A veteran reviewer points out the most common miscues he’s seen applicants make on the Significance, Innovation and Approach sections — the heart of the NIH application — and suggests ways to avoid them. Among the mistakes: Choosing the wrong grant mechanism, making the Specific Aims too dependent on each other, failure to clearly state what’s “significant” about your proposal, and providing too much or too little detail about your approach.
You probably know that the Significance, Innovation, and Approach sections are at the heart of the NIH grant application. They make up a six- to 12-page narrative in which you explain the expected benefits of your research, demonstrate what you plan to do differently, and show your experimental approach to discovering new science.
Where do PIs most often go wrong in this critical portion of the application?
Dr. Paul Spearman, Division Chief of Pediatric Infectious Diseases at Emory University, who has served on NIH grant-award committees and reviewed hundreds of applications, offered some suggestions in a webinar, “Making the Pieces Work Together: NIH Grant Sections Significance, Innovation, and Approach,” hosted by PI Leader.
Here are the five mistakes he says he’s seen most often:
1. The PI has chosen the wrong application. “In a five-year R01, there should be some comprehensive approaches and multiple experiments that tie into a common theme and achieve your overall aim,” says Spearman.
He’s seen applications for R21 grants (which are usually for simpler approaches and shorter periods of time) that read like something “that’s been squashed down from an R01.” And he’s seen the opposite — R21 grant applications involving one experiment done three times stretched into an R01 application.
Suggestion: Get advice from an NIH program officer (PO) when in doubt whether your approach is comprehensive enough to qualify for R01 grants or focused enough to qualify for an R21.
2. In the Approach section, the Specific Aims are too dependent on each other. The “aims” are the research goals you will attempt to accomplish when you conduct the experiments you describe. Rule of thumb: Keep them as independent as possible.
“If the reviewer decides, ‘I’m not confident Aim 1 will work, so Aim 2 and Aim 3 are dead,’ you have a tough criticism to overcome,” says Spearman.
If you have aims that depend on each other, you are better off placing them all under a single subheading. Spearman cites the following as a good example from a successful grant application: “We realize that Aim 2 is an ambitious aim with multiple components. We have elected to present these experiments within a single overarching aim, rather than create two separate aims, because the biochemical and microscopic techniques are designed to be complementary in reaching the same goal.”
Result: If the reviewer doesn’t think this aim will work, you still have other bites at the apple in other aims. Each aim stands alone, even if they have multiple parts.
3. The PI fails to clearly state what’s significant. “You want to go directly to what you are going to achieve that’s different,” says Spearman.
Cautionary example: “HIV is a retrovirus that has caused a worldwide epidemic of AIDS. More than 33 million people are affected with HIV globally. As a retrovirus, HIV integrates into the host chromosome. Anti-virals are not without complications; resistance to current drugs occurs frequently.”
As Spearman says, “That’s not good enough. This is basic and correct information, but it doesn’t say what you plan to do or what’s significant about your proposal.”
Better: Include a clear statement that follows the above, such as,“This proposal is designed to discover more about anti-viral drugs and see what can be done to reduce resistance.”
4. The PI assumes the innovation is understood through his description of the experiments. “Don’t make the reviewer guess what the innovation is,” says Spearman. Keep in mind that the NIH reviewer may not be an expert in your discipline.
Suggestion: Mark the Innovation section clearly, and keep it short — one or two paragraphs should be enough. Some ideas that might be innovative: Novel equipment, novel uses for the equipment, and new ways to collect or analyze data. Focus on why this approach is better than past approaches. And don’t be afraid to use words like “novel” and “innovative,” Spearman says.
For example, Spearman says you can start your section: “Experiments outlined in this application will employ a novel approach to generate broad-based immune responses to HIV. In this study, we’ll employ innovative B-Cell stimulation methods …”
5. The Approach section’s level of detail is either too general or too specific. Spearman admits getting the right level of detail is difficult, and lays out an example of each:
Too general: “Macaques will be immunized with a cocktail of VLPs together with synthetic GM-CSF. At appropriate time points, assays of immune function will be performed to assess the resulting immune response. We will perform both B and T cell assays. Macaques will be challenged after SIV with three doses of immunogen, and the inhibition of viral replication resulting from vaccination analyzed.”
What’s wrong with it: “You need to lay out exactly what assays you’re doing and what you’re really looking for in terms of immune-response and the exact time points,” says Spearman.
Too specific: “Vaccine will be prepared by mixing a 0.5 ml aliquot of VLP from each of the clade B isolates in Tris-buffered saline (TBS, 01M NaCl, 10 mM Tris-Cl) and sterile filter-ing the end product. Vaccine will be stored at -80 degrees in the veterinary pharmacy, with bar coding to link to the pharmacy system.”
What’s wrong with it: Reviewers don’t need to know about your storage plans and the bar-coding link.
Better: Explain the experiments briefly and what you hope to achieve, but don’t give a step-by-step explanation of all the specifications.