A one-two punch on clinical trials from Ruxandra Teslo and Willy Chertman today: first their on-point agenda for clinical trial abundance as a guest post in Slow Boring, then Ruxandra’s longer essay which has been so thoroughly research that even yours truly gets a name-check. As I noted elsewhere, every US institution has made one bade tradeoff after another in how it conducts clinical trials to the point that it’s impossible to conduct a RECOVERY trial equivalent over here. That needs to change.

On my way back from #ASH24 I’ll go back through the abstract book and check out how many cell therapy oral presentations were given by investigators from China. This is the first meeting I’ve attended since 2019 and the difference is striking. Kudos!

PCA maps are the new PET scan, only with zero clinical relevancy instead of at least some. Much more subjective, too! #ASH24

100% of patients developed grade ≥3 neutropenia. “The safety profile was mild” #ASH24

Seeing those PET scans after CAR-T 5–10 years ago was transformative but it has now become superfluous. Yes, yes, that was a nice anecdote, can I now please see some data? #ASH24

Quote of the week is from Adam Mastroianni:

For example, the National Institutes of Health don’t like funding anything risky, so a good way to get money from them is to show them some “promising” and “preliminary” results from a project that, secretly, you’ve already completed. When they give you a grant, you can publish the rest of the results and go “wow look it all turned out so well!” when actually you’ve been using the money to try other stuff, hopefully generating “promising” and “preliminary” results for the next grant application. Which is to say, a big part of our scientific progress depends on defrauding the government.

The article is mostly about Paul Feyerabend, author of Against Method and self-proclaimed scientific anarchist. Recommended.

Some weekend links, old and new:

• A Case Against the Placebo Effect
• Frank Auerbach and the unexamined life
• The Worst Generation (from the year 2000!)
• Merlin Mann on The Great Discontent (2013!)

Yes, yes, reform the NIH. But while we’re in the finger-pointing mode, why not mention the waste in money and time stemming from the way biotech finance works? Beauty contests, herding around fads, billions of dollars wasted on courting KOLs for treatment that will never be approved. It’s all there…

The same week Alexey Guzey proposed abolishing the NIH, two more essays popped up:

• Distinguishing the real from invented problems with the NIH, from Sasha Gusev, himself an NIH-funded geneticist
• The NIH Needs Reform: Here are 10 Sensible Suggestions from Joseph Marine, a cardiologist

A few things came to mind:

• You can clearly see the difference in backgrounds. Gusev’s essay is an “insider-y”, show-me-what-we’re-doing-wrong approach. Marine’s is outward-looking-in, dealing more with perception of the NIH.
• Marine makes several immediately actionable proposals which are the policy equivalent of politicians kissing babies but since these days any politician seen kissing a baby would be called a creep (or worse) I suspect that even those modest proposals would become divisive.
• Neither states conclusively what the NIH is for. Is its mission to give out grants? Advance biomedical science? Or help people live longer and/or better? I’d say it’s that last one and that everything else is means to that end.
• So if we see the NIH as a grant-giving machine, I guess we could give it a passing grade. The awardees certainly seem happy! But in the last 30 years we saw several massive public health crisis, from the obesity epidemic to the opioid murders to the bungled response to the pandemic so from that standpoint at least there is room for improvement.
• Gusev’s essay does not at all consider the opportunity cost of the current system. He lists length of grant proposals as an “invented problem” and unironically writes (emphasis mine):

The last NIH proposal I submitted was about ~150 pages which might indeed seem daunting. But only ~12 pages of that was dedicated to science and will be the focus of study section reviewers (and I can also assure you that I wish I had more than 12 pages to work with). The remainder was some combination of budgets, resumes for all of the personnel involved, descriptions of the data and resources, and contractual language between the NIH and my institution. Nearly all of it was handled by experienced grants administrators in my department who can put these documents together in a matter of hours.

• You don’t have to be an expert in probability and statistics to see how this “invented problem” leads to a winner-takes-all system, the winner being a handful of investigators in a handful of institutions. This is an incredible systemic risk that can lead to billions of dollars wasted and set back an entire field of study by decades.
• I want to read something from Adam Mastroianni on the topic of NIH reform.

Abolish the NIH is an unnecessarily divisive title but the core idea is interesting: sunset extramural NIH funding over 10–15 years through natural expiration of grants and, in parallel, set up alternative mechanisms which otherwise would have no room to breathe. Worth considering.