Unsolicited advice for a triaged grant

A scientist on Twitter lamented the other day that she had her A0 grant triaged. As an expert in triaged and unfunded grants who eventually overcame to get funded R01s, here’s some unauthorized, off-the-cuff advice.

What happened to this scientist’s grant that caused it to be triaged? Of course I don’t know for sure, but I’m willing to bet one reviewer read the grant carefully and saw strengths as well as weaknesses, but the other reviewer was dismissive with a cursory read. The problem is, without uniform enthusiasm, triage happens. Due to flat/declining funding over the past dozen years, competition is more intense today than ever before and study sections are encouraged to triage grants mercilessly.

I may seem vague, but that’s intentional. With a triaged grant, the problem is not likely to be with the details of the methodology but rather with the overall excitement for the proposal. When she wrote the grant she probably thought very carefully about the experimental design and feasibility of experiments. What was missing was zazz.  That’s right.  The missing ingredient was essentially jazz hands.

From 30,000 feet, the Specific Aims page, you want your reviewers to be thinking, “Wow!! Can she do that??” The rest of the grant is focused on making the case that, “you bet your ass I can.”

I’ve had discussions about whether a triaged grant can be salvaged for resubmission. While there’s always stories of grants going from triage to funded, this is the exception. Experienced hands put a triaged grant on the shelf for year, and try something completely different. Preliminary data, may be recycled, but a new approach, a new set of Aims are needed. This is debatable of course but what’s not debatable is that there was a serious enthusiasm gap and the grant needs to be rethought.

My tweep commented that “I really liked this grant!” Let me be provocative and say that this was part of the problem. If you “like” your grant, who is going to love it? you don’t need to like your grant, you should be psychotically passionate about it. You should have scary eyes for your aims, and bring unreasonable amounts of firepower to bear. I like to watch the lobby scene of the Matrix to get the idea.  In The Matrix analogy, the experimental tools of your experimental design are the guns.  Note how Neo and Trinity treat their weapons,  dropping them when they are spent and moving on without hesitation.  Do Neo and Trinity “like” their guns?  Tools are used simply to achieve the goal.

Another problem with a scientist “liking” her grant is that it sets her up for feeling discouraged by its rejection. Nut up. This is business. Don’t get discouraged, get angry. Take a couple of personal days for reflection, but then pick yourself up, dust yourself off and get back into the fray. Keep writing.

Change of gears.  The PubScience in me wants to say,  “Hey, young ‘uns, let’s cut the B.S., you’re listening to advice from old man telling you how to act like him.  An alternative explanation for a rejected grant, is that the NIH only likes to fund old people.

I’m being facetious, but only a little.  Who still thinks it’s a good idea to have the fate of  creative and groundbreaking ideas decided upon by a committee monoculture? I agree completely that the NIH grant process needs to be rebooted, as @MBEisen and @Drugmonkeyblog have discussed (and I refer you to them for a more systematic and objective (?) discussion).

Briefly, and irreverently, my view on what’s wrong with the NIH process is that the smarter people try to be, the more danger there is in them being dumb asses.  This view of course was influenced by my own sordid grant history.  My currently R01 funded project is not what I started out with — I had two projects that failed agonizingly to obtain successful R01 funding, after 3 rounds of grant reviews each.  First one, then the other broke my heart as the A2 scores came back nearly the same as the A1 score, unfundable, after massive efforts to respond to A1 reviews.  (@drugmonkeyblog recently wrote about this phenomenon)  It’s deeply ironic to me that the “deal-breaker” criticism of each grant was neutered by the passage of time.   My first R01 application included an Aim on making and using a mouse knock-in model of the disease I was studying.  The final judgement was that without the engineered embryonic stem cells in hand, there was no way the grant should be funded.  It was rational decision on the part of the reviewers.  I was depressed, but their judgement seemed fair.  And yet, a similar knock-in model was later successfully created by another lab, and the insights it has yielded have yet to live up to our hopes.  To my mind, the “alternate approaches” I outlined in my grant may have been the better approach.

The case of my second project makes me smile even more ruefully.  Although I now had a disease model in hand, my experiments were considered  unworthy because my model did not, in my reviewers’ opinion, adequately recapitulate human disease.  The primary reason I pursued my Myc-driven model of acute myeloid leukemia (AML) was that it looked, to my hematology-trained eyes, exactly like human AML.  But, the scientist experts on study section noted, my mice had AML that was oligoclonal (comprised of not a single malignant clone, but several), and this was clearly not the case for the human disease.  Case closed.  Sigh.  Except… now, a few years later, we know that human AML is, in fact, oligoclonal.  Oops.

People often inquire about the experiments I proposed in that grant, but we had to drop working on it.  My bottom line is that while the writer of an unscored R01 needs to do some serious re-working, the NIH also has some serious re-working to do to address the reality that the job of a scientist has become predominantly about playing the grant game, which takes years of experience for most of us, rather than rewarding the smartest creative minds, which are usually younger than the grey-beards we reward now.

If your loved one is sick, you need to tweet about it

The last Pub Style Science on patient blogs was a blast, as usual, but there was something more I wanted to say about medicine and interweb communication. Still thinking about what social media can do for medicine because I’ve been on service recently spending hours and hours working with leukemia (and lymphoma and myeloma) patients, fighting a myriad of problems with them. Mostly, of course, it’s their diagnosis, a horrible disease that is the enemy. But a fight against cancer can be a long battle and there are countless small issues that are much of the day-to-day work.  With a cold, statistical eye, I don’t know how significant the “little things” are to someone’s overall survival, but I feel they matter, at the very least for a person’s quality of life, and also for the patients’ families who have a strong desire to care for their loved ones in the best possible way.

The simple mechanics of patient care–did the nurse have the items she needed when she needed them?  Was a problem dealt with promptly or did wait until after the weekend?– can cause significant anxiety for patients and their families.  These days, when there is drama, my first instinct is, “I should tweet that,” I should make some noise, get some attention to the issue, maybe putting a spotlight on the problem will help fix it.  But I must not.

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Does the on-line community realize that this simple act is not acceptable in the hospital, I wonder?  Sure, there are privacy issues, HIPAA concerns (which are distinct IMO), but I feel the greatest damper on speaking openly, the over-arching concern, is a culture of fear based on concerns of liability and lawsuits. The hospital has “patient liaisons” that hear complaints.  What these folks do is, in fact, risk management. Will a patient sue?  Will a federal regulator impose a hefty penalty?  The sad reality is that in 2014 the financial risks involved with open communication supersede any potential benefits.

This means that there are untapped potential benefits to be had.  Brilliant people with investor backing are working overtime to develop internet-based technologies for a new era of medicine.  Big data.  Genome sequencing.  Quantified selves. Eric Topol is right that the medical industrial complex is ripe for “creative destruction.” The old ways of delivering medical care are going to change significantly in the next 10 years, many predict.  Established players and start-ups are putting resources into ideas that they hope will get them a piece of the huge healthcare money pie.

The Pub Style philosophy is that science should have an open-door accessibility. It reminds me that the tech needed for Schumpeter’s gale in medicine might be relatively low tech.  Simplification is likely to be a critical element in a transformative process, especially now that are (finally) enormous pressures to reduce costs. Giving voice to frustrated health care customers is a simple idea that could be a growth industry. What will seem in retrospect as a simple solution is waiting to be invented, and it may just as likely come from a college dropout working in his basement as it is to come from a university or large corporation.