I worked for a summer at a medical device engineering consulting firm that did a lot of "we will tell you how to get your new device FDA approved" which amounted to a lot of "what is this comparable to so that you don't need to prove everything from scratch" and "how do you explain that to the regulators with the right buzzwords to get them to agree" -- it seems to me that the drug trial situation is the same. You can get everyone on board for a new trial system/design as soon as you get it through the regulators even once. The issue is someone has to be willing to risk a huge amount of money (even if it's 1/10 the price of the "standard way") to do the new trial and probably spend half again as much on extra lawyers and extra time arguing with the regulators to get something approved, then everyone will follow. This feels like exactly the kind of thing that VC is intended for, just that it's hard to convince someone to spend $200 million to test the theory.
Relatedly: it seems like this is one of the under-researched topics. Balsa should endow a chair for study of the regulatory process somewhere other than Adam White's at... CATO? ... Look to examples like the book Bending the Rules about the process shenanigans the regulators can pull around changes in administrations to protect their pet regulations in spite of comments and such.
You capture the profits by lowering your cost to develop in perpetuity and that should increase your expected long term profit since you get a drug patent and have monopoly on any drug you get approved for 25 years. You don’t capture all of the potential profits of any reduction in regulatory burden, but that’s not the same thing as capturing no profit. The issue is the risk avoidance -- if you get a new trial paradigm approved and then five years later it turns out that you missed a major negative side effect the courts are going to blame you a la the Ford Pinto case and the FDA is going to suffer reputational harm, so no one wants to risk it. Note that Moderna has spent years trying to get an mRNA vaccine approved and was on the verge of going bankrupt prior to the Covid vaccine. Also note that a massive number of drug trials don’t pan out because the drug doesn’t work at scale, so this may have been tried with startup money (though very different from tech VC) and still failed and then never revisited. You need to do the new paradigm on a bunch of drugs until one is efficacious and tested this way, then fight the regulatory fight after that. So if you have something *really* promising, your financial backers will generally rather spend the extra money to definitely get it approved than wait 5 more years and spend *potentially* less just to fight the regulatory fight. This screams “get some rich guy to light 10 billion dollars on fire just to spite the FDA,” if you want to actually do it.
Side note: you may be thinking “why don’t we get Secret Congress to force the FDA to allow a specific new paradigm that is sufficiently well defined by amending the authorizing statute?” And the answer is that Congress has done similar things (see: the legal requirement for the FAA to find a leaded gas alternative) and they’ve been effectively thwarted by the regulators for something like 40 years before finally happening this year, despite happening in regular Congress and with frequent oversight hearings where the regulators get yelled at hard. It would be even less effective through Secret Congress.
When I read the post about the inefficiency of the biotech sector, my thought was "this is pretty much the same in all sectors, so why should biotech be any different?"
Most people are deeply inefficient and most companies seem to be set up in such a way as to make that even worse. I suspect the main reasons they survive anyways are some combination of "economies of scale", "customer laziness" (it's amazing how little shopping around buyers seem to do in B2B), and "they're all doing it"...
Even tech startups, once they start growing, apparently import so many people with deeply ingrained corporatism that they become middle-management-infested bloat companies engaged mostly in reporting and meetings.
Seems like Canada is in the middle of a bit of a moral panic around this policy. There are lots of vague insinuations that they're feeding the poor into the gas chambers, while all of the actual anecdotes boil down to someone who qualified for euthanasia for medical reasons really being made more miserable and suicidal by their desperate poverty than by the qualifying medical issue. To me it seems pretty clear that if you're scandalized by that situation you should be looking at ways to reduce poverty, not at tightening up who can qualify for euthanasia.
Seems like the Platonic ideal of why not both. Not putting too much stock in the anecdotes but if the 5% number is true it sounds like a lot especially if it is going to be rising and they are going to allow requests based on mental health.
I don't really see the benefit of tightening up the euthanasia standards, seems like it's motivated mainly by embarrassment about living in a society where many people choose euthanasia.
I am just unusually pro-suicide here? I think that's a choice people should be allowed to make.
I think "assisted suicide" is a more accurate description than homicide, or even some softer term like "invited homicide." To me the important distinction is that it's a decision that's under the control of the person dying, not anyone else.
I'm considering getting boosted to reduce the risk that I'll be too sick to help care for my first child, due in February, but hesitant because my last vaccine dose really kicked my ass. I was too fatigued to do much of anything. At one point I was frustrated with my lack of output and decided to unload the dishwasher. I broke a serious sweat and had to take a nap to recover.
If there's no protection against infection past 1-2 months or so, it's probably not worth it for me, but I can't find such metrics.
Studies aren't great, we are against learning things. My model says, it'll help somewhat probably for at least ~6 months. I think being about to have an infant is a good reason. Get knocked on your ass now while you can, before you get knocked on your ass for real. Because that's gonna happen for sure.
Every time <s>euthanasia</s> assisted suicide comes up in the news (California before this, Netherlands before that, probably forgetting others), I find myself wondering if it's a good concept __in general__, nevermind the particulars around criteria and gatekeeping. We have strong norms against bog-standard suicide for <long list of reasons>. And I'll grant there are certain unfortunate situations where death is probably preferable than the callous insistence on barely-living, which dominates so many ugly terminal-care decisions. But to mirror another comment, it really seems like the correct course would be to address poverty, disease, homelessness, mental illness, etc. rather than sanction an exit valve that we normally work really hard to keep shut.
(I also think of all the old-fashioned exit valves which we've eliminated in the march to enlightenment...barbaric in many ways, to be sure, but at least that's deriving __some__ value from a life, rather than wasting it? I'd hope that assisted-suicide patients at least sign up for organ donation or something, to be blunt about it...)
Maybe all you galaxy brains can help me with this. Got Moderna in March 2021 with mild sides, J&J booster in December 2021 with a few hours of injection site pain (mix n match, seemingly lower risk of myo/pericarditis), COVID in July 2022. ~55 V02 max, not overweight, 30yo, male, but I'd like to travel a bit this winter without being laid low by COVID, and see some elderly family as well. Is there a clear winner for me between Novavax and bivalent mRNA booster?
It would be great if we lived in a world where we were permitted to know such things. I'd go with the bivalent booster but I would be completely unshocked if it turned out I was wrong.
I worked for a summer at a medical device engineering consulting firm that did a lot of "we will tell you how to get your new device FDA approved" which amounted to a lot of "what is this comparable to so that you don't need to prove everything from scratch" and "how do you explain that to the regulators with the right buzzwords to get them to agree" -- it seems to me that the drug trial situation is the same. You can get everyone on board for a new trial system/design as soon as you get it through the regulators even once. The issue is someone has to be willing to risk a huge amount of money (even if it's 1/10 the price of the "standard way") to do the new trial and probably spend half again as much on extra lawyers and extra time arguing with the regulators to get something approved, then everyone will follow. This feels like exactly the kind of thing that VC is intended for, just that it's hard to convince someone to spend $200 million to test the theory.
Relatedly: it seems like this is one of the under-researched topics. Balsa should endow a chair for study of the regulatory process somewhere other than Adam White's at... CATO? ... Look to examples like the book Bending the Rules about the process shenanigans the regulators can pull around changes in administrations to protect their pet regulations in spite of comments and such.
The problem with VC is you can't capture the profits, right? If you get the new method approved than everyone else can do it too.
You capture the profits by lowering your cost to develop in perpetuity and that should increase your expected long term profit since you get a drug patent and have monopoly on any drug you get approved for 25 years. You don’t capture all of the potential profits of any reduction in regulatory burden, but that’s not the same thing as capturing no profit. The issue is the risk avoidance -- if you get a new trial paradigm approved and then five years later it turns out that you missed a major negative side effect the courts are going to blame you a la the Ford Pinto case and the FDA is going to suffer reputational harm, so no one wants to risk it. Note that Moderna has spent years trying to get an mRNA vaccine approved and was on the verge of going bankrupt prior to the Covid vaccine. Also note that a massive number of drug trials don’t pan out because the drug doesn’t work at scale, so this may have been tried with startup money (though very different from tech VC) and still failed and then never revisited. You need to do the new paradigm on a bunch of drugs until one is efficacious and tested this way, then fight the regulatory fight after that. So if you have something *really* promising, your financial backers will generally rather spend the extra money to definitely get it approved than wait 5 more years and spend *potentially* less just to fight the regulatory fight. This screams “get some rich guy to light 10 billion dollars on fire just to spite the FDA,” if you want to actually do it.
Side note: you may be thinking “why don’t we get Secret Congress to force the FDA to allow a specific new paradigm that is sufficiently well defined by amending the authorizing statute?” And the answer is that Congress has done similar things (see: the legal requirement for the FAA to find a leaded gas alternative) and they’ve been effectively thwarted by the regulators for something like 40 years before finally happening this year, despite happening in regular Congress and with frequent oversight hearings where the regulators get yelled at hard. It would be even less effective through Secret Congress.
When I read the post about the inefficiency of the biotech sector, my thought was "this is pretty much the same in all sectors, so why should biotech be any different?"
Most people are deeply inefficient and most companies seem to be set up in such a way as to make that even worse. I suspect the main reasons they survive anyways are some combination of "economies of scale", "customer laziness" (it's amazing how little shopping around buyers seem to do in B2B), and "they're all doing it"...
Even tech startups, once they start growing, apparently import so many people with deeply ingrained corporatism that they become middle-management-infested bloat companies engaged mostly in reporting and meetings.
Best wishes on your covid recovery!
Fascinatingly, the Canadian man who requested euthanasia entered into that thread: https://twitter.com/ah_farsoud/status/1592673542533156864
Seems like Canada is in the middle of a bit of a moral panic around this policy. There are lots of vague insinuations that they're feeding the poor into the gas chambers, while all of the actual anecdotes boil down to someone who qualified for euthanasia for medical reasons really being made more miserable and suicidal by their desperate poverty than by the qualifying medical issue. To me it seems pretty clear that if you're scandalized by that situation you should be looking at ways to reduce poverty, not at tightening up who can qualify for euthanasia.
Seems like the Platonic ideal of why not both. Not putting too much stock in the anecdotes but if the 5% number is true it sounds like a lot especially if it is going to be rising and they are going to allow requests based on mental health.
I don't really see the benefit of tightening up the euthanasia standards, seems like it's motivated mainly by embarrassment about living in a society where many people choose euthanasia.
I am just unusually pro-suicide here? I think that's a choice people should be allowed to make.
I think "assisted suicide" is a more accurate description than homicide, or even some softer term like "invited homicide." To me the important distinction is that it's a decision that's under the control of the person dying, not anyone else.
What are you talking about? Nobody's claiming that these aren't voluntary.
A formalised crowd funding site for open source research would be doable.
Have you seen any studies about the efficacy of the bivalent booster in preventing infection?
The only things I can find measures antibody titers, but not rates of infection: https://www.nejm.org/doi/full/10.1056/NEJMoa2208343
https://www.biorxiv.org/content/10.1101/2022.10.22.513349v1.full.pdf
https://www.biorxiv.org/content/10.1101/2022.10.24.513619v1.full.pdf
I'm considering getting boosted to reduce the risk that I'll be too sick to help care for my first child, due in February, but hesitant because my last vaccine dose really kicked my ass. I was too fatigued to do much of anything. At one point I was frustrated with my lack of output and decided to unload the dishwasher. I broke a serious sweat and had to take a nap to recover.
If there's no protection against infection past 1-2 months or so, it's probably not worth it for me, but I can't find such metrics.
Studies aren't great, we are against learning things. My model says, it'll help somewhat probably for at least ~6 months. I think being about to have an infant is a good reason. Get knocked on your ass now while you can, before you get knocked on your ass for real. Because that's gonna happen for sure.
Every time <s>euthanasia</s> assisted suicide comes up in the news (California before this, Netherlands before that, probably forgetting others), I find myself wondering if it's a good concept __in general__, nevermind the particulars around criteria and gatekeeping. We have strong norms against bog-standard suicide for <long list of reasons>. And I'll grant there are certain unfortunate situations where death is probably preferable than the callous insistence on barely-living, which dominates so many ugly terminal-care decisions. But to mirror another comment, it really seems like the correct course would be to address poverty, disease, homelessness, mental illness, etc. rather than sanction an exit valve that we normally work really hard to keep shut.
(I also think of all the old-fashioned exit valves which we've eliminated in the march to enlightenment...barbaric in many ways, to be sure, but at least that's deriving __some__ value from a life, rather than wasting it? I'd hope that assisted-suicide patients at least sign up for organ donation or something, to be blunt about it...)
Best wishes on your recovery OP.
Maybe all you galaxy brains can help me with this. Got Moderna in March 2021 with mild sides, J&J booster in December 2021 with a few hours of injection site pain (mix n match, seemingly lower risk of myo/pericarditis), COVID in July 2022. ~55 V02 max, not overweight, 30yo, male, but I'd like to travel a bit this winter without being laid low by COVID, and see some elderly family as well. Is there a clear winner for me between Novavax and bivalent mRNA booster?
It would be great if we lived in a world where we were permitted to know such things. I'd go with the bivalent booster but I would be completely unshocked if it turned out I was wrong.