Vaccines that are brought to clinical trials have a 33.4% approval rate, which seems like a reasonable estimate of the chances that this vaccine works if executed correctly. Note that this is from trials conducted from 2000-2015.
I probably have a roughly 5% chance of catching COVID before I’m vaccinated. Given my age, COVID would put me at a 0.2% risk of death. Let’s double that to account for suffering and the risk of long-term disability.
If I value my life at $10,000,000, then an intervention that gives me a 33.4% chance of avoiding a 5% chance of a 0.4% chance of death is worth $668. So it seems like I’d want to be vaccinating at least one other person in order for this to be worthwhile.
I welcome any further thoughts on this expected value calculation. In particular, I think it’s possible that I’m dramatically underestimating the risk and potential severity of long-term symptoms. It doesn’t take much additional risk to make this project worthwhile for a single person.
Regarding the 33.4% approval rate: based on what I’ve learned about traditional vaccine development and production in the last few months, I am not at all surprised. Both peptide and RNA vaccines are effectively “state of the art” technologies compared to traditional vaccine techniques. It’s like comparing modern non-invasive out-patient surgery to the 1970′s equivalent.
You need look no further than the russian and chinese vaccines—those use the rather crude technology of “throw big chunks of inactivated virus particles at the immune system and hope that the immune system guesses the right antibodies to deal with the live version.”
Both peptide and RNA vaccines are instead, “we have identified very specific antibodies which we know are effective both from the serum of recovered patients and from computational modeling, then use exactly the minimal protein sequences needed to generate those antibodies.”
Both the russian and chinese vaccines use chunks of proteins that are thousands (and likely tens of thousands) of amino acids long, in a mostly inactivated form. The immune system has no idea what to latch onto, what will be effective at stopping replication, but it does generate a bunch of randomish antibodies anyway just in case. In a lot of people, this is enough to take the edge off getting stick.
The peptide and RNA vaccines on the other hand, are extremely narrow. The radvac vaccine for example targets 9 specific virus protein sequences, the shortest of which is 10 amino acids long, and the longest of which is 25. Each of these sequences is from an empirically likely effective antibody, found in real people who have really recovered.
A lot of people have been working really hard for the last year to discover, understand, and know these things. It’s the foundation for how the mRNA vaccines work.
I seems my intuition is well-founded here. According to Sarah Constantin the peptide here are selected in silico and not based on antibodies developed by infected people.
Sarah Constantin is confused, and likely has not spent significant time reviewing the vaccine design. From page 32 of the whitepaper:
“Empirical evidence should dominate selection criteria. Here are some best types of evidence:
Mapping of epitopes in blood and other samples collected from convalescent patients (ideally stratified by severity of illness). This can be accomplished by a few primary means:
3D structural studies and modeling of neutralizing antibody binding to a viral antigen (e.g. Spike protein)
Mapping of linear B-cell epitopes by binding antibodies in convalescent sera to a library of peptides representing viral antigens. A strong signal in a linear epitope mapping study does not guarantee that the epitope peptide in the context of a vaccine will trigger the production of an antibody that binds to this epitope within the context of the virus. However, it is a good indicator that this is at least possible. Peptides can be constrained to approximate native conformation, making it more likely to bind the native epitope.
Mapping of T-cell epitopes by stimulating convalescent T-cells with epitope peptides, and measuring their response (e.g. cytokine secretion; ELISpot)
Epitope peptides from a peptide vaccine that has shown protection against infection
Successful use of epitope peptides in vaccines that elicit antibodies (or serum) effective in virus neutralization assays. B-cell epitopes that allow antibody binding to the virus but don’t block viral function might increase risk of antibody-dependent enhancement.
Mapped epitopes that are effective in virus neutralization assays (e.g. peptides compete with viral sequences in cellular infection assays).
Successful use of epitope peptides in vaccines that elicit T-cell responses, or peptides shown to stimulate T-cells or cytokine production in ELISpot or other T-cell assay in cells from convalescents.”
Speaking about what are the best types of evidence is different from demostrating that this evidence exists for individual sequences.
If we start with the list the first is Spike 802-823cir. They provide no citations to papers for this and changed the structure in a way the believe to be benefitial (likely based on in silico modelling).
Spike 802-823cir: FSQ c LPDPSKPSKRSF c EDLLF ( Cys4, Cys17 disulfide) IN TESTING, vaccine Generations 5, 6, 7, 8. 9 To preserve the loop structure present in the native conformation, we substituted cysteines for amino acids 4 (Ile>Cys) and 17 (Ile>Cys).
They perform the substitution to keep the shape that our immune system is looking for by recreating a disulfide bond that to form a loop with the same sequence the B-cells are targeting in the virus.
While I agree their expression was “potentially beneficial” (or close) it seems clear to me the point was our B-cells are bonding to that loop and if there are not other aspect in the larger peptide that lead the cell to that site for bonding, construction the loop via the disulfide bond they introduce logically should result in triggering an immune response.
I’m not sure why they would need to provide some type of citation for this, much less that they would even have a source for this specific application.
The argument about the substition of the amino acids looks to me like it rests completely on in silicio modeling.
logically should result
That’s theory-based reasoning and not empirical evidence based. Sarah Constantin says that everything is theory-based reasoning (supported by computer modeling) and Dentin argues that they not only do theory-based reasoning but also have empiric evidence for individual peptides.
While it does seem there was a certain amount of shotgun aproach following a few different lines of reasoning, that critism is difficult to square with actually reading the paper. It looks like the peptide selection was largely empirical and cited. The decisions about how to actually package that info into a vacine is largely educated guesswork (as you say theory, supported by computer modeling).
“Mapping of linear B-cell epitopes by binding antibodies in convalescent sera to a library of peptides representing viral antigens. A strong signal in a linear epitope mapping study does not guarantee that the epitope peptide in the context of a vaccine will trigger the production of an antibody that binds to this epitope within the context of the virus. However, it is a good indicator that this is at least possible.”
Or as I understood from elsewhere: present antibodies from recovered people to every possible short peptide sequence and see which ones they actually attacked. Make the inference that people with less severe infection had better antibodies than those with more severe symptoms in the event antibodies differed. Package a selection of promising looking pepties into a vacine; choose enough that there’s likely multiple effective peptides even if 2/3rds of the choices are duds.
I also don’t understand her comments about the peptide ‘not neutralising COVID in cell [culture]’ - why would it? The peptide is just an antigen to get the body to raise an immune response; on its own it doesn’t kill COVID.
I was also confused about that. I’m sure some kind of cell-culture method is useful for testing vaccines, but I don’t know exactly what’s involved. Just culturing immune cells, maybe?
Both the russian and chinese vaccines use chunks of proteins that are thousands (and likely tens of thousands) of amino acids long, in a mostly inactivated form.
The Russian vaccine, unlike the Chinese one, is not an inactivated virus. It uses an adenovirus vector for delivery of genetic material that makes the body’s cells synthesise antigen material, much like the AstraZeneca/Oxford vaccine.
A vaccine brought to clinical trials has already overcome many more hurdles than this has.
I’m not sure what your level of background knowledge is, but I heard that the Moderna vaccine was designed in two days. Clearly they did not do any significant in vitro or in vivo testing in that timespan. Maybe they did some in-vitro before human trials, I don’t know; that would support an argument against using “vaccine brought to clinical trials” as a reference class.
But the deeper point which this is trying to operationalize is “vaccine design just isn’t that hard”, in the sense that we don’t need to test many designs to find one which works. People basically-know-how-to-design-vaccines, maybe not to quite the same extent as people basically-know-how-to-design-bridges, but to enough of an extent that experimental verification just isn’t necessary in order to get a >50% chance that the design works, especially for relatively-mechanical designs like mRNA or peptides.
Under this view, the reasons we don’t see nearly-every vaccine trial succeed are (1) commercial vaccines are harder than lab (especially if you want no boosters, easy logistics, etc), and (2) diseases which are harder-than-average will naturally end up with disproportionately many trials, and (3) out-of-date companies take time to die off.
The in vitro testing had already been done before those two days; they had the basic structure of the vaccine known, so once they had a virus sample they could fill in the blank (the spike protein of this particular virus rather than another in its ‘family’) with high confidence that it would work. One of the two days, IIUC, was spent synthesizing a sample vaccine and running some very-short-term tests.
This, again, has only simulation to support that it’s hitting the correct target at all. There is no indication that any of that has been done, by the authors or anyone else; IIUC there is not a clear path for doing short-term tests for this type of vaccine.
Also, it’s not my background knowledge that you should be comparing to, it’s Sarah’s. And I literally believe there is no one in the world who can be more trusted to reason clearly, well-informedly, correctly, and with humility and arrogance in their respective correct places than Sarah Constantin. Evaluating biomedical research has been her job for many years, with some gaps, and she’s really good at rationality, Aumann-level good. The bare fact that Sarah C thinks this is very unlikely to work is conclusive on its own.
How does the “vaccine design just isn’t that hard” align with these points?
a) Average time to develop a vaccine for a new virus is many years
b) There is still no HIV vaccine after 35 years of well-funded research
c) Until a few months ago, there were no approved coronavirus vaccines for humans
I’m prepared to accept that “bureaucracy” is the main cause for the delays in standard big company vaccine development and approval.
But if it’s easy to develop vaccines, why has there been no coronavirus vaccine previously? Why is there still no vaccine for SARS 1 or MERS or the common cold? Why was this Radvac idea or something similar not rolled out pre-Covid? (or was it? maybe nasal vaccines are easier?)
Anyway, I’m just stuck on the logical conflict between “it’s easy to develop a coronavirus vaccine” and “we’ve never had one (approved) before.” Any thoughts?
First, I expect a disproportionate number of vaccine trials are for “unusually difficult” viruses, like HIV. After all, if it’s an “easy” virus to make a vaccine for, then the first or second trial should work. It’s only the “hard” viruses which require a large number of trials.
But if it’s easy to develop vaccines, why has there been no coronavirus vaccine previously? Why is there still no vaccine for SARS 1 or MERS or the common cold? Why was this Radvac idea or something similar not rolled out pre-Covid?
I expect this is still mainly a result of regulatory hurdles. Clinical trials are slow and expensive, so there has to be a pretty big pot of gold at the end of the rainbow to make it happen. Also, companies tend to do what they already know how to do, so newer methods like mRNA or peptide vaccines usually require a big shock (like COVID) in order to see rapid adoption.
I agree with the point of your comment, that vaccines brought to clinical trials is a suboptimal reference class. However, I think that this is a locally invalid argument:
Would you conclude that, because some lines of code can navigate a rocket to the moon, that your code is pretty likely to navigate a rocket to Mars?
A computational model plus grounding in theory, if done right, should increase our confidence in the the efficacy of a sequence of peptides taken from the virus above the efficacy we’d assume for a random sequence of peptides.
How much? Can’t say.
As others have pointed out here, we on the other hand are comparing a new and perhaps much more effective means of designing a vaccine to the methods that were used from 2000-2015, which may be less effective. Hence, perhaps the reference class is suboptimal in the opposite direction as well.
I have no way to know how to weigh these competing factors. So I think the best thing to do is to start with the basic formula I concocted above, then modify it based on our intuitions about these other factors.
Alternatively, you could very justifiably stick with the rule “I don’t take untested medications.” Although as someone else pointed out, if you have that rule then perhaps you should also make sure to not use any drugs? I don’t have the answer, but wanted to try and provide some clarity for people who are considering breaking the “take no untested medications” rule.
You’re missing the very real possibility of long-term negative side-effects from the vaccine, such as triggering an auto-immune disease or actually increasing your susceptibility, both mentioned in the whitepaper (whose risk-assessment I would be pretty sceptical of). I would think of this as more a trade-off between risks of side effects and COVID risks, rather than whether or not you can afford it.
Yes. The differential tradeoff is how one should evaluate this. The only reason my evaluation came out in favor of trying the radvac vaccine is because I have a high-risk event coming up in the next few months, and I am extremely unlikely to be able to acquire a commercial vaccine before then.
Vaccines that are brought to clinical trials have a 33.4% approval rate, which seems like a reasonable estimate of the chances that this vaccine works if executed correctly.
I don’t follow. Don’t vaccines have trials on cells, mice, primates, before clinical? So unless radvac has also done similar testing, this 33.4% isn’t comparable.
Do you value your life at ten million? As in, would you take a 50% chance of death for five million? If so, why are you not smuggling drugs or whatever?
Well, a couple of researchers estimated that drug mules made a median of $1313 back in 2014, so I’d need to smuggle a lot of cocaine to earn that much. Seems like it would take a while...
Say my life expectancy from now is 50 years and I work at an hourly salary of $30 (~$60k yearly salary) then I implicitly value the remaining 310,250 hours of my waking life at something like $9.3m total. This breaks down if offered larger probabilities of death and larger amounts of money (e.g. opportunity cost) but $10m seems like a sensible place to start for a Fermi calculation.
In this case we don’t even have to worry about larger probabilities of death—the calculation here is essentially an expected gain of 1.2 days of life for $1000 which comes to about $50 per hour of waking life. Instead of making a vaccine only for myself I would be better just to take half a week unpaid leave and gain the same amount of time for a cost of only $600.
That’s is an easy calculation. Life value can change later and there might be a more attractive bet you will be forgoing by taking this one, say 10 million for 50% chance of dying.
Vaccines that are brought to clinical trials have a 33.4% approval rate, which seems like a reasonable estimate of the chances that this vaccine works if executed correctly. Note that this is from trials conducted from 2000-2015.
I probably have a roughly 5% chance of catching COVID before I’m vaccinated. Given my age, COVID would put me at a 0.2% risk of death. Let’s double that to account for suffering and the risk of long-term disability.
If I value my life at $10,000,000, then an intervention that gives me a 33.4% chance of avoiding a 5% chance of a 0.4% chance of death is worth $668. So it seems like I’d want to be vaccinating at least one other person in order for this to be worthwhile.
I welcome any further thoughts on this expected value calculation. In particular, I think it’s possible that I’m dramatically underestimating the risk and potential severity of long-term symptoms. It doesn’t take much additional risk to make this project worthwhile for a single person.
Regarding the 33.4% approval rate: based on what I’ve learned about traditional vaccine development and production in the last few months, I am not at all surprised. Both peptide and RNA vaccines are effectively “state of the art” technologies compared to traditional vaccine techniques. It’s like comparing modern non-invasive out-patient surgery to the 1970′s equivalent.
You need look no further than the russian and chinese vaccines—those use the rather crude technology of “throw big chunks of inactivated virus particles at the immune system and hope that the immune system guesses the right antibodies to deal with the live version.”
Both peptide and RNA vaccines are instead, “we have identified very specific antibodies which we know are effective both from the serum of recovered patients and from computational modeling, then use exactly the minimal protein sequences needed to generate those antibodies.”
Both the russian and chinese vaccines use chunks of proteins that are thousands (and likely tens of thousands) of amino acids long, in a mostly inactivated form. The immune system has no idea what to latch onto, what will be effective at stopping replication, but it does generate a bunch of randomish antibodies anyway just in case. In a lot of people, this is enough to take the edge off getting stick.
The peptide and RNA vaccines on the other hand, are extremely narrow. The radvac vaccine for example targets 9 specific virus protein sequences, the shortest of which is 10 amino acids long, and the longest of which is 25. Each of these sequences is from an empirically likely effective antibody, found in real people who have really recovered.
Like I said, very, very different technologies.
That seems to me like a strange statement. In what way are amino acids sequences in the peptides “from antibodies”?
It’s my impression that the peptides in question are the antigens to those particular antibodies.
Yes; sorry I was unclear. Those peptides generate the antibodies we care about, that are known to be effective against the full virus.
It’s unclear to me to what extend we know this and your description looks to me like it asserts that we know things that are very hard to know.
A lot of people have been working really hard for the last year to discover, understand, and know these things. It’s the foundation for how the mRNA vaccines work.
Perhaps take a look through this:
https://www.sciencedirect.com/science/article/pii/S2319417020301530
I seems my intuition is well-founded here. According to Sarah Constantin the peptide here are selected in silico and not based on antibodies developed by infected people.
Sarah Constantin is confused, and likely has not spent significant time reviewing the vaccine design. From page 32 of the whitepaper:
“Empirical evidence should dominate selection criteria. Here are some best types of evidence:
Mapping of epitopes in blood and other samples collected from convalescent patients (ideally stratified by severity of illness). This can be accomplished by a few primary means:
3D structural studies and modeling of neutralizing antibody binding to a viral antigen (e.g. Spike protein)
Mapping of linear B-cell epitopes by binding antibodies in convalescent sera to a library of peptides representing viral antigens. A strong signal in a linear epitope mapping study does not guarantee that the epitope peptide in the context of a vaccine will trigger the production of an antibody that binds to this epitope within the context of the virus. However, it is a good indicator that this is at least possible. Peptides can be constrained to approximate native conformation, making it more likely to bind the native epitope.
Mapping of T-cell epitopes by stimulating convalescent T-cells with epitope peptides, and measuring their response (e.g. cytokine secretion; ELISpot)
Epitope peptides from a peptide vaccine that has shown protection against
infection
Successful use of epitope peptides in vaccines that elicit antibodies (or serum)
effective in virus neutralization assays. B-cell epitopes that allow antibody binding
to the virus but don’t block viral function might increase risk of
antibody-dependent enhancement.
Mapped epitopes that are effective in virus neutralization assays (e.g. peptides
compete with viral sequences in cellular infection assays).
Successful use of epitope peptides in vaccines that elicit T-cell responses, or
peptides shown to stimulate T-cells or cytokine production in ELISpot or other
T-cell assay in cells from convalescents.”
Speaking about what are the best types of evidence is different from demostrating that this evidence exists for individual sequences.
If we start with the list the first is Spike 802-823cir. They provide no citations to papers for this and changed the structure in a way the believe to be benefitial (likely based on in silico modelling).
Doesn’t this speak to your concern:
They perform the substitution to keep the shape that our immune system is looking for by recreating a disulfide bond that to form a loop with the same sequence the B-cells are targeting in the virus.
While I agree their expression was “potentially beneficial” (or close) it seems clear to me the point was our B-cells are bonding to that loop and if there are not other aspect in the larger peptide that lead the cell to that site for bonding, construction the loop via the disulfide bond they introduce logically should result in triggering an immune response.
I’m not sure why they would need to provide some type of citation for this, much less that they would even have a source for this specific application.
The argument about the substition of the amino acids looks to me like it rests completely on in silicio modeling.
That’s theory-based reasoning and not empirical evidence based. Sarah Constantin says that everything is theory-based reasoning (supported by computer modeling) and Dentin argues that they not only do theory-based reasoning but also have empiric evidence for individual peptides.
While it does seem there was a certain amount of shotgun aproach following a few different lines of reasoning, that critism is difficult to square with actually reading the paper. It looks like the peptide selection was largely empirical and cited. The decisions about how to actually package that info into a vacine is largely educated guesswork (as you say theory, supported by computer modeling).
“Mapping of linear B-cell epitopes by binding antibodies in convalescent
sera to a library of peptides representing viral antigens. A strong signal in a
linear epitope mapping study does not guarantee that the epitope peptide
in the context of a vaccine will trigger the production of an antibody that
binds to this epitope within the context of the virus. However, it is a good
indicator that this is at least possible.”
Or as I understood from elsewhere: present antibodies from recovered people to every possible short peptide sequence and see which ones they actually attacked. Make the inference that people with less severe infection had better antibodies than those with more severe symptoms in the event antibodies differed. Package a selection of promising looking pepties into a vacine; choose enough that there’s likely multiple effective peptides even if 2/3rds of the choices are duds.
I also don’t understand her comments about the peptide ‘not neutralising COVID in cell [culture]’ - why would it? The peptide is just an antigen to get the body to raise an immune response; on its own it doesn’t kill COVID.
I interpreted this to mean antibody against the peptide.
I was also confused about that. I’m sure some kind of cell-culture method is useful for testing vaccines, but I don’t know exactly what’s involved. Just culturing immune cells, maybe?
Do you have doubts? It seems plausible to me?
The Russian vaccine, unlike the Chinese one, is not an inactivated virus. It uses an adenovirus vector for delivery of genetic material that makes the body’s cells synthesise antigen material, much like the AstraZeneca/Oxford vaccine.
This is an inappropriate reference class. This has no in vitro testing conducted; it’s entirely a computational model. ““Peptide” just means “sequence of amino acids.” Would you conclude that, because some lines of code can navigate a rocket to the moon, that your code is pretty likely to navigate a rocket to Mars?”. A vaccine brought to clinical trials has already overcome many more hurdles than this has. Generally in vitro testing (I think both for safety and efficacy), in vivo safety testing (in rats!), and some scaled-up testing in other animal models.
This isn’t a vaccine candidate. This is a promising research lead for a vaccine candidate.
I’m not sure what your level of background knowledge is, but I heard that the Moderna vaccine was designed in two days. Clearly they did not do any significant in vitro or in vivo testing in that timespan. Maybe they did some in-vitro before human trials, I don’t know; that would support an argument against using “vaccine brought to clinical trials” as a reference class.
But the deeper point which this is trying to operationalize is “vaccine design just isn’t that hard”, in the sense that we don’t need to test many designs to find one which works. People basically-know-how-to-design-vaccines, maybe not to quite the same extent as people basically-know-how-to-design-bridges, but to enough of an extent that experimental verification just isn’t necessary in order to get a >50% chance that the design works, especially for relatively-mechanical designs like mRNA or peptides.
Under this view, the reasons we don’t see nearly-every vaccine trial succeed are (1) commercial vaccines are harder than lab (especially if you want no boosters, easy logistics, etc), and (2) diseases which are harder-than-average will naturally end up with disproportionately many trials, and (3) out-of-date companies take time to die off.
The in vitro testing had already been done before those two days; they had the basic structure of the vaccine known, so once they had a virus sample they could fill in the blank (the spike protein of this particular virus rather than another in its ‘family’) with high confidence that it would work. One of the two days, IIUC, was spent synthesizing a sample vaccine and running some very-short-term tests.
This, again, has only simulation to support that it’s hitting the correct target at all. There is no indication that any of that has been done, by the authors or anyone else; IIUC there is not a clear path for doing short-term tests for this type of vaccine.
Also, it’s not my background knowledge that you should be comparing to, it’s Sarah’s. And I literally believe there is no one in the world who can be more trusted to reason clearly, well-informedly, correctly, and with humility and arrogance in their respective correct places than Sarah Constantin. Evaluating biomedical research has been her job for many years, with some gaps, and she’s really good at rationality, Aumann-level good. The bare fact that Sarah C thinks this is very unlikely to work is conclusive on its own.
How does the “vaccine design just isn’t that hard” align with these points?
a) Average time to develop a vaccine for a new virus is many years
b) There is still no HIV vaccine after 35 years of well-funded research
c) Until a few months ago, there were no approved coronavirus vaccines for humans
I’m prepared to accept that “bureaucracy” is the main cause for the delays in standard big company vaccine development and approval.
But if it’s easy to develop vaccines, why has there been no coronavirus vaccine previously? Why is there still no vaccine for SARS 1 or MERS or the common cold? Why was this Radvac idea or something similar not rolled out pre-Covid? (or was it? maybe nasal vaccines are easier?)
Anyway, I’m just stuck on the logical conflict between “it’s easy to develop a coronavirus vaccine” and “we’ve never had one (approved) before.” Any thoughts?
Good questions.
First, I expect a disproportionate number of vaccine trials are for “unusually difficult” viruses, like HIV. After all, if it’s an “easy” virus to make a vaccine for, then the first or second trial should work. It’s only the “hard” viruses which require a large number of trials.
I expect this is still mainly a result of regulatory hurdles. Clinical trials are slow and expensive, so there has to be a pretty big pot of gold at the end of the rainbow to make it happen. Also, companies tend to do what they already know how to do, so newer methods like mRNA or peptide vaccines usually require a big shock (like COVID) in order to see rapid adoption.
I agree with the point of your comment, that vaccines brought to clinical trials is a suboptimal reference class. However, I think that this is a locally invalid argument:
A computational model plus grounding in theory, if done right, should increase our confidence in the the efficacy of a sequence of peptides taken from the virus above the efficacy we’d assume for a random sequence of peptides.
How much? Can’t say.
As others have pointed out here, we on the other hand are comparing a new and perhaps much more effective means of designing a vaccine to the methods that were used from 2000-2015, which may be less effective. Hence, perhaps the reference class is suboptimal in the opposite direction as well.
I have no way to know how to weigh these competing factors. So I think the best thing to do is to start with the basic formula I concocted above, then modify it based on our intuitions about these other factors.
Alternatively, you could very justifiably stick with the rule “I don’t take untested medications.” Although as someone else pointed out, if you have that rule then perhaps you should also make sure to not use any drugs? I don’t have the answer, but wanted to try and provide some clarity for people who are considering breaking the “take no untested medications” rule.
You’re missing the very real possibility of long-term negative side-effects from the vaccine, such as triggering an auto-immune disease or actually increasing your susceptibility, both mentioned in the whitepaper (whose risk-assessment I would be pretty sceptical of). I would think of this as more a trade-off between risks of side effects and COVID risks, rather than whether or not you can afford it.
Yes. The differential tradeoff is how one should evaluate this. The only reason my evaluation came out in favor of trying the radvac vaccine is because I have a high-risk event coming up in the next few months, and I am extremely unlikely to be able to acquire a commercial vaccine before then.
I don’t follow. Don’t vaccines have trials on cells, mice, primates, before clinical? So unless radvac has also done similar testing, this 33.4% isn’t comparable.
Do you value your life at ten million? As in, would you take a 50% chance of death for five million? If so, why are you not smuggling drugs or whatever?
Well, a couple of researchers estimated that drug mules made a median of $1313 back in 2014, so I’d need to smuggle a lot of cocaine to earn that much. Seems like it would take a while...
Say my life expectancy from now is 50 years and I work at an hourly salary of $30 (~$60k yearly salary) then I implicitly value the remaining 310,250 hours of my waking life at something like $9.3m total. This breaks down if offered larger probabilities of death and larger amounts of money (e.g. opportunity cost) but $10m seems like a sensible place to start for a Fermi calculation.
In this case we don’t even have to worry about larger probabilities of death—the calculation here is essentially an expected gain of 1.2 days of life for $1000 which comes to about $50 per hour of waking life. Instead of making a vaccine only for myself I would be better just to take half a week unpaid leave and gain the same amount of time for a cost of only $600.
Obviously this has some assumptions baked in (like that I don’t value my job) but If It’s Worth Doing, It’s Worth Doing With Made-Up Statistics.
That’s is an easy calculation. Life value can change later and there might be a more attractive bet you will be forgoing by taking this one, say 10 million for 50% chance of dying.