TR01l Grants: What does transformative mean?

Sep 11 2008 Published by under Careerism, Grant Review, Grantsmanship, NIH

The NIH has announced the much anticipated 'transformative' R01 funding program. The mechanism has been dubbed the T-R01, apparently, soon to be pronounced simply 'troll', I have very little doubt.

The purpose of the T-R01 Program is to support exceptionally innovative, original or unconventional research that will allow investigators to seize unexpected opportunities and cultivate bold ideas regardless of the anticipated risk. T-R01 funding will support inventive and innovative studies intended to transform current paradigms in biomedical or behavioral sciences.

The Guide announcement indicates that the first round of applications are due on Jan 29, 2009.
Let's take a look.


Five years of support may be requested, there is no cap on the budget up to the program cap (of $25M, I guess, phew; actually they anticipate making up to 60 awards).
There will be no resubmissions or renewals permitted, this is a one shot deal.
Okay, so how do they view this concept of transformative, anyway?

The goal of the Transformative Research Projects Program is to provide support for individual scientists or collaborative investigative teams who propose transformative approaches to major contemporary challenges. To be considered transformative, projects must have the potential to create or overturn fundamental scientific paradigms through the use of new and novel approaches. Successful projects will be expected to have a major impact in a broad area of biomedical or behavioral research. Consistent with this highly transformative focus, projects supported under the T-R01 program will reflect ideas substantially different from mainstream concepts being pursued in the investigator's laboratory or elsewhere.

blah, blah, blah....in short, we don't know either!
Well, they do have some areas of focus...

Understanding and Facilitating Human Behavior Change

Behavior change is critical to the prevention, management, and treatment of many important health conditions. However, the initiation and maintenance of behavior change can be very difficult,...invites proposals ... working to understand basic mechanisms of behavior change at the biological, behavioral and social levels and developing innovative approaches to intervention. Questions of particular interest include how the interaction between neural, biological, behavioral, psychological, and social factors result in initial and sustained behavior change (possibly best understood via transdisciplinary approaches including neuro- and behavioral economics, affective neuroscience, and approaches that focus on "will power" or behavior regulation).

Waaaaaeeeeel. Hm. Now true, getting people to stop doing things that are bad for them like overeating, eating junk, engaging in risky sexual practices, taking drugs, jumping out of airplanes, etc is very hard to do. And it will radically transform some attitudes in NIH land to permit something as wishywashy as "behavior change" to get a shot at the high profile, latest-n-greatest bucks. But as usual, I'm not seeing where this stuff requires a new mechanism. Better approaches to review, sure. But everyone could benefit from better approaches to review!

Complex 3-Dimensional Tissue Models
...tissues and organs are 3-dimensional structures, their physiology and pathophysiology are currently studied in vitro with 2-dimensional techniques, in which key phenotypic and functional characteristics are often lost. Development of complex 3-dimensional tissue models... It is anticipated that these human tissue models might ultimately be adapted to high throughput screening platforms to conduct studies of environmental stressors or for pre-clinical drug discovery.

Yeah, see, we already have "complex 3-D tissue models"....we call them animal models. Next?

Functional Variation in Mitochondria in Disease
Mitochondria are one of the most complex and important organelles found in eukaryotic cells. .... Mutations in mitochondrial DNA lead to a diverse collection of diseases that are challenging to diagnose and treat, and where precise mechanisms of disease pathogenesis remain elusive. Mitochondrial dysfunction has also been implicated in aging and in many chronic disease states including cancer, Parkinson's, diabetes mellitus, Alzheimer's, hepatic and cardiovascular diseases.

I don't know much about mitochondria beyond Charles Wallace, frankly. Still, this smells exactly like "few people have been working on mitochondria and gee, we'd like to know more". Could have handled this with a couple of RFAs, no?

Transitions from Acute to Chronic Pain
More than 30 million Americans suffer from unrelieved chronic pain. Management strategies often fail, in part because an individual's susceptibility to chronic pain is highly variable, the identification of those destined to transition from acute to chronic pain is difficult, and, once pain has become chronic, changes may have occurred that cannot be easily reversed.

I think I better leave this one to a much more knowledgeable blogger. [Update: Actually juniorprof previously posted on this issue, which I apparently forgot.]

Formulation of Novel Protein Capture Reagents
A comprehensive analysis of the human proteome

bzzt. Sorry, but wanging on about -omes is old hat now, not 'transformative'. Thanks for playing. In fact this -ome stuff is in the middle of the most dangerous zone, i.e., just after the latest buzz has been funded out the wazoo and we don't yet have a good handle on whether it will be productive.

Providing an Evidence Base for Pharmacogenomics
In the future, prescribing decisions will be increasingly guided by genetic tests that can predict risk and effectiveness of treatments for individual patients. However, few evidence-based guidelines have been established linking individual genetic variations to medication response profiles. Proposals are sought under this T-R01 initiative that will establish and validate the predictive value of genetic profiling for creating clinical practice guidelines.

Now this one sounds pretty interesting.
Conclusion: Score me fairly unimpressed at the present. We have this meme afoot in NIH land that the traditional review process is conservative and stifles innovation. True. So apparently the solution is to invent some new mechanism with poorly defined (perhaps inevitably) criteria and run with it.
Yuk. If the problem is that all of review is too conservative, hey, how about fixing that problem for everyone?
If you have your pet whingers who can't get their wackaloon grants through study section, how is this going to help? The only way it is going to work is to have the other wackaloon out-there geniuses on the panels, right? .....and again, you could have done that anyway. Not to mention picked up any old grants you wanted.
This leaves us with the frightening possibility that the NIH simply does not ever see any proposals that are wackaloon, out-there genius and yet still thinks our current scientific workforce can come up with such proposals if they just beg hard enough...That, my friends is an empirical question.

9 responses so far

  • PhysioProf says:

    I submitted some wackaloon shit as a an R21 looking to screen for some possible novel drug targets for intractable human pain. The motherfucking assholes who reveiwed the grant hit me hard on my failure to justify the need for novel pain treatments, you know, because we already have so many that work so perfectly that intractable pain is, like, not even a big problem. The fucker went to A2 and still never got funded.
    And this motherfucking study section was an INTERNAL NINDS STUDY SECTION. Those motherfucking assholes should have known PAIN!!!!!!!
    Maybe I'll recast the motherfucker as one of these thingies.

  • Forgive my naivety, but how will the "innovative, high risk, original and/or unconventional research" T-RO1 differ from the "exploratory/developmental" R21 mechanism? Is this just a matter of semantics?

  • whimple says:

    The NIH will never fund truly transformative projects, because in order for a project to really make a difference to consensus thinking it is necessary for the best current evaluation of that project be that the project will fail. I just don't see a study section ever giving a fundable score to a project that in their heart-of-hearts they think will come up with nothing, no matter how cool it would be if the proposal could actually be pulled off.
    The NIH should be explicit: "We will fund 60 projects. We expect and require that 58 of these projects will generate no useful results, even with best effort of the researchers involved."
    How many paradigms can you overturn anyway?

  • DrugMonkey says:

    sixty, whimple! Transform or die, baby.

  • juniorprof says:

    On the pain-oriented one; there is already some controversy on this one including an email clarification to the listserv for a major pain society from a program officer trying to clarify what exactly they are looking for. Rumor has it, at least for the "acute to chronic pain" roadmap directive, that this is going to be accompanied by a pain-specific study section. This is something that many of us have been clamoring for for a long time. Its not clear if inclusion on the roadmap was a means to that end or if it was included on its own merits. I'd like to think both.
    study section was an INTERNAL NINDS STUDY SECTION. Those motherfucking assholes should have known PAIN!!!!!!!
    Why'd it go to NINDS and not to SCS ? One would imagine that they would have understood the need for novel analgesics.

  • PhysioProf says:

    Why'd it go to NINDS and not to SCS ? One would imagine that they would have understood the need for novel analgesics.

    Because the NINDS exploratory/developmental R21 mechanism is all reviewed internally.

  • Questions of particular interest include how the interaction between neural, biological, behavioral, psychological, and social factors result in initial and sustained behavior change (possibly best understood via transdisciplinary approaches including neuro- and behavioral economics, affective neuroscience, and approaches that focus on "will power" or behavior regulation).
    Ugh. I'm sure you would love to know that fMRI projects such as this one (Who Can You Trust?) could be in the running.
    And this motherfucking study section was an INTERNAL NINDS STUDY SECTION. Those motherfucking assholes should have known PAIN!!!!!!!
    If you want the study section members to really know pain, why don't you inject them with formalin or complete Freund's adjuvant right before the panel review?

  • NM says:

    "Understanding and Facilitating Human Behavior Change Behavior change is critical to the prevention, management, and treatment of many important health conditions."
    I'm pretty sure this is already covered by combinations of clinical medicine and public health intervention programs.

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