While the news has been fast and furious on many fronts, Covid is not one of them.
Except that, this week, I got it.
On Monday evening, I started having chills. They seem better during the day, worse at night, slowly improving.
That night, I was almost entirely unable to sleep. I would lie down to sleep, and my body would be having none of it, I’d simply be lying down in bed for the whole night for multiple nights straight. The third night was somewhat better. The third night did finally include a lot of coughing, which for now seems to have gone away.
I thank everyone on Twitter and elsewhere for the well wishes.
Needless to say, I am somewhat tired and not at full capacity. That is the main thing I am feeling right now - very, very tired and low energy. Other aspects are manageable.
You do not want to get this. It sucks. It is a bad time.
It also is something that ultimately has not been so bad. It will pass. Life goes on.
My main writing focus this week until I got sick was assembling my post on everything that happened with FTX. I hope people find it helpful.
Executive Summary
I have Covid. It is no fun, but I should be fine.
Remarkably little broader Covid news.
Beijing seeing a spike in cases.
Let's run the numbers.
The Numbers
Predictions
Predictions from Last Week: 250k cases (+4%) and 2,400 deaths (+20%).
Results: 244k cases (+0%) and 2,139 deaths (+7%).
Predictions for Next Week (not a holiday yet): 250k cases (+2%) and 2,250 deaths (+5%)
There was some bounce back in deaths, but it still looks like the break in southern cases was for real. A combination of weather and variants seems like it should push case counts up slightly. For now, all seems quiet.
Deaths
Cases
Physical World Modeling
Oh look, we are intentionally creating strains of Covid-19 resistant to Paxlovid. Great.
Oh look, another study that says that people who get Covid-19 will later be in poorer health than people who did not get Covid-19, without controls, so thanks for that.
Paxlovid rebounds in 19% of study, versus 7% rebounds for controls (study).
In Other Covid News
White House seeks more Covid funding in lame-duck session. I don’t know why it would be forthcoming.
White House extending ‘Covid emergency’ until at least April. Still finding it useful, likely because Congress tied policy to the state of emergency. Seems like somthing to avoid.
Beijing reports 462 Covid cases on 11/14. It is very much Lucy and the Football territory at this point to assume Chinese Zero Covid will fail, yet they have weakened controls recently so it does seem highly plausible this has pushed them over the edge.
Other Medical and Research News
Open offices lead to 62% more sick days than individual offices, six person rooms lead to 30% less sick days than open plans. My guess is these ratios are a lot narrower with kids involved, a lot more important without them.
I am seeing stories about the Canadian legalization of assisted suicide that suggest it is turning into something deeply scary. Some reports say it already accounts for 5% of Canadian deaths, and there are things like this.
Some anecdotes about clinical trials and how impossible we have made doing them at any reasonable cost, with typical prices at hundreds of thousands of dollars per patient.
The story starts with incestuous, insider-only requests for proposals that include fifty pages of useless boiler plate, followed by 20-person meetings in which firms defend their breakdown of costs and every little decision they are making, then a vibes-based final verdict among those who meet the criteria, so the whole process was meaningless from the start except as negative selection for extreme inadequacy.
Now we have a vendor to do the trial. Then they have to do a similar process to find hospitals, some of which will handle things with no issues and some of which will be endless headaches. You will be quoted $176,370 for an unglorified SQL database with which to track drug distribution, and it will take several months to get set up. You will still need to manually generate your own ‘worksheets’ for exams, which then will need manual integration into the electronic systems. You will pay five figures for specialized advertising copy to recruit patients and it will come back with blatant grammatical errors, clear misunderstandings about the patient population and low-quality stock images. All of this and more will each require 10+ hour-long meetings for each item, each with 5+ participants.
I will quote the closing thoughts:
Why is this industry so cursed? Some hypotheses:
There is fundamentally a lack of talent flowing into the space, because everyone smart is eaten by tech or finance (the only reason I had any insight into this at all was because I was an ML-focused engineer in a biotech company heavily funded by tech VCs)
Everyone who is reasonably smart and joins this industry eventually either leaves or simply gives up on any hope of positive change to the status quo; to justify the state of affairs to themselves, they invent nonsensical copes about how things couldn’t be any other way
The massive amount of undocumented specialist knowledge that you need to efficiently run a clinical development program strongly favors incumbents, preventing new market entrants from easily competing on the basis of cost or competenceーe.g., it doesn’t matter if your firm has 170 IQ engineers if they simply don’t know all the One Weird Tricks about how to get around the FDA’s catch-22s
Because the cost of failure is so high, well-capitalized companies will always favor established methods, even if they are slow and inefficient, as long as they present a reasonable chance of getting the job done eventually
To effectively run a clinical trial, you must hire on a large number of ex-pharma professionals for their specialized knowledge, and that fundamentally degrades the culture of the company beyond recognition
To be honest, I don’t have any great solutions to propose. The problems seem nearly intractable in their scope and magnitude. Even if a return to positive real rates leads to a renewed focus on the “world of atoms,” it could take decades for the industry to become more efficient!
Good luck!
The FDA gets mentioned there at the end as the reason why you need to hire pharma execs, but what struck me most about the whole thing was the lack of regulatory barriers. All of this inefficiency and terribleness mostly seems like… unforced errors. You could choose to not do these things, if you had a corporate culture that wasn’t completely f***ed already.
Thus, if you were to start a new company to do clinical trials at a fraction of the cost, this is something that could totally work without having to cut any corners whatsoever, except that you’d need to solve the problem of hiring the pharma execs without having them poison the culture. Which means you want their specialized knowledge without also having to give them other influence or power. Can it be done?
I don’t know. I’d love to see people try.
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.
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.