Strategies for your #A2asA0 Resubmissions

A query came into the blog email box about how to deal with submitting a new grant based on the prior A1 that did not get funded. As you know, NIH banned any additional revisions past the A1 stage back in 2009. Recently, they have decided to stop scrutinizing “new” applications for similarity with previously reviewed and not-funded applications. This is all well and good but how should we go about constructing the “new” grant, eh? A query from a Reader:

Do you use part of your background section to address reviewer comments? You’re not allowed to have an introduction to the application, but as far as I can tell there is no prohibition on using other parts of the application as a response to reviewers.

I could see the study section as viewing this a) innovative, b) a sneaky attempt to get around the rules, c) both a and b.

I am uncertain about the phrasing of the Notice where it says “must not contain an introduction to respond to the critiques from the previous review“. In context I certainly read this as prohibiting the extra page that you get for an amended application. What is less clear is whether this is prohibiting anything that amounts to such introduction if you place it in the Research Strategy. I suspect you could probably get away with direct quotes of reviewer criticisms.

This seems unwise to me, however. I think you should simply take the criticisms and revise your proposal accordingly as you would in the case of an amended version. These revisions will be sprinkled throughout the application as appropriate- maybe a change in the Significance argument, maybe a new Experiment in Aim 2, maybe a more elaborated discussion of Potential Pitfalls and Alternative Approaches.

Given the comments, perhaps you might need to state some things twice or set off key points in bold type. Just so the next set of reviewers don’t miss your point.

But I see no profit in directly quoting the prior review and it just wastes space.

Clarity

This sentence gave me cold chills.

Younger scientists need protection from the ambitions of their elders.

Science: happy.

I see Twitter based networks of newishly transitioned scientists forming and I cannot wait to see some collaborative papers emerge.

Get on it Tweepers!

CPDD 2014: The XLR-11 synthetic cannabinoid is looking nastier by the day

A session on synthetic cannabinoids at the Experimental Biology meeting in April included a talk on nephrotoxicity consequent to use of synthetic cannabinoid products. I covered it in a post. As with a prior report of Cases in Wyoming, the scientist from Oregon reported being able to identify XLR-11 in two of the cases presented. There is not much available on PubMed at the moment regarding the effects of this cannabimimetic. (The XLR-11 structure at the right is courtesy of “meodipt” who submitted it to the Wikipedia page for free use.)

New data presented by Michael Gatch at the recent meeting of the College on Problems of Drug Dependence in San Juan, PR (lovely venue, btw) caught my eye because of an unusual property of XLR-11. Previously, Gatch has looked at a lengthy series of synthetic cathione (“bath salt”) drugs in mouse locomotor and rat drug-discrimination assays. This new work is similar, save for the different drug class, so if you want some background reading, that prior paper would be a good complement.

The key, for me, was the drug-discrimination data. This is an assay in which animals are trained to discriminate saline from a reference drug, in this case good old Δ⁹Tetrahydrocannabinol (THC). In essence the rat is reinforced for responding on one lever if it has received saline just prior to the operant session and on the other lever if it has received THC. Then, on critical test days, you can substitute a dose of some other drug and determine the extent to which the rat responds on the drug-paired versus saline-paired lever. As I’ve mentioned before, this seems imprecise to the newcomer since seemingly any intoxicant would be scored as “drug” to a rat. Not so. They are actually highly specific in categorizing drugs of similar pharmacological activity.

The interesting thing in the presentation by Gatch was that he showed time-course with bins of about 5 minutes after the start of the session. One drug, XLR-11, popped out as having rapid onset of activity (i.e., full THC responding at 5 min when it takes maybe 10 or 15 for this to occur for THC itself) and a short duration of action (THC-lever responding disappeared after about 15 minutes). I say it popped out because out of a series of cannabimimetic drugs he presented, this one was the only one to have this profile (to my recollection).

This is interesting because in a general sense this tells me two things. First, this is the profile of a drug that is going to engender rapid on/off subjective effects and therefore very likely frequent re-dosing. From a comparative perspective this sounds like enhanced abuse liability to me…i.e., better chances of causing addiction.

The second aspect only hit me when I recalled that XLR-11 was the compound associated with nephrotoxicity. Now, admittedly, it may be the case that XLR-11 itself has a pyrolosis product produced during the smoking of plant matter containing it. But it also strikes me that this rapid on/off pharmacological profile might lead to recreational users simply using more of the products containing this compound than they ever would of products containing some longer acting synthetic cannabinoid. And that might get us back to thinking about what is contained in the various plants used in the products being sold to users.

Science

Cool result! Yay!

Control verification fails inexplicably. Ugh. How can this be?

Running obvious other control….works. So first control was valid, meaning the negative result was also valid.

Scrutinizes data……AHA!

Actually explains the design flaw in our first control! YAY!

New experiment planned.

PSA on reporting conflicts during academic presentations

The joke about how you’d like to have some financial conflicts of interest to declare, but sadly you have none, is no longer amusing.

Knock it off.

Quality of grant review

Where are all the outraged complaints about the quality of grant peer review and Errors Of Fact for grants that were scored within the payline?

I mean, if the problem is with bad review it should plague the top scoring applications as much as the rest of the distribution. Right?

Thought of the Day

Once you understand your PI is a data addict and your role as a trainee is a codependent enabler, things go much better.

How do you unpoison a sub-field?

We all know the signs.

A small group of successful, egotistical scientists who view themselves as being in mortal combat with each other.

A few trainees or hangers-on who have signed on under each warring camp.

A scientific topic of mutual interest.

But then there are the good people. The ones who want to advance the topic and care much less about who gets Ultimate Credit. The ones who think the field should, would and could be much farther along if the Big Folks would just stop their petty infighting and paranoid ravings.

We need the Big Cheeses…they do decent work and they have the ear of Program. They have the reputational chops to pull off ambitious projects. If only they would do so.

So side stepping them altogether is not an option.

But we cannot continue letting them clog things up with their egos and competitions.

So far, all I have is a vague idea of an alliance of the like minded, lower-down decent people in the subfield. But I don’t know how to make this work yet.

How do you draw the poison?

Who are you, what are you doing here and why do you keep looking at me? VII: "You know nothing Jon Snow"

I have an extra special reason for this annual event, so hook me up, Dear Reader. (I might even explain why in a few weeks.)

This post is a meme for you, the readers of this blog, to take more than the usual spotlight you enjoy here in the comments. This is especially for you lurkers (in case you didn’t notice, the email field can be filled with nonsense like dev@null.com). For the the veterans, yes I know who you are but feel free to update us on any changes in the way you interact with the blog…especially if you’ve lost touch with the content, been dismayed or just decided that I’m not who you thought at first, ideas-wise.

1) Tell me about yourself. Who are you? Do you have a background in science? If so, what draws you here as opposed to meatier, more academic fare? And if not, what brought you here and why have you stayed?

2) Have you told anyone else about this blog? Why? Were they folks who are not a scientist?. Ever sent anything to family members or groups of friends who don’t understand your career?

3) How did you find us and how do you regularly follow us? through Twitter, Facebook and/or other beyond-RSS mechanisms?

If you blog, and I know many of you do, go ahead and post your own version of this. Take the time to get to know your audience and ask the lurkers to come out and play. You’ll be most pleasantly surprised how many take you up on it.

[This is all the fault of Ed Yong. Head over the the last iteration to see all the gory details and links to prior comment threads.]

I’m Your Huckleberry

This is a guest appearance of the bluebird of Twitter happiness known as My T Chondria. I am almost positive the bird does some sort of science at some sort of US institution of scientific research.

---

 

I’m your biased reviewer. I’ve sat on study sections for most of the years I’ve been a faculty member and I’m biased. I’m exactly who Sally Rockey and Richard Nakamura are targeting in their call for proposals to lessen bias and increase impartial reviewing of NIH applications.

Webster’s defines bias as “mental tendency or inclination” listing synonyms including “predisposition, preconception, predilection, partiality, and proclivity”. When I review a grant from an African American applicant, I have a preconception of who they are. I refine that judgment based on their training, publications and productivity.

I should share that I’m also biased in my review of applicants who have health issues, are women, are older than 30 and have children. I’ve had every one of these types of trainees in my lab and my experiences with them lead me to develop partiality and preconceptions that impact my opinions and judgments. Parts of my preconceptions arise from my experiences with these trainees in my as well those I interacted with while serving on my University’s admission committee. I was biased when I performed those duties as well.

Anyone who pretends to be utterly impartial is dangerous and hurtful to those we say we value as a scientific community. I am frankly stunned to see so many tone deaf and thoughtless comments claiming they are deeply offended at the at this ‘mindless drivel’.

Dr Marconi is just one of many scientists who claim, “I’ve never seen this, so it must not be true”. Scientist’s careers are based on things that cannot be seen, but we collect and interpret data and develop an understanding based on that which we cannot see. Data has been collected and the results are alarming and open for active debate.

Bias is far more insidious than racism. Racists reveal themselves and their ignorance and are often dismissed by ‘educated’ society for their extremist views. Bias is far subtler. Even if it results in an imperceptible change in scoring, we are in a climate where these things matter. Where razor fine decisions are being made on funding.

It’s the people who are sure they have no bias that I fear. I know I have bias. We are simply incapable of being utterly impartial and anyone who says they are impartial is dangerously obtuse to these problems at best and a liar at worst.

Impressions of the "no-cost extension" of your NIH grant.

It has recently come to my attention that not everyone views the no-cost extension (NCE) of a NIH grant the same way I do.

When the interval of support is over for many of the NIH grant mechanisms, the PI (actually the University or Institute, of course) can request a NCE. This means that while the NIH is not going to give out any additional money past the original award, the University may continue to spend any un-expended funds. My experience has been that NCE requests, particularly the first year, are approved by default.

I am pretty sure that you are supposed to follow the usual rules for rolling money from one funded interval to the next funded interval, i.e., it is supposed to be only 25% of the prior year or less. Also, if you have a great excuse for why you have slightly more than 25% left over I would think this would not be a huge problem.

Personally, I have requested a NCE essentially by default for every grant award that permits it and assuming that the competing renewal has not been approved in time to keep the funded intervals rolling.

There are my own local institutional reasons for doing so, mostly having to do with moderate red tape factors.

I thought that it was sort of required in order to submit a competing continuation (now called “renewal”) application. I have one grants management assurance that this is not the case but I would still want to check up on how that works. After all, with the new A2 as A0 rules, can’t we just submit a competing continuation application for a grant which has been unfunded for 5 years? 10 years? Wait….google…google….NIAID says:

Is there a window of time that a PI can submit an application as a renewal? Must the original grant still be active?

No. The grant need not be active and there is no time limit for a renewal application. However, reviewers will probably be concerned by major gaps.

If a significant amount of time has elapsed, indicate what you have done in the interim. Highlight any preliminary data you may have obtained, and show that your planned research is current with the latest science.

OK, maybe I learned something this year. I mean, I’m sure I have read that before about renewals but somehow it never really connected up.

Also, for some reason maybe I thought that reviewers would be more confident that you were actively working on the project past the end date if you could say it was in NCE.

My question for the peanut gallery today is, how seriously do you take the NCE when you see it mentioned in a Biosketch or elsewhere in the grant proposal? Is it just meaningless…as in “of course they applied for a NCE, duh” or below notice altogether? Does apply only when it is a competing continuation / renewal of the grant which is in NCE?

In a related vein, does it “count” as current research funding? Do you see a grant in NCE and mentally chalk it up under the PI or other Key Personnel’s “funded grants”? In the Biosketch does it go under “completed” or “ongoing” Research Support?

Do you assume it might be pending renewal if it is not the prior interval of the grant you are reviewing now?