Yesterday, the US FDA responded to a submission for Emergency Use Authorization (that was submitted 146 days earlier) for use of fluvoxamine "for the outpatient treatment of adults 24 years and older...to prevent progression to severe COVID-19 and/or hospitalization" (p. 2).

The FDA's conclusion is:

Due to limitations in the available clinical study results for fluvoxamine in the proposed patient population, lack of compelling in vitro and in vivo data to support the proposed [mechanism of action] of fluvoxamine for the treatment of mild COVID-19 disease, and context of increasingly available therapies with well-characterized [mechanisms of action] and consistent efficacy results in nonhospitalized patients, the FDA cannot reasonably conclude that fluvoxamine may be effective for the treatment of COVID-19. As such, FDA has determined that the criteria for issuance of an EUA are not met at this time.

While the FDA has concluded that the existing clinical data are insufficient to support the issuance of an EUA, these data suggest that further clinical investigation may be warranted. (p. 24, emphasis mine)

Personally, I'm disappointed. I've supported the fluvoxamine trials with my personal dollars, and directed more funding from the FTX Foundation to the same trialists for other drug trials (which I remain very, very excited about). But the most productive thing to do with that disappointment is to dig in to the FDA's reasoning in their decision, and decide what's to be done next regarding fluvoxamine.

Important note: This post isn't speaking for the FTX Foundation, the TOGETHER Trial team, the fluvoxamine EUA application team, or anyone but myself in my personal capacity. The FTX Foundation has funded the TOGETHER Trial and committed to additional

I replicated my estimation of population-average IFR for Africa-ex-South-Africa (henceforth "Africa"), using the same methodology as my India calculations. Africa is significantly demographically younger than either India or the US -- the top quintile of age in Africa starts at 39, India at 49, and the US at 61.

I estimate that the age effect creates an Africa population-average IFR 20% that of the US rate (i.e., a US rate 4.94× greater), assuming age-uniform infection rates and no difference in medical care. This effect is driven by the reduced population share of age>70 in Africa (just 18% that of the US).

My work is here, and here's the primary chart:

In my India analysis, I wrote:

The effect of medical care differences on IFR-by-age curves is of first-order importance to this analysis; as an example, if lack of care were equivalent to 12 years in fatality-rate terms, it would triple India population-average IFR to 0.75%. (...)

A corresponding statistic is that if lack of care were equivalent to 18 years in fatality-rate terms, it would raise Africa IFR to the US level of 0.63%. My tentative hypothesis is that Africa Covid-19 fatality is likely of less concern than regions with meaningfully older populations.

If you'd like to redo these calculations for a population of interest to you, you're welcome to clone the sheet and copy your own numbers into the "Africa pop by age raw" tab. PopulationPyramid.net has easily-formatted CSVs on many countries / regions, but you

Abstract:

India's demographic average age is younger than that of the US. This implies that the strongly age-varying Covid-19 infection fatality rate (IFR) could cause a lower population-average IFR in India than in an older nation such as the US, all other factors being equal (spoiler: they're not).

I estimate that the age effect creates an India population-average IFR 39% that of the US rate (i.e., a US rate \(2.58\times\) greater), assuming age-uniform infection rates and no difference in medical care. This effect is driven by the reduced population share of age>70 in India (just 35% that of the US).

I do not attempt to model age-varying infection rates (which I expect would slightly decrease India fatality rates relative to the US), do not attempt to model selection pressure on patients' immune systems (which I expect would make India fatality rates modestly lower), and do not model environmental factors such as air pollution (which I expect would make India fatality rates higher).

Finally, this predicted effect is extremely sensitive to the IFR-by-age curves; if shortages in medical capacity cause higher IFR in the 45-69 age groups (representing 22% of population), India population-average IFR could be many times greater. I believe this sensitivity (which will also be present in developing economies experiencing Covid-19 outbreaks in the future) should urgently motivate research into IFR by age under triage and shortage conditions.

I recently read a preliminary analysis of estimated Covid-19 infection and fatality numbers in India which suggested an observed IFR in India significantly lower than estimates of US IFR.

I wrote in January about vaccines and public health, and I wanted to retract my bottom-line recommendation about which vaccine to get -- if you have a choice -- in Hong Kong. Appointments opened to residents 16+ yesterday, so this post is coming a bit late, but oh well. Here we are.

If you're in Hong Kong and have choices, my personal recommandation is that you get an appointment for the BioNTech (Pfizer) vaccine as soon as possible. (If you are in Hong Kong and have a HKID, the link to book a vaccine in English is here -- click the red "Book Vaccination" box at the left.)

In the rest of this post, I'll describe how my thinking has changed on the argument I expressed in my January post.

(1)

When I wrote in January, I was looking at a massive shortfall in vaccine demand in the US and assuming that it couldn't happen here in Hong Kong. In hindsight, I was extremely wrong.

In the first 57 days of the government vaccination program, 16.3 doses have been given for every 100 persons in Hong Kong, at an average rate of 21,500 doses/day (government source). On Friday at 9am, all residents 16+ became eligible to book appointments, and "about 31,300 new vaccination bookings [were] made online" in the 13 hours before and 11 hours after the opening. I'm not sure whether this is 31k people with 62k appointments, or 16k people with 31k appointments.

Even if it's 62k new appointments in the first-day rush, that's still only 2.4x the daily processing rate (26,100 doses given in the same 24

Zvi Mowshowitz's new policy is not to link to the New York Times, and he's willing to entertain the policy of not linking to NYT reporters' Twitters (though hasn't pulled the trigger yet). I understand where he's coming from -- Cade Metz's piece on Scott Alexander was really, really not good.

Scott Aaronson has a numbered list of 14 theses issues and won't talk with Cade Metz, even to explain quantum complexity, without a full explanation on how the piece on Slate Star Codex happened. Also understandable; the article really was quite bad.

Then there's social pressure going around not to read the Times. I think this is a mistake. It is important to understand what rhetoric the paper chooses to use, for the same reason that it's important to occasionally look at what's happening on the other side of a chessboard. I wouldn't claim it's in the top-5 most important things to read to understand the world (or even the top 10), but I believe it's part of a complete breakfast a useful exercise, at least sometimes. Certainly it's a good skill to train.

Today, I was holding a physical copy of the Times's international edition -- mostly by accident -- which was a surprisingly good opportunity to practice the technique of carefully separating substance from spin. The rest of this post is a worked example of this 'careful reading' technique on the front-page article that happened to catch my eye. Let's read the Times!

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Here's the article (NYT paywall, of course, and I don't know if the online edition matches the print international edition, sorry).

First, ignore the headline entirely.

Then, read each paragraph. Read slowly,

Another may be sick too, and sick to death, and this affliction may lie in his bowels, as gold in a mine, and be of no use to him;
but this bell that tells me of his affliction, digs out, and applies that gold to me: if by this consideration of another's danger, I take mine own into contemplation, and so secure myself...

I was talking with a friend the other day, and the topic turned to vaccines. It's expected that the Sinovac and Pfizer vaccines will become available roughly simultaneously in Hong Kong, and so the question was, which vaccine we'd would prefer to receive.

Two topics that came up were safety and efficacy...

(1)

On safety, one can ask whether the Sinovac vaccine should be trusted quite as much as the ones developed in the West. (Hey, one can ask just about anything...)

Well, medically speaking, CoronaVac is a relatively conventional killed-virus vaccine. There's significant trial data available on it, as it has been given to more than a million people in mainland China since it received EUA in July. They've had months to observe side effects.

The issue is that that trial data is in the hands of Sinovac, a state-owned enterprise. And the question, then, is whether the Chinese authorities might have EUA'd the vaccine even if it had side effects that would make you, personally, balk. If it did, and even if it was massively good for society as a whole to get it, you might prefer to pass on getting it in your arm.

But that's just speculation; how likely is it to be true? Well, if CoronaVac's minor negative effects would be suppressed

This is the second in a series of reports on my decision-making process and decisions in allocating the $500k funding pool from the January 2019 CEA donor lottery. This writeup on my phase-2 grant recommendations is released simultaneously with my writeup of phase 1, which also provides a broader introduction to my personal background, philosophical foundation, and initial process.

While the decision-making process for phase 1 was largely completed prior to the widespread understanding of the scope of the Covid-19 pandemic, phase-2 grantmaking began in March 2020 and specifically focused on neglected responses to the pandemic. This writeup outlines what I can reconstruct of my process and opinions at the time, and discusses my thoughts on room for further funding.

As with the previous report, this writeup represents independent work and is not coauthored or endorsed by CEA, the organizations or individuals mentioned, or my employer. Grantee organizations and individuals were given one week to review a draft of relevant segments (except for COVID-END, who I neglected to contact before publication through my own mistake), though final editorial decisions were mine.

Overall summary

In phase 2, CEA accepted my recommendations to grant (in decreasing order of grant size):

• $100k to Fast Grants, for rapid regranting to academic research projects related to Covid-19.
• $80k to COVID-END, to reduce duplication in Covid-19-related research and accelerate evidence-based policy responses worldwide.
• $15k to the Bottleneck Fund, for regranting to global interventions in water and sanitation to prevent the spread of Covid-19.
• $6.4k to Ian David Moss, for consulting work supporting