[fullmetal]

In fact, as inexpensive, oral and widely available medications, and a nutritional supplement, the combination of hydroxychloroquine, azithromycin or doxycycline, and zinc are well-suited for early treatment in the outpatient setting.

So you really need a four-substance cocktail in the right proportions to test against a control. I mean...maybe. But you could also just say "Water cures the virus!" and when it doesn't, just start adding real drugs to water and then figure out which combo works before reannouncing "Water cures the virus! We told you so!"

If the four-drug combo works, okay. But dexamethasone and remdesivir are still out there as marginally positive therapies too, right? I feel like we should be asking for those first, if we should come down with covid today.

In any case, I don't think the sham group America's Frontline Doctors were advocating for a four-drug combo. More likely, they were set up and funded by the Tea Party Patriots and co-sponsored by Breitbart...

[fullmetal]

In fact, as inexpensive, oral and widely available medications, and a nutritional supplement, the combination of hydroxychloroquine, azithromycin or doxycycline, and zinc are well-suited for early treatment in the outpatient setting.

So you really need a four-substance cocktail in the right proportions to test against a control. I mean...maybe. But you could also just say "Water cures the virus!" and when it doesn't, just start adding real drugs to water and then figure out which combo works before reannouncing "Water cures the virus! We told you so!"

If the four-drug combo works, okay. But dexamethasone and remdesivir are still out there as marginally positive therapies too, right? I feel like we should be asking for those first, if we should come down with covid today.

In any case, I don't think the sham group America's Frontline Doctors were advocating for a four-drug combo. More likely, they were set up and funded by the Tea Party Patriots and co-sponsored by Breitbart...

[BostonCard]

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.

My personal experience with the FDA is that they are tough but fair and rarely arbitrary or capricious. I know that it is often review division dependent, so my experience may not be universal.  I know for a fact that FDA reviewers are willing to change their minds if the data support doing so.  To quote a former FDA reviewer friend of mine, "in God we trust; all others must bring data".

Also, the FDA rarely will reject an endpoint out of hand, but unless it is a hard endpoint or one that has been the basis for approval in the past, they will require a strong justification and/or validation before allowing it.  Most often, we will get an answer like, "prior to acceptance of X as an endpoint, it will need to be validated as a meaningful and relevant outcome through x, y, and z."

BC

[BostonCard]

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.

My personal experience with the FDA is that they are tough but fair and rarely arbitrary or capricious. I know that it is often review division dependent, so my experience may not be universal.  I know for a fact that FDA reviewers are willing to change their minds if the data support doing so.  To quote a former FDA reviewer friend of mine, "in God we trust; all others must bring data".

Also, the FDA rarely will reject an endpoint out of hand, but unless it is a hard endpoint or one that has been the basis for approval in the past, they will require a strong justification and/or validation before allowing it.  Most often, we will get an answer like, "prior to acceptance of X as an endpoint, it will need to be validated as a meaningful and relevant outcome through x, y, and z."

BC

[M T]

Is anyone here saying that Dr. Risch's position is based on Trump's advocacy of the drug?  That's not what I read in his article.  Is anyone here equating him with a "kook with a white coat"? 

As for "the highest quality studies", I suggest a better term is "the accepted study," as the systematic review that BC referenced seems to be based on a single accepted (that is, accepted by that set of authors) study as far as prophylaxis is concerned (and only 2 accepted studies overall).  

Oh, that accepted study did NOT test the HCQ+Az combination that Dr. Risch is supporting (who emphasized "evidence for single agents cannot be extrapolated to apply to combined agents").  The study used only HCQ, not HCQ+Az.  If Dr. Risch's emphasis is correct, I'd think that a well-designed RCT study that uses a different drug is not a good study of the drug.  Indeed, when I looked back at the systematic review, it mixes studies of different drug combinations.  Considering Dr. Risch emphasized the impropriety of extrapolation, I'd expect that he'd say this systematic review is fatally flawed.

When you or that review says "the drug doesn't work", one of your first questions should be "Which drug?".

That said, I don't know that HCQ+Az has been shown to be effective as a prophylactic after exposure (or before).  (Dr. Risch also addresses safety.)  I would say that HCQ study and the particular systematic review apparently don't answer the question.

[M T]

Is anyone here saying that Dr. Risch's position is based on Trump's advocacy of the drug?  That's not what I read in his article.  Is anyone here equating him with a "kook with a white coat"? 

As for "the highest quality studies", I suggest a better term is "the accepted study," as the systematic review that BC referenced seems to be based on a single accepted (that is, accepted by that set of authors) study as far as prophylaxis is concerned (and only 2 accepted studies overall).  

Oh, that accepted study did NOT test the HCQ+Az combination that Dr. Risch is supporting (who emphasized "evidence for single agents cannot be extrapolated to apply to combined agents").  The study used only HCQ, not HCQ+Az.  If Dr. Risch's emphasis is correct, I'd think that a well-designed RCT study that uses a different drug is not a good study of the drug.  Indeed, when I looked back at the systematic review, it mixes studies of different drug combinations.  Considering Dr. Risch emphasized the impropriety of extrapolation, I'd expect that he'd say this systematic review is fatally flawed.

When you or that review says "the drug doesn't work", one of your first questions should be "Which drug?".

That said, I don't know that HCQ+Az has been shown to be effective as a prophylactic after exposure (or before).  (Dr. Risch also addresses safety.)  I would say that HCQ study and the particular systematic review apparently don't answer the question.

[lex24]

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.

I know of Risch because of his comments that popped up on numerous news websites. I don’t assume he made them for political purposes.  I know nothing of his political affiliations. I looked for numerous sources, including Newsweek, to see if at least his statements were being accurately reported. I had no clue if he’s right or wrong. I accept that the weight of today’s scientific evidence is against him.  I understand him to be saying that it’s useful only if used very early on.  And again, I’m not saying, nor have I ever said he’s right.

I admit I want him to be.  Again not for political reasons but because it would be a positive development. And yes I know that’s not the way science works.

[lex24]

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.

I know of Risch because of his comments that popped up on numerous news websites. I don’t assume he made them for political purposes.  I know nothing of his political affiliations. I looked for numerous sources, including Newsweek, to see if at least his statements were being accurately reported. I had no clue if he’s right or wrong. I accept that the weight of today’s scientific evidence is against him.  I understand him to be saying that it’s useful only if used very early on.  And again, I’m not saying, nor have I ever said he’s right.

I admit I want him to be.  Again not for political reasons but because it would be a positive development. And yes I know that’s not the way science works.

[BostonCard]

Fauci has now come out saying "If a study that's a good study comes out and shows efficacy and safety for hydroxychloroquine or any other drug that we do, if you do it in the right way, you accept that scientific data, but right now today, the cumulative scientific data that has been put together, and done over a number of different studies, has shown no efficacy."

https://www.axios.com/fauci-trump-hydrox...ntent=1100

The irony is that there is already a cheap, readily available drug that cuts the proportion of hospitalized COVID-19 patients who die by about 1/5 (the effect is larger [~40%] in sicker patients).  It's called dexamethasone, it is available for pennies, and it has been proven effective in a large (1110 patient) randomized, placebo controlled study that's been published in a major medical journal.

https://www.nejm.org/doi/full/10.1056/NE...6?query=RP

Like Lex, I hope for positive developments that help us cut the death rate and improve the recovery time of patients with COVID-19.  So far, dexamethasone and remdisivir have proven at least somewhat effective.  I suspect that as more and more results come in, we'll see more successes, but a lot of failures as well.  That is the nature of drug development.  I never understood why anyone would hitch their wagon rhetorically to a particular drug, but here we are.  The world is littered with drugs that seemed to work in small observational studies that later failed.  And were it not for the president's pronouncements, I suspect antimalarials would be in the dustbin along with other failed drugs tried for COVID-19.  Like, does anyone talk about antiretrovirals anymore?  At one point they too were being looked at to repurpose for COVID-19, but when those trials failed, physicians just stopped using them and moved on.  This is why I believe the President's actions have been counterproductive, as I suspect resources are continuing to be wasted chasing the antimalarials (not saying anything is deliberate, but doctors are human too and I wonder if the initial results might have remained obscure had they not been amplified, and HCQ suffered the same fate as lopinavir/ritonavir when studies were negative).

BC

[BostonCard]

Fauci has now come out saying "If a study that's a good study comes out and shows efficacy and safety for hydroxychloroquine or any other drug that we do, if you do it in the right way, you accept that scientific data, but right now today, the cumulative scientific data that has been put together, and done over a number of different studies, has shown no efficacy."

https://www.axios.com/fauci-trump-hydrox...ntent=1100

The irony is that there is already a cheap, readily available drug that cuts the proportion of hospitalized COVID-19 patients who die by about 1/5 (the effect is larger [~40%] in sicker patients).  It's called dexamethasone, it is available for pennies, and it has been proven effective in a large (1110 patient) randomized, placebo controlled study that's been published in a major medical journal.

https://www.nejm.org/doi/full/10.1056/NE...6?query=RP

Like Lex, I hope for positive developments that help us cut the death rate and improve the recovery time of patients with COVID-19.  So far, dexamethasone and remdisivir have proven at least somewhat effective.  I suspect that as more and more results come in, we'll see more successes, but a lot of failures as well.  That is the nature of drug development.  I never understood why anyone would hitch their wagon rhetorically to a particular drug, but here we are.  The world is littered with drugs that seemed to work in small observational studies that later failed.  And were it not for the president's pronouncements, I suspect antimalarials would be in the dustbin along with other failed drugs tried for COVID-19.  Like, does anyone talk about antiretrovirals anymore?  At one point they too were being looked at to repurpose for COVID-19, but when those trials failed, physicians just stopped using them and moved on.  This is why I believe the President's actions have been counterproductive, as I suspect resources are continuing to be wasted chasing the antimalarials (not saying anything is deliberate, but doctors are human too and I wonder if the initial results might have remained obscure had they not been amplified, and HCQ suffered the same fate as lopinavir/ritonavir when studies were negative).

BC

[Goose]

It is not at all unusual for people in authority to hold on to ideas they have embraced long after virtually everybody else has decided they are dead ends. It happens all the time with projects that get cancelled and then resurrected by the CEO. Winston Churchill spent the first 4 years of WWII trying to perfect the "air mine" to destroy German aircraft. Never brought down any Germans, but did some of the British aircraft trying to deploy them.

Given all the things our current POTUS has done that were (IMHO) stupid beyond words, this one is minor. If everything else were going well, we could just accept it as a quirk and move on. However, since we do have a few other problems, his continual return to this one is more annoying than it might be otherwise.

[Goose]

It is not at all unusual for people in authority to hold on to ideas they have embraced long after virtually everybody else has decided they are dead ends. It happens all the time with projects that get cancelled and then resurrected by the CEO. Winston Churchill spent the first 4 years of WWII trying to perfect the "air mine" to destroy German aircraft. Never brought down any Germans, but did some of the British aircraft trying to deploy them.

Given all the things our current POTUS has done that were (IMHO) stupid beyond words, this one is minor. If everything else were going well, we could just accept it as a quirk and move on. However, since we do have a few other problems, his continual return to this one is more annoying than it might be otherwise.

[Snorlax94]

“BRASILIA (Reuters) - Brazilian President Jair Bolsonaro said on Thursday he was taking antibiotics for an infection that left him feeling weak, chuckling in an online video about "mold" in his lungs, having spent weeks in isolation after catching the novel coronavirus.”

Isn’t a fungal infection a possible side effect from prolonged use of azithromycin, say from a hydroxychloroquine/z-pack combo?

[Snorlax94]

“BRASILIA (Reuters) - Brazilian President Jair Bolsonaro said on Thursday he was taking antibiotics for an infection that left him feeling weak, chuckling in an online video about "mold" in his lungs, having spent weeks in isolation after catching the novel coronavirus.”

Isn’t a fungal infection a possible side effect from prolonged use of azithromycin, say from a hydroxychloroquine/z-pack combo?