Interpreting Pink Sheets part 2

Nov 14 2017 Published by under Uncategorized

Category: Critiques of Premise. Premise can be hard to interpret what is wanted and what is meant. But basically, you answering the question of "what has been done to suggest that this project is interesting/going to change things?".

This is from Rev 1:

  • While the proposed studies are potentially significant as they may have great translational implication, the proposal suffers primarily
    from the lack of strong scientific premise. 

Here is an example of premise critique (from these reviews, but with subject matter obscured) that is hard to understand. Background: there exists a human pathophysiology (say ConditionA). There is an intervention (InterventionB)that causes some problems (ProbC) . The proposal is to use an animal that mimics CondA, determine the mechanism that makes for the problems associated with IntervB, and proposes a potential way to address those.

It is questionable that the proposed animal model mimics the physiologic problem in [the group of patients proposed here] who have had the standard clinical intervention. The applicant did not make it clear that if the pathophysiology observed in this model [to mimic  the human initial problem, not the intervention] is attributable to the problem human patients, or a simple consequence of making the model. This model was initially developed to test [something else from the PI]. Thus, the previous publications and preliminary results do not support the scientific premise.

How to parse this? My reading: the PI had an model that was good for looking at some other aspect of physiology, but decided that it actually mimics CondA, the human problem. The reviewer points out that the model proposed for CondA has not been validated for CondA. And therefore because the project involved creating CondA and then applying IntervB, the project couldn't tell if the result, ProbC stemmed from CondA or IntervB.

The PI and team could show that their model of generating CondA followed by IntervB duplicates ProbC. The trouble is, are they really testing IntervB?

Rev 2 echoes these concerns:

Scientific Premise: The investigators provide no background or supporting preliminary data in the Significance section. The background provided in subsequent sections is very superficial and does not adequately support their proposed project.

Remember, this proposal did not get discussed. Therefore, Rev 1 & Rev 2 had the same thoughts independently. When our proposals get triaged & not discussed (yes, our, I've been triaged many times) it hurts. Yet, when the reviewers have the same concerns, this is a big red flag being waved.

Especially because here is Rev 3 on premise:

There is no specific statement of scientific premise. The central hypothesis is that [IntervB] causes [ResultC] through three nonexclusive mechanisms... Each of these could contribute to [CondA].

This is exactly the same problem as Rev 1 & Rev2. However, this isn't obvious immediately if you just read through the reviews. The strategy I find useful is to go through a collate the problems across reviewers. Find what each reviewer says about premise, about significance, about innovation. Line up the comments by topic. Then things like this jump out at you.

Writing this and the previous post took some effort on my part. The reason for pointing this out is to say that reading and understanding reviews takes some effort, even when its your proposal, your own best beloved baby. And one must be prepared to perform radical surgery on that best beloved. Here, rewriting to address this problem is not going to be easy. The group needs to consider the model they are proposing and why it works the way it does. But if they just brush off this criticism with a one sentence reply, or include a statement in the significance that says "The premise of this work is.." and re-iterate what they have said before, they will not get funded. Even if they had entirely different reviewers. These reviewers are all saying the same thing and all seeing the same problem. Take this as the gift it is, address the problem, and work towards funding.

4 responses so far

  • JL says:

    Thank you again for writing your blog. I come regularly. Today, I came here directly as soon as I got home from the lab hoping for Part 2. Yea! These are so helpful.

  • potnia theron says:

    Aww.. thanks.

  • ND ESI says:

    I want to echo the same sentiment as JL. Despite the lack of active discussions, reading your blog posts (both current and past) have been very helpful. Thank you for taking the time to write this up!

    • potnia theron says:

      I am happy to have discussions, and try to answer most of the posts. Right now, I'm in the middle of my worst/busiest teaching, so I don't always get back. BUT! if you have questions, etc, feel free to post 'em here, or send me an email.

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