Sustaining the Clinical Translational Research Workforce: Training and Empowering the Next Generation of Investigators

Abstract

There is mounting concern that clinician scientists are a vanishing species, and that the pipeline for clinical translational research (CTR) investigators is in jeopardy. For the majority of current junior CTR investigators, the career path involves first obtaining a National Institutes of Health (NIH) funded K-type career development award, particularly K08 and K23, and subsequently an NIH R01. This transition, popularly referred to as K2R, is a major hurdle with a low success rate and gaps in funding. In this Perspective, the authors identify factors that facilitate K2R transition and important aspects of increasing and sustaining the pipeline of CTR investigators. They also highlight significant differences in success rates of women and those underrepresented in biomedical research. Early career exposure to research methodology, protected time, multidisciplinary mentoring, and institutional “culture shift” are important for fostering and rewarding team science. Mentoring is the single most important contributor to K2R success, and emerging evidence suggests that formal mentor training and team mentoring are effective. Leadership training can empower junior investigators to thrive as independent CTR investigators. Future research should focus on delineating the difference between essential and supplemental factors to achieve this transition, and mentoring methods that foster success, including those that promote K2R transition of women and those underrepresented in biomedical research. The Clinical Translational Science Awards National Consortium is well positioned to test existing models aimed at shortening the timeframe, increasing the rate of K2R transition, and identifying strategies that improve success.

The crisis in developing and sustaining a career in biomedical research has been summarized recently in a high-profile perspective paper.¹ Although the proposed strategies “to rescue U.S. biomedical research from its systemic flaws” are applicable to basic, clinical, and translational scientists, the perspective paper did not emphasize the unique challenges faced by MD or MD-PhD clinician investigators who conduct clinical translational science research (CTR). Unlike PhD scientists, clinician scientists have ample opportunities that are already in place for “alternate” career paths both in academia and the private sector, which are often more financially rewarding and gratifying, at least in the short term. Furthermore, clinician scientists’ clinical responsibilities are unpredictable and the even more crippling demand on their time compared with basic scientists frequently conflict with their research responsibilities.

Most importantly, there is a shortage of newly minted clinician scientists, unlike the current over production of PhD scientists. Many preeminent clinician scientists have been sounding the alarm of the vanishing clinical investigators for decades.^2–4 The crisis persists in spite of a recently doubled National Institutes of Health (NIH) budget and the creation, since the 1990s, of NIH individual mentored K awards that are directed at junior faculty clinical scientists. Two NIH K awards focused primarily on patient oriented research are particularly relevant for the purpose of this Perspective: K08 (Mentored Clinical Scientist Research Career Development Award) and K23 (Mentored Patient-Oriented Research Career Development Award).

While overall-funded NIH grant applications nearly doubled from 1998 to 2007, most of the increase reflects awards to PhD investigators. Indeed, the number of NIH-funded clinician scientists has not increased despite the establishment of NIH new investigator programs, a trainee loan repayment program, and NIH family-friendly initiatives. Furthermore, the success rate for new R01 (Research Project Grant) applications decreased by one-third, and there is a greying of NIH awardees, including first time awardees.⁵ These statistics sparked debates as to whether the paradigms for physician training, including those for MD-PhD and K awardees, should be reinvented^6–8 and how institutions should invest in their junior clinicianinvestigators.^6,9 These discussions culminated recently in the NIH Physician-Scientist Workforce Working Group report.¹⁰

Increasing the Pipeline

The NIH Clinical and Translational Science Awards (CTSA) program was started in 2006 to strengthen and support CTR. It currently supports a national consortium of 62 academic health centers to transform and accelerate CTR. Recognizing the urgent need to increase the pipeline of CTR investigators, the CTSA has emphasized Research Education and Career Development (EdCD) of junior CTR investigators since its inception. CTR trainees learned by enrolling in formal course work and performing mentored research to increase team science competencies.⁶

In addition, the CTSA-funded institutional KL2 Mentored Clinical Research Scholars program supported a subset of high-potential and high-achieving medical professionals, such as MD, PhD, MD-PhD and equivalent, who are junior faculty in academic health centers. The proposed career paths for these elite KL2 Scholars are to obtain an individual K or R award at the end of their two to three years of KL2 support and subsequently achieve independent research grants, such as a R01. Transitioning from mentored to independent investigator status is primarily focused on NIH K grant awardees and their transition to NIH R01 grants, referred to as the K2R transition.

In 2012, the CTSA National EdCD Committee established the “Mentored to Independent Investigator Working Group” to identify the best practices and barriers for the K2R transitioning of KL2 Scholars. The Committee focuses on the acquisition of NIH R01 grants by K awardees because publically available data on K and R01 awards are available from the NIH,^5,11 and they account for the majority of career development and independent research grants, respectively. In this Perspective, we provide the Committee’s mindset on and approach to the K2R transition based on a review of literature published between 1980 and 2014, as well as our collective experience as educators and mentors to this target population. We begin with a discussion of the challenges to sustaining and diversifying the CTR pipeline, and then we consider best practices of K2R programs and the factors critical to long-term CTR success. We conclude with recommendations for future research.

Sustaining the Pipeline: The K2R Transition Challenge

For the majority of junior CTR investigators, obtaining an individual K08 or K23 award is a landmark first step towards becoming an early-career investigator.⁶ Data from the NIH Office of Extramural Research^3,5 show that between 2003 and 2013, the success rates for obtaining K08 or K23 awards fluctuated between 35–45%, and 80% of the K awardees subsequently applied for an R-series grant. Data from an earlier period (1997–2003) that tracked all 3,000 K08 and K23 awardees show that their K2R transition rate was 20% at five years after initial K funding, increased progressively between years five to eight, and reached a plateau at 40% at 10 years.¹² Importantly, K23 awardees with MD degrees are four times more likely than non-K funded MD applicants to obtain independent grant funding.¹¹ This “K advantage” makes a compelling case for continuing the K award programs for MD CTR investigators. However, the K2R process is tortuous and prolonged, requiring multiple grant submissions and resubmissions, and the success rate is suboptimal. Thus there is indeed a crisis in sustaining the CTR investigator pipeline.

Because K2R funding peaks at eight years after initiation of K funding,^3,12 more than half of K awardees who apply for R01 grants will experience a three year gap of funding from termination of a K award to acquisition of an R award. This funding gap will likely lengthen in the present austere NIH funding climate. Therefore, there is an urgent need for continued institutional support during the K2R transition gap in order to retain the talent pool and maximize return on investment for the NIH, the junior CTR investigators, and their sponsoring academic institutions.

Diversifying the Pipeline

Additionally, mechanisms to increase the K2R success of women and those underrepresented in biomedical research should be developed to ensure a diverse and vibrant CTR workforce. The importance of diversity is underscored by the launching of the NIH Common Fund’s “Enhancing the Diversity of the NIH-Funded Workforce” initiative.¹³ Women now constitute a large proportion of the academic physician workforce (43% of assistant professors), NIH K awardees (44% of K23, 29% K08)¹¹ and CTSA KL2 Scholars (54%). Compared with male K awardees, women K23 awardees have a lower R01 application rate,¹⁴ as well as lower K2R success rates compared with men (19% versus 25% at five years, and 36% versus 46% at 10 years.)¹² Paradoxically, this transition gap cannot be simply accounted for by whether or not women have children (similar gaps were found among men with and without children).¹² The gap is even more acute for underrepresented racial groups, which account for 5% and 8% of K08 and K23 awardees, respectively.¹¹ A survey involving five CTSA academic health centers reports that race-based barriers include perceived lack of mentoring, isolation, difficulties in cross-cultural communications, discrimination, and differential performance expectations.¹⁵

Toward Best Practices for K2R Success

Best practices for training CTR investigators and promoting their K2R transitions are evolving. Results from institutional and national specialty specific research development programs suggest that intensive interventions, such as grant writing workshops, and career support mechanisms, including mentoring, promote K2R transition.¹⁶ Additional common features include formal structured training such as coursework, protected research time, a strong research environment, and hands-on research experience. In a comparison of centralized and decentralized career development programs within a single academic health center, Brown and colleagues¹⁷ reported that centralized training and mentoring oversight, like those built into the KL2 Scholars program, increase the likelihood of a junior CTR investigator securing future independent research funding. Data from the Harvard School of Public Health’s Program in Clinical Effectiveness reveal that predictors for future success in obtaining R funding include younger age (less than 40 years old) at time of program enrollment, generalist status, timely commencement of research publications, and early submission of extramural grants.¹⁸

It is generally agreed that the ingredients for successful K2R transition include formal mentorship, rigorous research training, sufficient protected time, adequate research support, collaborative and collegial interactions, pilot funding, and an academic culture that supports young CTR investigators.¹⁹ Some of these recommendations were endorsed by a recent Institute of Medicine report on the CTSA enterprise.²⁰ However, there are few rigorous studies to identify factors that promote K2R transition, ensure long-term CTR career success, and limit attrition in the CTR workforce.

To facilitate research in this domain, Rubio and colleagues propose a theoretical model that potentially can be used to assess the relative importance and interplay between multiple factors that contribute to long term CTR success.²¹ This model incorporates extrinsic (financial success, promotion, leadership positions, grants, and publications) and intrinsic (job, career, and life satisfaction) factors. Some of these characteristics could be improved through interventions at the institutional level. These include: empowering CTR junior investigators through institutionally supported K2R programs; mentor training; and leadership training programs.

Formal K2R programs

Recently, several institutions in the CTSA consortium have begun to offer structured K2R transition programs. For a few examples, see Harvard Catalyst’s Grant Review and Support Program (http://catalyst.harvard.edu/services/grasp/) and the University of North Carolina’s North Carolina Translational & Clinical Science Institute’s R-Writing Group (http://tracs.unc.edu/index.php/services/education/r-writing-group). Most programs are focused on preparation of R01 or equivalent grants. Venues include small group writing workshops with rigorous timelines for grant deliverables and online grant writing and progress tracking tools. These programs require substantial institutional investment, but anecdotal evidence suggests that they increase K2R success. Additional research will be necessary to identify best practices that produce the best outcomes and are also cost effective so that they can be broadly adopted by other academic health centers.

Mentoring and mentorship training

Mentorship is universally recognized as necessary and critical to biomedical research careers,²² including those of CTR investigators.^23–25 Although mentoring matters, particularly in the current hypercompetitive medical research and healthcare environment, the mentor-mentee relationship has increasingly become a casualty of competition and crushing time demands in academia. This erosion parallels that occurring in the hypercompetitive corporate environment.²⁶

The traditional academic mentoring model pairs a junior trainee with a more experienced senior investigator in the same academic discipline.²⁷ Recently, there is a move beyond the traditional dyadic model to mentoring networks that include interdisciplinary and peer mentoring.²⁸ This is a natural evolution for CTR investigator mentoring: CTR is by definition interdisciplinary and team based, and it is difficult for a single mentor to perform diverse mentoring functions. Specifically, emphasis on the mentor-mentee relationship is reciprocal and the partnership must be cultivated through bidirectional exchanges.

Mentoring at its best should support the mentees’ career functions as well as psychosocial personal functions. A survey of those CTR faculty who initiated their K08 and K23 awards between 2006 and 2009 shows that the majority were satisfied with current mentoring relations, and that mentor behaviors, such as level of collegiality and positive outlook, appear to be directly associated with mentees’ career satisfaction.²⁹ Furthermore, mentees perceived that their mentors were effective in supporting many aspects of career functions, including modeling professional and ethical behavior, teaching knowledge and skills, advising about getting work published, and serving as role models and advocates. However, the survey also revealed that CTR mentors were perceived to be considerably less effective in other career aspects and particularly in promoting psychosocial personal functions. These latter aspects include facilitating professional networking, advising on negotiation for resources, preparing for career advancement, and particularly navigating work and life balance. Notably, 52% of the women and 40% of the men were “very or somewhat dissatisfied” with their work-life balance. These “softer” skills are critical to the professional and personal development of the CTR investigator, and therefore should be emphasized in mentor training. Additionally, mentees should be trained to acquire skills to optimize the mentor-mentee relationship and navigate challenging professional and personal domains.

With the recognition of the importance of effective mentoring, there is now a substantial literature on defining mentoring competencies, mentoring outcome metrics, and best practices for developing effective mentor-mentee relations.^24,25 In addition, several CTSA funded academic health centers have recently instituted campus-wide mentor training programs and early results are positive.³⁰ A report from a multisite randomized controlled trial of a CTR mentor training curriculum is particularly encouraging: 15 CTSA academic health center sites and one non-CTSA center used a standardized competency based research mentor training program (eight hours total) and found that both mentors and mentees reported significant perceived gains in multiple mentoring competencies.³¹ The success across multiple institutions suggests that this mentor training program can be adapted to each institution’s unique structure, mission, and resources. Training mentors to foster resilience and increase persistence may improve K2R transition and sustain the CTR investigator pipeline.³² Mentoring of women and junior investigators from other underrepresented groups in the biomedical research workforce can be improved by increasing awareness of more inclusive mentoring styles.^33–35 We anticipate that the recently launched NIH Diversity Initiative’s National Research Mentoring Network will provide additional evidence-based guidelines for improving mentoring of the underrepresented groups.¹³

In conclusion, we believe that identifying, supporting, and improving the skills of mentors and mentees through competency-based training is a critical ingredient for K2R success. Furthermore, the mentor training momentum must be sustained by creating an organizational culture that values mentorship.³⁶ This may include providing mentors with a stipend, protected time, and recognizing their contributions in promotion deliberations and in institution-wide venues.²⁷

Leadership training

In addition to empowering trainees through mentorship, there is increasing recognition that junior investigators can be empowered with leadership training as well.^37–39 Leadership training increases emotional intelligence, negotiation and conflict management skills, teamwork, influence, coping, managing time and relations, and political acumen. For example, even though negotiations for resources, protected time, and promotion are crucial to career success, a recent study of former K awardees showed that they feel ill equipped to negotiate and view negotiation as an adversarial process.⁴⁰ Empowering junior CTR investigators with these critical “soft” skills will enable them to better navigate the complex landscape of academic health centers. The challenges include the current constrained economic environment and crippling and conflicting demands on their time. Early empirical data from formal institutional leadership development programs for physicians and clinical investigators of both genders support this view.³⁸ In addition, national women faculty career development programs are also effective,³⁹ although they are not specifically targeted at CTR investigators.

Strategies for a durable and diverse CTR workforce will also require a culture change to recognize the importance of work life balance and cultural diversity. This is borne out by surveys in medical and business literature. Burnout and dissatisfaction with work life balance contribute to attrition of potentially successful CTR investigators.^40,41 For example, in one single-center survey, burnout rates were approximately twice as high in faculty over 35 years of age relative to residents, and in women relative to men (22% versus 10%).⁴¹ Groups that are underrepresented in biomedical research had the highest burnout rate (30%, compared with 18% for Caucasians).

Recommendations for Future Research

There are significant gaps in our knowledge and understanding of proven best practices for ensuring the highest degree of success in K2R transition. We believe that new and improved methods for tracking this transition should be employed at a national level. In the case of CTR investigators, the CTSA national consortium is positioned to conduct further research for developing the best practices to facilitate their K2R transition.

Future research should focus on objective measures to determine and delineate the difference between essential and supplemental factors to achieving successful K2R transition. This can be done by implementing and testing existing models such as Rubio and colleagues’ comprehensive career success model.²¹ Further, it would be useful to conduct additional research on the aspects of mentoring that are most crucial for early investigators to move their careers forward. These studies may be difficult to conduct, particularly in the absence of prospectively defined or contemporaneous control groups. However, preliminary data on long-term follow up of mentor development programs strongly suggest that testing this hypothesis is possible.³⁰ The CTSA Consortium could also use its national resources to assess specific programmatic components of K award training programs that contribute to K2R success.

Future research should also examine mechanisms to improve success of women and groups that are underrepresented in biomedical research in competing for research project grants and sustaining their academic careers. Current published information regarding CTR training programs and their impacts on women and underrepresented minorities is mostly based on opinion and survey data. Additional studies are needed to identify major barriers and the methods to reduce them. Models for such programs could be developed and tracked for efficacy.

It is important to recognize that K2R is only one metric for career success and that equivalent non-federal (e.g., foundations and industry) or Veterans Administration grant mechanisms support the careers of many successful CTR investigators. Moreover, with the emerging emphasis on interdisciplinary, team-based translational research, the paradigm is likely to shift such that a broader view of “independence” will be adopted. For example, establishing oneself as the leader of a major multi-investigator program (such as NIH’s U01 Cooperative Agreement Research Project) may evolve as a new additional benchmark for successful academic advancement. Therefore the future metric of an individual R01 may shift and we foresee that there will be growth in the number of Co-Principal Investigator/Project Director grant applications for “independent” researchers. The promotion and tenure committees will, out of necessity, increasingly recognize and reward investigators for teamwork.

In summary, the academic literature includes many successful models for promoting transition from mentored to independent investigator status. More research will be needed to refine the mentoring practices and other proposed interventions that are most effective in this endeavor. The CTSA Consortium is well positioned to test existing models aimed at increasing the rate of K2R transition and to identify specific programmatic components of K award training programs that contribute to success. These evidence based recommendations for promoting K2R success will be critically important for increasing, sustaining, and diversifying the pipeline for CTR investigators.