Transcript GOOD APPLICATION

Grant Weaknesses

Research Problem: Hypothesis -ill-defined, lacking,
faulty, diffuse, unwarrented.

Research Problem: Significance - unimportant,
unimaginative, unlikely to provide new information.

Experimental Design: Study group or Controls inappropriate composition, number, or
characteristics.

Experimental Design: Technical Methodology questionable, unsuited, defective.
Grant Weaknesses (cont’d)

Experimental Design: Data Collection Procedures - confused
design, inappropriate instrumentation, timing or conditions.

Experimental Design: Data Management and Analysis vague, unsophisticated, not likely to provide accurate and
clearcut results.

Investigator - Inadequate expertise or familiarity with literature
in the research area, poor past performance or productivity on
an NIH grant, insufficient time to be devoted to project.

Resources - inadequate institutional setting, support staff,
laboratory facilities, equipment or personnel, restricted access
to appropriate patient population, insufficient.
GOOD IDEA

Hypotheses
Significant; testable; supporting rationale

Aims
Focused, test hypotheses, not overly ambitious; not
superficial

Preliminary Data
Rationale for hypotheses; demonstrate capability;
correct interpretation

General Considerations
not merely data gathering; describe next logical steps
GOOD SCIENCE

Planning
logical organization, rationale for methods selected;
alternatives; controls

Details
brief when P.I.s methods; extensive when methods of
others

Critical assessment
Problems and pitfalls; assumptions and limitations;
justify level of sophistication

Statistical Aspects
Statistical design/power; supportive consultant
GOOD APPLICATION

Basic Considerations
read and follow all instructions; clear and lucid style;
never assume reviewers “will know what you mean”;
seek presubmission review by colleagues.

Administrative
obtain appropriate signatures

Duration and Budget
moderate and realistic period; only appropriate funds
to accomplish research

Justification
personnel: the role and percent effort; equipment:
necessity and availability.
GOOD APPLICATION (cont’d)

Consultants
technical advise in preparing application; supportive
letter

Research Plan
follow page limits and suggestions above; proper care
and approvals for human subjects and vertebrate
animals.

Appendix
include appropriate supplementary data; do not
include essential material

Amended Application
assess whether amended proposal is likely to be
successful; be responsive to reviewers critique; be
positive; do not be vindictive and sarcastic
Good Biological and Clinical Science

A significant biological or clinical problem; describe the likelihood of
altering current clinical practice.

Research based on logical, well-defined, and testable hypotheses
and associated specific aims

Demonstrated critical assessment of preliminary data and literature.

Well-defined, justified use of human subjects; compare with the
value of similar studies in animals

Full consideration of human-subject issues in Application Form 398.

Consideration of any potential medical problems or side effects
arising from the new procedures.

Appropriate and accurate methods for clinical and biological patient
assessment; if methods utilized are somewhat simplistic and
possibly unsophisticated, explain how the technology to be utilized is
powerful enough to answer the questions posed.
Statistical Design

Statistical methods should be appropriate for data to be collected

If possible and appropriate, consider randomized, double-blind
prospective study designs.

Carefully estimate the incidence of the observed effect in normal or
control populations

Show proper selection of control populations including matching for
age, sex, race, color, clinical conditions, etc.

Provide the statistical rationale and methodology to determine the
number of subjects required for each subject cohort; dropout and
withdrawal must be considered; statistical power assumptions
should be well defined

Typically, statistical consultants are required in the preparation of
applications and the performance of studies; often, independent data
units or centers are established to implement the study and allow the
P.I. to remain unaware of patient assignment to treatment or control
groups.
Patient Population
 Well defined, homogeneous subject population and control
 Clearly defined entry criteria
 Clearly defined exclusion criteria based on current or past
diseases, utilization of specific medications, or the results of
laboratory and clinical tests
 Clearly defined recruitment procedures to be followed
 Availability of a suitable patient population as well as any prior
experience with that group of individuals.
 Prior experience in recruiting and entering patients in a clinical
study
Data Quality
 Criteria for collecting, analyzing, and assessing clinical
and laboratory data; define the accuracy of all data
collected, including intra- and interoperator errors
 Compliance monitoring
 Monitoring procedural rigor for issues such as
randomized and dosage modification
 Monitoring by statistical unit (and P.I. where appropriate)
for treatment benefits and side or toxic effects
 Collaborative, multiinstitutional studies require special
organizational structures to assure the uniformity of
testing at each clinical unit
P.I. Qualifications and Experience
 Strong qualifications as a biological and
clinical investigator
 Prior experience in clinical studies
 Basic science skills may not translate to
clinical studies
Common Misconceptions
about the Review Process
 The reviewers share your interest and enthusiasm in
the proposal
 The reviewers have expertise relevant to the subject
of your proposal
 All reviewers either have, or will make, time to read
your proposal in detail
 The reviewers will be fair and impartial in assessing
the merits of your proposal
Specific Aims Section
IMPORTANT FACTS
 One of the most important sections in the grant
application and most difficult to write
 One of the only sections that will be read by all of the
reviewers of your application
 It must quickly engender enthusiasm for your idea
 The flow of logic must be compelling
Minimal Requirements
for an Aims Sections
 Brief introduction; knowns; unknowns; problem and
why it is important to solve
 Long-range goal
 Objective of this application
 Central hypothesis & how formulated
 Rationale
 Why you are best qualified (e.g., preliminary data,
unique reagent, research environment)
 Specific aims
 Innovation, expectations and impact
Specific Aims Section
INTRODUCTORY PARAGRAPH
Begins the flow of logic necessary to convert the
reviewers to an advocate for your grant
 Should open with what’s important to the mission of
the funding agency
 Should summarize the most important knowns that
are related to the problem
 Unknowns highlight gap in knowledge base
 Conclude with why gap is a problem
Specific Aims Section
LONG-RANGE GOAL
 This is not the goal of the current application
 This is the goal of the overall program (of which the
current application is a part)
 Be realistic; do not overstate or overanticipate your
capabilities
Specific Aims Section
OBJECTIVE OF THIS APPLICATION
 Must be a step toward attainment of the long-term
goal
 Defines the purpose of the proposed research
 Must be phrased in such a way that the central
hypothesis clearly grows out of it.
Specific Aims Section
CENTRAL HYPOTHESIS
 Make certain that you write a real hypothesis:
“A tentative assumption made in order to draw out
and test its logical or empirical consequences.”
Webster’s Dictionary
 Most grant applications must be hypothesis-driven
Key Point
Tie the narrative for each of the aims together but avoid
having feasibility of one aim dependent upon a
particular outcome of another aim.
HYPOTHESIS: Components of automobile exhaust
accelerate the degradation of statuary in Washington,
D.C.
AIM 1: To determine the content of sulfur, lead and
copper in statuary as a function of age.
AIM 2: To correlate improved condition of statuary with
introduction of unleaded gasoline in the Washington,
D.C. area.
Scope of Background
 Describe what is known
 Describe what is not known
 Describe what needs to be done
 Emphasize how your results will meet the
stated need, i.e., solve problems that you
have highlighted.
Preliminary Studies
 Inadvisable to submit without some
preliminary studies; the more the better
 You must be able to convince the reviewer
that you are not relying exclusively on the
work of others.
Preliminary Studies
 Published Studies:
 Describe first; include limited technical date
 Include one or two figures/tables for each
 Provide reprints in the appendix
 Unpublished Studies:
 Describe in more complete technical detail
 Acknowledge level of reliability
Approach to Budget for
NIH Modular Applications
 $25,000 direct cost increments up to $250,000
 Provide budget justification for personnel (position,
role, and percentage effort)
 Include total cost estimate, not breakout, for
consortium/contractual arrangements
 Other support section provided “just-in-time”
 Applications over $250,000/year must include
detailed initial and subsequent year budget
Budget: Personnel
 Expect personnel costs to be your highest
 Ensure that you justify each person with respect to
both effort and expertise
 Percentage effort/salary can vary during the budget
period; NSF limited to 2/9ths
 “TBA” positions are the most vulnerable
 Credibility can be lost, either by over-or
underestimating needs (number & effort)
The Summary
 Will be read by all reviewers
 Must convey all of the application’s essential
information
 Must be written in plain English, because it
will be used to summarize the agency’s
investment
 It must convey infectious enthusiasm for the
project
In-House Review of Your Application
This is an absolute necessity!
 Get review from knowledgeable colleagues
 Give your colleagues time enough to help
 Don’t ask for help while you are still making
changes
Supplemental Material
Submitted After the Deadline
 Correct an important error
 Provide an important piece of missing information
 Embellish your qualifications/publications
BUT REMEMBER
 Supplementals are a hassle to the organizer of the review
 Supplementals can irritate reviewers
 Supplementals mailed close to the time of review may not
be read
Grantsmanship Terminology
 GRANT:
A funding award from the sponsor to an investigator, through
his institution, to support designated work described in a
written proposal. The sponsor generally has relatively little
or no involvement in the work of the grant but does monitor
performance. A grant is usually for a stipulated period of
time or level of support. RFAs and R01s culminate in
grants.
 RFA
“Request for application” Based on congressional mandates,
NIH sets aside funds for particular public health topics and
solicits grant proposals from the scientific community. The
specific research question and methods are proposed by the
investigator. NIH uses the RFA mechanism (over the RFP) if
they feel more developmental work is needed, especially
with respect to cost estimates.
Grantsmanship Terminology (cont’d)
 RFP:
“Request for proposal” NIH solicits proposals from the
scientific community to accomplish a specific scope of
work that is outlined in the RFP. Requirements are very
specific and must be covered precisely by the applicant
in his proposal. Both RFAs and RFPs are instituteinitiated requests designed to stimulate research in areas
designated by NIH advisory committees.
 Study Section:
A committee of external advisors to the NIH which carries
out reviews of research applications in a general area of
research, usually meeting regularly three times a
calendar year for 2-3 days to perform these reviews.
Study sections usually contain 12-25 regular members
with ad hoc reviewers called when special expertise is
needed.
Grantsmanship Terminology (cont’d)
 Priority Score:
The score assigned to a research application
by a member of a study section that reflects
that individual’s judgment regarding the
scientific merit of the proposal. Also, the
score assigned to the grant application as
computed from the scores of individual
reviewers.
Scoring
1.0-1.5
Outstanding
1.5-2.0
Excellent
2.0-2.5
Good
2.5-3.0
Fair