Davidmanheim

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Maybe Antivirals aren’t a Useful Priority for Pandemics?

Definitely not expert enough to confidently answer this, but I thought the answer was obviously yes - I don't think there are any diseases where it doesn't happen as a natural part of response. (Even HIV is mostly fought off quickly, but in cases where it spreads, it infects enough immune cells that it persists and eventually destroys the immune system.)

Maybe Antivirals aren’t a Useful Priority for Pandemics?

That's a good point. I seem to recall that the efficacy of (most) antivirals as prophylaxis against most diseases is approximately nil, and we can't easily do COMPARE-style studies for prophylaxis, so I'm unsure if, in general, this is a good strategy. (And I don't think HCTs for trying this out early on using a battery of drugs would be ethical, even ignoring sample size requirements, though perhaps animal studies could be done quickly.)

But I definitely think post-exposure prophylaxis is potentially promising, if it's likely to work. The two challenges are that 1) it requires contact tracing far better than what we saw during COVID - though we often manage such contact tracing for HIV, so it's not at all impossible, and 2) in most countries, I can't imagine that the prescription / medical system would adapt fast enough to allow such prescriptions, short of them actually becoming super-competent at response. So if this is a good idea, we need lots of preparation to actually make sure it can be used. 

Alternatively, I guess it could be used very early on to slow / stop initial spread, but for the cases I'm most concerned about, I don't know how we'd know enough to try the strategy then.

Maybe Antivirals aren’t a Useful Priority for Pandemics?

Thanks so much for the excellent feedback. I've updated a bit, but I don't think we disagree as much as it seems at first glance, or I'm not understanding your position. In general, I think you're responding about antivirals in general, and I was talking about antivirals specifically as a response option for during a nascent pandemic. But I do see a few points of clear disagreement.

1) Biological diversity & over-updating from one disease

Antivirals work poorly everywhere. The "best" antivirals we have for flu, like tamiflu, don't have any significant clinical impact, according to all of the studies not run by the company making it.  And yes, antivirals are relatively more important for diseases that don't have vaccines, but as I noted, HIV antiretrovirals are weak and only work slowly and in combinations, and "highly successful" seems like a weird claim given how long it took and how complex it is.

And I agree that vaccines aren't always practical for all diseases, at least yet. But that doesn't lead me to think that we might be successful with antivirals.

[Edit to add: "The success of COVID vaccines... does not, in my view, imply that they will be a sufficient defense against most or all possible threats."

No, but finding vaccines not working says nothing about the success of other approaches - nothing guarantees that anything works, so pessimism on one front doesn't justify optimism on another, even if it causes us to invest differently.]

2) Future promise of antivirals vs current performance

I think I agree with all of this, which is why I think antiviral work should continue to be funded. But none of this makes me think it's a valuable target for emergency response.
  
3) Portfolio theory and scientific innovation

Agreed on our inability to pick winners, and the difficulty of exactly choosing relative investment amounts - but again, I'm not talking about foundational research, where a diversity of approaches are really important, I'm talking about last-ditch emergency response. We need more and faster COMPARE-like trials for extant treatments, but new drugs seem like a dumb place to put money if we need results this year.

Maybe Antivirals aren’t a Useful Priority for Pandemics?

Given the failure of antivirals to work even prophylactically, and the fundamental issues I mentioned, I don't think that is the key issue.

Maybe Antivirals aren’t a Useful Priority for Pandemics?

Yes, treatments definitely ameliorate risks from not finding vaccines - but it seems that effective new treatments were far harder to find than vaccines.

And yes, clearly symptomatic treatment with extant drugs is important - dexamethasone, but also prone positioning, and basic parts of treatment like pulse oximetry and ensuring sufficient fluids. But these don't need 100-day crash research programs for new treatments, which is what was proposed, they need RECOVERY-like trials (perhaps more expansive, covering more parts of clinical care,) to start on day 1, instead of waiting months to start.

How well did EA-funded biorisk organisations do on Covid?

It's still unclear, and the developing world detection and survival rates are a bit uncertain. I think you could probably get a decent approximation by looking at test positivity rates and testing volume compared to death rates over time in different countries, but I'm not going to put together the model to do it. 

We're doing something related with IFR estimates by age at 1DaySooner, but using seroprevalence data, i.e. only where there is really good data for the estimate. I don't have results of that yet.

How well did EA-funded biorisk organisations do on Covid?

Seems unlikely that <1/3 of all cases were detected at this point, since the recent outbreaks had far higher detection rates than the initial ones.

How well did EA-funded biorisk organisations do on Covid?

"And yet lots and lots of people far less credentialed than CHS epidemiologists had correctly figured out by the first week of March that it was smart to wear a mask"

Not sure how much this is an answer - as I said in a different response, the question isn't whether CHS was right (much less right about one specific thing,) but whether they did better overall than the other policy-influencing organizations.

How well did EA-funded biorisk organisations do on Covid?

I think the key question for CHS, or even Amesh specifically, is whether they outperformed other organizations, and by how much - i.e. were investments in CHS positive contributions to response overall. And they / he could have done almost arbitrarily bad in February, and still overall have vastly outperformed the alternatives.

And I think that it's clear that CHS's work was impactful in increasing preparedness in the US, even if the level of preparedness was far short of what was needed.

(Note that I have personal biases about this, and know many of the people at CHS.)

A proposal for a small inducement prize platform

I would find this useful. But:

- What is the likely market size for this platform?
- How much would it cost to develop? (Including escrow infrastructure?)
- What would the fees for use be / need to be to keep the platform afloat?

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