Preparation of the Research-Grant Application: Opportunities and Pitfalls

Eaves GN (1984) “Preparation of the Research-Grant Application: Opportunities and Pitfalls”, Grants Magazine (reprinted in Preparing a Research Grant Application to the National Institutes of Health, 1984), 7(3):151_157.

The research-grant application provides excellent opportunities for novice investigators to illustrate qualifications, for experienced researchers to substantiate accomplishments, and for all to demonstrate their potential for success. Here's how...

Whether referred to as "grantsmanship" or "researchmanship," the scholarship required for a successful research-grant application is as demanding as that for a lecture, a report for publication, or a textbook. Preparation of a grant application is a scholarly endeavor that combines the values of a scientist and the skills of a scholar: dedication, enthusiasm, standards of excellence, intellectual honesty, ethicality, disciplined thinking, and clear writing. In response to the intense competition for grants, however, the scholar may separate the grant application from its academic counterparts and place it in a category of activity in which timing, persistence, demonstrable experience, persuasion, and productivity seems as important as quality, skill, and logic.

No longer is it possible to obtain a research grant by submitting a merely acceptable grant application; the application must be superior. On the basis of my professional experience with all aspects of the peer-review process used by the National Institutes of Health, especially impressions from the written reports of the scientific and technical review, I have concluded that the single most important requirement for a beginning investigator's successful competition for a grants is a demonstration of outstanding qualifications. These qualifications are not the kind usually present in a biographical sketch, such as advanced degrees and publications, but the demonstrated ability to think clearly and logically, to express logical thought concisely and cogently, to discriminate between the significant and the inconsequential, to display technical prowess, to handle abstract thought, to analyze data objectively and accurately, and to interpret results confidently and conservatively. These capabilities characterize scholarship, and it is through scholarship that an applicant for a research grant can demonstrate his qualifications.

The research-grant application provides numerous opportunities to demonstrate qualifications and scholarly attributes, and it easily reveals faulty thinking, hasty preparation, superficiality, and inexperience.

Many reviewers assess these strengths and weaknesses by answering seven fundamental questions about an application:

  1. Are the aims logical?
  2. Is the hypothesis valid?
  3. Are the procedures feasible, adequate, and appropriate for the research proposed?
  4. Is the research likely to produce new data and concepts or confirm existing hypotheses?
  5. What is the significance and originality of the proposed study in its scientific field?
  6. Are the principal investigator and the staff qualified to conduct the proposed work, as judged by their demonstrated competence, academic credentials, research experience, and productivity?
  7. Are the facilities, equipment, and other resources adequate for the proposed work, and is the environment conducive to productive research?

The research-grant application provides numerous opportunities to demonstrate qualifications and scholarly attributes, and it easily reveal faulty thinking, hasty preparation, superficiality, and inexperince.

The instructions for the application forms used by the United States Public Health Service offer guidance in the form of four questions:

  1. What do you intend to do?
  2. Why is the work important?
  3. What has already been done?
  4. How are you going to do the work?

This series of questions points out the necessity for carefully reading and analyzing instructions before writing an application. The third question is not in parallel with the other questions; its passive voice seems to be referring to your knowledge of the published archives. By comparing the question to its corresponding section of the scientific text of the application, one can readily see what is meant:

  • SPECIFIC AIMS (What do you intend to do?)
  • SIGNIFICANCE (Why is the work important?)
  • PRELIMINARY STUDIES (What has already been done?)
  • EXPERIMENTAL PLAN (How are you gong to do the work?)

The third question would more appropriately read: "What have you already done?"

To demonstrate the opportunities and pitfalls in the preparation of a grant application, I have expanded the four sections of the application form used by the Public Health Service into the following outline:

  • AIMS
    • Hypothesis
    • Objectives
  • SIGNIFICANCE
    • Background
    • Literature
    • Gaps to be filled
    • Importance
  • PRELIMINARY STUDIES
    • Design
    • Methods
      • Innovations
      • Limitations
      • Difficulties anticipated
      • Alternative approaches
      • Sequence
    • Analysis of date
    • Interpretation of anticipated results

Aims

Begin the text of the application with a concise statement of the general purpose or major objective of the proposed research. This statement, often in combination with the limited objectives, or specific aims, will usually provide the hypothesis to be tested. The opportunity here is to guide the reviewer, at the very beginning of the text, toward an understanding of exactly what you want to do.

The hypothesis must be valid; it is usually based on logical expectations derived from your own work or your work and that of others. The hypothesis should be important in its specific field and have potential value for biomedical research. You must be able to test the hypothesis by feasible procedures.

The terms "objectives," "specific aims," "hypothesis," and "goals" are often used interchangeably. The specific aims are exact statements of what you want to accomplish in the proposed project. Choose these goals carefully and logically, and state them clearly and concisely. Relate the specific objectives directly to the hypothesis, or major objective, and be sure that they are reasonable and attainable.

Familiarity with unpublished material is simply knowledge of the research activities and accomplishments of other investigators in your field; it is achieved through personal interactions in the "invisible college" to which most successful researchers belong.

Significance

In the significance section, I have included four topics: background, literature, gaps, and importance. The "background" is frequently misunderstood to be the section called "literature." The background is a description of the research activities that led to the project you are proposing. For example, are you proposing to pursue in greater depth an observation from some previous research project? Or, have you recently encountered some clinical trend that needs exploration and explanation? Collect the information thoroughly, organize it logically, and be sure that it justifies your proposal.

The literature section is one of the most important in the application because it permits you to demonstrate early in the text that you have the ability to discriminate wisely. This section offers the opportunity to demonstrate your qualifications by proving that you are thoroughly familiar with your field, that you understand it, and that you have a balanced knowledge of it. Use the opportunity to show that you are aware of discrepancies and inaccuracies in the published archives and that you have a comprehensive view of published and even unpublished material in your field. To the beginning investigator, the idea of being familiar with the unpublished material may seem unreasonable. Familiarity with the unpublished is simply knowledge of the research activities and accomplishments of other investigators in your field; it is achieved through personal interactions in the "invisible college' to which most successful researchers belong.

Identify the gaps that the project is intended to fill. If the gap does not seem obvious or dramatic, explain how the results of your research would advance our understanding of your area of research. For example, the proposal may be to develop techniques that would facilitate further research or permit the early diagnosis of some pathologic condition.

The instructions for the Public Health Service application direct you to "state concisely the importance of the research described in this appliation by relation the specific aims to longer term objectives." The intent of the authors of that directive is not clear, but many assume it means that the "specific aims," previously referred to as "objectives." should contribute directly to the overall goal or hypothesis. That interpretation is as obvious as the assumption that the importance of the gap the research would fill is the same as the importance of the research, which it may be. Many applicants use the "gaps" and "importance" parts of the significance section to explain the projected importance of the specific proposal, such as the eventual practical value of the research or the clinical application to which the proposed research could lead.

Preliminary Studies

The section on preliminary studies is where you can report the results of your pertinent preliminary investigations. The application form of the Public Health Service permits you to provide also "any other information that will help establish the experience and competence of the investigator to pursue the proposed project." The opportunities in this section are two of the most important in an application. Especially during times of fiscal constraints, reviewers tend to become conservative and to reserve their enthusiasm for research that has the greatest likelihood of success. To be able to demonstrate, by reporting the results of preliminary experiments, that the proposed research is feasible and the hypothesis readily testable inspires confidence in reviewers. Additional indications of probably success are manuscripts submitted for publication. Use them in an appendix to the application as important proof of feasibility, preliminary results, and qualifications.

If you are a beginning investigator submitting your first application and worried because you do not yet have a professional reputation, remember that you will have already impressed the reviewers, in the literature section, by your familiarity with the field and your capability for keen and wise discrimination between the significant and the banal, the valid and the presumed. You can readily prove that you can do the work proposed by reporting that you have already done some of it. The section on preliminary studies provides opportunities that you must not fail to take.

Experimental Plan

The experimental plan will probably be the easiest part of the application for you, once you have decided such crucial considerations as how much detail to provide in your logically conceived plan. You will want to convince the reviewers that the methods you propose to use are appropriate to the specific aims already described, that you are familiar with the methods as a result of direct experience with them, and that the methods, unless innovative, are well established. If established methods cannot serve your purpose, describe how you have modified existing methods to bypass technical difficulties. If you need to provide extensive detail, you should consider the use of an appendix for that material. Do not let too much detail distract the reviewers from your goal, but do not leave too much to their imagination either. You must let the reviewers know that you are familiear with the methods used in your field of research. If standard methods are not adequate, describe why the methods you have chosen, or modified, are more suitable and why they may offer advantages over other methods. Make sure that the methods correspond to the specific aims and are in the same logical order.

For the specific methods, and for the entire project, anticipate the technical difficulties that you are likely to encounter, and explain what you would do about them. If you do not anticipate difficulties, the reviewers will. The extent of an applicant's awareness of probably obstacles is a favorite point for criticism, especially from reviewers who are active and experienced investigators, as most are. Let the reviewers know that you are well aware of likely difficulties and limitations and that you have already developed alternative approaches to get around potential difficulties and to compensate for inherent deficiencies in the methods and procedures.

The description of the sequence of experiments is simply a recapitulation of the logical order that corresponds to the aims and the methods. If the experimental plan is logical, the sequence will have been apparent from that important, first mention of the overall goal and the specific objectives. A detailed timetable may not be necessary or practical. Provide a realistic estimate of how much you hope to accomplish during each year requested and state whether you anticipate delays in actually conducting the proposed experiments because you may be setting up a new laboratory, just beginning your research career, or moving to another institution.

A difficult task for the beginning investigator is the prediction of the kinds of results - not the exact results - that can be expected. These general expectations are based on awareness of the underlying principles and complexities of the subject you are studying. Since you should be able to predict whether the data would support or deny your hypothesis, you should be able to state, in advance, the limits to be observed in the interpretation of the results. Reviewers often criticize applicants for not realizing the potential value and limitations inherent in the anticipated results. As a simple example, you would know in advance whether you might be able to extrapolate findings from an in vitro experiment to an in vivo situation.

If you are a beginning investigator submitting your first application and worried because you do not yet have a professional reputation, remember that you will have already impressed the reviewers, in the literature section, by your familiarity with the field and your capability for keen and wise discrimination between the significant and the banal, the valid and the presumed.

Test for Success

When you prepare the outline and draft of your grant application, ask yourself the following questions about the specific sections of the expanded outline.

Aims

Hypothesis. Is my hypothesis valid and important in this particular sphere of investigation, and is it testable by feasible procedures?

Objectives. Are my specific aims logical, carefully chosen, well defined, clearly stated, reasonable, and attainable?

Significance

Background. Have I collected throughly, reviewed critically, and organized logically the data and events that led to the present proposal, and does this background information justify the "next step," which is this proposal?

Literature. Have I proved that I am sufficiently familiar with this type of research by demonstrating a thorough understanding and a balanced knowledge of the pertinent literature, and have I emphasized or clarified discrepancies?

Gaps To Be Filled. Would the results of my research fill a defined gap in our knowledge or advance our understanding of this subject? Or will it facilitate the development of valuable techniques or experimental models, or lead to rational treatment for some pathologic condition?

Importance. Is my work important, particularly in the relation of my specific objectives to the hypothesis, or is the work likely to yield new conclusions that will have general biological value or practical clinical significance?

Preliminary Studies

Feasibility. Have my preliminary experiments demonstrate that the methods, procedures, techniques, and protocols are feasible, adequate, and appropriate, and that my hypothesis is therefor readily testable?

Qualifications of Investigator. Have my educational background, research experience, and preliminary experiments demonstrated that I am qualified to perform the study, that I have potential for doing productive work, that I have the technical competence and skills needed for the proposed work, and that my results would be reliable and inspire confidence in my peers?

Experimental Plan

Design. Is my experimental plan original, appropriate, valid, carefully designed, straightforward, well organized, logically conceived, and lucidly described?

Methods. Are my experimental methods reasonable and appropriate for the proposed investigation, carefully documented, well established, under my technical control, promising, and clearly described? Do the methods correspond to the specific aims?

  • Innovations. Am I using innovative procedures to overcome difficult technical problems? Are these innovative procedures feasible and well within my competence and experience? Do these new procedures have obvious and clearly described advantages over the standard techniques, now in use?
  • Advantages. Have I anticipated and adequately discussed potential difficulties and obstacles in the approach chose? Have I carefully considered the advantages and disadvantages of each method?
  • Limitation. Have I recognized the limitations of the methods and how these limitations can influence the analysis and interpretation of the experimental results?
  • Difficulties Anticipated. Am I fully aware of difficulties that may be encountered in the conduct of the experimental plan and of the specific methods? Have I convinced the reviewers that I will be able to circumvent anticipated, as well as unexpected, difficulties?
  • Alternative Approaches. Have I proposed logical and appropriate alternatives to any experimental obstacles that might be encountered?
  • Sequence. Have I developed my research plan in a carefully focused, step-by-step, straightforward manner? Have I demonstrated that I have a clear understanding of the order or sequence of experiments as I would conduct them?
  • Analysis of Data. Have I given careful attention to the type of results that could be expected, so that I can analyze only valid and relevant data?
  • Interpretation of Anticipated Results. Have I demonstrated an awareness of the underlying principles and the associated complexities of the area under study so that I can interpret my results appropriately?

Continue to revise and refine the draft until you are satisfied with your answer to each question. When you can confidently answer each question affirmatively, you will have the basis for a successful proposal.