Grant Weaknesses Research Problem Hypothesis illdefined lacking faulty

Grant Weaknesses Ø Research Problem: Hypothesis -ill-defined, lacking, faulty, diffuse, unwarrented. Ø Research Problem: Significance - unimportant, unimaginative, unlikely to provide new information. Ø Experimental Design: Study group or Controls inappropriate composition, number, or characteristics. Ø Experimental Design: Technical Methodology questionable, unsuited, defective.

Grant Weaknesses (cont’d) Ø Experimental Design: Data Collection Procedures - confused design, inappropriate instrumentation, timing or conditions. Ø Experimental Design: Data Management and Analysis vague, unsophisticated, not likely to provide accurate and clearcut results. Ø 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. Ø Resources - inadequate institutional setting, support staff, laboratory facilities, equipment or personnel, restricted access to appropriate patient population, insufficient.

GOOD IDEA Ø Hypotheses Significant; testable; supporting rationale Ø Aims Focused, test hypotheses, not overly ambitious; not superficial Ø Preliminary Data Rationale for hypotheses; demonstrate capability; correct interpretation Ø General Considerations not merely data gathering; describe next logical steps

GOOD SCIENCE Ø Planning logical organization, rationale for methods selected; alternatives; controls Ø Details brief when P. I. s methods; extensive when methods of others Ø Critical assessment Problems and pitfalls; assumptions and limitations; justify level of sophistication Ø Statistical Aspects Statistical design/power; supportive consultant

GOOD APPLICATION Ø Basic Considerations read and follow all instructions; clear and lucid style; never assume reviewers “will know what you mean”; seek presubmission review by colleagues. Ø Administrative obtain appropriate signatures Ø Duration and Budget moderate and realistic period; only appropriate funds to accomplish research Ø Justification personnel: the role and percent effort; equipment: necessity and availability.

GOOD APPLICATION (cont’d) Ø Consultants technical advise in preparing application; supportive letter Ø Research Plan follow page limits and suggestions above; proper care and approvals for human subjects and vertebrate animals. Ø Appendix include appropriate supplementary data; do not include essential material Ø 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 Ø A significant biological or clinical problem; describe the likelihood of altering current clinical practice. Ø Research based on logical, well-defined, and testable hypotheses and associated specific aims Ø Demonstrated critical assessment of preliminary data and literature. Ø Well-defined, justified use of human subjects; compare with the value of similar studies in animals Ø Full consideration of human-subject issues in Application Form 398. Ø Consideration of any potential medical problems or side effects arising from the new procedures. Ø 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 Ø Statistical methods should be appropriate for data to be collected Ø If possible and appropriate, consider randomized, double-blind prospective study designs. Ø Carefully estimate the incidence of the observed effect in normal or control populations Ø Show proper selection of control populations including matching for age, sex, race, color, clinical conditions, etc. Ø 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 Ø 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 Ø Well defined, homogeneous subject population and control Ø Clearly defined entry criteria Ø Clearly defined exclusion criteria based on current or past diseases, utilization of specific medications, or the results of laboratory and clinical tests Ø Clearly defined recruitment procedures to be followed Ø Availability of a suitable patient population as well as any prior experience with that group of individuals. Ø Prior experience in recruiting and entering patients in a clinical study

Data Quality Ø Criteria for collecting, analyzing, and assessing clinical and laboratory data; define the accuracy of all data collected, including intra- and interoperator errors Ø Compliance monitoring Ø Monitoring procedural rigor for issues such as randomized and dosage modification Ø Monitoring by statistical unit (and P. I. where appropriate) for treatment benefits and side or toxic effects Ø Collaborative, multiinstitutional studies require special organizational structures to assure the uniformity of testing at each clinical unit

P. I. Qualifications and Experience Ø Strong qualifications as a biological and clinical investigator Ø Prior experience in clinical studies Ø Basic science skills may not translate to clinical studies

Common Misconceptions about the Review Process Ø The reviewers share your interest and enthusiasm in the proposal Ø The reviewers have expertise relevant to the subject of your proposal Ø All reviewers either have, or will make, time to read your proposal in detail Ø The reviewers will be fair and impartial in assessing the merits of your proposal

Specific Aims Section IMPORTANT FACTS Ø One of the most important sections in the grant application and most difficult to write Ø One of the only sections that will be read by all of the reviewers of your application Ø It must quickly engender enthusiasm for your idea Ø The flow of logic must be compelling

Minimal Requirements for an Aims Sections Ø Brief introduction; knowns; unknowns; problem and why it is important to solve Ø Long-range goal Ø Objective of this application Ø Central hypothesis & how formulated Ø Rationale Ø Why you are best qualified (e. g. , preliminary data, unique reagent, research environment) Ø Specific aims Ø 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 Ø Should open with what’s important to the mission of the funding agency Ø Should summarize the most important knowns that are related to the problem Ø Unknowns highlight gap in knowledge base Ø Conclude with why gap is a problem

Specific Aims Section LONG-RANGE GOAL Ø This is not the goal of the current application Ø This is the goal of the overall program (of which the current application is a part) Ø Be realistic; do not overstate or overanticipate your capabilities

Specific Aims Section OBJECTIVE OF THIS APPLICATION Ø Must be a step toward attainment of the long-term goal Ø Defines the purpose of the proposed research Ø Must be phrased in such a way that the central hypothesis clearly grows out of it.

Specific Aims Section CENTRAL HYPOTHESIS Ø 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 Ø 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 Ø Describe what is known Ø Describe what is not known Ø Describe what needs to be done Ø Emphasize how your results will meet the stated need, i. e. , solve problems that you have highlighted.

Preliminary Studies Ø Inadvisable to submit without some preliminary studies; the more the better Ø You must be able to convince the reviewer that you are not relying exclusively on the work of others.

Preliminary Studies Ø Published Studies: Describe first; include limited technical date Include one or two figures/tables for each Provide reprints in the appendix Ø Unpublished Studies: Describe in more complete technical detail Acknowledge level of reliability

Approach to Budget for NIH Modular Applications Ø $25, 000 direct cost increments up to $250, 000 Ø Provide budget justification for personnel (position, role, and percentage effort) Ø Include total cost estimate, not breakout, for consortium/contractual arrangements Ø Other support section provided “just-in-time” Ø Applications over $250, 000/year must include detailed initial and subsequent year budget

Budget: Personnel Ø Expect personnel costs to be your highest Ø Ensure that you justify each person with respect to both effort and expertise Ø Percentage effort/salary can vary during the budget period; NSF limited to 2/9 ths Ø “TBA” positions are the most vulnerable Ø Credibility can be lost, either by over-or underestimating needs (number & effort)

The Summary Ø Will be read by all reviewers Ø Must convey all of the application’s essential information Ø Must be written in plain English, because it will be used to summarize the agency’s investment Ø It must convey infectious enthusiasm for the project

In-House Review of Your Application This is an absolute necessity! Ø Get review from knowledgeable colleagues Ø Give your colleagues time enough to help Ø Don’t ask for help while you are still making changes

Supplemental Material Submitted After the Deadline Ø Correct an important error Ø Provide an important piece of missing information Ø Embellish your qualifications/publications BUT REMEMBER Ø Supplementals are a hassle to the organizer of the review Ø Supplementals can irritate reviewers Ø Supplementals mailed close to the time of review may not be read

Grantsmanship Terminology Ø 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 R 01 s culminate in grants. Ø 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) Ø 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. Ø 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) Ø 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