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7/27/2019 How Not to Write an Unsuccessful Grant
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How Not to Write an
Unsuccessful Grant Proposal
Daniel Clauw, M.D.
Assistant Dean of Clinical and Translational Research
Director, Center for the Advancement of Clinical Research
The University of Michigan
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What is the end result you are aiming for?
Good science by a good investigator.
10% of applications:
Bad idea, but capableInvestigator.
15% of applications:
Great idea, proposedby the perfect person
to test it.
25% of applications:
Good idea, but
Investigator is unpreparedto do the work.
Table developed by James Ferrara, M.D.
50% of applications:
Bad idea, and poorlyprepared investigator.
- Science +
-
Investigato
r
+
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How to Get a Grant
Design a sound study
Write a good grant
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Early Steps in Clinical
Research
The idea
The hypothesisThe design
The study subjects Can I do it?
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The idea
Most clinicians can come up with
good ideas about clinical research
based on gaps in existingknowledge
Has question been asked before?
If not, why?
If so, how does my question or design
add to the existing literature?
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At the Beginning . . .
Think of the End
At the inception of a clinical researchproject, ask a series of questions aboutthe end product:
Who is the audience?
Where would the article be published if itis successful?
Is a negative study interesting orpublishable?
Howwould the results impact clinicalcare
i.e. Who would care?
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The First in a Series of
Compromises
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Potential audience
Academics
Peer review processPracticing clinicians
Regulatory agencies (e.g. FDA)
Industry (marketing bias)
Public
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Early Steps in Clinical
Research
The idea
The hypothesis
The design
The study subjectsCan I do it?
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Developing the Study
Hypothesis / Goal(s)
A surprising number of even establishedclinical researchers begin designing the
study before they define the hypothesisKeep It Simple (KISS)
Unless you are in the position to do a
hypothesis-generating study, have asingle primary hypothesis and no morethan 2 3 secondary objectives
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Early Steps in Clinical
Research
The idea
The hypothesis
The design
The study subjectsCan I do it?
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Compromises in
Study Design
Efficacy Effectiveness
Long trial Short trial
Single site MulticenterRandomized, Blinded Not
Active comparator Placebo Open
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Early Steps in Clinical
Research
The idea
The hypothesis
The design
The study subjectsCan I do it?
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Inclusion and Exclusion
Criteria
Might be most important aspect of studydesign with respect to:
Ability to recruit subjectsFor clinical trials, this will largely
determine:
Efficacy of treatment
Placebo response rate
For mechanistic studies, this needs tobe considered for both patient (clearly
define) and control groups
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Selecting Participants
Heterogeneous Homogeneous
Extrapolatabi l i ty o f results Smal ler n, more respon sive
Tertiary Care Population
Easy to f ind / un responsive High placebo response
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Selecting Controls
Should ideally have all of thecharacteristics of the patient, except thecondition being studied
Not always possibleControlling for confounds
Sampling
StatisticsWhat is a healthy normal control?
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Recruitment
Exist ing pat ients
Easy to find
Pre-screened
Stay in study longer
Advert is ing
Apples vs. oranges
> Screen failures
Higher placebo and
drop-out rates
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Early Steps in Clinical
Research
The idea
The hypothesis
The design
The study subjectsCan I do it?
R
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Resources
Do I have enough? Mentorship
Individual
Institutional (K-30, K-12)
Patients / subjects Do I have enough?
Do I have the right ones?
Staff
Money Federal grants
Institutional resources (e.g. GCRC)
Foundations
Industry
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How to Get a Grant
Design a sound study
Write a good grant
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OK, so maybe you dont need this guys
book. But you need some of his skills . . . .
.
Get FREE
Money from
the Government!!!
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Besides good research, you need
Communication Skills
Marketing Skills
Management Skills
Flexibility and ingenuity (who can you sell
your research to?)
Ability to follow directions, even the
apparently meaningless onesAbility to plan ahead and commit significant
time
Adapted from Christine Black, UM DRDA
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When? Earlier than you think
Internal vs. external deadlines
Should get science of grant done in plenty oftime to have others read final grant, and thebest people to read grant have the least timeto do so
Administrative shell of grant typically needs tobe turned in 10 days before grant is due
Study design issues, and especially samplesize calculations, are necessary foradministrative shell
Need for preliminary data
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Do your homework:
What has the agency funded recently?(CRISP, Community of Science,www.guidestar.org for foundations).
Read recentsuccessful applications bycolleagues.
The program officers are your resource,contact them early and often.
Colleagues are essential for collaboration andconsultation; senior colleagues may knowwho will likely review your grant.
Consult a biostatistician early in the process.
http://www.guidestar.org/http://www.guidestar.org/7/27/2019 How Not to Write an Unsuccessful Grant
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Do your homework, part 2:
Check study section rosters!
Search the literature to determine roster
members expertise.
If there are content area experts on the
study section, does your literaturereview cite their (appropriate)publications?
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Do your homework, part 3:
Are their aspects of your project or methodology
that may need extra justification because they
will be unfamiliar to this roster of people?
For foundation grants, trustees or boards may
make funding decisions, so be sure that key
sections like specific aims are in lay language.
P.S. Do not attempt to contact reviewers!
Inouye, S.K., Fiellin, D.A. An Evidence-Based Guide to Writing Grant Proposals for
Clinical Research,Ann Intern Med. 2005;142:274-282
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Relationships are key:
Step 1: Get the right team together. Find
people with expertise in different, specific
areas: working with this specific patient
population, using this specific methodology ortechnique, statistically analyzing this type of
data, etc.
Step 2: Buy your grants administrator a nice
gift. You will be depending on this person!
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Why you should be nice to your
grants administrator:
This is the easy part.
The challenge will be figuring out the
indirect cost rate.
Chronicle of Higher Education, Carol Cable
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Care and feeding of the reviewer:
They are
Overworked (they will at most spend a few
hours reviewing your grant)
Mindful of the need to further their owncareers
Not interested in doing outside homework in
a new topic area just so they can understand
your proposal Mature
Translation: they dont want to strain their eyes deciphering figures and captions that youve
shrunk down to 8-point font!
Adapted from Christine Black, UM DRDA
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Care and feeding of the reviewer,
part 2:
Assume reviewers are intelligent and savvy
about research
..but perhaps have little in-depth experience
in your area of interest.
Avoid jargon and topic-specific abbreviations.
Many reviewers will read only the abstract
and/or specific aims.
Inouye, S.K., Fiellin, D.A. An Evidence-Based Guide to Writing Grant Proposals for
Clinical Research,Ann Intern Med. 2005;142:274-282
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Care and feeding of the reviewer,
part 3:
Make reviewer like you and your study in firsttwo pages so that you start with a 1.0
Teach them something new
Convince them that you are the best person inthe world to do this terrific study
Science Fiction Novel approach the world willbe a better place after this study is done
Disneyland approach make them smile while
you are sucking money out of their wallets
If you can start with a 1.0 and eliminatetargets youll be fine
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Targets
Controversial aspects of a grant
Its OK to do it, but dont write it
Omissions
Failure to follow rules
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Common Problems in Applications
(from NIH and NIAID)
Lack of knowledge of published relevant work
Lack of experience in the proposed
methodology or techniques
Uncertainty concerning future directions
Unrealistically large amount of work
Failure to discuss potential obstacles or
alternative approaches
Adapted from Christine Black, UM DRDA
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Major issues identified in NIH grant
proposals:
Results from a review of pink sheets from 66
R01 applications; the authors categorized
major problems found in unfunded grants.
Findings presented for each major grant
section.
Inouye, S.K., Fiellin, D.A. An Evidence-Based Guide to WritingGrant Proposals for Clinical Research, Ann Intern Med.
2005;142:274-282
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Abstract
The broad, long-term objective is . . . .
The Hypothesis is . . . .
The Specific Aims are . . . .
The Research Design is . . . . The health-related relevance of this project is
. . . .
Avoid
First person
Excessive summary of past accomplishments
Amounts of money
Going outside the box
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Specific Aims/Hypotheses
This (and abstract) are most important parts of a grant. Write this early in the process, send it around, and keep
re-writing to make it clearer, stronger, and more concise.
This should be a two page executive summary of the
following 23 pages of the grant. Writing tips:
to one page of setting the stage
Extremely clear, (one sentence if possible) hypothesis
Specific aims (between 2 and 4) stated as actionitems
Todetermine, evaluate, confirm, show . . . .
Common critiques:
Poorly Focused
Too Ambitious
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Comments from NIH Reviewer
In addition to proposing a research design that
is a fishing expedition, the applicant also
proposes to use every type of bait and piece
of tackle known to mankind.
Adapted from Christine Black, UM DRDA
S i l d i f T i i
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Special advice for Training
(e.g. K-) awards Safe study is more important than ground-breaking
science.
Should be a study that leads to other studies, no matter
what the results.
Serves as a vehicle for your training. Should ideally encompass all of the elements of a
research project, especially those that you have
inadequate experience with.
Environment Increasing preference for mentoring teams.
Letters are extremely important, and read for any nuances.
If your mentor cannot take the time to write a strong > 2
page letter, they may not have the time or commitment tomentor ou.
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Background and Significance
Begin by describing current state of science.
Identify knowledge gaps.
Justify the need for this specificstudy.
Move science forward, not just laterally.
Writing tips
Dont provide too much extraneousbackground information.
Dont overstate the significance of your study.
For each area covered in this section,explicitly state the relationship to yourproposed project.
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Comments from an NIH Reviewer
This application is characterized by ideas that
are both original and scientifically important.
Adapted from Christine Black, UM DRDA
Unfortunately the ideas that are scientificallyimportant are not original and the ideas that
are original are not scientifically important.
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Preliminary Studies
Should demonstrate:
Feasibility
You can recruit the required study participants.
The team has successfully worked together.
Promising data
Youve partly done what you are asking for
money to do.
If there are novel methodologies that are beingused, that these have been fully developed
Writing tips:
Abstract of each study is good start.
Show how each study links to the proposed work.
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Methods
At least 50% of the page allowance should go
to methods.
Underdeveloped or vague methods are the
most common reviewer complaint. Describe the study design in detailhowwill
you randomize, blind, select controls, etc.
Inclusion/exclusion criteria justify your
criteria and address any biases they may
cause.
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Methods, part 2
Availability of participants
esp. with regards to women, minorities, and children.
Data collection and procedures:
Discuss each instrument you propose to use Describe quality assurance or staff training
Consider a table of variables:
Variable Instrument Characteristics
(when available)
Reference
Level of Function SF-36 Functional
Sub-score
Sensitivity:
Specificity:
Reliability:
Ref.
Auto-antibody
level
SuchandSuch Assay Sensitivity:
Specificity:
Ref.
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Interventions and Outcomes
Ensure adequate randomization and
blinding. What will happen if the blind is
broken?
Ensure standardization of your
intervention. Will you provide training?
Ensure your intervention is meaningful.
Ensure that adherence is monitored.
Clearly define all outcome measures.
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Statistical Analysis
Work with your biostatistician often and early.
Address what you will do about missing data.
Include realistic attrition rates in your powercalculations. Address what you will do with
data from subjects who drop out.
Present the plan clearly, referencing each
specific aim when appropriate.
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Writing style
Business not creative
Active voice
will or expect to not would like toor may
Anticipate questions
Target analogy
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Final Touches
Realistically assess weaknesses or potentialroadblocks and explain how you would overcomethem. Dont blow off this section its youropportunity to think strategically.
Provide a timetable or chart summarizing studyactivities.
Proofread. A lot. Then give it to others.
Follow all the directions with regards to fonts,margins, page limits, deadlines, etc.
Finish with enough time for administrative approval,signatures, etc. check with your grantsadministrator. This process may take 10 days ormore!
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How to deal with rejection:(Youre playing baseball, not shooting free throws)
1. Write scathing letter of rebuttal.
2. Throw it away.
3. Start with a paragraph of gratitude for
reviewers insight.4. List reviewers criticisms.
5. Do not try to convince reviewers that they
are idiots Address each criticism objectively in the
introduction to your resubmission.