How Not to Write an Unsuccessful Grant

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.


Great idea, proposedby the perfect person

to test it.


Good idea, but

Investigator is unpreparedto do the work.

Table developed by James Ferrara, M.D.


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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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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Research

The idea

The hypothesis

The design



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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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Research

The idea

The hypothesis

The design



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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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Research

The idea

The hypothesis

The design


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/


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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!



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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



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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.


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.


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.

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How Not to Write an Unsuccessful Grant