Hematology Grants Workshop

We have experienced several profound changes in funding from the National Institutes of Health (NIH) over the past decade. The “doubling” of the NIH budget led to an increase in applications that made the subsequent so-called “flat funding” years even more difficult. I say so-called because, when adjusted for inflation, funding was actually reduced in real terms. Likewise, the American Research Recovery Act (ARRA) grants have enormously helped investigators in the past 2 years. However, this will almost certainly expand the number of subsequent R01 applications, again stressing an overall flat NIH budget. While these fiscal realities don't preclude the success of an application, they do emphasize the need for careful grant preparation, and require unselfish time and effort by more senior faculty in mentoring trainees during this transition to independence.

I will provide additional thoughts derived from my own experiences and from what I have learned over two decades of mentoring junior faculty through career-development awards and into their first R01s. Some of my comments will clearly be redundant to those of Drs. Lee and Molldrem, while other comments will provide a more personal view.

Both Drs. Lee and Molldrem provide two key points that I would also like to emphasize: start early and develop the basic question or hypothesis first. I have found one major key to success is developing robust and concise specific aims. In fact, I believe this is so important, that in each institution where I have been in a leadership role, I have set up “specific aim committees” to assist junior faculty with their first grant applications. This reflects my bias that if one arrives at an excellent hypothesis (as Dr. Molldrem points out) and then develops tight, logical specific aims, the grant will more or less write itself. There is no better feeling than the “high” one gets from a grant emerging from well-planned specific aims. This requires time. I advise junior faculty to have a specific aim committee in place at least 3 months before the grant due date. The “committee” should be made up of three to four senior faculty who have served on an NIH study section. They don't really have to be experts in the area of the grant, but of course this helps. Importantly, the members of the Committee must be willing to spend the time it takes to read a short introduction to the work, the proposed specific aims, and to meet for about an hour two to three times over a month or so. It is very important that the committee members are accessible to you. Even as a “preeminent leader in the field,” if he/she is traveling or unable to meet with you in person during the time you need input, this will be less helpful to you.

Prior to the meeting of the specific aims committee, the applicant should prepare and circulate a short introduction (less than one page) and the proposed specific aims. At the initial specific aims committee meeting, the applicant should discuss the background and then propose the specific aims in a short introduction (I suggest no more than 20 minutes of a 1-hour meeting). It is the charge of the committee to constructively critique these aims. As Dr. Molldrem says, “leave your ego at the door.” Your expectation should be that the committee really tears apart and re-assembles the proposed specific aims. At its best this is an iterative process and usually requires additional meetings to arrive at a consensus. Before each subsequent meeting, the applicant should recirculate the newest version of the specific aims. In my experience, this process almost always results in dramatically different and improved specific aims. At the end of this process, the applicant should use the specific aims arrived at by consensus of this committee in combination with the accompanying hypothesis (which may also be changed in this process) to write the remainder of the grant, which then is simply a matter of supplying the preliminary data and experimental procedures to pursue these aims. I also advise that one or two members of the specific aims committee be asked to serve as “readers” of the drafted full grant. In some institutions, such as Cincinnati Children's Hospital Medical Center, a signoff of the full grant by a senior faculty member is required for the submission of NIH grants.

The new NIH guidelines reduce the previous 25-page limit to 12 pages. In my view, this places a certain disadvantage on new investigators, because the shortened format almost certainly adds more weight in the review process to the “previous accomplishments” of the applicant. In addition, the new “bullet” format of the reviews severely reduces the ability of the review process itself to guide the applicant in revising the application for a second submission. This new process therefore increases the importance of institutional faculty advice and local mentoring in the grant-writing and revising process. In the Hematology/Oncology Division at Children's Hospital Boston/Dana-Farber Cancer Institute, we have assigned (and pay for) one senior faculty member to assist all trainees in the transition between their fellowship and their first faculty position. This includes playing a major role in the development and submission of career-training awards. We ask fellows preparing their first federal grant to meet early with this faculty member, who then coordinates administrative issues related to the grant application with assigned administrative personnel and advises about the make-up of the specific aims committee and the “grant readers.” The faculty person also helps in deciding who should write collaboration letters and facilitates mentoring and division support letters with the administrative staff assigned to the applicants grant. This faculty member also then assists in reviewing the study section comments and in preparing the revised application. We and our trainees have found this to be enormously helpful, with our funding rate on first submission of training grants now more than 90%. This success of course also reflects the outstanding nature of the trainees, the training environment, and the mentors—all of which are key in career-development awards.

There are many NIH and other websites that provide guidance for preparing grants and I will not reiterate these. However, there are several points that I consistently see as criticisms or mistakes in the applications of new investigators. I would emphasize comments from both Drs. Lee and Molldrem (See Grant Writing for Junior Faculty session in this book): that it is very important to read and be acquainted with the grant instructions. Carefully follow these instructions and include all elements requested in the guidelines from the granting agency. This will prevent “last-minute” surprises raised by internal grant officers or other administrative personnel.

Study sections cite “overly ambitious proposals” almost universally in career-development awards critiques. During my initial K application, I remember feeling that I had to “cover” all eventualities and propose experiments to address these. The pressure to do this is understandable, but given the frequency of the criticism, one needs to “curb your enthusiasm.” On the other hand, it is important to choose a topic in which additional research is warranted and additional knowledge will be relevant to human disease. I also take the approach of not worrying too much about “overlap” until it is an actual funding overlap. In the application, it is acceptable to acknowledge potential overlap. If one is in the enviable position of have funding overlap, this can then simply be negotiated with the funding agencies involved.

Another key section that needs careful thought is “expected results, pitfalls, and alternative approaches.” Even for a seasoned grant writer, this section is often difficult to write. It may require some time to clearly think through the design flaws, potential implications of the experiments, and how one would proceed given certain problems. However, this component of the grant is critical and needs to be written thoughtfully and not as an afterthought. If the section is superficial and/or not included, it is very easy for the reviewer to use this to reduce the level of enthusiasm for an otherwise well-written grant. Remember, the number of grants funded is the minority and any component that is marked down reduces your changes of obtaining a fundable score.

I see increasing criticism from study sections on the lack of a statistical plan for evaluation of the data. This is no longer only expected for studies involving human research, but is now very often expected to determine the number of animals or the number of replicates required for experiments proposed in each specific aim. Having a biostatistics collaborator is often justified and well received by the study section.

A well-planned and clearly written career-development plan is essential for career-development awards. Remember, most study sections are reviewing a large number of grants in a limited time period. Anything you can do to make your “story” easier to read and comprehend will be greatly appreciated by the reviewers. This includes the use of figures that give an overall view of the planned experiments and critical pieces of data.

Success in obtaining grants is essential for success in carrying out meaningful and important research and for career development. In this short review, I have attempted to provide advice based not only on my 25 years of grant-writing experience, but more importantly on the lessons learned while mentoring many fellows and junior faculty in writing their first grants. The keys are allowing adequate time, obtaining critical advice and constructive criticism, and being careful in grant writing. Applicants shouldn't be discouraged if the application is not funded on the initial review. It is important to understand and learn from the reviewers' critiques and then to revise your proposal carefully to address their concerns. The option to revise based on reviewer comments and resubmit allows many grants to ultimately be funded.

Conflict-of-interest disclosure: The author declares no competing financial interests. Off-label drug use: None disclosed.

David A. Williams, MD, 300 Longwood Ave., Karp 08125, Children's Hospital Boston, Boston, MA 02115; Phone: (617) 919-2697; Fax: (617) 730-0934; e-mail: dawilliams@childrens.harvard.edu.