FUNDAMENTALS OF GLOBAL HEALTH RESEARCH: PLANNING, IMPLEMENTATION, & DISSEMINATION
Significance Section
Lecturer: Dr. Carey Farquhar
All great grant proposals are framed around a series of problems, from big to the more specific,
along with a series of potential solutions, as yet unrealized…until you get the grant money to
make those solutions move forward. We’ve previously discussed the hypotheses and specific
aims of your research plan. In this lecture, we will be focusing on the Significance section and
how it differs from the Approach. In the next lecture we’ll talk about Innovation.
Your research proposal has several key components starting with your title and your summary
or abstract. A large portion of this course will be spent discussing your research plan. Your
research strategy is the bigger part of your application’s research plan and is the ‘nuts and
bolts’ of your application, where you will describe the rationale for your research and the
experiments you will do to accomplish each Aim.
Significance Section
The significance section is about the problem or problems. It is what anyone might think about
as the background for the work that you're doing. Does the project address an important
problem or a critical barrier to the progress in the field? Is there a strong scientific premise for
the project? If the aims of the project are achieved, how will scientific knowledge, technical
capability, and/or clinical practice be improved? How will successful completion of the aims
change the concepts, methods, technologies, treatments, services, or preventive interventions
that drive this field?
As you're thinking about your aims, you have to think about the methods and about the
significance. To write that first paragraph of the specific aims you don't have to have written
your significance, but you have to at least have an idea of what's important and be able to
include it.
Essentially, the Significance section is about the problem or problems:
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Why are they important?
Whom do they impact?
Why is a solution currently missing?
What have people tried?
Why is a solution needed now?
What has happened that makes you think you and your team have a solution?
In which aim will you solve which problem?
Why is your team qualified to solve the problem?
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Goal of the Significance Section
Your number one goal of the Significance section is to engage your reader. Think about what
the main message is that you want to get across. You need to give the reviewers a compelling
reason for paying attention. You need to give compelling reasons for taking interest in your
project and for desiring its success. Use your Significance section to tell a compelling, yet
condensed, story of your project. Have you ever marveled at how great a film director can
condense a book into a few hours on film? Your goal is the same.
You don't want to provide a laundry list of papers and studies and give the general context for
what you're doing. What reviewers want is for you to specifically focus on the rationale for your
study and emphasize the knowledge that's out there. You should demonstrate that you
understand and have a good grasp of that literature but highlight the gaps that the proposed
project will fill. You want to convince the reviewers in a short amount of space that what you’re
doing is important and that you should be doing it.
Well-written grant proposals are always based on solving a problem that peers in your field
care about. Therefore, your Significance section needs to clearly delineate that problem, yet do
so without writing pages and pages of information. For specialist audience, it might be 1 ½ to 2
pages. For an audience that includes non-specialists in your field, it could be longer – about 2 to
4 pages. So, you will need to really condense it down to what's most important.
Comprehensive Familiarity with Literature
Familiarize yourself with the literature. As a junior investigator, it is critical that you
demonstrate your understanding of what’s out there. To establish your familiarity with the
relevant literature and points of view, you have to do a lot of reading. By now you should be
experienced at doing literature reviews and you need to read broadly about the topic, the
population, and the region. Find ways to pursue that reading by looking at key words, authors,
and study design.
While you're at it, you might as well write a review. That is a very common activity. Once you
get started in writing your first big grant, especially if it's in an area where others have not
consolidated the literature the way you are doing, it is very worthwhile to put it out there in a
reviewed format.
Keep notes on each article. Keep a table to list your articles, the key points for each one, and
what kind of study it is – is it an epidemiologic study, is it a cohort study, or a clinical trial – and
what are the key results and how do they tie back to your work.
Be critical and assess relevance. You should be able to look at a study and provide data that are
more valid than other types of studies. Therefore, it will be key to be critical and assess the
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relevance of your studies. This will also help you, so you can provide the evidence to your
mentor, who may not be familiar with your area of study.
Choosing Literature to Cite
Another critical aspect of the Significance section is being sure to show both sides of the story.
As with your entire proposal being very precise and thoughtful is going to be critical to being
successful. Take the time to edit and pay attention to the details, especially spelling and
formatting. And this holds true not just for the text but also for the citations and the reference
section. Read through your references, especially if you're using a program. Either correct it in
your EndNote file or manually correct it in your final product that you're going to be submitting.
Expect to cite dozens of references for even a small proposal. For a really small one, that may
be just two, three, or four pages, you might have half a dozen or a dozen references. For an
RO1, it could be 80 or more references. It’s also important to make sure that your citations
match up with each reference correctly.
Scientific Background – Think Before You Write
Read and carefully evaluate the scientific literature. You need to be clear and really
understand what you've been reading and summarize it in your head before you start to write.
Place your work that motivates the proposal in the context of the broader literature and decide
what is absolutely necessary to motivate a clear statement of the problem that needs to be
solved.
It will be important to make outlines and create headers to address the main points you want
to get across to really convince the reviewers that you know what you’re talking about and why
this is an important topic. Then, highlight each of the gaps and at the end of each paragraph
explain how your project is going to do X, Y, or Z.
Create Tables or Figures to Summarize Large Bodies of Literature
Example Table 1
Let’s look at an example. Here they have compiled all the studies that looked at incident HSV-2
among African women, which demonstrates that commercial sex workers, while they're highrisk, were at a similar risk to HSV-2 discordant couples. So, just one table has demonstrated
how comprehensive a review the person has done and then also made some really salient
points.
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Example Table 2
Here’s another example.
Here they have compiled all the papers that have talked about vegetables and prostate cancer
risk and put them into a table. You can see that there a few that may end up having a significant
association with wide confidence intervals, but a majority don’t show any association.
They could have easily written a paragraph stating there's no significance and then have all
eight or ten of these references afterwards, but this type of a figure really captures the
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message in a much better way. A table like this is useful because you can show that you're
including reputable studies and it’s very clear who the authors are.
Most of this is not so much about the topic or the details of the tables. It's more to emphasize
that a lot of work goes into this and you need to have the time to be able to do this work. Once
you have done all this work, think about writing a review paper. After you submit your grant,
write your review paper while you’re waiting for reviewers to get back to you.
Persuasive Writing
In the Significance section, you are trying to persuade and convince the reviewer. You need to
spend the time and space to explain fully why this is an important topic and a compelling
problem. If you don’t build up the challenge and the problem for the reviewer so that they have
a really strong desire to see it solved right now, then how likely is your grant going to get that
funding?
Building desire for your project requires persuasive writing, which includes the following
characteristics. Ethos: you are very clear with no contradictions and you're using correct syntax.
Logos: where you lead the reader on by explaining logically and rationally why we want to find
a solution to your problem. Pathos: you might not really think about this with scientific writing
but as you read through grants and examples, you'll see that you are pulling a bit on the
heartstrings sometimes. Here’s an example: “five million children are infected with HIV. These
children will not live past their second year of life if they're not treated with antiretrovirals.”
Pathos can appeal to reviewers’ emotions, which will help to get them on board with you.
Other tips include being really enthusiastic about what you do and convincing the reader that
what you're talking about matters, that you'll be able to make a difference with what you're
doing. Importantly, you need convince them that you're the right person, that you have that
expertise to be able to carry out what you're doing. Some of that will come out in your
biosketch, but even just the way you're writing and what you include in the Significance will
give them confidence that you've done your homework.
You also will want to excite your reviewers and the funding agency. The reviewers give the
initial score but ultimately it goes to a larger body, the council, and they will decide yes or no
based on the scores from the reviewers whether it gets funded.
What Are Gaps in the Literature?
It could be that the gap that you're trying to fill is a major gap—that your topic has actually not
been studied so there's nothing out there in the literature. This happens particularly if you start
thinking about a gap in a specific population or in a region or a subgroup.
It also might be a gap in that people haven't synthesized the literature in such a way and you're
going to be able to do it for them to move the field forward.
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A very common problem is that there are studies out there but they're not robust studies. They
have small sample sizes. Maybe they didn't find a difference, but they weren't powered to find
a difference. Their outcomes or their exposures were not measured well. Maybe the sample is
biased in some way, or the study design is poor. They didn't necessarily conduct the study well.
And you have to be a little careful. You can't say that all these other studies were terrible but
it's good to point out why you're doing this study if other studies exist. You have to bring to
people's attention that there is this gap in a respectful manner.
Significance Example
The example here is one of four paragraphs that would be in your Significance section.
Remember, the sentences in this section should not be the same as your specific aims but they
should sound somewhat similar.
The top line is your header statement, which can be done in different ways. Some people write
an entire sentence, as shown here, others just put a couple words up. Everyone has their own
style that works for them. It's always a good idea to have others review your proposal to make
sure that you're getting your points across.
The use of bold and underlining in the significance section and throughout the grant is also
important because the reviewers will be reading these relatively quickly. You want them to be
able to look at your significance section and clearly understand each of your main points. That's
why it will be important to always use succinct but descriptive sub-headers to break up the text
and compile figures to illustrate your problem or problems.
Let's take a closer look at a paragraph from a proposal that was successful to see how these
elements combine to make a strong case for significance… The paragraph has the header: “HIV
incidence is high among pregnant and postpartum women in stable partnerships…” Please read
the rest of the paragraph on your own and reflect on how it supports this statement about HIV
incidence. Press play to continue.
HIV-1 incidence is high among pregnant and postpartum women in stable partnerships. The
majority of women in sub-Saharan Africa are pregnant during their lifetime and most breastfeed
their infants for two or more years. A number of cohort studies in Africa have reported high risk
of HIV-1 acquisition during pregnancy and the postpartum period1-6. Pregnant women in the
Rakai study had a 2.16-fold increased HIV-1 incidence compared with non-pregnant women1,
and HIV-1 incidence rates during pregnancy and the postpartum period range from 2.3 to 7.6
per 100 person-years in the published literature, as shown in Figure 1 below1-6. This increased
susceptibility is biologically plausible as pregnancy results in major physiologic changes due to
increased hormone levels and an altered immune milieu which may influence HIV-1 acquisition.
Behavioral factors may also contribute to risk during and after pregnancy. In some studies men
have reported more external sexual relationships when their regular partners are pregnant or
immediately postpartum, behavior which could lead to incident HIV-1. With a fertility rate of ~5
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children per woman reported in 2008, women in sub- Saharan Africa may spend 10 or more
vulnerable years either pregnant or breastfeeding7. We conclude that the pregnant/postpartum
population represents a significant risk group, one that has not been the target of interventions
despite major efforts to eliminate infant HIV-infection globally.
Discussion of Example
There are several strong elements in this paragraph, including the fact that many references are
used to support the argument that HIV acquisition is high among pregnant women. In addition,
the use of specific numbers is excellent because it shows the magnitude of the increased risk
and high incidence. The whole paragraph also explains the reason for the high incidence and
then further explains why this is a particular problem in places where fertility rates are high,
and women breastfeed for long periods of time. The final sentence is a strong statement that
brings the reader back to the need for an intervention and ties this section to the main proposal
aims. These elements may not be present in every paragraph, but they need to be present
somewhere in the significance section for it to persuade the reader that your idea is important
and has a strong scientific premise.
Summary
Although you will emphasize your project’s significance throughout the application, the
Significance section should give the most details. Don’t skimp – the farther removed your
reviewers are from your field, the more information you’ll need to provide on basic biology,
importance of the area, research opportunities, and new findings.
Writing a really good Significance section is an art form that requires practice and patience.
Your job is to build desire for your project and to give a compelling reason for the question:
Why does this project deserve funding?
Here is a checklist that will help you do this:
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Describe concisely the scientific background for the study.
Introduce conceptually what's happening but also be specific
State explicitly what's unknown or controversial.
State why we're interested in answering this question.
As you go through your entire significance, emphasize how your study is going to fill that
gap and advance the field.
Explain how your study will positively impact science, public health and make a
difference on that larger societal level.
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