Reviving the vascular surgeon–scientist: An interim assessment of the jointly sponsored Lifeline Foundation/National Heart, Lung, and Blood Institute William J. von Liebig Mentored Clinical Scientist Development (K08) Program

Methods 

The von Liebig K08 program was designated for individuals holding a faculty appointment in vascular surgery and meeting the review and funding criteria for NHLBI K08 awards, based on applications submitted simultaneously to both NHLBI and the Lifeline Foundation in June of each year. Initial peer review and priority scoring was conducted by the special emphasis panel responsible for all NHLBI K-series applications, followed by secondary review and funding decisions by the NHLBI Advisory Council. Applicants successfully awarded NHLBI K08 funding were then reviewed by the Lifeline Foundation Research and Education Committee, and up to two individuals each year were selected to receive the supplemental salary support of the von Liebig K08 award. This additional salary stipend was designated in the amount necessary to achieve twice the annual total of salary support otherwise provided by the NHLBI K08 award.

The funding outcomes for all applications submitted to the von Liebig K08 program from 1999 to 2005 were tabulated from a review of AVA and NHLBI records, and overall funding rates for K08 awards were obtained from the NHLBI. The characteristics of successfully funded vascular surgeon K08 applicants and assessment of their research productivity were based on personal communication and review of individual curricula vitae that they provided. Peer-reviewed publications before and after the year of the K08 award were obtained by a search of the National Library of Medicine PubMed database, and original scientific publications were classified as being related to laboratory research or to clinical topics. Descriptive statistics were used to summarize the characteristics of the vascular surgeon K08 recipient cohort (means are presented ± the standard error).

Results 

Funding rates 

Between 1999 and 2005, 39 applications were submitted to the von Liebig K08 program (annual median, 6; range, 3 to 7). Of these, 14 applicants (36%) received the von Liebig K08 award, and five additional applicants (13%) received NHLBI K08 awards (all for 5 years’ duration), for an overall funding rate of 49% (median annual funding rate, 50%; Table I). During the same time period, the aggregate funding rate for all K08 applications submitted to NHLBI was 41% (annual range, 32% to 47%).

Table I. Funding outcomes for vascular surgeon K08 award applicants, 1999 to 2005

	Year of award	Applicants, n	Awards funded von Liebig K08, n (%)	Other NHLBI K08 awards, n (%)	Total K08, n (%)
	1999	6	2(33)	1(20)	3/6(50)
	2000	7	2(29)	0(0)	2/7(29)
	2001	6	2(33)	0(0)	2/6(33)
	2002	6	2(33)	2(33)	4/6(50)
	2003	4	2(50)	0(0)	2/4(50)
	2004	7	2(29)	2(29)	4/7(57)
	2005	3	2(66)	0(0)	2/3(66)
	Totals	39	14/39(36)	5/39(13)	19/39(49)

NHLBI, National Heart, Lung, and Blood Institute. The number of vascular surgeons submitting applications for the von Liebig K08 award program is listed for each year from 1999 through 2005, along with the number and percentage of applications funded (the number of applicants refers to those submitted during the previous calendar year). Other NHLBI K08 awards refers to K08 applications submitted by vascular surgeons for the von Liebig K08 program that received funding by NHLBI but not the von Liebig Award supplement.

Characteristics of award recipients 

Vascular surgeon K08 recipients included 16 with an MD degree (84%) and three with a combined MD/PhD degree (16%; Table II). All had completed a general surgical residency (median duration, 5.0 years; range, 5 to 7 years; mean, 5.2 ± 0.1 years) and a vascular surgery fellowship (median duration, 1.0 years; range, 1 to 2 years; mean, 1.2 ± 0.1 years). The median duration of faculty appointment (all at assistant professor level) was 2.0 years (range, 0 to 7 years; mean, 2.5 ± 0.4 years), and the median age at the time of the K08 application was 38.0 years (range, 34 to 42 years; mean, 37.6 ± 0.5 years). All vascular surgeon K08 recipients were engaged in an academic vascular surgery practice, with direct patient care responsibilities encompassing no more than 25% of total professional effort.

Table II. Characteristics of vascular surgeon K08 recipients, 1999 to 2005

	N = 19 (%)		Median (range)	Mean
	Age at application (years)		38.0(34-42)	37.6±0.5
	Years in faculty appointment		2.0(0-7)	2.5±0.4
	Degree
	MD	16(84.2)
	MD/PhD	3(15.8)
	Previous clinical training (years)
	Clinical residency		5.0(5-7)	5.2±0.1
	Clinical fellowship		1.0(1-2)	1.2±0.1
	Total clinical training		6.0(6-8)	6.3±0.1
	Previous research training
	Research during residency	18(94.7)
	Duration (years)		2.0(0-4)	1.9±0.2
	Research during fellowship	13(68.4)
	Duration(years)		1.0(0-1)	0.7±0.1
	Research during both	12(63.2)
	Total research (years)		2.5(1-5)	2.6±0.2
	Previous peer-reviewed publications
	Laboratory research		10.0(2-95)	15.2±4.7
	Clinical research/topics		8.0(2-61)	13.2±3.2
	Total publications		21.0(9-116)	28.4±6.2
	Previous research funding
	As a trainee
	All sources	9(47.4)
	NHLBI F32 or T32	6(31.6)
	American Heart Association	3(15.8)
	Surgical foundation/society	2(10.5)
	As a faculty member
	All sources	9(47.4)

NHLBI, National Heart, Lung, and Blood Institute.

The median amount of previous research training for vascular surgeon K08 recipients was 2.5 years (range, 1 to 5 years; mean, 2.6 ± 0.2 years). Eighteen recipients (95%) had performed laboratory-based research during general surgery residency (median duration, 2.0 years; range, 0 to 4 years; mean, 1.9 ± 0.2 years) and 13 (68%) during vascular surgery fellowship (median duration, 1.0 years; range, 0 to 1 years; mean, 0.7 ± 0.1 years). Twelve individuals (63%) had performed research during both residency and fellowship. Six of the recipients (32%) had received previous NIH support through an individual (F32) or institutional (T32) National Research Service Award (NRSA) during the time of their research training, three (16%) had held an award from the American Heart Association, and two (11%) had obtained scholarship funding through a nonprofit surgical foundation or academic society. The median number of peer-reviewed publications per recipient before the year of K08 application was 21.0 (range, 9 to 116; mean, 28.4 ± 6.2), including 10.0 research papers (range, 2 to 95; mean, 15.2 ± 4.7) and 8.0 clinical papers (range, 2 to 61; mean, 13.2 ± 3.2).

Vascular surgeon K08 recipients tended to be affiliated with academic institutions characterized by a well-developed research infrastructure, and all had been provided with appropriate time, laboratory space, and start-up research funding as part of their initial faculty appointment. Nine of the recipients (47%) had obtained nonfederal extramural research support before the year of initiating the K08 award from other sources, including the American College of Surgeons, the American Heart Association, the American Surgical Association, the Association for Academic Surgery, the Howard Hughes Foundation for Medical Research, the Lifeline Foundation, the Pacific Vascular Research Foundation, the Society of University Surgeons, and the Whitaker Foundation, as well as corporate and industry sponsors.

The research topics investigated by vascular surgeon K08 recipients covered a broad spectrum of problems related to basic vascular biology and peripheral vascular disease (Table III). Primary research mentors included MD (46%) and PhD (54%) scientists with principal appointments in basic science or clinical departments. All of these research mentors were productive senior scientists with independent NIH R01 funding, a solid track record of research training experience, and a well-established relationship with the vascular surgeon K08 recipient.

Table III. Research topics of vascular surgeon K08 recipients, 1999 to 2005

	Topic	Year
	Genetic engineering of a failure resistant vein graft	1999
	Control of endothelial translation by fluid shear stress	1999
	Modulating endothelial adaptation to flow	1999
	Inflammatory mechanisms of neointimal hyperplasia	2000
	Nitric oxide and smooth muscle cell proliferation	2000
	uPA receptor signaling and cell migration	2001
	MMP-9-dependent vessel wall remodeling is NO-dependent	2001
	Bone morphogenetic proteins in arterial remodeling	2002
	Thrombus resolution is CXC chemokine dependent	2002
	Collagen-binding integrins in intimal hyperplasia	2002
	The chemokine system in collateral artery formation	2002
	Measuring the efficacy of endovascular treatment of AAA	2003
	Collagen-IV remodeling in ischemic leg revascularization	2004
	Mechanisms of shear-regulated vein graft remodeling	2004
	Role of progenitor cells in hindlimb revascularization	2002
	Homocysteine/hypertension and vascular lesion formation	2004
	mTOR regulation of VSMC differentiation	2004
	Mitochondriopathy of chronically ischemic muscle	2005
	A tissue-engineered, small-diameter vascular graft	2005

uPA, Urokinase-type plasminogen activator; MMP, matrix metalloproteinase; NO, nitric oxide; mTOR, mammalian target of rapamycin; VSMC, vascular smooth muscle cells.

Research productivity and transition to independence 

Between January 1999 and December 2005, vascular surgeon K08 recipients contributed a cumulative total of 460 peer-reviewed publications to the literature, including 161 (35%) on laboratory research and 299 (65%) on clinical topics (Table IV). During the award period, each K08 recipient published a mean of 5.1 ± 0.8 articles per year (median, 5.5), including 1.9 ± 0.3 per year on laboratory research (median, 2.0) and 3.3 ± 0.6 per year on clinical topics (median, 3.5).

Table IV. Peer-reviewed publications by vascular surgeon K08 recipients, 1999 to 2005

	All Publications as Author/Co-Author
	Year of Award	1999	2000	2001	2002	2003	2004	2005	Total
	Cum. number of recipients	3	5	7	11	13	17	19
	Total publications	5	14	35	61	83	138	124	460
	Research (% of total)	2(40)	5(36)	17(49)	22(36)	22(27)	46(33)	47(38)	161(35)
	Clinical (% of total)	3(60)	9(64)	18(51)	39(64)	61(73)	92(67)	77(62)	299(65)
	Publications per recipient	1.7	2.8	5.0	5.5	6.4	8.1	6.5	5.5⁎
	Research	0.7	1.0	2.4	2.0	1.7	2.7	2.5	2.0⁎
	Clinical	1.0	1.8	2.6	3.5	4.7	5.4	4.1	3.5⁎

	First/Last author publications during period of K08 award	n (%)	Mean†
	Total publications	174
	Research publications, n (% of total)	67(38)
	Clinical publications, n (% of total)	107(62)
	Publications per recipient per year
	Total		2.3±0.6
	Research publications		0.8±0.2
	Clinical publications		1.6±0.5

⁎ Median † Mean ± standard error.

When publications during the period of award were assessed to include only those in which the vascular surgeon K08 recipient was either the first or last author, the cumulative total was 174 publications, including 67 (38%) on laboratory research and 107 (62%) on clinical topics (Table IV). The mean rate of first/last author publications after receipt of the K08 award was 2.3 ± 0.6 per recipient per year distributed as 0.8 ± 0.2 research publications and 1.6 ± 0.5 clinical publications.

By December 2005, nine (47%) of the 19 vascular surgeon K08 recipients had received promotion to associate professor of surgery with tenure during the period of the award, including all seven of those holding the K08 for at least 3 years. Five (26%) of the 19 recipients also held joint faculty appointments in a basic science department or graduate school.

As of June 2005, four recipients of the von Liebig K08 award and one recipient of an NHLBI K08 award had completed the 5 years of mentored research training supported by the award. All five of these individuals subsequently achieved independent investigator status, with three receiving NIH R01 research project grant support and two serving as individual project leaders on NIH program project grants. In addition, four other vascular surgeon K08 recipients had submitted NIH R01 applications by December 2005, with one obtaining independent funding and three others awaiting review and funding decisions. As of December 2005, four of the vascular surgeon K08 recipients had been invited to serve as members of an NIH initial review panel (study section) or research advisory committee.

Discussion 

Several interrelated factors have contributed to the decline in the number of surgeon investigators during the past two decades (Table V). The working hypothesis in developing the von Liebig K08 program was (1) that the most vulnerable period for the academic vascular surgeon occurs within the first 3 to 5 years of faculty appointment, and (2) that adequate and realistic salary support during this time would provide young vascular surgeon–scientists the stimulus and means to launch effective, competitive, and sustainable laboratory research programs. The Lifeline Foundation and NHLBI leadership thereby constructed the von Liebig K08 program to emphasize the importance of structured research mentorship and to foster greater familiarity with NIH peer-review and funding processes. This structure also permitted applicants who were sufficiently competitive for NHLBI K08 awards to receive funding, even when the foundation funds available permitted no more than two individuals each year to receive the von Liebig K08 salary supplement.

Table V. Factors contributing to the decline in National Institutes of Health funding for surgeon–scientists

	1.Fewer applications submitted for NIH grants by surgeons than other medical specialties 2.Applications submitted by surgeons less competitive than those from other investigators 3.Limited representation of surgeons on NIH study sections, panels, and councils 4.Deficiency and instability in the surgical research workforce (quality and quantity) a)Diminishing opportunity for surgical residents to engage in research b)Long discontinuities between initial research training and faculty appointment c)Competing clinical productivity demands during early career development d)Mid-career surgeons unable to commit sufficient effort to sustain independent research e)Few established surgical investigators remain in research throughout their careers

The results presented here indicate that the von Liebig K08 program has been a highly successful vehicle in stimulating research career development in vascular surgery. First, it is notable that beginning with the first year of the program, a substantial number of K08 applications have been submitted by vascular surgeons each year (range, 3 to 7). This indicates that under current training paradigms, the pool of potential vascular surgeon–scientists—those with adequate training, initial support, and interest in establishing research-based careers—has likely been sufficient.24

Second, vascular surgeon K08 applicants were funded at a slightly higher rate than the NHLBI average for K08 awards during the same time period (49% vs 41%), indicating that these applicants were equally competitive in this arena with applicants from other medical specialties. This counters the perception that vascular surgeons engaged in laboratory-based research might not be sufficiently competitive with their peers in other specialties and reinforces the view that an increase in funded vascular surgeons could be achieved if given an ample incentive to prepare and submit applications for funding.

Third, vascular surgeon K08 recipients were highly productive during the course of the award period, as indicated by a steady rate of peer-reviewed publications and research presentations, emerging national recognition, procurement of additional research support, and academic promotion. Even by relatively early measures these individuals have already made important contributions to the field of vascular surgery, and their ongoing involvement in research-based activities is a hopeful sign for the next generation of academic leaders in the specialty.

Although still too early to draw firm conclusions, it appears that by several measures the von Liebig K08 program is already achieving its intended long-term impact. Thus, all vascular surgeon K08 recipients who completed the 5-year period of mentored research have emerged to achieve independent investigator status, and several more appear poised to follow. It is also notable that within their respective institutions, each of these individuals has played an important role in collaborative scientific programs and in mentoring research experiences for medical students, surgical residents, and vascular surgery fellows, thereby stimulating further interest in vascular disease. The active participation of vascular surgeon K08 recipients in other NIH activities (study sections, advisory panels, and conferences) is also apparent, and this level of broader involvement will continue to be vital in sustaining the wider visibility and influence of vascular surgeon-scientists. The von Liebig K08 program has thereby proven to be a wise and fruitful investment by the vascular surgery community.

The NIH K-series awards would appear to represent an ideal funding mechanism to help meet the increasing challenge of research career development for clinician–scientists, being specifically designated for clinically trained individuals conducting mentored laboratory-based (K08) or patient-oriented (K23) research. Because the provisions of the NIH K08/K23 awards require a research training commitment of 75% of total professional effort, and because for many specialties the amount of salary provided is less than half the Association of American Medical Colleges median salary for individuals holding an appointment at the assistant professor level, there remains a significant fiscal discrepancy that may discourage investigators from seeking this means of support. The salary supplement provided by the von Liebig K08 award was designed to offset this discrepancy, thereby allowing the recipient to commit the required 75% effort to research career development while maintaining a reasonable measure of clinical activity. It is notable that this amount of clinical activity is considered a crucial provision for technically-demanding and rapidly-evolving specialties such as vascular surgery, in which junior faculty members must maintain and extend clinical capabilities acquired during training, establish credibility as attending physicians and surgeons, and adopt new technical skills with emerging endovascular procedures, all alongside the development of research expertise.

Conclusion 

The von Liebig K08 program serves as one example of a successful partnership between private and public sectors to meet the ongoing challenges of research career development. This paradigm has recently been emulated to develop a similar K23 program for patient-oriented research in vascular surgery, and by salary-matching K08/K23 programs offered by other clinical specialties, such as cardiothoracic surgery and trauma surgery. Other potential solutions to stimulating research career development should also be considered and pursued, particularly to offset the disproportionate amounts of clinical activity between different medical and surgical specialties.25 For example, it might be feasible (and cost-neutral) to consider reducing the 75% effort requirement for K-series awards, perhaps to 50%, at least for certain clinically intense specialties. Another reasonable strategy would be to allow the proportionate percent effort for K-series awards to be calculated on the basis of a 40-hour workweek, rather than the percent of “total professional activity” as calculated at present. For an academic surgeon with professional demands that otherwise typically encompass 80 hours per week, this approach would permit a commitment of 30 hours per week to the K08/K23 program yet allow a considerable amount of remaining time for clinical practice and other professional activity. This approach also has the advantage that it would be equitable for all clinicians, regardless of specialty, thereby helping to restore equilibrium to a funding system that currently disfavors individuals in clinically demanding specialties.