[DocSavage87]

Just watched a lecture and Q&A with Arturo Casadevall @ Johns Hopkins on the large effort that sprouted up to use convalescent plasma.  Fascinating and great historical perspective on how it's been used repeatedly over the last century.  Didn't realize that they've administered CP to over 70,000 patients in US.

- Results show pretty health drops in mortality and works better if given early as one would expect.
- He strongly recommended its use as a prophylactic in high-risk situations since they feel it is not higher risk than just plasma.
- Will be used throughout the world, particularly in other countries that may not have easy access to advanced pharmaceuticals but will always have recovered patients.
- Since different doses can vary with the constituent ingredients it's a hard task to setup data tracking and analysis for pinpointing effective agents.

[DocSavage87]

Just watched a lecture and Q&A with Arturo Casadevall @ Johns Hopkins on the large effort that sprouted up to use convalescent plasma.  Fascinating and great historical perspective on how it's been used repeatedly over the last century.  Didn't realize that they've administered CP to over 70,000 patients in US.

- Results show pretty health drops in mortality and works better if given early as one would expect.
- He strongly recommended its use as a prophylactic in high-risk situations since they feel it is not higher risk than just plasma.
- Will be used throughout the world, particularly in other countries that may not have easy access to advanced pharmaceuticals but will always have recovered patients.
- Since different doses can vary with the constituent ingredients it's a hard task to setup data tracking and analysis for pinpointing effective agents.

[BostonCard]

Taking antibody rich plasma from patients who have recovered from COVID-19 looks to be a promising treatment for patients fighting the infection, and there is a long history of using convalescent plasma in other diseases.  Among Trump's endorsements, this is one of the less cockamamie.  However, enthusiasm for it seems to be outrunning the data, and Francis Collins Anthony Fauci have had to intervene to temper enthusiasm and make sure we get the data supporting its use before an EUA is granted.

https://www.nytimes.com/2020/08/19/us/po...id-19.html

As an aside, I think the Mayo clinic is being irresponsible in pushing plasma to the degree it has without setting up a randomized, placebo controlled trial.  I know that it is complicated.  I know that there is good reason to be enthusiastic about plasma.  But to give it to 66,000 people and not conduct a high quality trial with it represents a colossal missed opportunity.  WIth even a fraction of those patients enrolled in a randomized, placebo controlled trial, we would have a clear answer of whether the drug works by now.

BC

[BostonCard]

Taking antibody rich plasma from patients who have recovered from COVID-19 looks to be a promising treatment for patients fighting the infection, and there is a long history of using convalescent plasma in other diseases.  Among Trump's endorsements, this is one of the less cockamamie.  However, enthusiasm for it seems to be outrunning the data, and Francis Collins Anthony Fauci have had to intervene to temper enthusiasm and make sure we get the data supporting its use before an EUA is granted.

https://www.nytimes.com/2020/08/19/us/po...id-19.html

As an aside, I think the Mayo clinic is being irresponsible in pushing plasma to the degree it has without setting up a randomized, placebo controlled trial.  I know that it is complicated.  I know that there is good reason to be enthusiastic about plasma.  But to give it to 66,000 people and not conduct a high quality trial with it represents a colossal missed opportunity.  WIth even a fraction of those patients enrolled in a randomized, placebo controlled trial, we would have a clear answer of whether the drug works by now.

BC

[DocSavage87]

Taking antibody rich plasma from patients who have recovered from COVID-19 looks to be a promising treatment for patients fighting the infection, and there is a long history of using convalescent plasma in other diseases.  Among Trump's endorsements, this is one of the less cockamamie.  However, enthusiasm for it seems to be outrunning the data, and Francis Collins Anthony Fauci have had to intervene to temper enthusiasm and make sure we get the data supporting its use before an EUA is granted.

https://www.nytimes.com/2020/08/19/us/po...id-19.html

As an aside, I think the Mayo clinic is being irresponsible in pushing plasma to the degree it has without setting up a randomized, placebo controlled trial.  I know that it is complicated.  I know that there is good reason to be enthusiastic about plasma.  But to give it to 66,000 people and not conduct a high quality trial with it represents a colossal missed opportunity.  WIth even a fraction of those patients enrolled in a randomized, placebo controlled trial, we would have a clear answer of whether the drug works by now.

BC

I already had started a thread about convalescent plasma after my institution hosted Casadevall's talk.  He's one of the main initiators of the effort and wrote the WSJ op-ed on it back in March.  He showed some data and mentioned the backlash about the lack of well-controlled trial.  The data he presented I think was from the expanded access program and was not controlled.

From the NYTimes piece, it sounds like part of the problem is that people don't want to risk getting placebo because they feel strongly enough about the utility of it.  I agree that they need some hard data.  It's a problem though when some docs feel strongly enough about it (and would consider non-treatment to be unethical), *and* they have the means to do it outside the clinical trial.  So really it's the expanded access program that's at fault?

[DocSavage87]

Taking antibody rich plasma from patients who have recovered from COVID-19 looks to be a promising treatment for patients fighting the infection, and there is a long history of using convalescent plasma in other diseases.  Among Trump's endorsements, this is one of the less cockamamie.  However, enthusiasm for it seems to be outrunning the data, and Francis Collins Anthony Fauci have had to intervene to temper enthusiasm and make sure we get the data supporting its use before an EUA is granted.

https://www.nytimes.com/2020/08/19/us/po...id-19.html

As an aside, I think the Mayo clinic is being irresponsible in pushing plasma to the degree it has without setting up a randomized, placebo controlled trial.  I know that it is complicated.  I know that there is good reason to be enthusiastic about plasma.  But to give it to 66,000 people and not conduct a high quality trial with it represents a colossal missed opportunity.  WIth even a fraction of those patients enrolled in a randomized, placebo controlled trial, we would have a clear answer of whether the drug works by now.

BC

I already had started a thread about convalescent plasma after my institution hosted Casadevall's talk.  He's one of the main initiators of the effort and wrote the WSJ op-ed on it back in March.  He showed some data and mentioned the backlash about the lack of well-controlled trial.  The data he presented I think was from the expanded access program and was not controlled.

From the NYTimes piece, it sounds like part of the problem is that people don't want to risk getting placebo because they feel strongly enough about the utility of it.  I agree that they need some hard data.  It's a problem though when some docs feel strongly enough about it (and would consider non-treatment to be unethical), *and* they have the means to do it outside the clinical trial.  So really it's the expanded access program that's at fault?

[BostonCard]

When I was in medical school, everyone "knew" that hormone replacement therapy was good for post-menopausal women, and specifically, in addition to treating symptoms, also reduced the risk of cardiovascular disease.  It was based on large number non-randomized studies, including the very large nurses health study (https://www.2minutemedicine.com/nurses-h...cs-series/).  The knowledge was so well engrained that when the women's health initiative proposed doing a randomized, placebo-controlled study, a number of experts in the field objected, saying it would be unethical to give some women placebo when hormone replacement so obviously works.

Suffice it to say, the WHI showed that not only do hormone replacement not work, but there looked to be some harm

https://www.nhlbi.nih.gov/science/womens...iative-whi

But even after the WHI showed evidence of harm, not all physicians believed the data, given the decades of experience and dozens of observational studies showing that hormone replacement reduced the risk of death (to be fair, there are benefits of HRT and some subrgroups do seem to benefit).  However, the furore it caused was so bad, that a second study was commissioned.

An obvious way to do get around the placebo problem would be a head-to-head trial against remdisivir.  Then patients are guaranteed to get at least one treatment, and you can figure out which is better.

BC

[BostonCard]

When I was in medical school, everyone "knew" that hormone replacement therapy was good for post-menopausal women, and specifically, in addition to treating symptoms, also reduced the risk of cardiovascular disease.  It was based on large number non-randomized studies, including the very large nurses health study (https://www.2minutemedicine.com/nurses-h...cs-series/).  The knowledge was so well engrained that when the women's health initiative proposed doing a randomized, placebo-controlled study, a number of experts in the field objected, saying it would be unethical to give some women placebo when hormone replacement so obviously works.

Suffice it to say, the WHI showed that not only do hormone replacement not work, but there looked to be some harm

https://www.nhlbi.nih.gov/science/womens...iative-whi

But even after the WHI showed evidence of harm, not all physicians believed the data, given the decades of experience and dozens of observational studies showing that hormone replacement reduced the risk of death (to be fair, there are benefits of HRT and some subrgroups do seem to benefit).  However, the furore it caused was so bad, that a second study was commissioned.

An obvious way to do get around the placebo problem would be a head-to-head trial against remdisivir.  Then patients are guaranteed to get at least one treatment, and you can figure out which is better.

BC

[Goose]

It appears that the FDA is going to slow down a bit based on objections from some fairly heavy hitters.
https://www.nytimes.com/2020/08/19/us/po...id-19.html
It is certainly too bad that the Mayo Clinic didn't design a "better" trial, because they certainly had a large "N". The FDA has been behaving in a very FDA way lately, and I guess on the whole I think that is a good thing.
https://www.cbsnews.com/news/fda-rejects...aceutical/

[Goose]

It appears that the FDA is going to slow down a bit based on objections from some fairly heavy hitters.
https://www.nytimes.com/2020/08/19/us/po...id-19.html
It is certainly too bad that the Mayo Clinic didn't design a "better" trial, because they certainly had a large "N". The FDA has been behaving in a very FDA way lately, and I guess on the whole I think that is a good thing.
https://www.cbsnews.com/news/fda-rejects...aceutical/

[BostonCard]

I already had started a thread about convalescent plasma after my institution hosted Casadevall's talk.  He's one of the main initiators of the effort and wrote the WSJ op-ed on it back in March.  He showed some data and mentioned the backlash about the lack of well-controlled trial.  The data he presented I think was from the expanded access program and was not controlled.

Thanks, I merged the two threads.

BC

[BostonCard]

I already had started a thread about convalescent plasma after my institution hosted Casadevall's talk.  He's one of the main initiators of the effort and wrote the WSJ op-ed on it back in March.  He showed some data and mentioned the backlash about the lack of well-controlled trial.  The data he presented I think was from the expanded access program and was not controlled.

Thanks, I merged the two threads.

BC

[BostonCard]

Pot, meet Kettle.

https://www.fiercebiotech.com/biotech/pr...asma-delay

Trump, speaking at a press conference Wednesday and having already been hit with blowback over his endorsement of other unapproved therapies, said: “You have lot of people over there [the FDA] that don't want to rush things. They want to do it after Nov. 3,” implying the reason was political and aimed at denting his reelection chances.

BC

[BostonCard]

Pot, meet Kettle.

https://www.fiercebiotech.com/biotech/pr...asma-delay

Trump, speaking at a press conference Wednesday and having already been hit with blowback over his endorsement of other unapproved therapies, said: “You have lot of people over there [the FDA] that don't want to rush things. They want to do it after Nov. 3,” implying the reason was political and aimed at denting his reelection chances.

BC

[DocSavage87]

When I was in medical school, everyone "knew" that hormone replacement therapy was good for post-menopausal women, and specifically, in addition to treating symptoms, also reduced the risk of cardiovascular disease.  It was based on large number non-randomized studies, including the very large nurses health study (https://www.2minutemedicine.com/nurses-h...cs-series/).  The knowledge was so well engrained that when the women's health initiative proposed doing a randomized, placebo-controlled study, a number of experts in the field objected, saying it would be unethical to give some women placebo when hormone replacement so obviously works.

Suffice it to say, the WHI showed that not only do hormone replacement not work, but there looked to be some harm

https://www.nhlbi.nih.gov/science/womens...iative-whi

But even after the WHI showed evidence of harm, not all physicians believed the data, given the decades of experience and dozens of observational studies showing that hormone replacement reduced the risk of death (to be fair, there are benefits of HRT and some subrgroups do seem to benefit).  However, the furore it caused was so bad, that a second study was commissioned.

An obvious way to do get around the placebo problem would be a head-to-head trial against remdisivir.  Then patients are guaranteed to get at least one treatment, and you can figure out which is better.

BC

Head-to-head vs remdesivir is a good idea, particularly at this time since there's some clinical study support for remdesivir.  One of the issues could be defining what exactly is the nature of the convalescent plasma.  Unlike pharmaceuticals, CP is a mishmash of various substances that vary depending on donor.  Casadevall said one of the key things they are working on is identifying effective agents so CP can be categorized.  You could almost imagine "platinum", "gold", "silver", "copper", "tin" CP where the best CP is used directly and the worst grade is further processed through combination, purification, etc to maximize effectiveness while minimizing other issues arising from pooling plasma.

So the effectiveness of CP also depends on the selection of donors (when they recovered and titres of Ab, etc).  Not saying this is the reason why they shouldn't have started the randomized clinical trial earlier, but it's something that can have an impact on a study.

[DocSavage87]

When I was in medical school, everyone "knew" that hormone replacement therapy was good for post-menopausal women, and specifically, in addition to treating symptoms, also reduced the risk of cardiovascular disease.  It was based on large number non-randomized studies, including the very large nurses health study (https://www.2minutemedicine.com/nurses-h...cs-series/).  The knowledge was so well engrained that when the women's health initiative proposed doing a randomized, placebo-controlled study, a number of experts in the field objected, saying it would be unethical to give some women placebo when hormone replacement so obviously works.

Suffice it to say, the WHI showed that not only do hormone replacement not work, but there looked to be some harm

https://www.nhlbi.nih.gov/science/womens...iative-whi

But even after the WHI showed evidence of harm, not all physicians believed the data, given the decades of experience and dozens of observational studies showing that hormone replacement reduced the risk of death (to be fair, there are benefits of HRT and some subrgroups do seem to benefit).  However, the furore it caused was so bad, that a second study was commissioned.

An obvious way to do get around the placebo problem would be a head-to-head trial against remdisivir.  Then patients are guaranteed to get at least one treatment, and you can figure out which is better.

BC

Head-to-head vs remdesivir is a good idea, particularly at this time since there's some clinical study support for remdesivir.  One of the issues could be defining what exactly is the nature of the convalescent plasma.  Unlike pharmaceuticals, CP is a mishmash of various substances that vary depending on donor.  Casadevall said one of the key things they are working on is identifying effective agents so CP can be categorized.  You could almost imagine "platinum", "gold", "silver", "copper", "tin" CP where the best CP is used directly and the worst grade is further processed through combination, purification, etc to maximize effectiveness while minimizing other issues arising from pooling plasma.

So the effectiveness of CP also depends on the selection of donors (when they recovered and titres of Ab, etc).  Not saying this is the reason why they shouldn't have started the randomized clinical trial earlier, but it's something that can have an impact on a study.

[dabigv13]

Pot, meet Kettle.

https://www.fiercebiotech.com/biotech/pr...asma-delay

Trump, speaking at a press conference Wednesday and having already been hit with blowback over his endorsement of other unapproved therapies, said: “You have lot of people over there [the FDA] that don't want to rush things. They want to do it after Nov. 3,” implying the reason was political and aimed at denting his reelection chances.

BC

The fact he's bitching about this makes it pretty clear he tried to put his thumb on the scales. Very normal behavior between POTUS and FDA. How these things usually go.

[dabigv13]

Pot, meet Kettle.

https://www.fiercebiotech.com/biotech/pr...asma-delay

Trump, speaking at a press conference Wednesday and having already been hit with blowback over his endorsement of other unapproved therapies, said: “You have lot of people over there [the FDA] that don't want to rush things. They want to do it after Nov. 3,” implying the reason was political and aimed at denting his reelection chances.

BC

The fact he's bitching about this makes it pretty clear he tried to put his thumb on the scales. Very normal behavior between POTUS and FDA. How these things usually go.

[Goose]

So the effectiveness of CP also depends on the selection of donors (when they recovered and titres of Ab, etc).  Not saying this is the reason why they shouldn't have started the randomized clinical trial earlier, but it's something that can have an impact on a study.

As you probably already know, these characteristics also make it more difficult to build a therapy around CP. You don't know exactly what you have in the bag and the next bag may be real different. This is also a big reason monoclonal antibodies will be preferred when a "good" mix is determined. You get the same antibody concentrations each time so at least the dose delivered is precisely known. Unfortunately that is going to take some time, so CP needs to be evaluated, despite the difficulties. If monoclonals make it obsolete very quickly, so much the better.

[Goose]

So the effectiveness of CP also depends on the selection of donors (when they recovered and titres of Ab, etc).  Not saying this is the reason why they shouldn't have started the randomized clinical trial earlier, but it's something that can have an impact on a study.

As you probably already know, these characteristics also make it more difficult to build a therapy around CP. You don't know exactly what you have in the bag and the next bag may be real different. This is also a big reason monoclonal antibodies will be preferred when a "good" mix is determined. You get the same antibody concentrations each time so at least the dose delivered is precisely known. Unfortunately that is going to take some time, so CP needs to be evaluated, despite the difficulties. If monoclonals make it obsolete very quickly, so much the better.

[DocSavage87]

So the effectiveness of CP also depends on the selection of donors (when they recovered and titres of Ab, etc).  Not saying this is the reason why they shouldn't have started the randomized clinical trial earlier, but it's something that can have an impact on a study.

As you probably already know, these characteristics also make it more difficult to build a therapy around CP. You don't know exactly what you have in the bag and the next bag may be real different. This is also a big reason monoclonal antibodies will be preferred when a "good" mix is determined. You get the same antibody concentrations each time so at least the dose delivered is precisely known. Unfortunately that is going to take some time, so CP needs to be evaluated, despite the difficulties. If monoclonals make it obsolete very quickly, so much the better.

Sure, but we don't have monoclonal Abs yet, and there's some work to be done to determine the best agent as well.  Remember that the CP initiative started early March and was treating patients by beginning of April.  At that time it was compassionate care.  They need controlled studies but the track record of those pushing this Tx have a better track record than those pushing HCQ.  I think it shows how well-designed clinical studies need to be started ASAP before end-arounds allow word of mouth to build with increasing reluctance to participate in those critical studies.

[DocSavage87]

So the effectiveness of CP also depends on the selection of donors (when they recovered and titres of Ab, etc).  Not saying this is the reason why they shouldn't have started the randomized clinical trial earlier, but it's something that can have an impact on a study.

As you probably already know, these characteristics also make it more difficult to build a therapy around CP. You don't know exactly what you have in the bag and the next bag may be real different. This is also a big reason monoclonal antibodies will be preferred when a "good" mix is determined. You get the same antibody concentrations each time so at least the dose delivered is precisely known. Unfortunately that is going to take some time, so CP needs to be evaluated, despite the difficulties. If monoclonals make it obsolete very quickly, so much the better.

Sure, but we don't have monoclonal Abs yet, and there's some work to be done to determine the best agent as well.  Remember that the CP initiative started early March and was treating patients by beginning of April.  At that time it was compassionate care.  They need controlled studies but the track record of those pushing this Tx have a better track record than those pushing HCQ.  I think it shows how well-designed clinical studies need to be started ASAP before end-arounds allow word of mouth to build with increasing reluctance to participate in those critical studies.

[Goose]

Sure, but we don't have monoclonal Abs yet, and there's some work to be done to determine the best agent as well.  Remember that the CP initiative started early March and was treating patients by beginning of April.  At that time it was compassionate care.  They need controlled studies but the track record of those pushing this Tx have a better track record than those pushing HCQ.

For sure agree. There are well accepted mechanisms of action associated with CP. In no way can it be considered similar to the HCQ conjectures.

I think it shows how well-designed clinical studies need to be started ASAP before end-arounds allow word of mouth to build with increasing reluctance to participate in those critical studies.

Also agree. These studies take time, so the sooner the better. The studies may also reveal things about CP therapies that allow it to be even more effective that it is at present.  It may be some populations benefit much more than others, or that some dose profile work better than others.

[Goose]

Sure, but we don't have monoclonal Abs yet, and there's some work to be done to determine the best agent as well.  Remember that the CP initiative started early March and was treating patients by beginning of April.  At that time it was compassionate care.  They need controlled studies but the track record of those pushing this Tx have a better track record than those pushing HCQ.

For sure agree. There are well accepted mechanisms of action associated with CP. In no way can it be considered similar to the HCQ conjectures.

I think it shows how well-designed clinical studies need to be started ASAP before end-arounds allow word of mouth to build with increasing reluctance to participate in those critical studies.

Also agree. These studies take time, so the sooner the better. The studies may also reveal things about CP therapies that allow it to be even more effective that it is at present.  It may be some populations benefit much more than others, or that some dose profile work better than others.

[BostonCard]

Donald Trump is going to announce an EUA for convalescent plasma.


https://www.cnbc.com/2020/08/23/trump-wi...tment.html

So, with that, I think it's unlikely that we will get randomized trials of convalescent plasma in the US.  We will have to wait to see what other countries find.  I find the folks at Mayo to have been supremely irresponsible in not offering CP as part of a randomized, placebo controlled trial, at least once early findings were promising.

The kindest thing I can say is that at least the biological rationale for it is pretty strong, but still, at this point in the pandemic with number of people treated, we ought to have a much better picture of whether it is effective, what populations are most likely to benefit, when is the best time to give it, what are the side effects, how does it work with other therapy, etc?  Instead, all we have is "we think it should work, and it probably works best when given in the first three days".

BC

[BostonCard]

Donald Trump is going to announce an EUA for convalescent plasma.


https://www.cnbc.com/2020/08/23/trump-wi...tment.html

So, with that, I think it's unlikely that we will get randomized trials of convalescent plasma in the US.  We will have to wait to see what other countries find.  I find the folks at Mayo to have been supremely irresponsible in not offering CP as part of a randomized, placebo controlled trial, at least once early findings were promising.

The kindest thing I can say is that at least the biological rationale for it is pretty strong, but still, at this point in the pandemic with number of people treated, we ought to have a much better picture of whether it is effective, what populations are most likely to benefit, when is the best time to give it, what are the side effects, how does it work with other therapy, etc?  Instead, all we have is "we think it should work, and it probably works best when given in the first three days".

BC

[Goose]

Donald Trump is going to announce an EUA for convalescent plasma.


https://www.cnbc.com/2020/08/23/trump-wi...tment.html

So, with that, I think it's unlikely that we will get randomized trials of convalescent plasma in the US.  We will have to wait to see what other countries find.  I find the folks at Mayo to have been supremely irresponsible in not offering CP as part of a randomized, placebo controlled trial, at least once early findings were promising.

The kindest thing I can say is that at least the biological rationale for it is pretty strong, but still, at this point in the pandemic with number of people treated, we ought to have a much better picture of whether it is effective, what populations are most likely to benefit, when is the best time to give it, what are the side effects, how does it work with other therapy, etc?  Instead, all we have is "we think it should work, and it probably works best when given in the first three days".

BC

I guess the best justification for the EUA is that it should at least be safe, even if it turns out to not be tremendously effective.

[Goose]

Donald Trump is going to announce an EUA for convalescent plasma.


https://www.cnbc.com/2020/08/23/trump-wi...tment.html

So, with that, I think it's unlikely that we will get randomized trials of convalescent plasma in the US.  We will have to wait to see what other countries find.  I find the folks at Mayo to have been supremely irresponsible in not offering CP as part of a randomized, placebo controlled trial, at least once early findings were promising.

The kindest thing I can say is that at least the biological rationale for it is pretty strong, but still, at this point in the pandemic with number of people treated, we ought to have a much better picture of whether it is effective, what populations are most likely to benefit, when is the best time to give it, what are the side effects, how does it work with other therapy, etc?  Instead, all we have is "we think it should work, and it probably works best when given in the first three days".

BC

I guess the best justification for the EUA is that it should at least be safe, even if it turns out to not be tremendously effective.

[dabigv13]

Not necessarily. Any transfusion has certain risks, even if low in modern medicine.

Trump's politicization of the FDA continues, to the nation's detriment.

https://www.politico.com/news/2020/08/23...eat-400306

It's really infuriating how badly he is ***** this up. This will obviously make the majority of the country who opposes him less trustful of any eventual vaccine. It will make RCT's more difficult. It will make his minority of supporters, who are already more likely to spurn mask or other health measures, even more likely to see the pandemic as less critical or nearer to the end because of his miracle cure. It will make the scientists within the FDA even more wary of crossing Trump, perhaps encouraging them to approve an unsafe vaccine.

What it won't do is help any people with covid. As mentioned this is not a difficult therapy to find or administer if possibly indicated.

[dabigv13]

Not necessarily. Any transfusion has certain risks, even if low in modern medicine.

Trump's politicization of the FDA continues, to the nation's detriment.

https://www.politico.com/news/2020/08/23...eat-400306

It's really infuriating how badly he is ***** this up. This will obviously make the majority of the country who opposes him less trustful of any eventual vaccine. It will make RCT's more difficult. It will make his minority of supporters, who are already more likely to spurn mask or other health measures, even more likely to see the pandemic as less critical or nearer to the end because of his miracle cure. It will make the scientists within the FDA even more wary of crossing Trump, perhaps encouraging them to approve an unsafe vaccine.

What it won't do is help any people with covid. As mentioned this is not a difficult therapy to find or administer if possibly indicated.

[Goose]

I am going to crawl out on a limb here a bit and say the FDA was undoubtedly intending to issue an EUA for convalescent plasma until Dr. Anthony Fauci and Dr. Francis Collins,  (as well as others) raised their concerns. How much effect anybody else from the administration had on getting the FDA to proceed with the EUA is unknown. Given the other EUAs that have been given for COVID-19 related things, I think it would be very difficult for the FDA to not grant one in this case. I would expect that this therapy will be very closely followed by the FDA and the EUA will be withdrawn if any safety issues show up.
Unfortunately, this approval will probably greatly reduce the odds of a real placebo controlled study on this therapy. This therapy already suffers from the fact that nobody is going to make real money on it, so the incentive to do a real good clinical trial is lacking. Additionally, it is probable this therapy will be obsolete within a year, replaced by monoclonal antibodies and/or a vaccine.
As far as political pressure on the FDA goes, there often is some, from many quarters. In general, I think the worst effect of the pressure is that it creates the impression that any action the FDA eventually takes was not freely chosen. This undermines the FDA's credibility, usually for no reason. The FDA lives in the real world. They are very powerful, but they also know that people need the therapies they are asked to approve (or not). Usually, the FDA errs on the side of caution. With the COVID-19 epidemic, that is not nearly so true.

[Goose]

I am going to crawl out on a limb here a bit and say the FDA was undoubtedly intending to issue an EUA for convalescent plasma until Dr. Anthony Fauci and Dr. Francis Collins,  (as well as others) raised their concerns. How much effect anybody else from the administration had on getting the FDA to proceed with the EUA is unknown. Given the other EUAs that have been given for COVID-19 related things, I think it would be very difficult for the FDA to not grant one in this case. I would expect that this therapy will be very closely followed by the FDA and the EUA will be withdrawn if any safety issues show up.
Unfortunately, this approval will probably greatly reduce the odds of a real placebo controlled study on this therapy. This therapy already suffers from the fact that nobody is going to make real money on it, so the incentive to do a real good clinical trial is lacking. Additionally, it is probable this therapy will be obsolete within a year, replaced by monoclonal antibodies and/or a vaccine.
As far as political pressure on the FDA goes, there often is some, from many quarters. In general, I think the worst effect of the pressure is that it creates the impression that any action the FDA eventually takes was not freely chosen. This undermines the FDA's credibility, usually for no reason. The FDA lives in the real world. They are very powerful, but they also know that people need the therapies they are asked to approve (or not). Usually, the FDA errs on the side of caution. With the COVID-19 epidemic, that is not nearly so true.

[oregontim]

Trump's politicization of the FDA continues, to the nation's detriment.


https://www.politico.com/news/2020/08/23...eat-400306

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.

[oregontim]

Trump's politicization of the FDA continues, to the nation's detriment.


https://www.politico.com/news/2020/08/23...eat-400306

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.

[terry]

Recent article about some of the data behind this decision --

F.D.A. ‘Grossly Misrepresented’ Blood Plasma Data, Scientists Say

Many experts — including a scientist who worked on the Mayo Clinic study — were bewildered about where a key statistic came from.

https://www.nytimes.com/2020/08/24/healt...e=Homepage

Another similar article --

https://www.washingtonpost.com/health/20...tists-say/

[terry]

Recent article about some of the data behind this decision --

F.D.A. ‘Grossly Misrepresented’ Blood Plasma Data, Scientists Say

Many experts — including a scientist who worked on the Mayo Clinic study — were bewildered about where a key statistic came from.

https://www.nytimes.com/2020/08/24/healt...e=Homepage

Another similar article --

https://www.washingtonpost.com/health/20...tists-say/

[dabigv13]

He's gonna be a straight arrow on the vaccines though, no doubt. Just a minor hiccup, definitely not a Trump stooge.

[dabigv13]

He's gonna be a straight arrow on the vaccines though, no doubt. Just a minor hiccup, definitely not a Trump stooge.

[Goose]

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

[tweet]https://twitter.com/stevefda/status/1298071620414824452?s=21[/tweet]

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.

[Goose]

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

[tweet]https://twitter.com/stevefda/status/1298071620414824452?s=21[/tweet]

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.