Mechanisms for Mentored Career Development: The NIH Research Career Awards and Other National Awards

The transition from a postdoctoral fellow to an independent academic clinician-scientist is a major step in the career development of both physician-scientists and scientists interested in biological disorders. The vulnerability of this step, especially in the present climate of reduced funding possibilities, is well recognized by the National Institutes of Health (NIH) and other major scientific funding agencies, such as the American Society of Hematology (ASH), the American Heart Association (AHA), and the Leukemia and Lymphoma Society. Because the NIH grants remain the gold standard of such awards and because these awards tend to be for a substantial sum of support for 4 to 5 years, the NIH awards will be the focus of this presentation. Much of the presentation below applies to granting mechanisms through the National, Heart, Lung and Blood Institute (NHLBI) for physician-scientists, but certainly the general advice also applies to other NIH-funding sources through the National Cancer Institute (NCI) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and other national societies. Details of the available programs are best obtained from the website of each organization, or go to www.nih.gov and pick “Grants Funding Opportunities.”

The K08, K23 and the new K99/R00 Research Career Award (RCA) grant mechanisms are excellent means for beginning an academic career as a clinician-scientist. The K08 award is intended for individuals whose research is primarily laboratory based, while the K23 award is for investigators whose focus is patient-oriented research. The K99/R00 RCA award is for individuals somewhat further along in their career development who need a limited number of years of further mentoring prior to transitioning to an individual award. All of these grants remain strongly supported by the NIH as a mechanism for assisting junior faculty in achieving independence, but the availability of each award varies greatly between Institutions, and one needs to know both the official and unofficial status of each award in each Institution to know what would be best for an individual candidate. In this session, the details of how to successfully apply for these awards will be discussed primarily from the viewpoints of a recent successful applicant at the NIH and a senior scientist who has been involved in such reviews for the NHLBI. Most important to remember is that, unlike an RO1 application, these awards are mentored grant applications. Therefore, not only is the proposed science evaluated, but more importantly, the following components are evaluated: the candidate, the mentor, the career development plan, the potential of the proposed research to train the applicant for an independent career, and institutional support for the candidate.

In the application, candidates must demonstrate their potential to develop into independent researchers and a commitment to the physician-scientist pathway. Candidates must also provide a description of how this mentored award will enable them to accomplish their proposed career development objectives, both in the short and long term. Thus, letters that support the applicants’ clinical accomplishments as well as research potential are important. The productivity of the applicants’ prefellowship and fellowship years is important, as would be evidenced by having one or more first-authored research publications. If there are no publications, a strong body of preliminary data generated by the candidate may be acceptable for a K08 or K23 application. Abstracts, clinical reviews, and second-authored research papers carry less weight.

Sometimes applicants may be too early in their academic careers, and it may be more appropriate to apply for support either by an NIH-funded individual National Research Service Award (NRSA) or by an Institutional training T32 grant. Alternatively, applicants may be too qualified. Having a long track record of publications may suggest that the applicant would not benefit from additional mentoring or formal didactics by this career development mechanism. Most acceptable K08 and K23 candidates are either finishing their fellowship years, are instructors, or are early in their assistant professor positions. A K99/R00 applicant would have a more mature publication record and should be about to start or have just started a faculty position. Check with the appropriate Institution to see what grant mechanism would be most appropriate for you at your stage of career development.

The applicant needs to document a commitment to medical research. Previous efforts at the college level and efforts during medical school or residency are some ways to demonstrate commitment. Often, personal stories of an unusual nature may help candidates convince the reviewer of their outstanding potential. Previous research exposure, especially earning an MD/PhD dual degree or a master’s in a health-related field, certainly shows a commitment to a research career. Such applicants may be able to get by with a smaller body of published papers in their proposed area of research and can often successfully apply for a career development award earlier in their fellowship years.

However, the MD/PhD or MD/master’s candidates are often held to a higher standard. They should have publications from their thesis years and should propose didactic training and research that leads to additional growth in skills that go beyond those gained during the thesis effort. Sometimes less than 5 years of support from a K08 or K23 mechanism may be more justified for these applicants, as they need less mentoring and have a track record of publications that should allow earlier success at obtaining an RO1. These applicants may be better suited for a K99/R00 award. In addition, a strong letter of support from the thesis advisor normally accompanies such applications. Absence of such a letter and/or lack of publication(s) from the graduate work may markedly decrease enthusiasm.

The importance of the career development plan cannot be overstated. Ideally, this plan would describe how the applicant, in the course of conducting mentored research, would gain the knowledge and skills necessary to become an independent clinician-scientist. The description should not be limited to one or two key areas, but rather should span the full spectrum of training needed to become a successful independent investigator. Examples of questions to address include the following: Which specific laboratory skills does the applicant hope to acquire throughout the training period? If these involve techniques that are outside of the expertise of the mentor’s laboratory, how will this be accomplished? For experienced applicants (e.g., those with a PhD), it is important that the proposed training will result in learning and development of new skills, rather than being a continuation of skills already mastered. How will the applicant stay abreast of the latest events in the area of research? Local seminars and laboratory meetings are to be expected, and the applicant should highlight the special nature of any component that would be unusual and supportive of a quality-mentored experience. For example, attendance at the ASH Clinical Research Training Institute (CRTI) may enhance a K23 application if it was consistent with the career development plan. The reviewers may also look favorably on the applicant attending one or two key national conferences per year, but any more might seem potentially limiting to precious research time, as would an overly extensive Institutional conference and meeting schedule. How will the applicant improve upon skills needed for effective grant writing, manuscript preparation, and oral presentations? Finally, how will the applicant maintain and extend skills in clinical medicine? Ideally, all of these issues should be addressed by the mentor as well.

Formal training for many applicants often involves additional class work and may lead to a PhD or master’s degree. If these classes provide new knowledge/skills that are directly applicable to the applicant’s career goals, this formal training would be a positive component of the application. However, inappropriate, poorly described, or too much class work can be harmful to the application. Applicants with extensive prior research experience may elect not to complete any additional formal coursework, though that is rare. When formal coursework is described, its rationale should be provided, and the mentor and members of the applicant’s advisory committee should state their agreement with the details of the coursework and the rationale for taking them. Note that every applicant must receive training in the responsible conduct of research, and this should be clearly detailed in the application. The career development plan should also include a description of the structure (including the frequency, nature, and purpose) of the mentoring experience, which should be mirrored by the mentor. This is a critical component of a well-designed career development award as described in greater detail below.

The quality of the mentor is almost as important as the quality of the applicant. Mentors should engender confidence that they would be able to guide the applicant into a successful career as an independent clinician-scientist. Thus, the mentor must be a productive investigator in the area of research being pursued by the applicant. Mentors should also have strong research grant support. It is hard to envision how mentors could help support an applicant if they do not have the financial means to allow the applicants to complete their projects. Lack of research funds also reflects poorly on a mentor’s productivity and is a serious warning sign to reviewers.

Mentors should also have a strong training record. Both number of trainees and what they are presently doing are important. Often this is best presented in tabular form; the presence of sweeping statements about past trainees without presenting details on when they were mentored, what they had accomplished, and what they are presently doing may detract from the application. Lack of track records can limit enthusiasm for young investigators serving as single mentors. However, if more experienced co-mentors are included, scientists earlier in their careers can serve as mentors. Whether young investigators are more appropriately designated mentors or co-mentors depends on what is best for the applicant. Publication records and the grant support of young mentors may be more closely scrutinized than those of someone with an established training record. Records of established co-mentors—publications in the area of the application, grant support, and previous trainees—also need to be well documented. Co-mentors’ willingness to serve as such and the degree of time commitment must be clearly delineated in their letters. It should also be clear that they understand the details of the present application both in terms of the proposed science as well as career development activities.

Mentors should convey, in the Mentor’s Statement, their enthusiasm and knowledge of the applicant’s career development and provide a careful discussion of how the applicant’s career will be nurtured. This has to be done in detail and often involves a presentation of the informal and formal education that the applicant will undergo. The frequency of formal and informal meetings with the applicants, how often the applicants will meet with any advisory committee, and the goals of that committee need to be presented. Long-term issues of how the proposed research effort will be used to advance the applicant’s career should be addressed in detail. Often, this involves how the applicant will have an opportunity to develop an individual career niche separate from that of the mentor. It is very important that the mentor’s vision and that of the applicant’s are concordant. For example, if an applicant details specific coursework, the mentor should detail the same coursework.

Mentors should mention additional resources in terms of space, finances and/or protected time. This should coincide with statements made by the applicant and also in the Institutional letters, and should explain how these resources provide an outstanding opportunity for development. Distinct space at present or in the future, additional resources and their sources that can reasonably support the proposed effort, and details of the continued clinical commitment of the applicant should be discussed by the mentors and, if necessary, by the individual(s) providing that resource.

An advisory committee is an important consideration as a component of a mentored research experience. The details of the structure of the committee and the goals of this committee should be clearly stated. Ideally, its members have strong publication records in areas related to the applicant’s proposed research and have strong histories of mentoring. Inclusion of the members’ NIH CVs is useful. Letters indicating their willingness to serve on the advisory committee also should be included. These letters should state the willingness of the members to serve on the committee, the frequency of meetings, and the goals of these meetings to convince the reviewer that the committee will function as stated. Off-site committee members can be problematic. Such members should often be considered in addition to a strong local committee. Annual encounters at national meetings or when the advisor comes to town for family gatherings are not very convincing. The details of the advisory committee as described by the applicant and by the mentor must coincide with statements in the letters from each committee member.

The Institutional statement is another important aspect of K award applications and should be focused on the particular applicant. In the candidate’s statement, a description of how the institutional environment would enable the successful attainment of the proposed career development plan and research should be included. The Institutional letter should show familiarity with the applicants’ past and proposed future, but most importantly, should provide a clear commitment to the candidate as evidenced by detailing protected research time and release from duties that would interfere with the proposed research. The percentage of protected time should be identical in the candidate’s, mentor’s and Institutional statements, and should be reasonable. A day clinic is typically considered to be a 20% time commitment, and a month of on-service is typically 8%. Candidates who have 2 days of clinic per week and 2 months of inpatient service yearly are unlikely to convince reviewers that they have 75% protected time. Importantly, an institutional letter of support that shows a true commitment to the applicant by providing additional resources (e.g., research support and individual laboratory space) given up-front independent of grant funding can be very well received and enhances the applicant’s chances of having an outstanding application.

Most problematic can be an Institution’s commitment in terms of the academic title. Often, candidates are instructors at the time of the application. Ideally, applicants are about to attain or have just obtained assistant professor positions in either a tenure track or the clinical equivalent of such a track. Certainly, a candidate at assistant professor positions at quality Institutions is better received, as it shows a clear commitment to the applicant. An instructorship title with a statement that the applicant will be promoted to assistant professor upon the receipt of the career development award may be rational and reasonable from the Institution’s perspective, but does not show the strongest support for the applicant. Stronger support would be an Institutional letter indicating that, with continued productivity, the candidate’s promotion will occur independent of receipt of this award.

Unusual position titles, such as visiting research assistant professor, can be problematic and need to be carefully explained. Association at satellite institutions to a main University may also be problematic and needs careful explantation.

The proposed research effort is another important component of the application. Clearly, the applicant prepares this section; however, it is important that the mentor has reviewed this section and has helped guide the applicant in its final preparation. Too often, when a mentor declares that the applicant prepared the research section independently, the science section is problematic and is either too short or long, is not sufficiently mechanistic with testable hypotheses, presents the preliminary data in a poor fashion, or does not properly organize the application by accepted standards. This lack of mentoring at the first step of the career development process reflects badly on both the mentor and the applicant.

On the other hand, the application should not be that of the mentor. Certain language clues, such as repeatedly referring to published data from the mentor’s laboratory group as “we” when the applicant was not yet in the laboratory at the time of that publication, or showing as preliminary data published data from the mentor’s group that did not involve the applicant, reduces enthusiasm for the application. The inclusion of preliminary data derived by the applicant is of importance. Occasionally, it is appropriate to present the work of others in the mentor’s group, but it is best to clearly indicate its authorship.

Discussing every possible pitfall of grant application preparation is beyond the scope of this paper. However, one common defect is poor presentation of preliminary data and figures. Here are some important guidelines:

1. Minimize presentation of figures or data done by others. The Background can include data done by others.This includes prior research done in the mentor’s laboratory. Only rarely should such data be included in the Preliminary Data section. Certainly, 1 or 2 figures that represent the model to be tested or a flow chart of the study are to be encouraged.

2. All figures presented should be clear and readable. As we go to electronic submission, concerns over poorly presented data due to photocopying at the NIH becomes less critical, but the limitations of the PDF format should be kept in mind even if you have a larger version of the image in the Appendix. Remember, the reviewer may not go to the Appendix, so label all pertinent parts of the figure in large enough type to be easily readable.

3. Do not take data or figures directly from a PowerPoint slide, because precious page space for optimizing data presentation is wasted. Always be committed to designing figures specifically for the grant.

4. Always show important controls. The most common mistake is to leave out data necessary to convince reviewers that equal loadings were done in each lane of a gel.

5. Label the figures so that each item or band is identified. Make sure the x-axis and y-axis are labeled with the units studied.

6. Figure legends are very useful. Here, methodology can be presented in a succinct fashion, saving space in the overall flow of the grant. The number of times studies were done and the statistical analysis should be presented here as well.

7. Refer to each figure shown.

8. In the body of the grant, stick to the prescribed font size and spacing. If you cannot say what you want in the normal space limitation, it is clear that you need to have someone else (your mentor) help you express yourself more succinctly.

9. Follow the prescribed organization of the science. The Specific Aims (SA) should be the format for the entire scientific part of the grant. If you have SA1 with subSA1a and 1b and SA2 with subSA 2a and 2b, this format should be followed in the Abstract, Background, Preliminary Data and Proposed Methods. Every part of the scientific grant should repeat this same organization to provide greatest readability.

10. Alternative plans should be well laid out. One common concern that often needs to be addressed is when the entire grant is predicated on the success of a single experiment. If that bottleneck experiment does not work, then nothing else will follow. This difficult situation needs to be recognized by candidates and mentors, and should be avoided; if that is not possible, the grant should include a serious discussion of how the applicant intends to address the bottleneck problem.

11. Another common problem seen is concern over sufficient patient numbers to empower the proposed study in a single Institution setting within the time frame of the award. Again, the candidate and mentor need to carefully address these concerns and come up with viable alternatives.

12. Typos, spelling errors, and grammatic mistakes should be avoided. These errors can detract from the best of applications. Not only should applicants and mentors read and edit the application, but it is best if applicants can set the grant aside for 1 or 2 weeks and then re-read the grant with fresh eyes so that errors of meaning or omissions can be avoided.

13. Since these are mentored award grants, a short discussion near the end of how the proposed studies are unique and support the applicant’s career development separate from the mentor should be included. Long-term goals that might arise from the proposed studies should be tied in as well. A timeline of the entire mentoring experience should be included somewhere in the application and should go beyond just a checklist. A detailed narrative should also be included that makes an argument for the reasonableness of combining the proposed research with the proposed didactic studies and clinic time commitment.

It is important to set aside at least 2 to 3 months of full-time effort for the preparation of the grant. A major portion of this time commitment is to coordinate all the various components of the application and for editing of the scientific part and other components by at minimum the mentor and the applicant (more than once). In many applications, the applicants’ views of their proposed mentored experience is at variance with those of their mentors, advisory committee members, or Institutions. For example, if the applicant proposes certain didactic courses, the mentor should also propose these same courses. If the mentor says that the advisory committee will meet twice a year, it is problematic if the applicant says three times a year while the members of the committee either fail to mention frequency or state a different frequency. Each plan may be reasonable, but the lack of consistency decreases enthusiasm. The applicant also needs to have letters of support (and probably CVs) from collaborators correctly acknowledging the specific assistance that the applicant proposes to establish.

Finally, in this era of tight budgets, many worthy applications do not get funded on the first round. About a third to a half of grants will actually be triaged and not receive a score, although they will receive reviewers’ comments. Not getting a fundable score may be quite disheartening, but applicants should focus on the comments. Also, applicants should speak to the Scientific Review Administrators or Program Administrators to gain insights into what the issues may be and how to address them when resubmitting the application. For a K award, applicants have three chances to be funded. It is important to carefully respond to each concern in the Introduction to Revised Applications section.

The members of the review committee are often highly experienced at reviewing these applications and make a strong effort to give special consideration to resubmissions. However, the reviewers that may be assigned to a specific resubmitted grant may not necessarily be the same ones who originally saw the application. It is possible that new weaknesses may be discerned, so addressing the prior concerns is just the beginning point of a resubmission. New publications, preliminary data, and insights should be included as well to promote enthusiasm for the application.

In the end, some applications may not be supportable due to concerns with the applicant, the mentor, the design of the mentoring experience, the institutional support or the proposed studies. Applicants are urged to read each review, realizing that these reviews may provide important insights into issues related to their chosen career paths. These reviews provide an outstanding neutral third party that may provide invaluable insights into career direction. Applicants who are funded should also read the reviews, as they may provide important insights that may help in their quest towards their next career goal, the achievement of their first RO1 award.