📷 Reminds me of M.C. Escher’s Three Worlds (Tregaron Park, NW DC)
You don’t have to convince me that NIH grant funding needs to be reformed, but all this article in The Atlantic did was show that even people who get their funding from NIH (i.e. the two authors) have no clue about how NIH operates or what its mission is.
For instance, this assertion:
“… the NIH, the largest public funder of clinical trials in the United States, should also have been well positioned to create treatment guidance for doctors caring for patients hospitalized with a brand-new disease.”
is followed shortly by:
“Moreover, the NIH has mostly retreated from clinical research. By some estimates, the pharmaceutical and medical-device industries now sponsor about six times as many clinical trials as the NIH. In practice, this dynamic narrows the type of clinical-research questions being investigated; only new drugs and other products that can sell on the market receive rigorous scientific scrutiny.”
There is a hint there that Drs. Cary Gross and Ezekiel Emmanuel don’t differentiate between the NIH’s extramural activities, i.e. awarding grants to entities which are not NIH, its Intramural Research Program which conducts its own — usually high-risk high-reward and sometimes clinical — research, the individual institutes and investigators at the NIH who may contribute to creation of disease guidelines (its work on GVHD assessment is a good example), and the investigators at other institutions who and which may receive NIH funding who also contribute to those guidelines, maybe even as part of an NIH-funded grant.
The rest of the article is as jumbled. It highlights Drs. Kizzmekia Corbett and Barney Graham, correctly naming them “NIH scientists” (they were part of the Intramural Research Program when they worked on what was to become the Moderna vaccine), but as a counterpoint bring up a failing of the extramural program to fund Dr. Katalin Karikó’s mRNA research back in the 1990s. It talks about “NIH-sponsored clinical trials” without qualifying what that means (Which NIH? Financial or IND sponsorship?). It brings up the RECOVERY trial (full disclosure: I am a big fan of the trial) and faults the NIH for… not pushing for a single-payer system and unified electronic medical records that the UK has and which enabled RECOVERY, I guess?
It is clear that NIH needs to rethink its extramural funding mechanisms. Maybe make them more like the intramural program? Make some of them into a lottery (good opportunity for a randomized controlled trial there!)? Fund people not projects, as Gross and Emmanuel (and others long before them) propose?
But several attempts at reform have failed, often because of pushback by incumbent senior scientists who said that whoever proposed the change did not fully grasp what they were dealing with. And you know what: they were right. Do not attempt to reform something which you do not understand. As the first step in understanding, Matt Faherty’s 30+ thousand word report on the NIH is a good start. Mood affiliation pieces like the one in The Atlantic, not so much.
“Seoul is not a pretty town, not at least by most Western senses of beauty. It is a sprawling mix of the haphazard, with little seeming cohesion, beyond a shared culture. Two hundred and fifty square miles of building after building, of all styles, of all facades (glass, brick, stucco, tile, fake brick, fake stucco), jammed up against each other, almost all covered in visually loud, bright, large ads.”
Seoul was never on my list of must-see places and the first paragraph of this brilliant photo essay sums up why, but the rest of the essay — and those photos! — managed to tempt me.
📷 Reminds me of M.C. Escher’s Three Worlds (Tregaron Park, NW DC)
📷 Nature is obviously a fan of Escher.
“It was a small trial, just 18 rectal cancer patients, every one of whom took the same drug. But the results were astonishing. The cancer vanished in every single patient, undetectable by physical exam, endoscopy, PET scans or M.R.I. scans.”
You shouldn’t judge an article by its headline, so how about the first few paragraphs?
“Dr. Luis A. Diaz Jr. of Memorial Sloan Kettering Cancer Center, an author of a paper published Sunday in the New England Journal of Medicine describing the results, which were sponsored by the drug company GlaxoSmithKline, said he knew of no other study in which a treatment completely obliterated a cancer in every patient. “I believe this is the first time this has happened in the history of cancer,” Dr. Diaz said.”
So far we have “astonishing”, “vanished in every single patient”, “obliterated”, and the “first-time-in-history” gambit. Anything else?
“Dr. Alan P. Venook, a colorectal cancer specialist at the University of California, San Francisco, who was not involved with the study, said he also thought this was a first. A complete remission in every single patient is “unheard-of,” he said.”
“Unheard-of”! So be it.
Not until paragraph 18, long after it praised lack of toxicities in a 12-patient trial of a drug with a known side effect profile, and shortly after mentioning the C-word sandwiched between “remarkable” and “unprecedented” is it revealed that
“The inspiration for the rectal cancer study came from a clinical trial Dr. Diaz led in 2017 that Merck, the drugmaker, funded. It involved 86 people with metastatic cancer that originated in various parts of their bodies. But the cancers all shared a gene mutation that prevented cells from repairing damage to DNA. These mutations occur in 4 percent of all cancer patients.”
The “mutation” in questions is mismatch repair (MMR) deficiency is not actually a mutation, but that is this report’s least egregious journalistic error.
MMR deficient tumors respond well to immune checkpoint inhibitors. One of them, pembrolizumab, has broad FDA approval for all “advanced” (i.e. metastatic or unresectable) cancers with MMR deficiency. The goal of this most excellent study which absolutely should have been done is to see whether it can be used even earlier, to avoid possibly debilitating but potentially curative surgery.
And lo and behold, it can! Congratulations to the study team, immune checkpoint inhibitor manufacturers, and most of all to those people who are yet to develop an MMR-deficient tumor which is still resectable, but now maybe doesn’t need to be resected because it will melt away with immune checkpoint inhibition. NB: this is significantly less than the quoted 4%, which includes people whose cancers are advanced and who can already receive ICIs.
Note that I did not learn any of this from the new article, but rather from being a medical oncologist and reading the NEJM paper which is at least — let it not be said NYT does everything wrong — linked to early on.
How will others read it, one wonders?
“The Cotswolds are like Disneyland, they said. And I suppose that was meant to be pejorative. But as a kid I grew up going to Disney World, over and over, … and having the time of my life.”
I like Disney World, but it looks like I would really like the Cotswolds.
“We can’t keep making so many scientists tear out their hair over well-intentioned but near-infinite administrative requirements, as if that doesn’t distract from the actual science that they are supposed to be doing.”
“Many breakthroughs in scientific progress have required massive funding and national coordination. This is not one of them. All that needs to be done is allow expert research scientists to do the hands-on work that they’ve been trained to do.”
“…the sheer amount of regulation is so voluminous that if I had to actually read the guidelines that they want us to know about, I would never again be able to submit a grant”.
In communist Russia, the grant writes you!
Silly me, it’s not Russia, it’s the US of A.
📚 Calculated Risks was funnier than you’d expect from a book about statistical (in)numeracy. It’s healthy to laugh in the face of our inadequacies.