Transcript Clinical Grant Writing: Pearls and Pitfalls

Clinical Grant Writing:
Pearls and Pitfalls
James D. Lewis, MD, MSCE
University of Pennsylvania
Is the Clinician Researcher a
Dying Breed?
35000
30000
25000
MD or MD/PhD
Applications
Funded grants
20000
15000
10000
5000
0
1997
1998
1999
2000
2001
2002
Approx 25% of all grants to MD or MD/PhD
Kotchen et al. JAMA 2004;291:836-43
Human Studies Received
Lower Priority Scores
Percentage of Clinical and Nonclinical R01 Applications, by Priority Score
Kotchen, T. A. et al. JAMA 2004;291:836-843.
Review Panel Experience –
Little Evidence of Bias
290
Median Score
280
270
260
Clinical applications
250
Nonclinical
applications
240
230
220
1-25% 26-50% 51-75% >75%
% Grants Reviewed That Are Clinical
Kotchen, T. A. et al. JAMA 2004;291:836-843.
Where Do Clinical
Applications Go Wrong?
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Aims
Background
Preliminary studies
Methods
Limitations section
Abstract & Specific Aims
• Only sections that most panel
members will read (if they even
read these)
• Sell the whole story in a few
paragraphs
• State your hypothesis, aims, and
design
Specific Aims Need To Be
Specific
• Identify risk factors for exacerbation of
Crohn’s disease
– Vague
• To determine whether consumption of
non-aspirin NSAIDs is associated with
exacerbation of Crohn’s disease
– Specific
What Does This Have To Do
With Grant Writing?
A Hypothesis Is Essential
• P01, R01, K08, K23, K01
– Hypothesis testing is essential
• R03
– Hypothesis testing preferred
– Also fundable
• Proof of principle
• Feasibility
• Hypothesis generation?
Aims Must Be Achievable
Background Section
Background Section
• Tell a story - Not a review article
• Refer to your prior work if appropriate
• Selected references
– Demonstrate your knowledge of the field
– Reviewers’ articles?
• Conclusion of background section –
Need for your proposed study is
obvious!!!
Preliminary Studies
• Support for your hypothesis
– Present your background research that led
to current hypothesis
• Feasibility
– Required data available
– Study population available
– Measurement tools accurate / responsive
– You and your team’s qualifications
Sell Yourself
• Dr. Smith is an Assistant Professor of
Medicine at XYZ University. She has a
master’s degree in Clinical Epidemiology from
ABC Univ. She has more than X years
experience in caring for patients with IBD and
conducting research in the field. Her previous
research experience includes … (refs). Of
particular relevance to this application, she …
Methods Section
Form = Function
Methods Section
• Details essential
• Address each aim
– Inclusion / Exclusion criteria
– Data collection
– Analyses
– Potential limitations
Inclusion / Exclusion Criteria
• Appropriate to achieve aim
– Will answer question
– Obtainable
• “Reagent grade patients”
– Stephen Targan circa 2000
• Internal validity usually more
important than generalizability
Data Collection
• How will every item be measured?
• Primary data collection
– Instruments
– Assays (biochemical, endoscopy, etc)
• Secondary data analysis
– Limited by quality of existing data
– Must justify accuracy of data
Statistical Issues
• Every aim needs a separate analysis
plan
• Define outcome and exposure variables
– How will the variable be categorized?
(continuous, dichotomous, quintiles, etc.)
• Rationale for statistical plan
– Get biostatistical help!!!!
Sample Size – Don’t Make a
Rookie Mistake
Sample Size
• Easy target for the reviewer
• Always based on assumptions
• Provide data or references to
justify your assumptions
Logistics: Who, When, & How
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Sample/CRF transportation
Data entry
Monitoring
Data cleaning and analysis
Timeline
Human Subjects Concerns
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Is your study ethical?
Appropriate safety measures?
Women, children and minorities?
Funding R01 human subject proposals
– No human subject concerns – 24.9%
– Human subject concerns – 12.5%
Kotchen, T. A. et al. JAMA 2004;291:836-843.
No Clinical Study Is Perfect
Limitations
• Identify your limitations
– The reviewers will see them anyway
• Explain why they will not
compromise your results and
interpretation
– Not a real problem
– Your design will prevent the problem
• If you don’t explain it, the reviewer
won’t see why it is not a problem
Example
• The CDAI is an imperfect measure of disease
activity, albeit with sensitivity and specificity for
active CD both greater than 90%. Any
misclassification resulting from use of the CDAI
should be nondifferential. As such, any bias should
be toward the null hypothesis. Because of the
small degree of misclassification with the CDAI,
the small amount of bias resulting from use of the
CDAI would not be expected to obscure a clinically
important affect of NSAIDs on disease activity. In
addition, we have increased our sample size by
15% to account for the possibility of nondifferential misclassificaiton bias resulting from use
of the CDAI.
Details
• Every sentence counts
• Defend every statement
–Empiric data - best
–References – good alternative
–Rationale – better than nothing
Non-Science Mistakes
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Formatting rules
Budget rules
Time frame
Spelling and grammar mistakes
Table and figure numbers
Missing expertise - biostatistician
Letters of support
Non-Science Mistakes
• Run out of energy for final aim
Cohort
C-C
RCT
ITT
SS
Plan Ahead
• 6 to 12 months to prepare a submission
• Get feedback from investigators at your
institution
– Minimum of 2 weeks before deadline
• Assume the deadline is 48 hours early
• Last day for final proof reading and
collating
If At First You Don’t
Succeed…
• Find out why
• Reviewers critiques are the roadmap to
revising your proposal
• Need to address every critique in a
resubmission
• Make it easy for the reviewers to see
how you responded
If At First You Don’t
Succeed…
• Try, try again
• Anticipate at least one resubmission to
achieve a fundable score
• 1998 – 1999 Only 37% of those eligible
to submit revised applications did so
• While historically 30% of grants are
funded in a given cycle, more than 40 to
45% of grants are ultimately funded
Kotchen, T. A. et al. JAMA 2004;291:836-843.
Good Grants Produce
Good Science
Resources on the Web
• http://grants1.nih.gov/grants/new_invest
igators/index.htm
• http://grants1.nih.gov/training/careerdev
elopmentawards.htm
• http://grants1.nih.gov/grants/forms.htm