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It& #39;s difficult to get NIH grant applicants to believe that weaknesses like "interdependent aims" or "relevance to mammals/humans/in vivo unclear" or "scope too broad" or "insufficient experimental detail/discussion of alternatives" almost never mean what they say.
Almost always they mean one of two things.
Either your grant is not written w a clear compelling narrative using language understandable by a senior biology undergrad.
And/or the proposed science isn& #39;t perceived as super exciting.
Fixing "interdependence" "in vivo" "scope" etc w/o fixing underlying issue of clear compelling narrative making convincing case for excitement won& #39;t help.
BTW, "scope" can matter a lot, but only bcs too broad scope makes it impossible w space constraints to present a clear compelling narrative.
NIH reviewers are very loath to tell the truth & say "the writing is incomprehensible & the science is boring"...
No grant exists that doesn& #39;t have multiple of these kind of "weaknesses". They just don& #39;t get levied when the reviewer is stoked.
This is definitely w "lacking mechanistic insight" (i.e. "booooooring") & frequently w "fishing expedition" (if exciting, then it& #39;s "high impact screen").
Fixing weaknesses one-by-one w/o assessing what& #39;s the likely real underlying issue & dealing w it is a fool& #39;s errand
I mean the grant aims I posted on here last year that got low single-digit percentile, that grant could EASILY have been Not Discussed.
If I was reviewing that grant & found it boring or difficult to follow, I could find NUMEROUS weaknesses to justify quite weak score.
It wasn& #39;t bcs of a combination of (1) I am really good at putting myself in the shoes of an undergrad senior bio major reader 
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(2) I was lucky enough to get reviewers that, on the whole, were stoked by what they were reading.
