. But hey, if you’re going to have someone licking them, someone else has to step in with the rag right afterwards, and they’d better snap the thing so the big guy can hear it.

Sorry for the extensive quoting.

BC

[BostonCard]

Some thoughts on convalescent plasma:

https://blogs.sciencemag.org/pipeline/ar...e-politics

First, the medical aspects: in my view, for what that’s worth, convalescent plasma is likely to be at least somewhat helpful to hospitalized coronavirus patients. I think that its safety profile is likely to be good as well, and I really have no problem with it being used.

As Goose has noted, this is a stopgap measure until monoclonal antibodies (or cocktails) make it through clinical trials.

All of these considerations are taken care of by dosing monoclonal antibodies instead of the isolated antibody fractions, and as mAbs become more available, I would expect convalescent plasma to become less widely used. There are costs and production aspects to rolling out mAbs, but biologically, they are the perfected version of what convalescent plasma is trying to achieve.

The piece makes a very good point about the scientific drawbacks of being too lose with emergency use authorizations.

The problem is that we still haven’t generated any controlled clinical data on how useful it is. The Mayo-led data that were talked about during yesterday’s press conference had no control group, making that key question impossible to really answer. This shows the perverse danger of being too free with emergency use. If you just turn everyone loose on a bunch of therapies, they will be used under all sorts of conditions and the chances of getting a useful read on any of them go down. Look at our current situation: we have data on over 35,000 patients who have received convalescent plasma, but we still don’t have a good comparison to not receiving it. It shouldn’t have happened this way.

I think I've made this point before, and Mayo holds a lot of the blame here.  But also, the IND shouldn't have been a blank check to enroll thousands of patients in an uncontrolled study.  Maybe you get a couple hundred uncontrolled patients, and then the FDA should have said that it is time to move to a randomized, controlled study.

Finally, that leads us to the political aspect of this, damn it all. Yesterday’s press conference was announced the night before by the White House as concerning “a major therapeutic breakthrough”. The president and his allies echoed this language, with phrases like “historic breakthrough”, “a truly historic announcement”, and so on. It wasn’t. Convalescent plasma has been used for many decades in other infectious diseases, and it was tried very early on in the first countries affected by the coronavirus. Announcing an Emergency Use Authorization this late in the game for it in the US is, as I tried to convey in the above paragraph, closer to being something that we should be vaguely ashamed about.

And... yikes!

Commissioner Hahn’s and Sec. Azar’s obsequious statements yesterday (and the mangling of the statistics to make everything look rosier) were terrible to see. And the FDA’s own web site announcement includes the phrase “Another Achievement in Administration’s Fight Against Pandemic” in the headline, which is a first, to the best of my knowledge, since the FDA is not supposed to be tied to any particular presidential administration and is not supposed to be shining anyone’s shoes. But hey, if you’re going to have someone licking them, someone else has to step in with the rag right afterwards, and they’d better snap the thing so the big guy can hear it.

Sorry for the extensive quoting.

BC

[g1313]

Minor quibble on the last point - the FDA is the "Food and Drug Administration" is it possible that is the "Administration" they are referring to in the headline, and not the presidential administration?

On the other hand, this is somewhat belied by the statement in the FDA announcement from Azar that does specifically reference the Trump Administration.

[g1313]

Minor quibble on the last point - the FDA is the "Food and Drug Administration" is it possible that is the "Administration" they are referring to in the headline, and not the presidential administration?

On the other hand, this is somewhat belied by the statement in the FDA announcement from Azar that does specifically reference the Trump Administration.

[BostonCard]

Despite "administration" being in the title, the FDA refers to themselves as "the Agency".

BC

[BostonCard]

Despite "administration" being in the title, the FDA refers to themselves as "the Agency".

BC

[chrisk]

Hahn fires spokeswoman Emily Miller after convalescent plasma debacle.

She had joined the FDA a week earlier from the White House.

https://www.cnn.com/2020/08/28/politics/...index.html

[chrisk]

Hahn fires spokeswoman Emily Miller after convalescent plasma debacle.

She had joined the FDA a week earlier from the White House.

https://www.cnn.com/2020/08/28/politics/...index.html

[BostonCard]

This Emily Miller?

https://www.prnewswire.com/news-releases...77543.html

BC

[BostonCard]

This Emily Miller?

https://www.prnewswire.com/news-releases...77543.html

BC

[chrisk]

This Emily Miller?

https://www.prnewswire.com/news-releases...77543.html

BC

Based on her wikipedia entry and the Daily Beast article on her firing, she creates controversy wherever she goes. It is not surprising she lasted only 11 days at the FDA despite being assigned from the White House.

[chrisk]

This Emily Miller?

https://www.prnewswire.com/news-releases...77543.html

BC

Based on her wikipedia entry and the Daily Beast article on her firing, she creates controversy wherever she goes. It is not surprising she lasted only 11 days at the FDA despite being assigned from the White House.

[oldalum]

from an ID specialist's blog post on an NEJM website:

"Never mind that . . . the randomized trials of this treatment have so far been disappointing.
Or that the observational data the FDA used to justify their action come from an unpublished study not yet subject to peer review.
Or that the very experts employed by the government to review plasma’s safety and efficacy have as recently as last week raised important concerns about the lack of convincing evidence for this treatment.
Or that this action by the FDA will almost certainly jeopardize any existing randomized trials of convalescent plasma in the United States.
Or that the person from the FDA who reviewed the plasma data had his name redacted from the memo.
. . . I have not heard from a single ID specialist who believes this action was supported by existing data, and indeed our professional society agrees.
Convalescent plasma may work to help people with COVID-19. But if it does, we don’t know how much, or who are the most likely to benefit, or how to select the right donors. . . .
For the true evidence, we’ll have to wait for the randomized, controlled clinical trials.
The ones going on in other countries."

[oldalum]

from an ID specialist's blog post on an NEJM website:

"Never mind that . . . the randomized trials of this treatment have so far been disappointing.
Or that the observational data the FDA used to justify their action come from an unpublished study not yet subject to peer review.
Or that the very experts employed by the government to review plasma’s safety and efficacy have as recently as last week raised important concerns about the lack of convincing evidence for this treatment.
Or that this action by the FDA will almost certainly jeopardize any existing randomized trials of convalescent plasma in the United States.
Or that the person from the FDA who reviewed the plasma data had his name redacted from the memo.
. . . I have not heard from a single ID specialist who believes this action was supported by existing data, and indeed our professional society agrees.
Convalescent plasma may work to help people with COVID-19. But if it does, we don’t know how much, or who are the most likely to benefit, or how to select the right donors. . . .
For the true evidence, we’ll have to wait for the randomized, controlled clinical trials.
The ones going on in other countries."