The problem here is that the political polarization is around 'trust the experts'. The Republicans are right on the substance (in retrospect the data proves health experts were obviously wrong) but they are right for all the wrong reasons. Democrats cannot admit the experts were wrong without taking a huge L and the toxicity of the present day GOP prevents moderates and reasonable liberals from taking their side. This is a perfect example of why normal people utterly despise politics.
More than a decade ago, the Board on Science, Technology and Economic Policy of the National Academy of Sciences held a session with 5 CTOs from big pharma. We talked about how to get drugs to market earlier. The lives saved would be extraordinary, on the same order of magnitude as deaths due to Covid. The conclusion was to replace stage 3 drug trials with a new set of rules: Drugs that were cleared from Stage II would be placed into an Investigational Phase, and during this phase, any doctor could prescribe the drug but all events and medical records would be reported to a 24x7 monitoring center, and drug use could be stopped at anytime based on events. Simple. Using state of the art technology. Drugs could maybe get to market years earlier, and costs would go down. Seemed sensible then. Essential now. Almost no chance of ever happening.
There's a minor error in the chart caption, which says that figures are rounded to the nearest million dollars but instead rounds to the nearest ten million (hundredth of a billion).
The infuriating part of this is this should be a nonpartisan issue where politicians can quietly work behind the scenes and pass meaningful reforms. Instead it's become a hyper partisan issue with neither side presenting anything close to a tangible policy idea.
It's less depressing and more mind boggling. It's a low salience issue. If you asked most people about whether the federal government should be doing studies on disease including Covid-19 I am 100% confident it would get overwhelming support. But once you start talking about Fauci the Republicans get up in arms and we're stuck.
I kinda wish Biden had told Fauci to retire, not because Fauci is bad but because he's become a lightning rod and that's stopping actual reform.
It's good that doctors have discretion to use approved medicines in ways that haven't yet been tested because there are some medical conditions that are so rare that it's extremely difficult to run clinical trials on them. When the incidence is from 1–10 in a million, sometimes they have to make an educated guess!
One of the things that makes long Covid so difficult to study right now is that we don’t really have a good case definition which makes it difficult to recruit patients. There was one good quality study that found that the only symptom that was more common in people who had had the virus vs those who had not was loss of smell. That study was probably not large enough to detect rarer syndromes like the post viral syndromes we have with other viruses an almost certainly occur with this virus. Still, it suggests that the estimates that 10% of Covid cases lead to long Covid are a massive overestimate. I’d say that’s actually a good thing.
One of the problems with a lack of high-quality science is that low quality science ends up being used when estimating the incidence of stuff like long Covid. Some of the studies with high estimates of long Covid don’t have a control group, which is really important because the pandemic had massively disrupted the lives of everyone and that will affect everyone’s health status. Others do not confirm that the people in the study have actual evidence of Covid infection (positive pcr test, antibodies, T cell response) in order for them to be included in the long Covid group. And the NIH should be demanding that the science it funds is high quality because otherwise we waste time on stuff that has little chance of working.
Unfortunately I suspect long Covid has been too politicized in the US to ever get useful data. Honestly though, the US is bad at this type of research anyway so I have a lot more faith in some European country to get valuable data at some point. And if no European country considers it worth researching, that’s a strong argument against its being a significant problem beyond what we already know about usual post-viral syndromes that we already know exist
Bioethicist are to important medical research what environmentalists/housing advocates are to new home construction? They are so caught up in their own bull$hit that they end up doing more harm than good?
And while there’s most certainly a need for them they need less power and less control of policy.
It’s interesting how much people on the left want to talk about Ivermectin (because it appears to be a political winner for them) and how little they want to talk about where the virus came from. It is increasing likely the scientists that saved us are the ones that infected us in the first place. It’s like a Marvel movie.
Even if one assumed, for the sake of argument, that the lab leak hypothesis is correct, it was not Chinese scientists who saved us, but scientists at places like Pfizer and Moderna.
I am not saying it’s the exact same scientists. I do want to say...I am very pro science. The way the vaccines were created is an amazing human accomplishment. So amazing that it makes one wonder if messy around with viruses in labs like Wuhan is actually worth it?
The vaccines would not have been developed nearly as quickly without prior research into the SARS virus. A lot of time and effort went into understanding the structure and functioning of the SARS spike protein as well as its infection effects. The results of that research as well as some of the techniques that were developed in the course of carrying it out were directly applicable to studying 2019-nCoV.
Maybe not if some of that research leaked out of a lab and infected the world. I think their is much more nuance to this than we are getting in the public discourse. For instance you end with saying studying viruses is very much worth it. As if I’m advocating for not studying viruses. Not true. I’m advocating for being prudent about risk reward based on an ever changing world of scientific knowledge and technology.
If COVID started with a lab leak..is it not a fair question did we get the risk reward right? With mRNA does certain kinds of vaccine research still make sense? Twenty years ago it made a lot of sense for me to have a land line phone. Now it makes not nearly enough sense to justify the costs. Things change.
You are kitbashing a lot of concerns here in ways that produce nonsensical analysis.
To take one example, if you take the lab-leak hypothesis as your preferred outbreak cause, that still leaves a whole spectrum of responses available. Improving lab protocols is a fairly obvious one that would not necessarily require all that much change. But if you premise your assessment of that spectrum of options on a set of other assumptions about "scientists" or "China" or "Big Pharma" or whatever, it leads you down the road of shrinking those options such that you stop appreciating them.
You also need to disentangle the actors, here, i.e. you wrote, "I’m advocating for being prudent about risk reward based on an ever changing world of scientific knowledge and technology," but WHO are you advocating prudence for? The Wuhan lab was overseen by the Chinese government. What is your channel for advocating increased "prudence" on the part of the CCP? Like, how would that work in the real world? How do we keep Chinese labs from obtaining viral specimens in Chinese territory and experimenting with gain-of-function research funded by the Chinese government?
I don’t have a preferred outbreak cause. I have a preference for knowing the truth.
I appreciate science. I am not sure what appreciation I need to have for China. Scientists are human. Most do good things, a few don’t. I am not disillusioned by this.
Yes, getting other countries to do good things is hard. Nuclear weapons come to mind. I don’t have good answers on nuclear proliferation and I don’t have good answers on how to deal with viruses. But that doesn’t mean concern doesn’t have merit. If I could get China to do what America wants I’d be the most successful diplomat ever.
I think there are many things worth thinking about here. First where did this virus come from? Many people seem to respond with what does it matter? Does it change anything? I think it does. Why ever investigate why any bad thing happens? It matters.
If this virus was caused by humans what does justice look like? Even if it’s totally an accident. No worries, we all make mistakes. This makes an oil spill look like a spilled cup of coffee.
To be clear I am not saying any person, country, or company did anything with malice here. I have no reason to believe that. But negligence can be quite costly.
It’s interesting to me we are so cavalier about virus research and so conservative about nuclear power plants.
I know in many circles the lab leak has been debunked. I don’t see it that way. If COVID came from a lab leak it’s really not so different than Ultron who was also a lab leak who started mutating.
It seems like the fundamental problem with the FDA approval process at least is that it's both an *approval* (the drug is now legal to sell and prescribe) and a de facto *requirement* that insurance companies cover the drug, even if it's not that effective in most cases. It's not like dietary supplements, where no one has to buy them. My uninformed take is that there should be some way for the FDA to say, this drug is safe and might be effective in some narrow cases, but we don't need to be requiring insurance companies to prescribe it since there's limited evidence on efficacy.
I'm retired from the biopharma industry and put out a daily newsletter on COVID during most of 2020, stopping when the first vaccines were authorized for experimental use late in the year. I was equally frustrated by the slow pace at NIH and they should have done more to harness the vast clinical trial networks in the US. Most of the early intervention trials were quickly designed and up and running in the UK (first to show the benefits of steroid treatment). NIH had experience in both the HIV/AIDs and cancer areas where they set up large multi-center networks some of which are still up and running (I wrote up a white paper on how this could be adapted to COVID research). This has to go down as a failure even though there are NIH efforts that are ongoing right now.
Observational trials are also incredibly useful. I was part of the industry group that developed and funded an exploratory approach to the use of observational data from medical records to look at both drug safety and efficacy. We involved FDA in the planning of this and, not wanting to get into all the gory details, it successfully morphed into a large multi-national group. The Observational Health Data Sciences and Informatics (or OHDSI, pronounced "Odyssey") program is a multi-stakeholder, interdisciplinary collaborative to bring out the value of health data through large-scale analytics. They mobilized quite early in the pandemic and set up an number of good research protocols to look at a variety of interventions. As commentator Allan Thoen notes below, these kinds of research protocols can be useful in ongoing work.
I don't know whether one can put up web links in the comments section. there is a very good YouTube video up on the TOGETHER Trial by 'Biotech and Bioinformatics with Prof Greg' Google will be your friend if you want to watch it. It's a good description of new trial designs. Such designs are being used by industry and Matt should have been more clear on this.
In the beginning of the pandemic, NIH issued a few NOSIs (Notice of Special Interest) for proposals on broad questions of SARS-CoV-2, including molecular biology and etiology. These dried up within a couple of months, even before their expiration as the small amount of money allocated was already spent. Now the only NOSIs are around downstream effects of COVID, messaging to underserved populations, and the like - nothing on biology or new treatments: https://grants.nih.gov/grants/guide/COVID-Related.cfm#active
In 2020, I submitted an R21 (two-year grant for exploratory research - $275k) to NIH on one of the SARS-CoV-2 proteins, for which we had a couple of publications already. It wasn't funded with the feedback being "there's already too many people working on this". Totally fair on the merits, but you might have thought in the first year of the pandemic that NIH would have wanted more people turning their research to SARS-CoV-2.
Talking to others, mine was a common experience. A collaborator had already developed a promising small-molecule inhibitor that not only worked in vitro against the virus, it even worked in a small humanized mice trial. They submitted an R01 (typical 5-year NIH research grant - ~$2m) proposal, which was not funded with typical stock criticisms.
Now, I don't want this to come off as a "woe is me" post; this isn't to say that my or my collaborator's proposals should have been funded no questions asked! But it's not just us. Having been on the other side of the equation, reviewing proposals for NIH in the last year, I can say there was no special attention paid to COVID-related proposals (if anything, it was more like an eye-roll at yet another one).
Maybe this is kind of self-serving, but it seems a bit tragic to me that after spending trillions of dollars to manage and mitigate the effects of COVID, we can't shake loose even a few billion for basic research.
Addendum: I have defended NIH before as the best way to decide what projects should be funded, and I still contend it's significantly better than the private grants that a lot of people are fond of. My complaint is that the high-level decision makers (e.g., Congress) didn't really prioritize SARS-CoV-2 research.
I review grants for an institute that offers lots of small pilot grants with seed money to get programs of research up and running. We put out calls, and ran extra sessions to get money out faster, etc. People just submitted whatever they wanted to do anyway with the word "COVID" worked in there somewhere. We did this for the first year. I only ever saw 1 application that was legitimately on COVID. (Which wasn't funded...)
I don't have numbers in front of me but I feel pretty confident that a majority of NIH grants were directed towards SARS-CoV-2 research. I'm skeptical that they didn't prioritize it. I think it's more likely that they were simply flooded with requests and had to turn a lot of them down. Do you think the NIH should have been given more money or that they aren't doing a good job at picking which research to fund? If it's the latter we would need to look at which grants were approved.
A majority of NIH grants were absolutely not directed towards SARS-CoV-2 research, nor would I expect them to be! It's a nearly $40b agency in a typical year; you don't want everyone to drop everything they're doing just to work on this.
https://covid19.nih.gov/funding It looks like they've spent almost $5b on COVID-related research (over two years), but that covers everything from basic science to trials to vaccine delivery. I don't know want to come off as complaining too much about this, but I imagine most people would have assumed like you that there was a huge pivot to COVID when it really wasn't the case at all.
I get the “too many people already working in the field” but they really ought to be prioritizing groups that already have some experience with it and have some promising results.
Mice bred to resemble humans in certain key ways. It's a standard in pre-human trial research, though I'm not enough of a biologist to know if there are multiple lines for different types of human equivalency or how similar they actually are.
Two broad types: one is not so much bred but is genetically engineered to possess bits of human DNA. The other type is literally grafting bits of humans onto (or into) the mice, such as human tumors or replacing mice immune cells with human immune cells.
I am 100% on board with the sentiment that the clinical trial could and should have been done faster and it is a tragedy that more hasn't been done.
I think there are a few extra facts that might add some nuance to the situation:
1) The NIH did in fact have around 6 (non-vaccine) platform trials as part of its ACTIV trial research program (and associated ACTT trials). But they are largely too small and too slow.
The best known output of this is in the ACTIV-2 trial (outpatients) which by itself tested around half a dozen monoclonal antibodies under a common protocol so that results could be compared and the trials could be supported by NIH.
The biggest disappointment is the ACTIV-1 trial (hospitalised patients). Basically all the hospitalised patient recommendations come from the UK RECOVERY trial which has randomised ~44,000 patients and figured out dexamethosone helped by mid-2020. ACTIV-1 has (I think?) randomised around 3,000 which may be quite underpowered to detect small but important impacts on mortality.
Most hope is for the ACTIV-6 trial, which is the US govt trying out a structure like the ones you've promoted here. Started way too late, but they actually have 2 different doses of ivermectin (probably won't work but good to really put a nail in this coffin) and also fluticasone and fluvoxamine (much better chance of working and are cheap).
2) The PANORAMIC trial in the UK may be the fasting enrolling therapeutic trial in recent history and has a jaw-dropping ~22,000 patients randomised to Merck's antiviral (molnupiravir) and has done this over the past 4-5 months. This is already around 10 times the size of Merck's original controversial trial! It could give a much cleaner answer than the original trial did. Interestingly, the trial protocol includes a pre-specified 'economic analysis' as well to basically figure out if giving these antivirals to less at risk (50s and vaccinated) people is worth it to the NHS.
Our ability to reduce mortality is hugely hampered by the slow recruitment of these trials and I hope someone who can do something about it reads your piece and acts.
As an aside, I was offered participation in ACTIV 6 when I was diagnosed with covid in Jan. However, I had a mild case that was improving by the time I was contacted a day after the positive result, which was a few days into symptoms (probably omicron, 3x vaccinated) and my personal cost-benefit assessment was that no personal medication side effects were worth taking a new medicine at that point, so I passed.
The problem here is that the political polarization is around 'trust the experts'. The Republicans are right on the substance (in retrospect the data proves health experts were obviously wrong) but they are right for all the wrong reasons. Democrats cannot admit the experts were wrong without taking a huge L and the toxicity of the present day GOP prevents moderates and reasonable liberals from taking their side. This is a perfect example of why normal people utterly despise politics.
More than a decade ago, the Board on Science, Technology and Economic Policy of the National Academy of Sciences held a session with 5 CTOs from big pharma. We talked about how to get drugs to market earlier. The lives saved would be extraordinary, on the same order of magnitude as deaths due to Covid. The conclusion was to replace stage 3 drug trials with a new set of rules: Drugs that were cleared from Stage II would be placed into an Investigational Phase, and during this phase, any doctor could prescribe the drug but all events and medical records would be reported to a 24x7 monitoring center, and drug use could be stopped at anytime based on events. Simple. Using state of the art technology. Drugs could maybe get to market years earlier, and costs would go down. Seemed sensible then. Essential now. Almost no chance of ever happening.
There's a minor error in the chart caption, which says that figures are rounded to the nearest million dollars but instead rounds to the nearest ten million (hundredth of a billion).
The infuriating part of this is this should be a nonpartisan issue where politicians can quietly work behind the scenes and pass meaningful reforms. Instead it's become a hyper partisan issue with neither side presenting anything close to a tangible policy idea.
It's less depressing and more mind boggling. It's a low salience issue. If you asked most people about whether the federal government should be doing studies on disease including Covid-19 I am 100% confident it would get overwhelming support. But once you start talking about Fauci the Republicans get up in arms and we're stuck.
I kinda wish Biden had told Fauci to retire, not because Fauci is bad but because he's become a lightning rod and that's stopping actual reform.
terrific post
It's good that doctors have discretion to use approved medicines in ways that haven't yet been tested because there are some medical conditions that are so rare that it's extremely difficult to run clinical trials on them. When the incidence is from 1–10 in a million, sometimes they have to make an educated guess!
One of the things that makes long Covid so difficult to study right now is that we don’t really have a good case definition which makes it difficult to recruit patients. There was one good quality study that found that the only symptom that was more common in people who had had the virus vs those who had not was loss of smell. That study was probably not large enough to detect rarer syndromes like the post viral syndromes we have with other viruses an almost certainly occur with this virus. Still, it suggests that the estimates that 10% of Covid cases lead to long Covid are a massive overestimate. I’d say that’s actually a good thing.
One of the problems with a lack of high-quality science is that low quality science ends up being used when estimating the incidence of stuff like long Covid. Some of the studies with high estimates of long Covid don’t have a control group, which is really important because the pandemic had massively disrupted the lives of everyone and that will affect everyone’s health status. Others do not confirm that the people in the study have actual evidence of Covid infection (positive pcr test, antibodies, T cell response) in order for them to be included in the long Covid group. And the NIH should be demanding that the science it funds is high quality because otherwise we waste time on stuff that has little chance of working.
Unfortunately I suspect long Covid has been too politicized in the US to ever get useful data. Honestly though, the US is bad at this type of research anyway so I have a lot more faith in some European country to get valuable data at some point. And if no European country considers it worth researching, that’s a strong argument against its being a significant problem beyond what we already know about usual post-viral syndromes that we already know exist
Can I just second the sense of the despair about institutions and politics?
What is going on with Pavloxid introduction? I would have expected a greater impact on mortality and hospitalization by now.
Bioethicist are to important medical research what environmentalists/housing advocates are to new home construction? They are so caught up in their own bull$hit that they end up doing more harm than good?
And while there’s most certainly a need for them they need less power and less control of policy.
It’s interesting how much people on the left want to talk about Ivermectin (because it appears to be a political winner for them) and how little they want to talk about where the virus came from. It is increasing likely the scientists that saved us are the ones that infected us in the first place. It’s like a Marvel movie.
Even if one assumed, for the sake of argument, that the lab leak hypothesis is correct, it was not Chinese scientists who saved us, but scientists at places like Pfizer and Moderna.
I am not saying it’s the exact same scientists. I do want to say...I am very pro science. The way the vaccines were created is an amazing human accomplishment. So amazing that it makes one wonder if messy around with viruses in labs like Wuhan is actually worth it?
The vaccines would not have been developed nearly as quickly without prior research into the SARS virus. A lot of time and effort went into understanding the structure and functioning of the SARS spike protein as well as its infection effects. The results of that research as well as some of the techniques that were developed in the course of carrying it out were directly applicable to studying 2019-nCoV.
So, yes, studying viruses is very much worth it.
Maybe not if some of that research leaked out of a lab and infected the world. I think their is much more nuance to this than we are getting in the public discourse. For instance you end with saying studying viruses is very much worth it. As if I’m advocating for not studying viruses. Not true. I’m advocating for being prudent about risk reward based on an ever changing world of scientific knowledge and technology.
If COVID started with a lab leak..is it not a fair question did we get the risk reward right? With mRNA does certain kinds of vaccine research still make sense? Twenty years ago it made a lot of sense for me to have a land line phone. Now it makes not nearly enough sense to justify the costs. Things change.
You are kitbashing a lot of concerns here in ways that produce nonsensical analysis.
To take one example, if you take the lab-leak hypothesis as your preferred outbreak cause, that still leaves a whole spectrum of responses available. Improving lab protocols is a fairly obvious one that would not necessarily require all that much change. But if you premise your assessment of that spectrum of options on a set of other assumptions about "scientists" or "China" or "Big Pharma" or whatever, it leads you down the road of shrinking those options such that you stop appreciating them.
You also need to disentangle the actors, here, i.e. you wrote, "I’m advocating for being prudent about risk reward based on an ever changing world of scientific knowledge and technology," but WHO are you advocating prudence for? The Wuhan lab was overseen by the Chinese government. What is your channel for advocating increased "prudence" on the part of the CCP? Like, how would that work in the real world? How do we keep Chinese labs from obtaining viral specimens in Chinese territory and experimenting with gain-of-function research funded by the Chinese government?
It's just an analytical train to nowhere.
I don’t have a preferred outbreak cause. I have a preference for knowing the truth.
I appreciate science. I am not sure what appreciation I need to have for China. Scientists are human. Most do good things, a few don’t. I am not disillusioned by this.
Yes, getting other countries to do good things is hard. Nuclear weapons come to mind. I don’t have good answers on nuclear proliferation and I don’t have good answers on how to deal with viruses. But that doesn’t mean concern doesn’t have merit. If I could get China to do what America wants I’d be the most successful diplomat ever.
I think there are many things worth thinking about here. First where did this virus come from? Many people seem to respond with what does it matter? Does it change anything? I think it does. Why ever investigate why any bad thing happens? It matters.
If this virus was caused by humans what does justice look like? Even if it’s totally an accident. No worries, we all make mistakes. This makes an oil spill look like a spilled cup of coffee.
To be clear I am not saying any person, country, or company did anything with malice here. I have no reason to believe that. But negligence can be quite costly.
It’s interesting to me we are so cavalier about virus research and so conservative about nuclear power plants.
Huh?
I know in many circles the lab leak has been debunked. I don’t see it that way. If COVID came from a lab leak it’s really not so different than Ultron who was also a lab leak who started mutating.
It seems like the fundamental problem with the FDA approval process at least is that it's both an *approval* (the drug is now legal to sell and prescribe) and a de facto *requirement* that insurance companies cover the drug, even if it's not that effective in most cases. It's not like dietary supplements, where no one has to buy them. My uninformed take is that there should be some way for the FDA to say, this drug is safe and might be effective in some narrow cases, but we don't need to be requiring insurance companies to prescribe it since there's limited evidence on efficacy.
This is relatively new and seems promising: https://epicresearch.org/
They aggregate medical record data across health care organizations with the aim of quick turnaround research.
I'm retired from the biopharma industry and put out a daily newsletter on COVID during most of 2020, stopping when the first vaccines were authorized for experimental use late in the year. I was equally frustrated by the slow pace at NIH and they should have done more to harness the vast clinical trial networks in the US. Most of the early intervention trials were quickly designed and up and running in the UK (first to show the benefits of steroid treatment). NIH had experience in both the HIV/AIDs and cancer areas where they set up large multi-center networks some of which are still up and running (I wrote up a white paper on how this could be adapted to COVID research). This has to go down as a failure even though there are NIH efforts that are ongoing right now.
Observational trials are also incredibly useful. I was part of the industry group that developed and funded an exploratory approach to the use of observational data from medical records to look at both drug safety and efficacy. We involved FDA in the planning of this and, not wanting to get into all the gory details, it successfully morphed into a large multi-national group. The Observational Health Data Sciences and Informatics (or OHDSI, pronounced "Odyssey") program is a multi-stakeholder, interdisciplinary collaborative to bring out the value of health data through large-scale analytics. They mobilized quite early in the pandemic and set up an number of good research protocols to look at a variety of interventions. As commentator Allan Thoen notes below, these kinds of research protocols can be useful in ongoing work.
I don't know whether one can put up web links in the comments section. there is a very good YouTube video up on the TOGETHER Trial by 'Biotech and Bioinformatics with Prof Greg' Google will be your friend if you want to watch it. It's a good description of new trial designs. Such designs are being used by industry and Matt should have been more clear on this.
In the beginning of the pandemic, NIH issued a few NOSIs (Notice of Special Interest) for proposals on broad questions of SARS-CoV-2, including molecular biology and etiology. These dried up within a couple of months, even before their expiration as the small amount of money allocated was already spent. Now the only NOSIs are around downstream effects of COVID, messaging to underserved populations, and the like - nothing on biology or new treatments: https://grants.nih.gov/grants/guide/COVID-Related.cfm#active
In 2020, I submitted an R21 (two-year grant for exploratory research - $275k) to NIH on one of the SARS-CoV-2 proteins, for which we had a couple of publications already. It wasn't funded with the feedback being "there's already too many people working on this". Totally fair on the merits, but you might have thought in the first year of the pandemic that NIH would have wanted more people turning their research to SARS-CoV-2.
Talking to others, mine was a common experience. A collaborator had already developed a promising small-molecule inhibitor that not only worked in vitro against the virus, it even worked in a small humanized mice trial. They submitted an R01 (typical 5-year NIH research grant - ~$2m) proposal, which was not funded with typical stock criticisms.
Now, I don't want this to come off as a "woe is me" post; this isn't to say that my or my collaborator's proposals should have been funded no questions asked! But it's not just us. Having been on the other side of the equation, reviewing proposals for NIH in the last year, I can say there was no special attention paid to COVID-related proposals (if anything, it was more like an eye-roll at yet another one).
Maybe this is kind of self-serving, but it seems a bit tragic to me that after spending trillions of dollars to manage and mitigate the effects of COVID, we can't shake loose even a few billion for basic research.
Addendum: I have defended NIH before as the best way to decide what projects should be funded, and I still contend it's significantly better than the private grants that a lot of people are fond of. My complaint is that the high-level decision makers (e.g., Congress) didn't really prioritize SARS-CoV-2 research.
I review grants for an institute that offers lots of small pilot grants with seed money to get programs of research up and running. We put out calls, and ran extra sessions to get money out faster, etc. People just submitted whatever they wanted to do anyway with the word "COVID" worked in there somewhere. We did this for the first year. I only ever saw 1 application that was legitimately on COVID. (Which wasn't funded...)
I don't have numbers in front of me but I feel pretty confident that a majority of NIH grants were directed towards SARS-CoV-2 research. I'm skeptical that they didn't prioritize it. I think it's more likely that they were simply flooded with requests and had to turn a lot of them down. Do you think the NIH should have been given more money or that they aren't doing a good job at picking which research to fund? If it's the latter we would need to look at which grants were approved.
A majority of NIH grants were absolutely not directed towards SARS-CoV-2 research, nor would I expect them to be! It's a nearly $40b agency in a typical year; you don't want everyone to drop everything they're doing just to work on this.
https://covid19.nih.gov/funding It looks like they've spent almost $5b on COVID-related research (over two years), but that covers everything from basic science to trials to vaccine delivery. I don't know want to come off as complaining too much about this, but I imagine most people would have assumed like you that there was a huge pivot to COVID when it really wasn't the case at all.
I get the “too many people already working in the field” but they really ought to be prioritizing groups that already have some experience with it and have some promising results.
I'm almost afraid to ask what a "humanized mice trial" is.
In this case, I believe it just means they engineer human ACE2 into it so SARS-CoV-2 can infect it.
Mice bred to resemble humans in certain key ways. It's a standard in pre-human trial research, though I'm not enough of a biologist to know if there are multiple lines for different types of human equivalency or how similar they actually are.
Two broad types: one is not so much bred but is genetically engineered to possess bits of human DNA. The other type is literally grafting bits of humans onto (or into) the mice, such as human tumors or replacing mice immune cells with human immune cells.
Well that can’t possible go wrong.
Well that can’t possible go wrong.
It's mice that are being groomed by Disney for don't ask what.
Mice can get through the tiniest of openings, which means that they can sneak into your home and groom your children.
Sorry for the spoiler, but someone had to blow the whistle.
I am 100% on board with the sentiment that the clinical trial could and should have been done faster and it is a tragedy that more hasn't been done.
I think there are a few extra facts that might add some nuance to the situation:
1) The NIH did in fact have around 6 (non-vaccine) platform trials as part of its ACTIV trial research program (and associated ACTT trials). But they are largely too small and too slow.
The best known output of this is in the ACTIV-2 trial (outpatients) which by itself tested around half a dozen monoclonal antibodies under a common protocol so that results could be compared and the trials could be supported by NIH.
The biggest disappointment is the ACTIV-1 trial (hospitalised patients). Basically all the hospitalised patient recommendations come from the UK RECOVERY trial which has randomised ~44,000 patients and figured out dexamethosone helped by mid-2020. ACTIV-1 has (I think?) randomised around 3,000 which may be quite underpowered to detect small but important impacts on mortality.
Most hope is for the ACTIV-6 trial, which is the US govt trying out a structure like the ones you've promoted here. Started way too late, but they actually have 2 different doses of ivermectin (probably won't work but good to really put a nail in this coffin) and also fluticasone and fluvoxamine (much better chance of working and are cheap).
https://www.nih.gov/research-training/medical-research-initiatives/activ/covid-19-therapeutics-prioritized-testing-clinical-trials
2) The PANORAMIC trial in the UK may be the fasting enrolling therapeutic trial in recent history and has a jaw-dropping ~22,000 patients randomised to Merck's antiviral (molnupiravir) and has done this over the past 4-5 months. This is already around 10 times the size of Merck's original controversial trial! It could give a much cleaner answer than the original trial did. Interestingly, the trial protocol includes a pre-specified 'economic analysis' as well to basically figure out if giving these antivirals to less at risk (50s and vaccinated) people is worth it to the NHS.
https://www.panoramictrial.org/
Our ability to reduce mortality is hugely hampered by the slow recruitment of these trials and I hope someone who can do something about it reads your piece and acts.
As an aside, I was offered participation in ACTIV 6 when I was diagnosed with covid in Jan. However, I had a mild case that was improving by the time I was contacted a day after the positive result, which was a few days into symptoms (probably omicron, 3x vaccinated) and my personal cost-benefit assessment was that no personal medication side effects were worth taking a new medicine at that point, so I passed.