[Genuine Realist]

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

[Genuine Realist]

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

[OutsiderFan]

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

[OutsiderFan]

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

[OutsiderFan]

I'm guessing this doctor touting HCQ that the Right Wing is elevating as credible, thinks you can also inject Lysol to kill the virus. I mean what credible MD doesn't know the perils of sex with demons and witches?

https://www.thedailybeast.com/stella-imm...hloroquine

[OutsiderFan]

I'm guessing this doctor touting HCQ that the Right Wing is elevating as credible, thinks you can also inject Lysol to kill the virus. I mean what credible MD doesn't know the perils of sex with demons and witches?

https://www.thedailybeast.com/stella-imm...hloroquine

[lex24]

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them.

---

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them. I’m glad we have you to tell us what is right and wrong.  Here’s his bio. Obviously a hack :

https://medicine.yale.edu/profile/harvey_risch/

[lex24]

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them.

---

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them. I’m glad we have you to tell us what is right and wrong.  Here’s his bio. Obviously a hack :

https://medicine.yale.edu/profile/harvey_risch/

[Genuine Realist]

I'm guessing this doctor touting HCQ that the Right Wing is elevating as credible, thinks you can also inject Lysol to kill the virus. I mean what credible MD doesn't know the perils of sex with demons and witches?

https://www.thedailybeast.com/stella-imm...hloroquine

I write a little note commenting on to extent to which politicization has interfered with public dialog here, and you respond with a screeching rant about the Right wing. Thanks for proving my point.

The writer is evidently the chief of the Yale Epidemiological Program (or some such), a respected professional, and making a point about the efficacy of the drug in certain clinical situations. So of course that has to be a cue for an hysterical denunciation.

[Genuine Realist]

I'm guessing this doctor touting HCQ that the Right Wing is elevating as credible, thinks you can also inject Lysol to kill the virus. I mean what credible MD doesn't know the perils of sex with demons and witches?

https://www.thedailybeast.com/stella-imm...hloroquine

I write a little note commenting on to extent to which politicization has interfered with public dialog here, and you respond with a screeching rant about the Right wing. Thanks for proving my point.

The writer is evidently the chief of the Yale Epidemiological Program (or some such), a respected professional, and making a point about the efficacy of the drug in certain clinical situations. So of course that has to be a cue for an hysterical denunciation.

[OutsiderFan]

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them.

---

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them. I’m glad we have you to tell us what is right and wrong.  Here’s his bio. Obviously a hack :

https://medicine.yale.edu/profile/harvey_risch/

He's not the hack to which I was referring.  Sorry if I conflated the two.

I am aware there has been some anecdotal success with HCQ and Zinc (as I think I posted in another thread).  But there really isn't any clinical evidence that HCQ is in anyway some sort of panacea or game-changer. Now, India, which was a great proponent of HCQ and used it as a prophylactic for doctors, has cooled to its efficacy as a worthwhile treatment.

This isn't a political issue for me. It's only about what will and won't work, based on evidence and facts. HCQ may have some marginal benefits, if used at the outset of infection with Zinc, but it's not material enough to really make much of a difference. The idea that if only we gave everyone HCQ, the pandemic would be gone, is just stupid on steroids.  So what exactly is the point, of pumping up HCQ, when it isn't a solution?

[OutsiderFan]

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them.

---

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them. I’m glad we have you to tell us what is right and wrong.  Here’s his bio. Obviously a hack :

https://medicine.yale.edu/profile/harvey_risch/

He's not the hack to which I was referring.  Sorry if I conflated the two.

I am aware there has been some anecdotal success with HCQ and Zinc (as I think I posted in another thread).  But there really isn't any clinical evidence that HCQ is in anyway some sort of panacea or game-changer. Now, India, which was a great proponent of HCQ and used it as a prophylactic for doctors, has cooled to its efficacy as a worthwhile treatment.

This isn't a political issue for me. It's only about what will and won't work, based on evidence and facts. HCQ may have some marginal benefits, if used at the outset of infection with Zinc, but it's not material enough to really make much of a difference. The idea that if only we gave everyone HCQ, the pandemic would be gone, is just stupid on steroids.  So what exactly is the point, of pumping up HCQ, when it isn't a solution?

[Genuine Realist]

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them.

---

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them. I’m glad we have you to tell us what is right and wrong.  Here’s his bio. Obviously a hack :

https://medicine.yale.edu/profile/harvey_risch/

He's not the hack to which I was referring.  Sorry if I conflated the two.

I am aware there has been some anecdotal success with HCQ and Zinc (as I think I posted in another thread).  But there really isn't any clinical evidence that HCQ is in anyway some sort of panacea or game-changer. Now, India, which was a great proponent of HCQ and used it as a prophylactic for doctors, has cooled to its efficacy as a worthwhile treatment.

This isn't a political issue for me. It's only about what will and won't work, based on evidence and facts. HCQ may have some marginal benefits, if used at the outset of infection with Zinc, but it's not material enough to really make much of a difference. The idea that if only we gave everyone HCQ, the pandemic would be gone, is just stupid on steroids.  So what exactly is the point, of pumping up HCQ, when it isn't a solution?

What the good doc is saying is that it's a useful drug, nor a miracle drug, underutilized because of the political backwash.

[Genuine Realist]

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them.

---

In this professor's view, the drug is a valuable treatment resource ignored for political reasons.

I don't have the expertise to evaluate this opinion, other than to note that the writer is highly credentialed and apparently with no axe to grind. 

It is fair to say that these oscillations in professional opinion, all delivered with emphasis and certitude, go a long way toward making the public cynical.

Watch for a coordinated Right Wing media hissy fit over this now. Anything that can deflect blame from the disaster of a federal response to the pandemic, rather than actually having a strategic plan to get it under control, will be tried. 

You know this is just so much bullshit because those who scream like stuck pigs about this won't mention one word about the downplaying of the virus or objecting to mask wearing, two things that had orders of magnitude greater impact on the pandemic's spread and the damage it has wrought in the U.S., than anything about HCQ. I could document more examples, or just point to Brazil, a country that has apparently been using HCQ, with similar results as the U.S. not using it.

Us Vs Them. I’m glad we have you to tell us what is right and wrong.  Here’s his bio. Obviously a hack :

https://medicine.yale.edu/profile/harvey_risch/

He's not the hack to which I was referring.  Sorry if I conflated the two.

I am aware there has been some anecdotal success with HCQ and Zinc (as I think I posted in another thread).  But there really isn't any clinical evidence that HCQ is in anyway some sort of panacea or game-changer. Now, India, which was a great proponent of HCQ and used it as a prophylactic for doctors, has cooled to its efficacy as a worthwhile treatment.

This isn't a political issue for me. It's only about what will and won't work, based on evidence and facts. HCQ may have some marginal benefits, if used at the outset of infection with Zinc, but it's not material enough to really make much of a difference. The idea that if only we gave everyone HCQ, the pandemic would be gone, is just stupid on steroids.  So what exactly is the point, of pumping up HCQ, when it isn't a solution?

What the good doc is saying is that it's a useful drug, nor a miracle drug, underutilized because of the political backwash.

[BostonCard]

Lex referred to this professor in this thread: https://thecardboard.org/board/showthrea...hloroquine

Here is his article in AJE.

The editorial was written in May.  As I noted, since May when the epidemiological articles came out, multiple randomized, placebo controlled trials of HCQ ± Azithromycin in a variety of settings of COVID-19 have come out, all of them showing no effect.  There is always a possibility that the negative results are due to the fact that the wrong population was sampled (too severe or too mild disease to benefit), or that it wasn't given at the right time (too soon, or too late).  However, my experience is that when multiple studies across a spectrum of disease and in a variety of settings are negative, it would not be compatible with a whopping effect in a particular subgroup or a particular setting.  At best the drug is of very limited benefit in a certain population in a particular setting, but most likely, hydroxychloroquine probably doesn't work for COVID-19.

Here is a recent systematic review of hydroxychloroquine ± azithromycin for COVID-19:

https://pubmed.ncbi.nlm.nih.gov/32683212/

Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low.

The drug isn't going unusued because of political considerations; it is going unused because it doesn't seem to work.  That's nothing personal against HCQ.  Most drugs don't work.  The likelihood of success of a drug entering clinical trials is 15% at best.  There are lots of very promising drugs that work in vitro, or in mice, or in theory, or in small observational studies, that don't work in randomized, placebo controlled studies.  I long ago learned not to get too attached to a particular program.

BC

[BostonCard]

Lex referred to this professor in this thread: https://thecardboard.org/board/showthrea...hloroquine

Here is his article in AJE.

The editorial was written in May.  As I noted, since May when the epidemiological articles came out, multiple randomized, placebo controlled trials of HCQ ± Azithromycin in a variety of settings of COVID-19 have come out, all of them showing no effect.  There is always a possibility that the negative results are due to the fact that the wrong population was sampled (too severe or too mild disease to benefit), or that it wasn't given at the right time (too soon, or too late).  However, my experience is that when multiple studies across a spectrum of disease and in a variety of settings are negative, it would not be compatible with a whopping effect in a particular subgroup or a particular setting.  At best the drug is of very limited benefit in a certain population in a particular setting, but most likely, hydroxychloroquine probably doesn't work for COVID-19.

Here is a recent systematic review of hydroxychloroquine ± azithromycin for COVID-19:

https://pubmed.ncbi.nlm.nih.gov/32683212/

Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low.

The drug isn't going unusued because of political considerations; it is going unused because it doesn't seem to work.  That's nothing personal against HCQ.  Most drugs don't work.  The likelihood of success of a drug entering clinical trials is 15% at best.  There are lots of very promising drugs that work in vitro, or in mice, or in theory, or in small observational studies, that don't work in randomized, placebo controlled studies.  I long ago learned not to get too attached to a particular program.

BC

[OutsiderFan]

BC, have you seen anything to suggest HCQ efficacy when delivered with Zinc?  And then, also at an early time in the virus' time in the host? These are the two variables I've seen discussed that have provided anecdotal positive impact. Still, it's hard for me to imagine that if even a very specific application of HCQ was efficacious, that it wouldn't have been more widely adopted. Again, politics has the middle of a donut to do with HCQ use or non-use. The people who think it does really need to get off their high horse about it.

[OutsiderFan]

BC, have you seen anything to suggest HCQ efficacy when delivered with Zinc?  And then, also at an early time in the virus' time in the host? These are the two variables I've seen discussed that have provided anecdotal positive impact. Still, it's hard for me to imagine that if even a very specific application of HCQ was efficacious, that it wouldn't have been more widely adopted. Again, politics has the middle of a donut to do with HCQ use or non-use. The people who think it does really need to get off their high horse about it.

[lex24]

Lex referred to this professor in this thread: https://thecardboard.org/board/showthrea...hloroquine

Here is his article in AJE.

The editorial was written in May.  As I noted, since May when the epidemiological articles came out, multiple randomized, placebo controlled trials of HCQ ± Azithromycin in a variety of settings of COVID-19 have come out, all of them showing no effect.  There is always a possibility that the negative results are due to the fact that the wrong population was sampled (too severe or too mild disease to benefit), or that it wasn't given at the right time (too soon, or too late).  However, my experience is that when multiple studies across a spectrum of disease and in a variety of settings are negative, it would not be compatible with a whopping effect in a particular subgroup or a particular setting.  At best the drug is of very limited benefit in a certain population in a particular setting, but most likely, hydroxychloroquine probably doesn't work for COVID-19.

Here is a recent systematic review of hydroxychloroquine ± azithromycin for COVID-19:

https://pubmed.ncbi.nlm.nih.gov/32683212/

Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low.

The drug isn't going unusued because of political considerations; it is going unused because it doesn't seem to work.  That's nothing personal against HCQ.  Most drugs don't work.  The likelihood of success of a drug entering clinical trials is 15% at best.  There are lots of very promising drugs that work in vitro, or in mice, or in theory, or in small observational studies, that don't work in randomized, placebo controlled studies.  I long ago learned not to get too attached to a particular program.

BC

---

Lex referred to this professor in this thread: https://thecardboard.org/board/showthrea...hloroquine

Here is his article in AJE.

The editorial was written in May.  As I noted, since May when the epidemiological articles came out, multiple randomized, placebo controlled trials of HCQ ± Azithromycin in a variety of settings of COVID-19 have come out, all of them showing no effect.  There is always a possibility that the negative results are due to the fact that the wrong population was sampled (too severe or too mild disease to benefit), or that it wasn't given at the right time (too soon, or too late).  However, my experience is that when multiple studies across a spectrum of disease and in a variety of settings are negative, it would not be compatible with a whopping effect in a particular subgroup or a particular setting.  At best the drug is of very limited benefit in a certain population in a particular setting, but most likely, hydroxychloroquine probably doesn't work for COVID-19.

Here is a recent systematic review of hydroxychloroquine ± azithromycin for COVID-19:

https://pubmed.ncbi.nlm.nih.gov/32683212/

Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low.

The drug isn't going unusued because of political considerations; it is going unused because it doesn't seem to work.  That's nothing personal against HCQ.  Most drugs don't work.  The likelihood of success of a drug entering clinical trials is 15% at best.  There are lots of very promising drugs that work in vitro, or in mice, or in theory, or in small observational studies, that don't work in randomized, placebo controlled studies.  I long ago learned not to get too attached to a particular program.

BC

And if I’m not mistaken a peer reviewed study came out in July suggesting it may be beneficial is used early. BC your word means more to me than most people on this board because you have a background to support it. But frankly in this climate I don’t see how you can make the blanket statement that politics has nothing to do with this. 

I mean we’re living in times where people try to burn down the courthouse in Oakland and the mayor gently chides them by essentially saying that they’re playing into Trimps hands. Pretty amazing.

[lex24]

Lex referred to this professor in this thread: https://thecardboard.org/board/showthrea...hloroquine

Here is his article in AJE.

The editorial was written in May.  As I noted, since May when the epidemiological articles came out, multiple randomized, placebo controlled trials of HCQ ± Azithromycin in a variety of settings of COVID-19 have come out, all of them showing no effect.  There is always a possibility that the negative results are due to the fact that the wrong population was sampled (too severe or too mild disease to benefit), or that it wasn't given at the right time (too soon, or too late).  However, my experience is that when multiple studies across a spectrum of disease and in a variety of settings are negative, it would not be compatible with a whopping effect in a particular subgroup or a particular setting.  At best the drug is of very limited benefit in a certain population in a particular setting, but most likely, hydroxychloroquine probably doesn't work for COVID-19.

Here is a recent systematic review of hydroxychloroquine ± azithromycin for COVID-19:

https://pubmed.ncbi.nlm.nih.gov/32683212/

Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low.

The drug isn't going unusued because of political considerations; it is going unused because it doesn't seem to work.  That's nothing personal against HCQ.  Most drugs don't work.  The likelihood of success of a drug entering clinical trials is 15% at best.  There are lots of very promising drugs that work in vitro, or in mice, or in theory, or in small observational studies, that don't work in randomized, placebo controlled studies.  I long ago learned not to get too attached to a particular program.

BC

---

Lex referred to this professor in this thread: https://thecardboard.org/board/showthrea...hloroquine

Here is his article in AJE.

The editorial was written in May.  As I noted, since May when the epidemiological articles came out, multiple randomized, placebo controlled trials of HCQ ± Azithromycin in a variety of settings of COVID-19 have come out, all of them showing no effect.  There is always a possibility that the negative results are due to the fact that the wrong population was sampled (too severe or too mild disease to benefit), or that it wasn't given at the right time (too soon, or too late).  However, my experience is that when multiple studies across a spectrum of disease and in a variety of settings are negative, it would not be compatible with a whopping effect in a particular subgroup or a particular setting.  At best the drug is of very limited benefit in a certain population in a particular setting, but most likely, hydroxychloroquine probably doesn't work for COVID-19.

Here is a recent systematic review of hydroxychloroquine ± azithromycin for COVID-19:

https://pubmed.ncbi.nlm.nih.gov/32683212/

Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low.

The drug isn't going unusued because of political considerations; it is going unused because it doesn't seem to work.  That's nothing personal against HCQ.  Most drugs don't work.  The likelihood of success of a drug entering clinical trials is 15% at best.  There are lots of very promising drugs that work in vitro, or in mice, or in theory, or in small observational studies, that don't work in randomized, placebo controlled studies.  I long ago learned not to get too attached to a particular program.

BC

And if I’m not mistaken a peer reviewed study came out in July suggesting it may be beneficial is used early. BC your word means more to me than most people on this board because you have a background to support it. But frankly in this climate I don’t see how you can make the blanket statement that politics has nothing to do with this. 

I mean we’re living in times where people try to burn down the courthouse in Oakland and the mayor gently chides them by essentially saying that they’re playing into Trimps hands. Pretty amazing.

[M T]

I wonder why the Yale professor has a different view than the systematic review BC referenced.  I'm sure he knew of that systematic review (published online July 11).

I looked at the systematic review. As I read it, of the studies involving HCQ for prophylaxis, they discounted all the studies but one.  While they gave their judgement of the studies (risk of bias, low quality, etc.), I didn't see the reason for those judgements.


So I looked at that one study (published June 3), which I'm also sure the Yale professor was aware of.  400+ subjects in each arm (avg age about 40, mostly health care workers), with medication or placebo starting within 4 days of apparent exposure.  They randomized the subjects so there obviously isn't any intentional biases.  I did wonder why they had a binary categorization of "high risk exposure" (10 minutes within 6' of positive cases without mask or shield).  [The rest of us can take away the fact that only about 1 out 8 total exposures were judged as getting the disease.]  Were there no subjects with much higher exposures (1 hour; 24 hour)?  Were all these indoor, small room exposures, or were some outdoor?  Were the subjects exposed to high risk situations (intubation), or to coughing individuals, or just to individuals that were mildly symptomatic?   Where in the progress of the progression of COVID were the exposures (pre-symptomatic/asymptomatic, early symptomatic, late symptomatic)?

What shocked me was that only 20 of the 113 subjects with probable COVID-19 had positive PCR tests.  Why didn't the study conduct those tests themselves?  "We assumed that health care workers would have access to Covid-19 testing if symptomatic; however, access to testing was limited throughout the trial period [mid-March - early May]"    AFAICT, the report does not indicate how many, if any, got negative PCR results.  Since they don't mention that, I guess any such results were for those that had a negative clinical diagnosis.   Three tested that positive during the 14 day period had no symptoms within 14 days but developed them later.  One tested positive during the 14 day period but never reported symptoms.

To me, this failure to test is almost enough to discount this study.  How many of the 700+ subjects that had no symptoms had an asymptomatic case?   The common belief is that the asymptomatic (or very mildly symptomatic) cases are on the order of the number of symptomatic cases.   If one hypothesizes that the total number of cases was 2x the detected cases, that would have made the percentages: Placebo 28.6% vs HCQ 23.6%.  Would that have been a significant reduction in cases?

Otherwise, I felt the study seemed pretty good (but this is not my area of expertise).

[M T]

I wonder why the Yale professor has a different view than the systematic review BC referenced.  I'm sure he knew of that systematic review (published online July 11).

I looked at the systematic review. As I read it, of the studies involving HCQ for prophylaxis, they discounted all the studies but one.  While they gave their judgement of the studies (risk of bias, low quality, etc.), I didn't see the reason for those judgements.


So I looked at that one study (published June 3), which I'm also sure the Yale professor was aware of.  400+ subjects in each arm (avg age about 40, mostly health care workers), with medication or placebo starting within 4 days of apparent exposure.  They randomized the subjects so there obviously isn't any intentional biases.  I did wonder why they had a binary categorization of "high risk exposure" (10 minutes within 6' of positive cases without mask or shield).  [The rest of us can take away the fact that only about 1 out 8 total exposures were judged as getting the disease.]  Were there no subjects with much higher exposures (1 hour; 24 hour)?  Were all these indoor, small room exposures, or were some outdoor?  Were the subjects exposed to high risk situations (intubation), or to coughing individuals, or just to individuals that were mildly symptomatic?   Where in the progress of the progression of COVID were the exposures (pre-symptomatic/asymptomatic, early symptomatic, late symptomatic)?

What shocked me was that only 20 of the 113 subjects with probable COVID-19 had positive PCR tests.  Why didn't the study conduct those tests themselves?  "We assumed that health care workers would have access to Covid-19 testing if symptomatic; however, access to testing was limited throughout the trial period [mid-March - early May]"    AFAICT, the report does not indicate how many, if any, got negative PCR results.  Since they don't mention that, I guess any such results were for those that had a negative clinical diagnosis.   Three tested that positive during the 14 day period had no symptoms within 14 days but developed them later.  One tested positive during the 14 day period but never reported symptoms.

To me, this failure to test is almost enough to discount this study.  How many of the 700+ subjects that had no symptoms had an asymptomatic case?   The common belief is that the asymptomatic (or very mildly symptomatic) cases are on the order of the number of symptomatic cases.   If one hypothesizes that the total number of cases was 2x the detected cases, that would have made the percentages: Placebo 28.6% vs HCQ 23.6%.  Would that have been a significant reduction in cases?

Otherwise, I felt the study seemed pretty good (but this is not my area of expertise).

[BostonCard]

A former FDA commissioner weighs in:

https://www.axios.com/hydroxychloroquine...ntent=1100

I would never say something "definitely" doesn't work just because I've been surprised before (though usually things go in the opposite direction; something I was "sure" would work doesn't).  But otherwise I agree with Gottlieb; the evidence points strongly to HCQ not working, based on the fact that the highest quality studies (large, randomized, placebo controlled studies with rigorous endpoints) consistently show the drug doesn't work.  That the medical evidence doesn't universally point in the same direction is par for the course in the medical literature, but I would focus on studies least likely to be affected by bias.

BC

[BostonCard]

A former FDA commissioner weighs in:

https://www.axios.com/hydroxychloroquine...ntent=1100

I would never say something "definitely" doesn't work just because I've been surprised before (though usually things go in the opposite direction; something I was "sure" would work doesn't).  But otherwise I agree with Gottlieb; the evidence points strongly to HCQ not working, based on the fact that the highest quality studies (large, randomized, placebo controlled studies with rigorous endpoints) consistently show the drug doesn't work.  That the medical evidence doesn't universally point in the same direction is par for the course in the medical literature, but I would focus on studies least likely to be affected by bias.

BC

[dabigv13]

The very simple fact of the matter is that the only reason anybody is still talking about this drug is because of Trump. Any prior admin FDA would never have approved it for emergency use based on the limited and poor data available at that point.

I really wonder why. The obvious thought is he has some financial interest, given how that has dictated his decision making for most of his life and presidency. I had thought that politically it could help to have some wonder drug to tout, and given 99+% of infected people will live, even a placebo would seem a wonder drug to the Trump supporter who took it and didn't die. That seems like too much 3d chess though.

[dabigv13]

The very simple fact of the matter is that the only reason anybody is still talking about this drug is because of Trump. Any prior admin FDA would never have approved it for emergency use based on the limited and poor data available at that point.

I really wonder why. The obvious thought is he has some financial interest, given how that has dictated his decision making for most of his life and presidency. I had thought that politically it could help to have some wonder drug to tout, and given 99+% of infected people will live, even a placebo would seem a wonder drug to the Trump supporter who took it and didn't die. That seems like too much 3d chess though.

[lex24]

A former FDA commissioner weighs in:

https://www.axios.com/hydroxychloroquine...ntent=1100

I would never say something "definitely" doesn't work just because I've been surprised before (though usually things go in the opposite direction; something I was "sure" would work doesn't).  But otherwise I agree with Gottlieb; the evidence points strongly to HCQ not working, based on the fact that the highest quality studies (large, randomized, placebo controlled studies with rigorous endpoints) consistently show the drug doesn't work.  That the medical evidence doesn't universally point in the same direction is par for the course in the medical literature, but I would focus on studies least likely to be affected by bias.

BC

Isn’t Gottlieb just saying it doesn’t work as a preventative measure?  I don’t think anyone disputes that. Is the Ford test more likely to be biased??

[lex24]

A former FDA commissioner weighs in:

https://www.axios.com/hydroxychloroquine...ntent=1100

I would never say something "definitely" doesn't work just because I've been surprised before (though usually things go in the opposite direction; something I was "sure" would work doesn't).  But otherwise I agree with Gottlieb; the evidence points strongly to HCQ not working, based on the fact that the highest quality studies (large, randomized, placebo controlled studies with rigorous endpoints) consistently show the drug doesn't work.  That the medical evidence doesn't universally point in the same direction is par for the course in the medical literature, but I would focus on studies least likely to be affected by bias.

BC

Isn’t Gottlieb just saying it doesn’t work as a preventative measure?  I don’t think anyone disputes that. Is the Ford test more likely to be biased??

[Goose]

Any prior "admin FDA" would never have approved it for emergency use based on the limited and poor data available at that point.

No prior FDA ever has been involved in anything like this epidemic. You may recall that the FDA was slammed for its slow approvals of some testing. The FDA is usually pretty immune to political pressure in the "normal" sense. They don't turn over the staff every time we get a new president, and they do not react well to attempts by the administration to influence their process or their speed. Many have lamented that they consider themselves a law unto themselves with no responsibility to anyone else. In reality, they are not immune to what is going on around them. They have both approved and not approved things recently that surprised lots of people. Since "off label" use of hydroxychloroquine was possible anyway, the approval really didn't change much. Reimbursement would be problematic in both cases, so no change there either.

[Goose]

Any prior "admin FDA" would never have approved it for emergency use based on the limited and poor data available at that point.

No prior FDA ever has been involved in anything like this epidemic. You may recall that the FDA was slammed for its slow approvals of some testing. The FDA is usually pretty immune to political pressure in the "normal" sense. They don't turn over the staff every time we get a new president, and they do not react well to attempts by the administration to influence their process or their speed. Many have lamented that they consider themselves a law unto themselves with no responsibility to anyone else. In reality, they are not immune to what is going on around them. They have both approved and not approved things recently that surprised lots of people. Since "off label" use of hydroxychloroquine was possible anyway, the approval really didn't change much. Reimbursement would be problematic in both cases, so no change there either.

[dabigv13]

Nothing in your post contradicts my point that the only reason we are talking about this drug, is Trump. He bizarrely claimed/lied to take it prophylactically, and criticized the FDA for revoking the EUA, based on nothing but his big ol brain. We know of whistleblowers within the FDA who were concerned that the initial push for drug was political and not scientific. Trump has continued to tout it, and seeks to find any kook with a white coat to back him. The only other national leader pumping it is his right wing, anti-science friend Bolsonaro, hardly a coincidence.

The FDA is usually pretty immune to political pressure in the "normal" sense.

Do you think our executive branch has been functioning normally the past 3 years?

Many have lamented that they consider themselves a law unto themselves with no responsibility to anyone else.

Who are the many you refer to here?

[dabigv13]

Nothing in your post contradicts my point that the only reason we are talking about this drug, is Trump. He bizarrely claimed/lied to take it prophylactically, and criticized the FDA for revoking the EUA, based on nothing but his big ol brain. We know of whistleblowers within the FDA who were concerned that the initial push for drug was political and not scientific. Trump has continued to tout it, and seeks to find any kook with a white coat to back him. The only other national leader pumping it is his right wing, anti-science friend Bolsonaro, hardly a coincidence.

The FDA is usually pretty immune to political pressure in the "normal" sense.

Do you think our executive branch has been functioning normally the past 3 years?

Many have lamented that they consider themselves a law unto themselves with no responsibility to anyone else.

Who are the many you refer to here?

[BostonCard]

The evidence has generally (but not universally) been negative in a number of different settings, including as a preventative, for patients with mild disease, and for hospitalized patients.  I think when Gottlieb said "early on" he meant "early on" in the pandemic (as in, back in March and April), not "early on" in the infection.

BC

---

Any prior "admin FDA" would never have approved it for emergency use based on the limited and poor data available at that point.

No prior FDA ever has been involved in anything like this epidemic. You may recall that the FDA was slammed for its slow approvals of some testing. The FDA is usually pretty immune to political pressure in the "normal" sense. They don't turn over the staff every time we get a new president, and they do not react well to attempts by the administration to influence their process or their speed. Many have lamented that they consider themselves a law unto themselves with no responsibility to anyone else. In reality, they are not immune to what is going on around them. They have both approved and not approved things recently that surprised lots of people. Since "off label" use of hydroxychloroquine was possible anyway, the approval really didn't change much. Reimbursement would be problematic in both cases, so no change there either.

That might make sense if the FDA were giving out EUA's to other drugs with a similar level of evidence (or lack thereof), but HCQ was the only drug that got an EUA on the basis of non-randomized trials.  I think HCQ aside, the FDA has been fairly responsible in terms of waiting for the results of randomized trials and then promptly offering an EUA, for example, in the case of remdisivir.  But hydroxchloroquine was an outlier in being given an EUA on the basis of flimsier evidence than any other COVID-19 drug.

BC

[BostonCard]

The evidence has generally (but not universally) been negative in a number of different settings, including as a preventative, for patients with mild disease, and for hospitalized patients.  I think when Gottlieb said "early on" he meant "early on" in the pandemic (as in, back in March and April), not "early on" in the infection.

BC

---

Any prior "admin FDA" would never have approved it for emergency use based on the limited and poor data available at that point.

No prior FDA ever has been involved in anything like this epidemic. You may recall that the FDA was slammed for its slow approvals of some testing. The FDA is usually pretty immune to political pressure in the "normal" sense. They don't turn over the staff every time we get a new president, and they do not react well to attempts by the administration to influence their process or their speed. Many have lamented that they consider themselves a law unto themselves with no responsibility to anyone else. In reality, they are not immune to what is going on around them. They have both approved and not approved things recently that surprised lots of people. Since "off label" use of hydroxychloroquine was possible anyway, the approval really didn't change much. Reimbursement would be problematic in both cases, so no change there either.

That might make sense if the FDA were giving out EUA's to other drugs with a similar level of evidence (or lack thereof), but HCQ was the only drug that got an EUA on the basis of non-randomized trials.  I think HCQ aside, the FDA has been fairly responsible in terms of waiting for the results of randomized trials and then promptly offering an EUA, for example, in the case of remdisivir.  But hydroxchloroquine was an outlier in being given an EUA on the basis of flimsier evidence than any other COVID-19 drug.

BC

[lex24]

The very simple fact of the matter is that the only reason anybody is still talking about this drug is because of Trump. Any prior admin FDA would never have approved it for emergency use based on the limited and poor data available at that point.

I really wonder why. The obvious thought is he has some financial interest, given how that has dictated his decision making for most of his life and presidency. I had thought that politically it could help to have some wonder drug to tout, and given 99+% of infected people will live, even a placebo would seem a wonder drug to the Trump supporter who took it and didn't die. That seems like too much 3d chess though.

Actually, the reason I talked about it is Prof Risch.  And his claims.  My reason is simple: I’m looking hard for anything positive.

But you nicely sum up the Us vs Them.

[lex24]

The very simple fact of the matter is that the only reason anybody is still talking about this drug is because of Trump. Any prior admin FDA would never have approved it for emergency use based on the limited and poor data available at that point.

I really wonder why. The obvious thought is he has some financial interest, given how that has dictated his decision making for most of his life and presidency. I had thought that politically it could help to have some wonder drug to tout, and given 99+% of infected people will live, even a placebo would seem a wonder drug to the Trump supporter who took it and didn't die. That seems like too much 3d chess though.

Actually, the reason I talked about it is Prof Risch.  And his claims.  My reason is simple: I’m looking hard for anything positive.

But you nicely sum up the Us vs Them.

[dabigv13]

I'm guessing the only reason you know this professor's name is because of his contrarian take on this drug, so I think you are the one who has succumbed to the politicization of the issue.

Can you name the many more numerous authors of studies that show the drug doesn't work?

My reason is simple: I’m looking hard for anything positive.

This is an incredibly human instinct. But it's not how science advances.

[dabigv13]

I'm guessing the only reason you know this professor's name is because of his contrarian take on this drug, so I think you are the one who has succumbed to the politicization of the issue.

Can you name the many more numerous authors of studies that show the drug doesn't work?

My reason is simple: I’m looking hard for anything positive.

This is an incredibly human instinct. But it's not how science advances.

[Goose]

Nothing in your post contradicts my point that the only reason we are talking about this drug, is Trump. He bizarrely claimed/lied to take it prophylactically, and criticized the FDA for revoking the EUA, based on nothing but his big ol brain. We know of whistleblowers within the FDA who were concerned that the initial push for drug was political and not scientific. Trump has continued to tout it, and seeks to find any kook with a white coat to back him. The only other national leader pumping it is his right wing, anti-science friend Bolsonaro, hardly a coincidence.

The FDA is usually pretty immune to political pressure in the "normal" sense.

Do you think our executive branch has been functioning normally the past 3 years?

No, I don't think the "executive branch" in the person of Trump and his appointees could be considered as "functioning normally" in the past 3 years. HOWEVER, it must be remembered that the vast majority of people who work for the executive branch are not political appointees and are not beholden to Trump or to God. These are the people who make things work day to day. They are the FDA and CDC and places like that, with all their flaws and advantages. Presidents come and go but these people stay for a very long time if they want to do so. The political appointees find out very quickly that "I was here when you came and I will be here when you are gone". For better or worse (right now, probably for better) the Chief Executive and his minions can only affect things in a limited way. That is probably the only thing holding our government together right now IMHO.

Many have lamented that they consider themselves a law unto themselves with no responsibility to anyone else.

Who are the many you refer to here?

I am referring to people I know in pharma who deal with the FDA on a regular basis. They have great respect for the FDA as an institution, and for many (not all) of the people who work there. There is no question that these people are aware that they have effectively absolute power. If they tell you that you must do something in your clinical trial, even if their reason makes no sense, you basically have to do it. Many of the people at the FDA are knowledgeable but not real willing to change their minds. Often they do a great job, but sometimes they don't.

As a group, they are very risk averse. They all seem to be aware that asking you to be more conservative than you want to be has no down side to the FDA. It may delay the treatment availability, in fact it may render the treatment financially infeasible because the trial cost would be too high. However, the public isn't going to know about that, and if somebody complains they can wrap themselves in the "protecting the public" flag.

Everybody recognizes the FDA has a tough job. They have to balance risk vs benefit. Generally they try hard to do that in a professional manner. They will almost universally err on the side of caution. Unfortunately, some of the standards they set are of necessity somewhat arbitrary, as the "right answer" isn't known. That is an area where they are often too hard-headed in my friends view. Some endpoints that have what appears to be reasonable justification are rejected out of hand. That is hard to deal with.

[Goose]

Nothing in your post contradicts my point that the only reason we are talking about this drug, is Trump. He bizarrely claimed/lied to take it prophylactically, and criticized the FDA for revoking the EUA, based on nothing but his big ol brain. We know of whistleblowers within the FDA who were concerned that the initial push for drug was political and not scientific. Trump has continued to tout it, and seeks to find any kook with a white coat to back him. The only other national leader pumping it is his right wing, anti-science friend Bolsonaro, hardly a coincidence.

The FDA is usually pretty immune to political pressure in the "normal" sense.

Do you think our executive branch has been functioning normally the past 3 years?

No, I don't think the "executive branch" in the person of Trump and his appointees could be considered as "functioning normally" in the past 3 years. HOWEVER, it must be remembered that the vast majority of people who work for the executive branch are not political appointees and are not beholden to Trump or to God. These are the people who make things work day to day. They are the FDA and CDC and places like that, with all their flaws and advantages. Presidents come and go but these people stay for a very long time if they want to do so. The political appointees find out very quickly that "I was here when you came and I will be here when you are gone". For better or worse (right now, probably for better) the Chief Executive and his minions can only affect things in a limited way. That is probably the only thing holding our government together right now IMHO.

Many have lamented that they consider themselves a law unto themselves with no responsibility to anyone else.

Who are the many you refer to here?

I am referring to people I know in pharma who deal with the FDA on a regular basis. They have great respect for the FDA as an institution, and for many (not all) of the people who work there. There is no question that these people are aware that they have effectively absolute power. If they tell you that you must do something in your clinical trial, even if their reason makes no sense, you basically have to do it. Many of the people at the FDA are knowledgeable but not real willing to change their minds. Often they do a great job, but sometimes they don't.

As a group, they are very risk averse. They all seem to be aware that asking you to be more conservative than you want to be has no down side to the FDA. It may delay the treatment availability, in fact it may render the treatment financially infeasible because the trial cost would be too high. However, the public isn't going to know about that, and if somebody complains they can wrap themselves in the "protecting the public" flag.

Everybody recognizes the FDA has a tough job. They have to balance risk vs benefit. Generally they try hard to do that in a professional manner. They will almost universally err on the side of caution. Unfortunately, some of the standards they set are of necessity somewhat arbitrary, as the "right answer" isn't known. That is an area where they are often too hard-headed in my friends view. Some endpoints that have what appears to be reasonable justification are rejected out of hand. That is hard to deal with.