Leucovorin now approved by FDA--will providers prescribe to ASD kids?

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

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Anonymous wrote:

Anonymous wrote:We live in NW but go to an autism specialist who actually has authored many studies on Leucovorin and autism. Look up drs Frye and Rossignol. They have data going back years. My dd has been on it for 5 years. They don’t put all of their patients on it. You need to do a FRAT test first to see if you have antibodies, etc. I hate that now everyone is jumping on board, regardless of if it will be effective. It’s not going to be effective for a large percentage of autism patients who don’t have a positive on the FRAT test.

It hasn't been widely studied, but folate receptor autoantibodies seem to have high prevalence in kids with autism-- perhaps as high as 75%.

But it is pretty incestuous research- basically all going back to Frye. That's suspicious. Either it is an incredibly interesting research that much of the medical community has been largely ignoring for unknown reasons, they're cooking the numbers somehow.

Not really that odd for researchers to specialize in a certain area.

It is odd for other researchers to not pick up promising research areas from
others.

You know what actually would have been great for RFK Jr to do? Announce an effort to assess which research efforts have the most potential and deserve the most federal funding. The search for genetic causes has taken up too much bandwidth - perhaps it is time to move on from that. perhaps it is time to focus less on the search for causes and more on effective therapies and treatments. Or perhaps it is time to redefine the categories so scientists can search for the causes of the more disabling forms of autism. But of course, this kind of effort would take time and resources and not allow brainworm to pretend like he alone was conquering the evil FDA.

You trust a centralized effort to do that more than distributed grant proposal reviews by subject matter experts?

Dude. You’re acting like the president and the head of HHS have no power to strategically shape federal and federally funded research. I can’t figure out if you are ignorant or doing this on purpose.

They certainly do. And they certainly have. What I don't get is why you want them to do that even more versus having the grant reviewers rate them on their merits.

I'd admit I haven't been a part of FDA or NIH grant review proposes, but I've done a part of them at several other agencies. I imagine it is similar. I don't think you understand the process of how grants get funded.

So let me get this straight - you believe that the US government has no power to strategically shape research agendas and all we can do is review the grant applications received? OK dude.

[Anonymous]

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Anonymous wrote:I would love to hear other people experiences with Leucovorin

Because we’re doing science by anecdote now I guess.

Ever hear of case studies?

Case studies are not the kind of evidence the FDA generally uses to determine the safety and efficacy of a medication.

It's been used for 70 years. We already know it's safe.

They put cocaine in cough syrup for 70 yesrs

Do you not realize that Leucovorin continues to be used?

… in cancer. Stop lying.

You compared the safety record of Leucovorin to the safety record cocaine. I'm not the one being disingenuous. You can argue we don't know how effective it is for ASD, but we already know it's safe.

That wasn’t me but for the record cocaine actually does have medical uses right now (as a topical anesthesia).

So do you think that makes the safety record of cocaine similar to the safety record of Leucovorin? Otherwise, what's your point?

The point is that saying a drug is safe and effective for one indication says literally nothing at all about whether it is safe and effective for a wholly different indication. If you cannot grasp this entirely basic and fundamental point then you probably shouldn’t be in this discussion.

Again, we don't know it is effective, but we do know it is safe. Safe doesn't necessarily mean there's absolutely no possibility of risk. We approve drugs and other substances while there is still small potential for risks, with after-market monitoring being used to catch exceptional events. Leucovorin has the substantial benefit over new drugs in that we already have a long safety history with the drug.

It's ridiculous to suggest it isn't safe. Particularly given the risks of other things that are available and generally accepted as safe- including prescription medications, supplements, and food ingredients.

No we do NOT KNOW if it is safe in the population it is now being touted for. It has side effects that absolutely could be more unsafe for kids with autism vs adults with cancer. Specifically, seizures and aggression are known side effects and these are bigger concerns for autism. AND there is also research connecting too much prenatal folate to autism.

We.do.not.know.

On that basis, almost nothing is "safe" for use in kids with autism because these kids often aren't part of clinical trial populations. Since you're saying a safety record for the general population shouldn't be used to infer safety in a subpopulation.

Again, you're being disingenuous. This is done all the time. Heck, look how often drugs get prescribed off-label because of how hard it is to run trials (particularly in kids).

Frankly, off-label use here would seem to be the right move, too. But clearly something has happened over the last 10 years, and particularly with this drug, to make some doctors lose their ability to weigh risks and potential benefits rationally and in the best interest of their patients. Why are they treating it so differently than something like guanfacine, another drug with a long safety history that is frequently prescribed for young kids with autism presenting with aggressive or self-injurious behaviors, despite those being off-label.

This is a drug being specific touted FOR kids with autism. So yes, it is relevant to ask how it specifically affects them. And of course the whole point is that this went far beyond off-label use, departing from how additional uses are added and making overblown claims not supported by the evidence.

More importantly while it may be an understandable stance for an individual parent with their doctor to use a med off-label under the background of slow or nonexistent goldstar research - that is far different from the people *literally in charge of the research* upending it. Trump and RFK jr are pretending like they aren’t the ones with the power to actually do the research our kids deserve. because they don’t actually care about our kids. They care about politics.

The reality of modern medicine is that doctors now want top-cover for prescribing medications- particularly in kids. Guanfacine was able to become common before those pressures shifted.

The only way we can really provide that top-cover is adding it to the label. If a doctor isn't satisfied there's a good risk-benefit tradeoff based on the available data, then they obviously don't need to prescribe it. It's not like they're trying to make this available OTC without a prescription.

Forgive me if I expect more from the people and institutions literally in charge of making the determinations of what can be prescribed safely. That’s the insane part. You’re saying that because our research and prescribing systems are not ideal that the people in charge of our research and prescribing systems have no other choice but to shrug their shoulders and say “the system sucks, take whatever”?

The status quo basically is: "there aren't great medications, but you can try these things."

And let's be clear, if the FDA updates the label, that isn't telling people to "try whatever." It is telling people to talk to their doctors about Leucovorin for kids with autism. It doesn't make it directly available to parents or patients. It doesn't tell doctors they need to offer to everyone with autism, or to anyone at all. It just makes it available as an option at a lower professional and legal risk to the prescribing physician. And a clearer path for insurance coverage.

No matter how much you insist that nothing out of the ordinary happened here, we all know it did. And all for the purpose of aggrandizement of Trump, not for the purpose of helping our kids. Where’s the funding for additional studies on leucovorin? maybe that was included in the announcement and I missed it.

You honestly sounds so childish. Just because you don’t know anything about people involved in the approval process of other things does not mean that they’re good people either. A lot of autistic kids were already taking this medication and as you can see from the SN section there have been people trying to get access to this medication since well before this and if Trump can make that happen even for his own crappy reasons then who tf cares? Not every parent wants to wait for additional studies and there are 50+ years of data on safety. And no my kid does not take leucovorin.

It’s childish to say that kids with autism actually deserve the best research and not quackery? OK.

DP. Conducting the best research doesn't have to mean also waiting years before trying safe drugs.

Yes it actually does. I’m not sure how many times you need that repeated.

It really doesn't. When to start using a drug is based on risk-benefit. This is a low-risk drug with promising benefits.

No it is is not. It is an untested drug and we don’t know the risks and benefits for the class of kids it is being targeted to.

I’m just going to quote the actual research experts again here:

“ The September 22 press conference held by U.S. Health and Human Services alarms us researchers … The data cited do not support the claim that Tylenol causes autism and leucovorin is a cure, and only stoke fear and falsely suggest hope when there is no simple answer.”

“With this in mind,” the group added, “we do not support any recommendation from the HHS or FDA regarding increased use of folinic acid. Instead, we call for a well-designed, large scale clinical trial of leucovorin (folinic acid) with all of the rigor needed (biomarkers, proper endpoints) and, most importantly, a pre-registered analysis plan.”

https://www.thetransmitter.org/spectrum/autism-experts-question-hhs-statements-on-tylenol-leucovorin/

It's not an "untested drug". The quality of the data is limited, but it isn't untested. Safety trials very frequently don't closely match the expected or intended population. The efficacy trials have been small, but at least four RCTs have had positive results.

Positive results that the 200 actual autism experts heavily hint are driven by unsound research methods.

And of course we are talking about an intended population where the drug side effects are very salient - the exacerbation or behavior and seizures in physically healthy autistic children - vs the population that has received the drug in the past (cancer patients facing potentially fatal chemo side effects).

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:We live in NW but go to an autism specialist who actually has authored many studies on Leucovorin and autism. Look up drs Frye and Rossignol. They have data going back years. My dd has been on it for 5 years. They don’t put all of their patients on it. You need to do a FRAT test first to see if you have antibodies, etc. I hate that now everyone is jumping on board, regardless of if it will be effective. It’s not going to be effective for a large percentage of autism patients who don’t have a positive on the FRAT test.

It hasn't been widely studied, but folate receptor autoantibodies seem to have high prevalence in kids with autism-- perhaps as high as 75%.

But it is pretty incestuous research- basically all going back to Frye. That's suspicious. Either it is an incredibly interesting research that much of the medical community has been largely ignoring for unknown reasons, they're cooking the numbers somehow.

Not really that odd for researchers to specialize in a certain area.

It is odd for other researchers to not pick up promising research areas from
others.

You know what actually would have been great for RFK Jr to do? Announce an effort to assess which research efforts have the most potential and deserve the most federal funding. The search for genetic causes has taken up too much bandwidth - perhaps it is time to move on from that. perhaps it is time to focus less on the search for causes and more on effective therapies and treatments. Or perhaps it is time to redefine the categories so scientists can search for the causes of the more disabling forms of autism. But of course, this kind of effort would take time and resources and not allow brainworm to pretend like he alone was conquering the evil FDA.

You trust a centralized effort to do that more than distributed grant proposal reviews by subject matter experts?

Dude. You’re acting like the president and the head of HHS have no power to strategically shape federal and federally funded research. I can’t figure out if you are ignorant or doing this on purpose.

They certainly do. And they certainly have. What I don't get is why you want them to do that even more versus having the grant reviewers rate them on their merits.

I'd admit I haven't been a part of FDA or NIH grant review proposes, but I've done a part of them at several other agencies. I imagine it is similar. I don't think you understand the process of how grants get funded.

So let me get this straight - you believe that the US government has no power to strategically shape research agendas and all we can do is review the grant applications received? OK dude.

Read this again. Maybe try it slower this time since you're having difficulties with comprehension:

"They certainly do. And they certainly have. What I don't get is why you want them to do that even more versus having the grant reviewers rate them on their merits."

Or maybe just get out of the Special Needs forum since it seems pretty clear you don't have a child with high support needs.

[Anonymous]

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Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:I would love to hear other people experiences with Leucovorin

Because we’re doing science by anecdote now I guess.

Ever hear of case studies?

Case studies are not the kind of evidence the FDA generally uses to determine the safety and efficacy of a medication.

It's been used for 70 years. We already know it's safe.

They put cocaine in cough syrup for 70 yesrs

Do you not realize that Leucovorin continues to be used?

… in cancer. Stop lying.

You compared the safety record of Leucovorin to the safety record cocaine. I'm not the one being disingenuous. You can argue we don't know how effective it is for ASD, but we already know it's safe.

That wasn’t me but for the record cocaine actually does have medical uses right now (as a topical anesthesia).

So do you think that makes the safety record of cocaine similar to the safety record of Leucovorin? Otherwise, what's your point?

The point is that saying a drug is safe and effective for one indication says literally nothing at all about whether it is safe and effective for a wholly different indication. If you cannot grasp this entirely basic and fundamental point then you probably shouldn’t be in this discussion.

Again, we don't know it is effective, but we do know it is safe. Safe doesn't necessarily mean there's absolutely no possibility of risk. We approve drugs and other substances while there is still small potential for risks, with after-market monitoring being used to catch exceptional events. Leucovorin has the substantial benefit over new drugs in that we already have a long safety history with the drug.

It's ridiculous to suggest it isn't safe. Particularly given the risks of other things that are available and generally accepted as safe- including prescription medications, supplements, and food ingredients.

No we do NOT KNOW if it is safe in the population it is now being touted for. It has side effects that absolutely could be more unsafe for kids with autism vs adults with cancer. Specifically, seizures and aggression are known side effects and these are bigger concerns for autism. AND there is also research connecting too much prenatal folate to autism.

We.do.not.know.

On that basis, almost nothing is "safe" for use in kids with autism because these kids often aren't part of clinical trial populations. Since you're saying a safety record for the general population shouldn't be used to infer safety in a subpopulation.

Again, you're being disingenuous. This is done all the time. Heck, look how often drugs get prescribed off-label because of how hard it is to run trials (particularly in kids).

Frankly, off-label use here would seem to be the right move, too. But clearly something has happened over the last 10 years, and particularly with this drug, to make some doctors lose their ability to weigh risks and potential benefits rationally and in the best interest of their patients. Why are they treating it so differently than something like guanfacine, another drug with a long safety history that is frequently prescribed for young kids with autism presenting with aggressive or self-injurious behaviors, despite those being off-label.

This is a drug being specific touted FOR kids with autism. So yes, it is relevant to ask how it specifically affects them. And of course the whole point is that this went far beyond off-label use, departing from how additional uses are added and making overblown claims not supported by the evidence.

More importantly while it may be an understandable stance for an individual parent with their doctor to use a med off-label under the background of slow or nonexistent goldstar research - that is far different from the people *literally in charge of the research* upending it. Trump and RFK jr are pretending like they aren’t the ones with the power to actually do the research our kids deserve. because they don’t actually care about our kids. They care about politics.

The reality of modern medicine is that doctors now want top-cover for prescribing medications- particularly in kids. Guanfacine was able to become common before those pressures shifted.

The only way we can really provide that top-cover is adding it to the label. If a doctor isn't satisfied there's a good risk-benefit tradeoff based on the available data, then they obviously don't need to prescribe it. It's not like they're trying to make this available OTC without a prescription.

Forgive me if I expect more from the people and institutions literally in charge of making the determinations of what can be prescribed safely. That’s the insane part. You’re saying that because our research and prescribing systems are not ideal that the people in charge of our research and prescribing systems have no other choice but to shrug their shoulders and say “the system sucks, take whatever”?

The status quo basically is: "there aren't great medications, but you can try these things."

And let's be clear, if the FDA updates the label, that isn't telling people to "try whatever." It is telling people to talk to their doctors about Leucovorin for kids with autism. It doesn't make it directly available to parents or patients. It doesn't tell doctors they need to offer to everyone with autism, or to anyone at all. It just makes it available as an option at a lower professional and legal risk to the prescribing physician. And a clearer path for insurance coverage.

No matter how much you insist that nothing out of the ordinary happened here, we all know it did. And all for the purpose of aggrandizement of Trump, not for the purpose of helping our kids. Where’s the funding for additional studies on leucovorin? maybe that was included in the announcement and I missed it.

You honestly sounds so childish. Just because you don’t know anything about people involved in the approval process of other things does not mean that they’re good people either. A lot of autistic kids were already taking this medication and as you can see from the SN section there have been people trying to get access to this medication since well before this and if Trump can make that happen even for his own crappy reasons then who tf cares? Not every parent wants to wait for additional studies and there are 50+ years of data on safety. And no my kid does not take leucovorin.

It’s childish to say that kids with autism actually deserve the best research and not quackery? OK.

DP. Conducting the best research doesn't have to mean also waiting years before trying safe drugs.

Yes it actually does. I’m not sure how many times you need that repeated.

It really doesn't. When to start using a drug is based on risk-benefit. This is a low-risk drug with promising benefits.

No it is is not. It is an untested drug and we don’t know the risks and benefits for the class of kids it is being targeted to.

I’m just going to quote the actual research experts again here:

“ The September 22 press conference held by U.S. Health and Human Services alarms us researchers … The data cited do not support the claim that Tylenol causes autism and leucovorin is a cure, and only stoke fear and falsely suggest hope when there is no simple answer.”

“With this in mind,” the group added, “we do not support any recommendation from the HHS or FDA regarding increased use of folinic acid. Instead, we call for a well-designed, large scale clinical trial of leucovorin (folinic acid) with all of the rigor needed (biomarkers, proper endpoints) and, most importantly, a pre-registered analysis plan.”

https://www.thetransmitter.org/spectrum/autism-experts-question-hhs-statements-on-tylenol-leucovorin/

It's not an "untested drug". The quality of the data is limited, but it isn't untested. Safety trials very frequently don't closely match the expected or intended population. The efficacy trials have been small, but at least four RCTs have had positive results.

Positive results that the 200 actual autism experts heavily hint are driven by unsound research methods.

And of course we are talking about an intended population where the drug side effects are very salient - the exacerbation or behavior and seizures in physically healthy autistic children - vs the population that has received the drug in the past (cancer patients facing potentially fatal chemo side effects).

No, the statements didn't even go that far. They called for larger and more consistent studies, but they didn't say the existing research was unsound.

By your logic, we shouldn't give approved psychotropic drugs to any kids with autism until there have been trials of significant size confirming safety and efficacy in the ASD subpopulation. Since, as you say, the risks and benefits could be different in that subpopulation. But of course we don't do that.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:We live in NW but go to an autism specialist who actually has authored many studies on Leucovorin and autism. Look up drs Frye and Rossignol. They have data going back years. My dd has been on it for 5 years. They don’t put all of their patients on it. You need to do a FRAT test first to see if you have antibodies, etc. I hate that now everyone is jumping on board, regardless of if it will be effective. It’s not going to be effective for a large percentage of autism patients who don’t have a positive on the FRAT test.

It hasn't been widely studied, but folate receptor autoantibodies seem to have high prevalence in kids with autism-- perhaps as high as 75%.

But it is pretty incestuous research- basically all going back to Frye. That's suspicious. Either it is an incredibly interesting research that much of the medical community has been largely ignoring for unknown reasons, they're cooking the numbers somehow.

Not really that odd for researchers to specialize in a certain area.

It is odd for other researchers to not pick up promising research areas from
others.

You know what actually would have been great for RFK Jr to do? Announce an effort to assess which research efforts have the most potential and deserve the most federal funding. The search for genetic causes has taken up too much bandwidth - perhaps it is time to move on from that. perhaps it is time to focus less on the search for causes and more on effective therapies and treatments. Or perhaps it is time to redefine the categories so scientists can search for the causes of the more disabling forms of autism. But of course, this kind of effort would take time and resources and not allow brainworm to pretend like he alone was conquering the evil FDA.

You trust a centralized effort to do that more than distributed grant proposal reviews by subject matter experts?

Dude. You’re acting like the president and the head of HHS have no power to strategically shape federal and federally funded research. I can’t figure out if you are ignorant or doing this on purpose.

They certainly do. And they certainly have. What I don't get is why you want them to do that even more versus having the grant reviewers rate them on their merits.

I'd admit I haven't been a part of FDA or NIH grant review proposes, but I've done a part of them at several other agencies. I imagine it is similar. I don't think you understand the process of how grants get funded.

So let me get this straight - you believe that the US government has no power to strategically shape research agendas and all we can do is review the grant applications received? OK dude.

Read this again. Maybe try it slower this time since you're having difficulties with comprehension:

"They certainly do. And they certainly have. What I don't get is why you want them to do that even more versus having the grant reviewers rate them on their merits."

Or maybe just get out of the Special Needs forum since it seems pretty clear you don't have a child with high support needs.

What I am saying is that the government can do a lot more than just passively receive grant applications and “grade them on their merits.” Rather than creating a research agenda that actually would result in SOUND recommendations for our kids, RFK Jr engaged in lies and delusions.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:We live in NW but go to an autism specialist who actually has authored many studies on Leucovorin and autism. Look up drs Frye and Rossignol. They have data going back years. My dd has been on it for 5 years. They don’t put all of their patients on it. You need to do a FRAT test first to see if you have antibodies, etc. I hate that now everyone is jumping on board, regardless of if it will be effective. It’s not going to be effective for a large percentage of autism patients who don’t have a positive on the FRAT test.

It hasn't been widely studied, but folate receptor autoantibodies seem to have high prevalence in kids with autism-- perhaps as high as 75%.

But it is pretty incestuous research- basically all going back to Frye. That's suspicious. Either it is an incredibly interesting research that much of the medical community has been largely ignoring for unknown reasons, they're cooking the numbers somehow.

Not really that odd for researchers to specialize in a certain area.

It is odd for other researchers to not pick up promising research areas from
others.

You know what actually would have been great for RFK Jr to do? Announce an effort to assess which research efforts have the most potential and deserve the most federal funding. The search for genetic causes has taken up too much bandwidth - perhaps it is time to move on from that. perhaps it is time to focus less on the search for causes and more on effective therapies and treatments. Or perhaps it is time to redefine the categories so scientists can search for the causes of the more disabling forms of autism. But of course, this kind of effort would take time and resources and not allow brainworm to pretend like he alone was conquering the evil FDA.

You trust a centralized effort to do that more than distributed grant proposal reviews by subject matter experts?

Dude. You’re acting like the president and the head of HHS have no power to strategically shape federal and federally funded research. I can’t figure out if you are ignorant or doing this on purpose.

They certainly do. And they certainly have. What I don't get is why you want them to do that even more versus having the grant reviewers rate them on their merits.

I'd admit I haven't been a part of FDA or NIH grant review proposes, but I've done a part of them at several other agencies. I imagine it is similar. I don't think you understand the process of how grants get funded.

So let me get this straight - you believe that the US government has no power to strategically shape research agendas and all we can do is review the grant applications received? OK dude.

Read this again. Maybe try it slower this time since you're having difficulties with comprehension:

"They certainly do. And they certainly have. What I don't get is why you want them to do that even more versus having the grant reviewers rate them on their merits."

Or maybe just get out of the Special Needs forum since it seems pretty clear you don't have a child with high support needs.

What I am saying is that the government can do a lot more than just passively receive grant applications and “grade them on their merits.” Rather than creating a research agenda that actually would result in SOUND recommendations for our kids, RFK Jr engaged in lies and delusions.

They can do more, but you wanted them to announce funded trials and studies on the spot. That's what they can't do.

[Anonymous]

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:

Anonymous wrote:I would love to hear other people experiences with Leucovorin

Because we’re doing science by anecdote now I guess.

Ever hear of case studies?

Case studies are not the kind of evidence the FDA generally uses to determine the safety and efficacy of a medication.

It's been used for 70 years. We already know it's safe.

They put cocaine in cough syrup for 70 yesrs

Do you not realize that Leucovorin continues to be used?

… in cancer. Stop lying.

You compared the safety record of Leucovorin to the safety record cocaine. I'm not the one being disingenuous. You can argue we don't know how effective it is for ASD, but we already know it's safe.

That wasn’t me but for the record cocaine actually does have medical uses right now (as a topical anesthesia).

So do you think that makes the safety record of cocaine similar to the safety record of Leucovorin? Otherwise, what's your point?

The point is that saying a drug is safe and effective for one indication says literally nothing at all about whether it is safe and effective for a wholly different indication. If you cannot grasp this entirely basic and fundamental point then you probably shouldn’t be in this discussion.

Again, we don't know it is effective, but we do know it is safe. Safe doesn't necessarily mean there's absolutely no possibility of risk. We approve drugs and other substances while there is still small potential for risks, with after-market monitoring being used to catch exceptional events. Leucovorin has the substantial benefit over new drugs in that we already have a long safety history with the drug.

It's ridiculous to suggest it isn't safe. Particularly given the risks of other things that are available and generally accepted as safe- including prescription medications, supplements, and food ingredients.

No we do NOT KNOW if it is safe in the population it is now being touted for. It has side effects that absolutely could be more unsafe for kids with autism vs adults with cancer. Specifically, seizures and aggression are known side effects and these are bigger concerns for autism. AND there is also research connecting too much prenatal folate to autism.

We.do.not.know.

On that basis, almost nothing is "safe" for use in kids with autism because these kids often aren't part of clinical trial populations. Since you're saying a safety record for the general population shouldn't be used to infer safety in a subpopulation.

Again, you're being disingenuous. This is done all the time. Heck, look how often drugs get prescribed off-label because of how hard it is to run trials (particularly in kids).

Frankly, off-label use here would seem to be the right move, too. But clearly something has happened over the last 10 years, and particularly with this drug, to make some doctors lose their ability to weigh risks and potential benefits rationally and in the best interest of their patients. Why are they treating it so differently than something like guanfacine, another drug with a long safety history that is frequently prescribed for young kids with autism presenting with aggressive or self-injurious behaviors, despite those being off-label.

This is a drug being specific touted FOR kids with autism. So yes, it is relevant to ask how it specifically affects them. And of course the whole point is that this went far beyond off-label use, departing from how additional uses are added and making overblown claims not supported by the evidence.

More importantly while it may be an understandable stance for an individual parent with their doctor to use a med off-label under the background of slow or nonexistent goldstar research - that is far different from the people *literally in charge of the research* upending it. Trump and RFK jr are pretending like they aren’t the ones with the power to actually do the research our kids deserve. because they don’t actually care about our kids. They care about politics.

The reality of modern medicine is that doctors now want top-cover for prescribing medications- particularly in kids. Guanfacine was able to become common before those pressures shifted.

The only way we can really provide that top-cover is adding it to the label. If a doctor isn't satisfied there's a good risk-benefit tradeoff based on the available data, then they obviously don't need to prescribe it. It's not like they're trying to make this available OTC without a prescription.

Forgive me if I expect more from the people and institutions literally in charge of making the determinations of what can be prescribed safely. That’s the insane part. You’re saying that because our research and prescribing systems are not ideal that the people in charge of our research and prescribing systems have no other choice but to shrug their shoulders and say “the system sucks, take whatever”?

The status quo basically is: "there aren't great medications, but you can try these things."

And let's be clear, if the FDA updates the label, that isn't telling people to "try whatever." It is telling people to talk to their doctors about Leucovorin for kids with autism. It doesn't make it directly available to parents or patients. It doesn't tell doctors they need to offer to everyone with autism, or to anyone at all. It just makes it available as an option at a lower professional and legal risk to the prescribing physician. And a clearer path for insurance coverage.

No matter how much you insist that nothing out of the ordinary happened here, we all know it did. And all for the purpose of aggrandizement of Trump, not for the purpose of helping our kids. Where’s the funding for additional studies on leucovorin? maybe that was included in the announcement and I missed it.

You honestly sounds so childish. Just because you don’t know anything about people involved in the approval process of other things does not mean that they’re good people either. A lot of autistic kids were already taking this medication and as you can see from the SN section there have been people trying to get access to this medication since well before this and if Trump can make that happen even for his own crappy reasons then who tf cares? Not every parent wants to wait for additional studies and there are 50+ years of data on safety. And no my kid does not take leucovorin.

It’s childish to say that kids with autism actually deserve the best research and not quackery? OK.

DP. Conducting the best research doesn't have to mean also waiting years before trying safe drugs.

Yes it actually does. I’m not sure how many times you need that repeated.

It really doesn't. When to start using a drug is based on risk-benefit. This is a low-risk drug with promising benefits.

No it is is not. It is an untested drug and we don’t know the risks and benefits for the class of kids it is being targeted to.

I’m just going to quote the actual research experts again here:

“ The September 22 press conference held by U.S. Health and Human Services alarms us researchers … The data cited do not support the claim that Tylenol causes autism and leucovorin is a cure, and only stoke fear and falsely suggest hope when there is no simple answer.”

“With this in mind,” the group added, “we do not support any recommendation from the HHS or FDA regarding increased use of folinic acid. Instead, we call for a well-designed, large scale clinical trial of leucovorin (folinic acid) with all of the rigor needed (biomarkers, proper endpoints) and, most importantly, a pre-registered analysis plan.”

https://www.thetransmitter.org/spectrum/autism-experts-question-hhs-statements-on-tylenol-leucovorin/

It's not an "untested drug". The quality of the data is limited, but it isn't untested. Safety trials very frequently don't closely match the expected or intended population. The efficacy trials have been small, but at least four RCTs have had positive results.

Positive results that the 200 actual autism experts heavily hint are driven by unsound research methods.

And of course we are talking about an intended population where the drug side effects are very salient - the exacerbation or behavior and seizures in physically healthy autistic children - vs the population that has received the drug in the past (cancer patients facing potentially fatal chemo side effects).

No, the statements didn't even go that far. They called for larger and more consistent studies, but they didn't say the existing research was unsound.

By your logic, we shouldn't give approved psychotropic drugs to any kids with autism until there have been trials of significant size confirming safety and efficacy in the ASD subpopulation. Since, as you say, the risks and benefits could be different in that subpopulation. But of course we don't do that.

This is what the researchers said we need:

“ well-designed, large scale clinical trial of leucovorin (folinic acid) with all of the rigor needed (biomarkers, proper endpoints) and, most importantly, a pre-registered analysis plan.”

Which heavily implies the existing studies were not well designed. Anyone can claims something is an “RCT” but cherry pick results and create apparent correlations by picking the end points after the trial is over.

And yes, a drug touted specifically for kids with autism needs to be fully tested for them. Not sure why this is even a question.

[Anonymous]

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Anonymous wrote:I would love to hear other people experiences with Leucovorin

Because we’re doing science by anecdote now I guess.

Ever hear of case studies?

Case studies are not the kind of evidence the FDA generally uses to determine the safety and efficacy of a medication.

It's been used for 70 years. We already know it's safe.

They put cocaine in cough syrup for 70 yesrs

Do you not realize that Leucovorin continues to be used?

… in cancer. Stop lying.

You compared the safety record of Leucovorin to the safety record cocaine. I'm not the one being disingenuous. You can argue we don't know how effective it is for ASD, but we already know it's safe.

That wasn’t me but for the record cocaine actually does have medical uses right now (as a topical anesthesia).

So do you think that makes the safety record of cocaine similar to the safety record of Leucovorin? Otherwise, what's your point?

The point is that saying a drug is safe and effective for one indication says literally nothing at all about whether it is safe and effective for a wholly different indication. If you cannot grasp this entirely basic and fundamental point then you probably shouldn’t be in this discussion.

Again, we don't know it is effective, but we do know it is safe. Safe doesn't necessarily mean there's absolutely no possibility of risk. We approve drugs and other substances while there is still small potential for risks, with after-market monitoring being used to catch exceptional events. Leucovorin has the substantial benefit over new drugs in that we already have a long safety history with the drug.

It's ridiculous to suggest it isn't safe. Particularly given the risks of other things that are available and generally accepted as safe- including prescription medications, supplements, and food ingredients.

No we do NOT KNOW if it is safe in the population it is now being touted for. It has side effects that absolutely could be more unsafe for kids with autism vs adults with cancer. Specifically, seizures and aggression are known side effects and these are bigger concerns for autism. AND there is also research connecting too much prenatal folate to autism.

We.do.not.know.

On that basis, almost nothing is "safe" for use in kids with autism because these kids often aren't part of clinical trial populations. Since you're saying a safety record for the general population shouldn't be used to infer safety in a subpopulation.

Again, you're being disingenuous. This is done all the time. Heck, look how often drugs get prescribed off-label because of how hard it is to run trials (particularly in kids).

Frankly, off-label use here would seem to be the right move, too. But clearly something has happened over the last 10 years, and particularly with this drug, to make some doctors lose their ability to weigh risks and potential benefits rationally and in the best interest of their patients. Why are they treating it so differently than something like guanfacine, another drug with a long safety history that is frequently prescribed for young kids with autism presenting with aggressive or self-injurious behaviors, despite those being off-label.

This is a drug being specific touted FOR kids with autism. So yes, it is relevant to ask how it specifically affects them. And of course the whole point is that this went far beyond off-label use, departing from how additional uses are added and making overblown claims not supported by the evidence.

More importantly while it may be an understandable stance for an individual parent with their doctor to use a med off-label under the background of slow or nonexistent goldstar research - that is far different from the people *literally in charge of the research* upending it. Trump and RFK jr are pretending like they aren’t the ones with the power to actually do the research our kids deserve. because they don’t actually care about our kids. They care about politics.

The reality of modern medicine is that doctors now want top-cover for prescribing medications- particularly in kids. Guanfacine was able to become common before those pressures shifted.

The only way we can really provide that top-cover is adding it to the label. If a doctor isn't satisfied there's a good risk-benefit tradeoff based on the available data, then they obviously don't need to prescribe it. It's not like they're trying to make this available OTC without a prescription.

Forgive me if I expect more from the people and institutions literally in charge of making the determinations of what can be prescribed safely. That’s the insane part. You’re saying that because our research and prescribing systems are not ideal that the people in charge of our research and prescribing systems have no other choice but to shrug their shoulders and say “the system sucks, take whatever”?

The status quo basically is: "there aren't great medications, but you can try these things."

And let's be clear, if the FDA updates the label, that isn't telling people to "try whatever." It is telling people to talk to their doctors about Leucovorin for kids with autism. It doesn't make it directly available to parents or patients. It doesn't tell doctors they need to offer to everyone with autism, or to anyone at all. It just makes it available as an option at a lower professional and legal risk to the prescribing physician. And a clearer path for insurance coverage.

No matter how much you insist that nothing out of the ordinary happened here, we all know it did. And all for the purpose of aggrandizement of Trump, not for the purpose of helping our kids. Where’s the funding for additional studies on leucovorin? maybe that was included in the announcement and I missed it.

You honestly sounds so childish. Just because you don’t know anything about people involved in the approval process of other things does not mean that they’re good people either. A lot of autistic kids were already taking this medication and as you can see from the SN section there have been people trying to get access to this medication since well before this and if Trump can make that happen even for his own crappy reasons then who tf cares? Not every parent wants to wait for additional studies and there are 50+ years of data on safety. And no my kid does not take leucovorin.

It’s childish to say that kids with autism actually deserve the best research and not quackery? OK.

DP. Conducting the best research doesn't have to mean also waiting years before trying safe drugs.

Yes it actually does. I’m not sure how many times you need that repeated.

It really doesn't. When to start using a drug is based on risk-benefit. This is a low-risk drug with promising benefits.

No it is is not. It is an untested drug and we don’t know the risks and benefits for the class of kids it is being targeted to.

I’m just going to quote the actual research experts again here:

“ The September 22 press conference held by U.S. Health and Human Services alarms us researchers … The data cited do not support the claim that Tylenol causes autism and leucovorin is a cure, and only stoke fear and falsely suggest hope when there is no simple answer.”

“With this in mind,” the group added, “we do not support any recommendation from the HHS or FDA regarding increased use of folinic acid. Instead, we call for a well-designed, large scale clinical trial of leucovorin (folinic acid) with all of the rigor needed (biomarkers, proper endpoints) and, most importantly, a pre-registered analysis plan.”

https://www.thetransmitter.org/spectrum/autism-experts-question-hhs-statements-on-tylenol-leucovorin/

It's not an "untested drug". The quality of the data is limited, but it isn't untested. Safety trials very frequently don't closely match the expected or intended population. The efficacy trials have been small, but at least four RCTs have had positive results.

Positive results that the 200 actual autism experts heavily hint are driven by unsound research methods.

And of course we are talking about an intended population where the drug side effects are very salient - the exacerbation or behavior and seizures in physically healthy autistic children - vs the population that has received the drug in the past (cancer patients facing potentially fatal chemo side effects).

No, the statements didn't even go that far. They called for larger and more consistent studies, but they didn't say the existing research was unsound.

By your logic, we shouldn't give approved psychotropic drugs to any kids with autism until there have been trials of significant size confirming safety and efficacy in the ASD subpopulation. Since, as you say, the risks and benefits could be different in that subpopulation. But of course we don't do that.

This is what the researchers said we need:

“ well-designed, large scale clinical trial of leucovorin (folinic acid) with all of the rigor needed (biomarkers, proper endpoints) and, most importantly, a pre-registered analysis plan.”

Which heavily implies the existing studies were not well designed. Anyone can claims something is an “RCT” but cherry pick results and create apparent correlations by picking the end points after the trial is over.

And yes, a drug touted specifically for kids with autism needs to be fully tested for them. Not sure why this is even a question.

Many drugs are prescribed for kids with autism without undergoing large-scale trials specifically in the autism population they're used in. ADHD drugs are one major example. Abilify was another example before its label was formally updated. Guanfacine is still frequently prescribed outside of the age group that had trials, and for indications that aren't listed on the label.

[Anonymous]

Calling for a large, pre-registered trial doesn’t mean the existing studies were poorly designed—it’s simply the natural next step in clinical research. Smaller RCTs are meant to generate evidence and refine endpoints before investing in large-scale trials. In fact, the reason researchers want a bigger study is precisely because the preliminary data have shown consistent, promising signals in autistic children with folate pathway issues. Large, multi-site trials take years to fund, design, and complete. Families facing daily challenges don’t always have the luxury of waiting a decade for “perfect” evidence. Medicine often advances by balancing what we know now with what we’re still learning. Leucovorin is not an experimental compound with unknown safety—it’s an FDA-approved medication long used in pediatrics for other indications, with a well-understood safety profile.

The existing smaller RCTs and open-label studies show improvements in communication and behavior in subgroups of autistic children with folate metabolism abnormalities. While these results need confirmation, they’re strong enough to suggest that some children may benefit. For a low-risk, potentially high-reward treatment, it’s reasonable for clinicians and parents—especially when biomarkers indicate susceptibility—to consider a trial of therapy now, rather than withholding it until a large trial eventually happens.

[Anonymous]

And again, if you don't want to prescribe it, you don't have to! And if you don't want to give it to your kid, you don't have to do that, either.

And of course you won't. You're simply here because of the politics, since you obviously don't have a child who is profoundly impacted by autism. Are you going to go on a crusade against experimental cancer drugs next or do you really just want to stick it to kids with autism?

[Anonymous]

Anonymous wrote:Calling for a large, pre-registered trial doesn’t mean the existing studies were poorly designed—it’s simply the natural next step in clinical research. Smaller RCTs are meant to generate evidence and refine endpoints before investing in large-scale trials. In fact, the reason researchers want a bigger study is precisely because the preliminary data have shown consistent, promising signals in autistic children with folate pathway issues. Large, multi-site trials take years to fund, design, and complete. Families facing daily challenges don’t always have the luxury of waiting a decade for “perfect” evidence. Medicine often advances by balancing what we know now with what we’re still learning. Leucovorin is not an experimental compound with unknown safety—it’s an FDA-approved medication long used in pediatrics for other indications, with a well-understood safety profile.

The existing smaller RCTs and open-label studies show improvements in communication and behavior in subgroups of autistic children with folate metabolism abnormalities. While these results need confirmation, they’re strong enough to suggest that some children may benefit. For a low-risk, potentially high-reward treatment, it’s reasonable for clinicians and parents—especially when biomarkers indicate susceptibility—to consider a trial of therapy now, rather than withholding it until a large trial eventually happens.

No, all RCTs should be designed with scientific integrity no matter how small. Also the FRAT test is not considered medically necessary by many insurance companies so the jury is out on that as well.

[Anonymous]

Anonymous wrote:And again, if you don't want to prescribe it, you don't have to! And if you don't want to give it to your kid, you don't have to do that, either.

And of course you won't. You're simply here because of the politics, since you obviously don't have a child who is profoundly impacted by autism. Are you going to go on a crusade against experimental cancer drugs next or do you really just want to stick it to kids with autism?

I am here because the politics are distorting the medical research process and vulnerable kids deserve the best research.

[Anonymous]

Anonymous wrote:

Anonymous wrote:And again, if you don't want to prescribe it, you don't have to! And if you don't want to give it to your kid, you don't have to do that, either.

And of course you won't. You're simply here because of the politics, since you obviously don't have a child who is profoundly impacted by autism. Are you going to go on a crusade against experimental cancer drugs next or do you really just want to stick it to kids with autism?

I am here because the politics are distorting the medical research process and vulnerable kids deserve the best research.

Find a different segment of the population to "advocate" for. Seriously. We've got enough problems as it is and there are plenty of other causes for you to focus on.

[Anonymous]

Anonymous wrote:

Anonymous wrote:And again, if you don't want to prescribe it, you don't have to! And if you don't want to give it to your kid, you don't have to do that, either.

And of course you won't. You're simply here because of the politics, since you obviously don't have a child who is profoundly impacted by autism. Are you going to go on a crusade against experimental cancer drugs next or do you really just want to stick it to kids with autism?

I am here because the politics are distorting the medical research process and vulnerable kids deserve the best research.

The effects that leucovorin has on "autism *" were published 15 years ago in well regarded, peer reviewed journals such as Molecule and Nature. And that was that because there is no money to be made in repurposing an out of patent drug.

In those 15 years, how many autistic people have been institutionalized, how many parents died before hearing their own children say a word, how many drowned after sloping, how many have been left to bang their heads against the floors alone in a room?

Thats the way the Medical Research process works. Burn it down.

* There is reason to believe that this isn't even ASD but a variation of CFD but none of your golden institutions have bothered to investigate.

[Anonymous]

Anonymous wrote:

Anonymous wrote:And again, if you don't want to prescribe it, you don't have to! And if you don't want to give it to your kid, you don't have to do that, either.

And of course you won't. You're simply here because of the politics, since you obviously don't have a child who is profoundly impacted by autism. Are you going to go on a crusade against experimental cancer drugs next or do you really just want to stick it to kids with autism?

I am here because the politics are distorting the medical research process and vulnerable kids deserve the best research.

In the decades and decades of "medical research process" you hold so dear, they never modeled the effect of high dose folate on the body? Doesnt sound like a process worth defending.