Thread by @HCCvPDAC

Is the NIH grant system broken? Shockingly, I have thoughts. Thoughts from both sides of the process, grantee and reviewer. Thoughts from a mid-career scientist. Thoughts as an employer. Thoughts as a mentor.
These are MY thoughts, attributable to no one else. Still with me?/1

Good!

Let’s set the groundwork. I’m a pancreatic cancer researcher. My work has always been funded by the NCI, which currently has an 8% payline. Ugh, right? /2

I specialize in cellular plasticity in pancreatic tumorigenesis. It’s a super-cool topic and tons of fun, and by studying it we’ve found out some really important stuff about pancreatic cancer biology. But, spoiler alert, it’s not going to lead to a therapy tomorrow./3

For those who have played along at home, my recent resubmitted R01 was first put in 2 years ago. It got a 14%. Not fundable. The reviews were, predictably, very generous. Too generous. Only one concrete, addressable critique. Not *just* addressable… *easily* addressable./4

You *NEED* to have something to respond to or you are, guess what? "Not responsive to previous reviews"/5

BTW, one other critique was *instead of studying this weird cell type you’ve found, you should target its most common protein marker for therapy*, which a) I knew the marker wasn’t specific for the weird cell type and b) NOT WHAT THE PROPOSAL WAS ABOUT./6

Reviewers? Don’t do this. Don’t tell someone to change their project focus entirely. If you don’t like the current project, that’s fine. Say that. Advice to refine it? Cool! So helpful! But “do this think I like better instead”? Just no. /7

My PO told me just to turn it right around with the new data (that I already had) and I’ll be… and I quote… “swimming in money”./8

Color me skeptical. I’ve heard the horror stories. Respond thoroughly to reviews, get different reviewers with different opinions about what’s wrong. Get a worse score than the first time./9

I asked if the Study Section had a stable roster.
“Totally”. /10

I resubmit. I put in the new data. I explained why changing my entire research strategy was not appropriate. And I waited. With dread. Did I mention I was skeptical?/11

21% /12

Critiques come back. *Clearly* not the same reviewers. Reviewer 1 - “not translational enough”. What happened to the SRO speech at start of the meeting reminding reviewers that the NCI also funds *basic science*? “Not translational enough” is supposed to be a verboten criticism.

Reviewer 2 criticizes me for not having changed my entire research strategy like the previous reviews suggested. ARGH!/14

I talk to the PO. “Oops, sorry. You need to change study sections. Reviewer 1 will never a let a non-translational grant get past him. You’ve got to get out of that panel.”/15

I go to another Study Section with my second A0. I include some new data (where is *that* money coming from?) and a bit of a revised plan based on it. /16

Not discussed /17

Screw that. This time the PO wouldn’t talk to me because of the ND. No advice to give, so why talk? Not wrong./18

Feeling pretty freakin’ awesome about myself at this point. My wife gets pissed at me frequently because I’m often lost in thought, especially for the couple of days right after I receive the summaries. /19

The lab is worried. I’m very “water off a duck’s back” with them because I don’t want them to worry about their jobs. It’s got to be the most stressful part of being a PI. Worrying not just about your trainees, but their families, if you don’t get your funding./20

Ok, I brush myself off and rework the grant again. It goes to a Special Emphasis Panel (for the youngsters- a study section for PIs that are in conflict with standing study sections, usually because they’re a member). /21

12%. Sigh. /22

Now we’re at the point we need to publish not just the preliminary data, but the results of some the experiments we proposed (Where did *that* money come from?). Which, if you do, you’ve scooped yourself and you have to come up with a whole new plan!/23

Don’t forget, the self-scoop is be made up entirely of data that the NCI wouldn't fund. And with a new plan, you’ve got to have new prelim data *and* convince a study section that the next steps are just as important as the ones they refused to support the first few times./24

What are the critiques? Most were cool and super complimentary./25

One reviewer clearly doesn’t believe in cellular plasticity so trashes one of the aims, calling it “farfetched”. (Oooh, but of course in the past couple of months we’ve finished that aim and it’s even cooler than we could have hoped. BTW, where did *that* money come from?). /26

Oh, yes… and the proposal is not translational enough. /27

Another reviewer clearly thought that reviewer was insane and had nothing but nice things to say. These reviewers ARE out there, people! Marry them if you have to. No wait, then they’d be COI. Don’t marry them./28

The last reviewer was nice, if a little wishy washy. They criticized 1 aim pretty harshly because I didn’t have the 6 allele mouse I needed in hand. NOT that the alleles haven’t been *created* yet. Just that they have not been BRED together yet. If only @DrBenNeel were there!/29

Oh and show data from those mice. In other words, “finish the aim, then we’ll talk.”/30

BTW, this was the reviewer that said I didn’t address sex as a biological variable when there was an entire paragraph about it. FYI, I underlined that paragraph without explanation in the resubmission because... I’m the devil./31

Cool new data added. Even preliminary data for “where’s your 6 allele mouse model” reviewer. I should be confident, right? So why not? Because there’s only a negligible chance the A1 will see any of the same reviewers. /32

Mo reviewers, mo problems. I know. I’ve been there. As a reviewer, I sweat bullets when I read the Intro and see they’ve been very responsive, but the advice was… just bad./33

Then I read the grant and see fundamental mistakes that I can’t ignore. I totally forgive cases where I simply have a different opinion. If you’re responsive and there’s not fatal flaw, you’re golden with me. /34

I hate to tell you this young ‘uns, but that’s really not the norm. And all it takes is one reviewer./35

And therein lies the problem. With an 8% pay line, all it takes is one reviewer. One reviewer who doesn’t have the right knowledge base. One reviewer who simply isn’t excited about your proposal. One reviewer who says “it’s not translational enough”. /36

One reviewer who had to comment on 10 other grants. One reviewer who was taking care of a sick kid and missed some major points./37

A stressed reviewer in a room full of stressed reviewers. Panel members who feel like they don’t have the expertise to make an informed decision, so they vote down the middle, with boundaries set in part by that one reviewer. That’s all it takes./38

By the time you’ve got your reviews, it will likely be the better part of a year before you can resubmit. And wait. And hope you won the reviewer lottery. At least this time.

Did I say "lottery"?/39

Is the system broken? You know the answer to that./40

End rant. I'd say "Thanks for coming to my Ted Talk" but I'm pretty sure Ted Talks are shorter./end

I failed to mention that I didn’t bother to resubmit. Waste of time. Went to a new A0, which got the 12%

Ack, I didn’t resubmit the *ND*! All others are worth resubmitting