At the very start of the textbook Fundamentals of Clinical Trials the authors make a distinction between clinical trials — comparing two or more different interventions — and clinical studies, which merely describe an intervention without comparing it to anything. So, there can be no such thing as a “Phase 1 trial”, since they typically involve a single drug at different doses and schedules. The only true trials, according to the authors, would fall under Phase 3, or Phase 2b at the earliest.

This is stupid, misleading, and not at all how the words “trial” and “study” are used by anyone else, including the biggest and most important drug regulatory agency in the world. There are many such pointless exercises of professorial power in medicine, including my favorite: whether the correct pronunciation of “+” in “7+3” is “plus” or “and”. They amount to nothing more than purity tests that award the wielders of the right language a false sense of precision. As Nassim Taleb wrote, nitpicking is the enemy of thought.

The rest of the book is good enough, but more on that later.

The National Cancer Advisory Board is as big of a deal as it sounds, but have a look at their Charter — Description of Duties in particular — and try not to yawn. I suspect whoever wrote this also writes grant application instructions. May this in part be why science is bogged down?

In any case, the Board meetings are open to public. The next one is on February 9, 2023 at 1:15pm EST and can be viewed at videocast.nih.gov. That website is itself a trove of excellent recordings unrelated to federal body deliberations: just last week there was a lecture on bacterial immune systems, here is my old boss talking about interleukin-15, and hey what’s this?

After a few months of intermittently kicking the tires on Dave Winer’s FeedLand, I’ve finally had the time to port over a few feeds from my preferred RSS reader. The wonderful thing about FeedLand is that you can easily follow my feed categories and read posts without having an account (which is fortunate, since new signups on Winer’s own server are on hold). The full list of feeds is here. There is even a feed of posts I liked! It’s feeds all the way down.

The Science category has your usual suspects but I had to dig deep for Medicine since many of the blogs I follow haven’t been updated in years and others have turned into HuffPost-level text mills. Fortunately, Substack enabled a resurgence of medical writing, with feeds enabled by default.

Did I mention NetNewsWire is a free, open source RSS reader available on MacOS and iOS, and can sync via iCloud? For the anti-Apple readers, Feedly is there, I guess?

This April will be 10 years since Elsevier aquired Mendeley, up until then the best reference manager around. And it took longer than expected, but it looks like they finally killed it.

To all the Mendeley refugees: Endnote is just as bad, and in many ways worse. Get Zotero.

Google Scholar alerts are a quick if crude way to be up-to-date with literature. In addition to journal articles and conference abstracts it also looks at U.S. patent applications, and despite the impenetrable legalese something will ocasionally turn up that is at least amusing, if not informative.

Today was one such occasion: a patent for a combination of two already approved drugs to treat toxicity of CAR T-cell therapy, by the group which, admittedly, was the first to give CAR T-cells to humans and the first to treat their side effects.

I may be showing my ignorance of U.S. patent law here but, how is this a thing? These drugs are already commercially available and widely used for exactly this indication. How would they enforce this patent, and how exactly would the patent help with development and commercialization of two drugs which are already on the market?

After reading Steven Johnson’s Where Good Ideas Come From I realized that not everyone makes the distinction between discoveries and inventions, Which is the first website that DuckDuckGo returned, and it is servicable, but I was flabergasted by the long list of nearly identical websites with domain names all some variant of “difference between”. This is how ChatGPT destroys Google. and this may be an example of a discovery masquerading as an invention. Nothing was created — the drugs were already there — the team merely discovered that those two drugs work in a specific indication. If this is deserving of a patent, should every drug combination be patented?

To be clear, I am not a lawyer — caveat lector — but the whole patent system needs an overhaul and making a clearer distinction between discoveries and inventions should be one of the items on the long list of things that need attention.

A lengthy overview of the implications of ML/AI to biology and drug discovery came out yesterday, and while I appreciate its enthusiasm and breadth, the answer to the question posed in the summary — What if this time is different? — is, sadly, no, probably not.

If you are giving a pre-recorded talk at a “hybrid” scientific conference, you can count on the number of people listening to you being functionally zero. Some may take photos of your slides, your face included.

Among the few Latin phrases I listed yesterday, I’ve somehow managed to miss my favorite: Ars longa, vita brevis.

Comes to mind each time I glance at my bookshelf.

The beginning of the year was busy enough for a short commentary I co-athored to come out without my noticing.

Briefly, the US government spent $10 billion procuring the anti-Covid drug Paxlovid after a study confirmed its efficacy in unvaccinated people exposed to the delta strain. It then proceeded to hand it out to everyone, including the vaccinated and boosted during the omicron wave, with no data on whether it is actually needed in that setting. A similar drug, molnupiravir, ended up not having any meaningful effect in those who received the vaccine despite preventing hospitalization and death in the unvaccinated.

Could those $10 billion have been better spent? We believe the answer is: yes. For a fraction of the cost, using the same network of local pharmacies as in the Test-to-Treat initiative, the federal government could have randomized the first 100,000–250,000 patients to Paxlovid, Molnupiravir, or usual care — an order of magnitude more than PANORAMIC as many in the American health care system would have been lost to follow-up. The study would have taken mere months to accrue and would have provided valuable information on the efficacy of these treatments in the U.S. population. As importantly, it would have provided an important precedent and infrastructure for more federally funded pragmatic randomized controlled trials of agents under EUA or accelerated approval. The precedent set instead was for government’s full support for use of drugs far outside of the tested indication.

You can read the whole thing here, without a paywall.

Further evidence that T cells are the best cells.