Research and research vascular surgery
nding in
James S. T. Yao, MD, PhD, Chicago, Ill.
Research, patient care, and teaching are three vital commitments for every trained surgeon. The priority of these commitments depends on the type ofsurgical practice. Regardless of the type of practice, the members of the Society for Vascular Surgery need to remember the original bylaws, which clearly state the first of seven objectives of the society) '~Fhe object of the Society shall be (1) to promote the study of and research in vascular disease . . . . " Thus the importance for every academic vascular surgeon to pursue research is clear and requires no further debate. The continuous lack of federal support for research and training of young academic surgeons has concerned many leaders.2~6To encourage younger surgeons to pursue research, this presentation reviews the current status of funding sources available for those interested in fulfilling the first objective of the Society. The presentation will also focus on the review process, as well as the current level o f support of vascular research by the National Institutes o f Health (NIH). S O U R C E OF R E S E A R C H F U N D I N G
In general, research support is derived from three main sources: fellowships or scholarships, research awards, and research grants. Fellowships or scholarships are normally used primarily for salary support. Both research awards and grants are for a designed study during a specified period. Sources of funding are available from (1) NIH, (2) American Heart Association and its local affiliates, (3) Veterans Administration (VA), (4) surgical societies, (5) private foundations or charitable organizations, and (6) private industry,
From the Department of Surgery, Division of Vascular Surgery, Northwestern University Medical School. Presented at the Society for Vascular Surgery Critical Issues Forum, New York, N,Y., June 18, 1989. Reprint requests: James S. T. Yao, MD, PhD, Department of Surgery, Division of Vascular Surgery, Northwestern University Medical School, 251 E. Chicago Ave., Suite 628, Chicago, IL 60611. 24/6/20457
84
For surgeons in training or near completion of training, applications for fellowships or scholarships are often a good start on the long journey. Table 1 outlines various types of fellowships, scholarships, and research awards offered by many surgical societies. Support from private foundations and charitable organizations are often competed at the local level. The level of funding or availability depends ~ the resources of the geographic location. Major sources of research funding are derived from the three national organizations such as the VA, the American Heart Association, and NIH. Veterans Administration
The VA Medical Rescarach Program was officially incorporated in the mission of the medical care program of the VA in September 1958. With the partnership of VA Medical Centers and University Medical Centers, the VA Medical Research Program provides a fertile ground for young surgeons to begin ~ their,research career. The annual allocation for VA medical research is about $200 million, 1.8% of the VA Health Services and Research Administration budget. The Medical Research Service in the VA Central Office supports the research of approximately 2500 VA scientists; more than 70% are p h y s i c i ~ who spend the majority of their time in patient care and engage in research on a less than full-time basis. 7 Research programs determined by the peer review system include (1) Research Review Group, (2) Merit Review, (3) Cooperative Studies, (4) Career Development, and (5) Special Research Ifiitiatives~ and Research Centers. The Research Advisory Group program provides initial and rapid start-up research support to young surgeons who arc newly recruited to VA medical centers. The award is of special help to start an initial project before either Merit Review or N I H funding. The Merit Reviev¢ Program is the ~ largest program within the VA Medical Research Service and is ideal for young investigators to pursue a more sustained form of research in his or her field of interest. A five-eighths VA-salaried position at a VA medical center is needed to qualify for funding. The career development program is open at all
Volume 12 Number 1 July 1990
levels to clinicians with doctoral degrees. It supports research training of clinicians seeking careers as clinician-researchers within the VA system.
American Heart Association In 1988 the American Heart Association invested more than $65.3 million in research. 8 Both research 'direction and fimding are dominated by cardiac,oriented physicians. The National Research Program offers (1) medical student research fellowships, (2) clinician-scientist awards, (3) special clinicianscientist awards, (4) established investigator awards, and (5) grants-in-aid. In addition to national tim& ing, local heart associations offer excellent opportunities for young investigators to start research projects. In 1988-1989 the American Heart Association ~"ocated its National Research Program dollars as follows: $12.2 million for grants-in-aid, $11.8 million for established investigatorships, $2.7 million f o r clinician-scientist awards, $731,000 for American Heart Association-Bugher Centers, and $662,000 for medical student research fellowships. Clinician-scientist awards encourage promising clinically trained physicians to undertake careers in investigative science. The awards allow 3 years of rigorous flail-time research training. Special funding is available for clinican-scientist awards in a special area of interest. The areas of interest are cell biology of the arterial wall; cellular mad molecular biology relevant to lipoprotein metabolism, arteriosclerosis, and treatment of hyperlipidemia; lipoprotein metabolism; arteriosclerosis; thrombolysis; thrombosis; and vascular disease. Established investigator awards provide stipend '£~,pport in the cardiovascular field, including stroke and related basic science problems. The 5-year awards assist promising physicians and scientists in developing independent research careers in academic medicine and biology. The grant-in-aid is the largest form of research ~program offered by the American Heart Association. Grants-in-aid provide from 1 to 3 years of support for well-defined research proposals. Each grant provides a maximum of $35,000 a year, plus 10% overhead. There is no salary for principal and collaborating investigators. All grant applications are sub-jected to a peer-review committee established by the American Heart Association. s National Institutes of Health NIH is comprised of 13 research institutes, the Division of Research Resources, two service divisions, a research hospital called the Clinical Center,
Research and researchfinding 85
Table I. Research fellowship or awards offerd by surgical societies Society for Vascular Surgery: E. I. Wylie Traveling Fellowship International Society for Cardiovascular Surgery: Liebig Foundation Award & Student Research Fellowship Program Midwestern Vascular Surgical Society: Guthrie Award Southern Vasoalar Surgical Society: Research Award Society for Clinical Vascular Surgery: Student Prize, Travel Award American Venous Forum: Research Award American Surgical Association: Foundation Fellowship American College of Surgeons: Loyal Davis Traveling Surgical Scholarship Fellowship (2 years) Society of University Surgeons: Research Award Association of Academic Surgeons: Research Award
the National Library of Medicine, the Fogarty International Center, and the National Center for Nursing Research. Extramural research by NIH is divided into two main categories: grants and contracts. Grants typically support regular research projects, program projects, academic research enhancement awards and centers, and other forms of assistance such as individual and institutional fellowship awards and various research career awards. Contracts are solicited through requests for proposals. More than three quarters of the budget of NIH is spent on work done in outside institutions, mostly universities and medical schools. Of 8546 applications reviewed by the National Advisory Countil and Board in October 1988, 6350 grants were traditional (R01), small business innovative research (SBIR), other research (RI5 and R29), and conferences (R13). 9a° Major research grants provided by NIH are as follows. Research Project Grant (R01). The Research Project grant is by far the most common form for research support by the NIH. The objective of the R01 grant is to support a discrete, specified project in an area representing the interests and competency of a principal investigator. First Independent Research Support and Transition (FIRST) Award (R29). The objective of the FIRST Award is to provide a sufficient initial period of research support for newly independent biomedical investigators to initiate their own research and demonstrate the merit of their own research ideas. These grants are intended to underwrite the first independent investigative efforts of an individual, to provide a reasonable opportunity to demonstrate creativity, productivity, and further promise, and to help in the transtion to traditional types of
Journal of VASCULAR SURGERY
86 Ya0
National Heart, Lung, and Blood Institute
Research Training and Development for MD Clinical Investigator Award (K08) Physician Scientist Award (Kll)
Research Project Grant
(R01) Short-Term Training of Health Professional Mechanism of Support
Students (T3S)
I I Years OI Stages Medical of Research Student Training and Development
Postdoctoral Training
Support (T32,T32m,F32) 1 I I I
I
First Independent Research Support and Transition Award
(R29)
I I I ]
Internship Early Residency ;oOcSl~raI
Early Career Development
Research Career Development Award
(K04)
I I I I I I I
Late Postdoctoral Independent Research Career Development
Preventive Cardiology Academic Award
(K07)
Senior Fellowship
(F33)
I I I I I Mid-Career Change New Techniques Mid-Career Change
Fig. 1. Recommended career development schedule by NIH. Mechanism of support refers to the types of grant one may seek through the Institutes. (Used with permission) N I H research project grants. It is ideal for young investigators to apply for this support before they apply for R01 grants FIRST Awards are made for a period of 5 years. These awards are not renewable. The total direct costs awarded must not exceed $350,000 for the 5 years, with no more than $100,000 for any i year. Principal investigators must make a maly significant commitment of time and effort, at least 50%, to the proposed research project. The Research Career Development Programs. There are several types of awards designed for research career development for potential investigators. All these awards are selected by national competition.
Research Career Development Award (K04). Candidates must have at least 3 years of postdoctoral experience and the award is for 5 years and is nonrenewable. The salary support is about $50,000 per year plus fringe benefits. Clinical Investigator Award (K08). The Clinical Investigator Award is designed to encourage newly trained clinicians to develop dinical and basic research interests and skills in the area of cardiovascular disease. In addition to salary support of up to $40,000 a year with fringe benefits, up to $10,000 a year will be provided for research support. The K08 grant is a 5-year grant that requires the applicant to commit 75% of his or her time to clinical or basic research.
Physician Scientist Award (Kll). The Physician Scientist Award is designed to encourage individuals with clinical training to develop research skills in a fimdamental science. Minority SchoolFaculty DevelopmentAward (K14). The Minority School Faculty Development Award is reserved for faculty of minority schools. Preventive Cardiology Academic Award (K07). As the name Preventive Cardiology Academic Award indicates, this is strictly for the development of ventive cardiology. Academic Research Enhancement Award (R15) . To avoid the tendency of the rich getting richer, the Academic Research Enhancement Award is reserved for those schools that have not been major participants in N I H programs. SBIR Program (R43, R44). The objective of the SBIR is to promote technologic innovation within the American small business community. Surgeons who have innovative ideas about developing new devices, instruments, and procedures with small companies are encouraged to apply. Phase I (R43) es-, tablishes the technical merit and feasibility of the proposal. Awards are for a maximum of $50,000 total costs (direct plus indirect costs) for a period not to exceed 6 months. Phase II (R44) continues the research and development efforts initiated in phase I, which are likely to result in commercial prod-
Volume 12 Number 1 July ~!990
ucts. Phase II awards are for a maximum of $500,000 total cost for a period nornaally not to exceed 2 years. National Research Service Awards. National Research Service Awards include postdoctoral fellowships (F32), senior fellowships (F33), and institutional training grants (T32). Support of scientific meetings (R13). The objective of the R13 grant is to assist in the support of scientific ~eetings or conferences (either domestic or international) that are directed toward areas of Public Health Service scientific program missions. Requests for applications. Periodically, N I H invites applications for a focused project on a specific topic. For instance, in 1987 the requests for applications on "Vascular Heating: Cell and Rheological Factors" was released and generated a response of 40 applic, ions. A special review committee is set up to review these grants. Grants that are not fimded may be resubmitted for an R01 grant through the usual process.
The above-mentioned grants or awards are open to vascular surgeons. However, it is important to take into consideration the stage of one's career before applying for these grants. Fig. 1 illustrates the recommendations by NIH. All grant applications to N I H are subjected to peer review. Most grants are reviewed by a panel of experts referred to as initial review groups. In the ~Division of Research Grants, the panels are usually called study sections. For applications related to vascular surgery, the main review body is the Surgery and Bioengineering Study Section. This study section consists of 18 members) ~ The composition of ~ s section includes general surgeons, cardiac surgeons, vascular surgeons, biomedical engineers, and basic scientists with expertise in such areas as biomaterials, pathology, hematology, and vascular biology. The section is headed by an executive secretary ~who will assign each proposal to a primary and secondary reviewer who are members of the study -group. Recently a reader or tertiary reviewer who does not prepare a report has been added to augument the discussion. The study section meets three times a year for 2 days. During the meeting the assigned reviewers lead the discussion of the application for which they prepared written critiques. In ~most instances a concensus is reached by the group and a recommendation of approval, disapproval, or deferral is made by majority vote. For each favorably recommended application, each member of the study section records a numeric rating that reflects his or her opinion of the scientific merit of the application. The rating scale ranges from 1.0 to 5.0, with 1.0
Research and researchfinding 87 being the best (outstanding, 1.0 to 1.5; excellent, 1.5 to 2.0; good, 2.0 to 2.5; satisfactory, 2.5 to 3.0; adequate, 3.0 to 3.5; fair, 3.5 to 4.0; and acceptable, 4.0 to 5.0). After the meeting the executive secretary averages the individual reviewers' ratings for each favorably recommended application and multiplies by 100 to provide a three-digit rating that is the priority score. The score is added to the "pink sheet" or summary statement, which is prepared by the executive secretary and sent to the grant applicant and the National Advisory Council of the N I H for approval. In addition to the priority score, a percentile figure is calculated. The percentile represents the relative position or rank of each priority score among the scores assigned by the particular study section at its last three meetings. The lower the numeric value of the priority score or percentile, the better the application. The percentile also appears on the pink sheet. The council's recommendations are forwarded to the director of the NIH, and he or she makes the final decision on funding. However, the director of the N I H can fund only a proposal that has been approved by the Advisory Council, and it is this restriction that prevents political interference. Once the investigator receives the pink sheet, which contains the critique and priority score, the applicant may submit a letter of rebuttal or alternatively withdraw the proposal or resubmit it. For the beginning applicant, if funding is not forthcoming (approved but not funded) it is advisable to resubmit the proposal incorporating changes according to the critique on the pink sheet. The applicant must be sure to indicate changes made within the body of the application by underlining them or using different print and explaining these changes in the introduction section. Resubmission is common and about one quarter of the grant applications are resubmissions. Success in applying for a research grant depends on the soundness of the design of the study. Several publications are now available to advise investigators how to prepare for a research grant. ~2-17In an article on how to apply for a research grant, Howie ~8 states that success depends on producing clear evidence of good questions that need to be answered, a capacity to make a promising attempt at finding the answer, reasonable opportunity to do the work in good conditions and within a defined period, and the need for specified financial support for the stated purpose. Brevity and organization are also important to the success of the application. 16 To be a successful applicant, one must understand the review process and what the reviewers are looking for. For reviewers the principal criteria for the initial
88
Journal of VASCULAR SURGF~Y
Ya0
Table II. Shortcomings of grant applications not approved or poorly rated by NIH
Table III. Numbers of grants in vascular surgery funded by NIH
Grants showing that shortcoming Shortcoming
Hypothesis: ill-defined, lacking, faulty, diffuse, unwarranted Research problems: significance unimportant, unimaginative, unlikely to provide new information Experimental design: study group or controls: inappropriate composition, number, or characteristics Experimental design: technical methodology: questionable, unsuited, defective Experimental design: data collection procedures: confused design, inappropriate instrumentation, timing, or conditions Experimental design: data management and analysis: vague Investigator: inadequate expertise or familiarity with literature in the research area, poor past performance, insufficient time to be devoted to project Resources: inadequate institutional se~ing, support staff, laboratory facilities, equipment, or personnel; restricted access to appropriate population; insufficient involvement or collaboration of colleagues and coinvestigators
No. %
120
47
77
30
103
40
168
66
104
41
80
31
43
17
9
4
Modified from Smith R. Br Med J 1988;296:691-5.
review of applications for research project grants include (1) scientific, technical, or medical significance and originality of the proposed research, (2) appropriateness and adequacy of the experimental approach and methods to be used, (3) qualifications and experience of the principal investigator and staff in the area of the proposed research, (4) reasonable availability of resources necessary to the proposed research, (5) reasonableness at the proposed budget and duration in relation to the proposed research, and, (6) where an application involves activities that could have an adverse effect on humans, animals, or the environment, the adequacy of the proposed means for protecting effects)° In addition to these criteria, the reviewer will also pay special attention to the hypothesis, the preliminary data demonstrating feasibility of the study, and the statistical design. The support staff is also especially important when complex basic science methods are involved in the proposal.
Grant
No.
Endovascular Cerebrovascular Vascular graft Ultrasonography Venous thrombosis Peripheral arterial disease Raynaud's syndrome Intestinal ischemia Renal artery disease Portal hypertension Total
19 7 7 3 11 13 10 2 2 6 80
Obviously not all proposals are successful. Applicants are encouraged to know the most comm~,~ shortcomings in failed proposals) 9 Table II outlines a survey by Cuca, 2° who reviewed 256 proposals that had been either disapproved or given a low priority score. Of the eight shortcomings listed, deficiency i~ methodology was the most common shortcoming (66%) followed by a poor hypothesis (47%). How good is peer review? The process of peer review has come under critical examination and is a subject of endless debate) 8,21 Nevertheless, the process is a fair system and is summarized superbly by Stephen Lock in his Rock Carling lecture. He stated, 'q~his instrument is fallible but it is the best we" have. "22 Who is a peer for peer-reviewed surgical research? The recent editorial by Jaffe23 has answered the question clearly, that is "another surgeon, of course." It is hoped that continuous participation of vascular surgeons in the study section will give surgeons a fair hearing of their research proposals. N I H - f u n d e d research in vascular surgery. Because of the broad scope of vascular surgery, NIHfunded research in this area is provided through several institutes and divisions; the assignment of the, source of ftmding depends on the relevance of the research to a particular organ, tissue, or disease. 24Ar present there is no information available regarding NIH-supported research under the disease category of vascular surgery. To survey the level of support in vascular surgery, an inquiry was made to the NIH for all grants funded under the category of vascular disease and surgery. A total of 3654 funded projects or grants with the tittle and abstracts of each project or grant was received (unpublished data). Unfortunately, the classification of vascular disease and surgery by NIH is too diffuse, with inclusion of nephritis, chronic renal failure, and various cardiac disorders that are unrelated to vascular surgery.
Volume 12 Number 1 Iulv 1990
Research and research finding
Table IV. N I H support for research career development (KO-4) and clinical ~investigator (KO-8) awards KO-4 No: applications No. approved Awarded (n/%) KO-8 No. applications No. approved Awarded (n/%)
89
Table V. Specialized Center for Research (P50) awards
1987
1988
43 42 14/32
25 24 7/29
29 20 18'/90
I5 12.
2/17
second request was then made with categories related to vascular disease and surgery, and 1066 abfacts were available for detailed analysis. The total funding for these 1066 grants and contracts was $204,319,127. The title and abstract of each project were then analyzed and categorized. These 1066 funded projects were derived from a wide variety of grants and support mechanisms. These include ROI, K04, K08, R29, P0I (program project), P50 (specialized center), P60 (National Research and Demonstration Center), and M 0 I (Clinical Research Center) Grants. Table III shows the number of grants =classified by the traditional terms in vascular ddisease or surgery. Eighty grants related to vascular surgery .....were awarded in 1988. It is of great interest to note the lack of funding in research on aortic aneurysm despite being ranked as the fifteenth most common cause of death in this country and the tenth leading cause of death among those above the age o f 55 years. 2s On the contrary, a rather nonfatal disease 2,ch as Raynaud's disease received strong support, and a total of i0 grants were awarded in this eate, gory. New technology such as endovascular surgery has also received satisfactory support. N I H funding for K04 and K08 is: less optimal. Only seven K08 and two K04 grants were awarded in i988, and in-formation on how many of these awards are assigned to vascular research is unavailable (Table IV) (unpublished data). However, it must be emphasized that vascular surgery and disease embraces a rather broad field. Thrombosis, hemodynamic phenomenon, biochemical factors, and recent interest in molecular biotogy, especially endothelial ceil research, are related to vascular disease. Many of these areas of interest are supported by intense research by specialized center or national demonstration centers~ Table V lists the targets of disease supported by N I H through the specialized centers for research. As stated clearly by
Disease
No.
Atherosclerosis Hypertension Ischemic heart disease Cerebrovascular disease Thrombosis
5 6 10 ~ 14t 4
¢Indudcs seven in ischemi¢ heart disease, one in peripheral vascular disease, one congential heart disease, and one in heart failure: tCerebrox.ascular Disease Research Centers under P50 and PO1 mechanisms.
Didisheim 24 in his presentation on National Heart, Lung and Blood Institute-funded research in vascular surgery at the Research Initiatives Meeting, NIH-supported research in vascular surgery is much better than it was I 0 years ago. Within the Division of Heart and Vascular Diseases of the National Heart, Lung and Blood Institute, a grant dealing with vascular surgery may be assigned to the Lipid Metabolism and Atherosderosis, Cardiac Disease, or Devices and Technology Branches depending on its focus. In Didisheim's analysis it is gratifying to note the increase of participation of vascular surgeons in NIH-funded research. O f the 28 grants on vascular grafts and vascular healing, 12 of the principal investigators, 3 of the coprincipal investigators, 17 of the coinvestigators, and 3 of the consultants are vascular surgeons. The recent award of a Specialized Center on Research program in vascular disease to University of Washington is also a welcome addition to the endeavor by members of the Society. SUMMARY The presentation summarized thc current status of funding available for vascular surgeons. In spite of the shrinking support for research by the federal government, there are oppommities for young investigators to pursue an academic career. Success of a grant application depends on preparation, design, and hypothesis. Potential applicants are encouraged to pay special attention to the many publications on how to prepare a research g r a n t ) 2"17 Although there is an increase in participation by vascular surgeons in NIH-supported research, the funding support and focus on vascular surgery remains unsatisfactory. Despite the high ranking of death from aortic aneurysm, there is virtually no funded project on aortic aneurysm in either basic or clinical study. New technology such as laser has received some support, but clinical trial comparing this modality with standard treat-
90
Journal of VASCULAR SURGERY
Ya0
ment is lacking and not forthcoming. The participation by vascular surgeons in the American Heart Association-ftmded research activities remains unknown, even though the American Heart Association claims to have spent millions on research in heart and vascular diseases. To promote the study of and research in vascular disease, the members of this distinguished Society need to guide young vascular surgeons to submit grant proposals to various organizations.
L
11.
12. 13.
14. 15.
REFERENCES 1. Shumacker HB Jr. The Society for Vascular Surgery: a history: 1945-1983. Society for Vascular Surgery, 1984. 2. Thompson JC. The role of research in the surgery of tomorrow. Am J Surg 1984;147:2-8. 3. Wyngaardeum JB. The support of clinical research and training by the National Institutes of Health: Introduction to the symposium. Arch Intern Med 1985;145:1241-4. 4. Lenfant C, Moskowitz J. The National Heart, Lung and Blood Institute: a plan for the eighties. Circulation 1983; 68:1141-4. 5. Healy B. Biomedical research: inlook and outlook. Cleve Clin J Med 1987;54:143-9. 6. Glickman RM. The future of the physician. Sci J Clin Invest 1985;76:1293-6. 7. Information for members of scientific review groups. Department of Veterans Affairs, Medical Research Service, 1989. 8. American Heart Association. Annual report, 1988. 9. NIH peer review notes. Division of Research Grants, Febmary 1989.
10. Orientation handbook for members of scientific review
16. 17.
18. 19. 20. 21. 22. 23. 24.
25.
groups. US Department of Health and Human Services, Public Health Service, National Institutes of Health, June 1989. NIH advisory committees. US Department of Health and Human Services, Public Health Service, National Institutes of Health, April 1989. SultzHA, SherwinFS. Grant writing for health professionals. Boston: Little, Brown and Co. 1981. Marks RG. Designing a research project: the basics of biomedical research methodology. Belmont, CA: Lifetime Learning Publications, 1982. Reif-Lehrer L. Going for the gold: some dos and don'ts f o r grant seekers. Scientist 1989;3:15-9. Pollock R, Balch CM. The NIH investigator award: how to write a training grant application. J Surg Res 1988;46:1-3. Niederhuber JE. Writing a successful grant application. J Surg Res 1985;39:277-81. Gordon SL. Ingredients of a successful grant application to the National Institutes of Health. J Orthop Res 1989;7:13841. Howie J. Apply for a research grant. Br Med J 1978;~ 1553-4. Smith R. Glimpses of the National Institutes of Health: review system and evaluation. Br Med J 1988;296:691-5. CucaJM. NIi-Igrant applications for clinical research: reasons for poor ratings or disapproval. Clin Res 1983;31:453-63. Relman AS, Angell M. How good is peer review? N Engl J Med 1989;321:827-9. Lock S. A difficult balance: editorial peer review in medicine. Philadelphia: ISI Press, 1986. Iaffe BM. Editorial: who is a peer for peer-reviewed surgical research? Surg Rounds 1989;2:11-2. Didisheim P. National Heart, Lung, and Blood Institutefimded research in vascular surgery. J VASC SUWG 1989; 10:563. Mortality for leading causes of death, United States-i986. Cancer Stat i990;40:12-5.
nding in
James S. T. Yao, MD, PhD, Chicago, Ill.
Research, patient care, and teaching are three vital commitments for every trained surgeon. The priority of these commitments depends on the type ofsurgical practice. Regardless of the type of practice, the members of the Society for Vascular Surgery need to remember the original bylaws, which clearly state the first of seven objectives of the society) '~Fhe object of the Society shall be (1) to promote the study of and research in vascular disease . . . . " Thus the importance for every academic vascular surgeon to pursue research is clear and requires no further debate. The continuous lack of federal support for research and training of young academic surgeons has concerned many leaders.2~6To encourage younger surgeons to pursue research, this presentation reviews the current status of funding sources available for those interested in fulfilling the first objective of the Society. The presentation will also focus on the review process, as well as the current level o f support of vascular research by the National Institutes o f Health (NIH). S O U R C E OF R E S E A R C H F U N D I N G
In general, research support is derived from three main sources: fellowships or scholarships, research awards, and research grants. Fellowships or scholarships are normally used primarily for salary support. Both research awards and grants are for a designed study during a specified period. Sources of funding are available from (1) NIH, (2) American Heart Association and its local affiliates, (3) Veterans Administration (VA), (4) surgical societies, (5) private foundations or charitable organizations, and (6) private industry,
From the Department of Surgery, Division of Vascular Surgery, Northwestern University Medical School. Presented at the Society for Vascular Surgery Critical Issues Forum, New York, N,Y., June 18, 1989. Reprint requests: James S. T. Yao, MD, PhD, Department of Surgery, Division of Vascular Surgery, Northwestern University Medical School, 251 E. Chicago Ave., Suite 628, Chicago, IL 60611. 24/6/20457
84
For surgeons in training or near completion of training, applications for fellowships or scholarships are often a good start on the long journey. Table 1 outlines various types of fellowships, scholarships, and research awards offered by many surgical societies. Support from private foundations and charitable organizations are often competed at the local level. The level of funding or availability depends ~ the resources of the geographic location. Major sources of research funding are derived from the three national organizations such as the VA, the American Heart Association, and NIH. Veterans Administration
The VA Medical Rescarach Program was officially incorporated in the mission of the medical care program of the VA in September 1958. With the partnership of VA Medical Centers and University Medical Centers, the VA Medical Research Program provides a fertile ground for young surgeons to begin ~ their,research career. The annual allocation for VA medical research is about $200 million, 1.8% of the VA Health Services and Research Administration budget. The Medical Research Service in the VA Central Office supports the research of approximately 2500 VA scientists; more than 70% are p h y s i c i ~ who spend the majority of their time in patient care and engage in research on a less than full-time basis. 7 Research programs determined by the peer review system include (1) Research Review Group, (2) Merit Review, (3) Cooperative Studies, (4) Career Development, and (5) Special Research Ifiitiatives~ and Research Centers. The Research Advisory Group program provides initial and rapid start-up research support to young surgeons who arc newly recruited to VA medical centers. The award is of special help to start an initial project before either Merit Review or N I H funding. The Merit Reviev¢ Program is the ~ largest program within the VA Medical Research Service and is ideal for young investigators to pursue a more sustained form of research in his or her field of interest. A five-eighths VA-salaried position at a VA medical center is needed to qualify for funding. The career development program is open at all
Volume 12 Number 1 July 1990
levels to clinicians with doctoral degrees. It supports research training of clinicians seeking careers as clinician-researchers within the VA system.
American Heart Association In 1988 the American Heart Association invested more than $65.3 million in research. 8 Both research 'direction and fimding are dominated by cardiac,oriented physicians. The National Research Program offers (1) medical student research fellowships, (2) clinician-scientist awards, (3) special clinicianscientist awards, (4) established investigator awards, and (5) grants-in-aid. In addition to national tim& ing, local heart associations offer excellent opportunities for young investigators to start research projects. In 1988-1989 the American Heart Association ~"ocated its National Research Program dollars as follows: $12.2 million for grants-in-aid, $11.8 million for established investigatorships, $2.7 million f o r clinician-scientist awards, $731,000 for American Heart Association-Bugher Centers, and $662,000 for medical student research fellowships. Clinician-scientist awards encourage promising clinically trained physicians to undertake careers in investigative science. The awards allow 3 years of rigorous flail-time research training. Special funding is available for clinican-scientist awards in a special area of interest. The areas of interest are cell biology of the arterial wall; cellular mad molecular biology relevant to lipoprotein metabolism, arteriosclerosis, and treatment of hyperlipidemia; lipoprotein metabolism; arteriosclerosis; thrombolysis; thrombosis; and vascular disease. Established investigator awards provide stipend '£~,pport in the cardiovascular field, including stroke and related basic science problems. The 5-year awards assist promising physicians and scientists in developing independent research careers in academic medicine and biology. The grant-in-aid is the largest form of research ~program offered by the American Heart Association. Grants-in-aid provide from 1 to 3 years of support for well-defined research proposals. Each grant provides a maximum of $35,000 a year, plus 10% overhead. There is no salary for principal and collaborating investigators. All grant applications are sub-jected to a peer-review committee established by the American Heart Association. s National Institutes of Health NIH is comprised of 13 research institutes, the Division of Research Resources, two service divisions, a research hospital called the Clinical Center,
Research and researchfinding 85
Table I. Research fellowship or awards offerd by surgical societies Society for Vascular Surgery: E. I. Wylie Traveling Fellowship International Society for Cardiovascular Surgery: Liebig Foundation Award & Student Research Fellowship Program Midwestern Vascular Surgical Society: Guthrie Award Southern Vasoalar Surgical Society: Research Award Society for Clinical Vascular Surgery: Student Prize, Travel Award American Venous Forum: Research Award American Surgical Association: Foundation Fellowship American College of Surgeons: Loyal Davis Traveling Surgical Scholarship Fellowship (2 years) Society of University Surgeons: Research Award Association of Academic Surgeons: Research Award
the National Library of Medicine, the Fogarty International Center, and the National Center for Nursing Research. Extramural research by NIH is divided into two main categories: grants and contracts. Grants typically support regular research projects, program projects, academic research enhancement awards and centers, and other forms of assistance such as individual and institutional fellowship awards and various research career awards. Contracts are solicited through requests for proposals. More than three quarters of the budget of NIH is spent on work done in outside institutions, mostly universities and medical schools. Of 8546 applications reviewed by the National Advisory Countil and Board in October 1988, 6350 grants were traditional (R01), small business innovative research (SBIR), other research (RI5 and R29), and conferences (R13). 9a° Major research grants provided by NIH are as follows. Research Project Grant (R01). The Research Project grant is by far the most common form for research support by the NIH. The objective of the R01 grant is to support a discrete, specified project in an area representing the interests and competency of a principal investigator. First Independent Research Support and Transition (FIRST) Award (R29). The objective of the FIRST Award is to provide a sufficient initial period of research support for newly independent biomedical investigators to initiate their own research and demonstrate the merit of their own research ideas. These grants are intended to underwrite the first independent investigative efforts of an individual, to provide a reasonable opportunity to demonstrate creativity, productivity, and further promise, and to help in the transtion to traditional types of
Journal of VASCULAR SURGERY
86 Ya0
National Heart, Lung, and Blood Institute
Research Training and Development for MD Clinical Investigator Award (K08) Physician Scientist Award (Kll)
Research Project Grant
(R01) Short-Term Training of Health Professional Mechanism of Support
Students (T3S)
I I Years OI Stages Medical of Research Student Training and Development
Postdoctoral Training
Support (T32,T32m,F32) 1 I I I
I
First Independent Research Support and Transition Award
(R29)
I I I ]
Internship Early Residency ;oOcSl~raI
Early Career Development
Research Career Development Award
(K04)
I I I I I I I
Late Postdoctoral Independent Research Career Development
Preventive Cardiology Academic Award
(K07)
Senior Fellowship
(F33)
I I I I I Mid-Career Change New Techniques Mid-Career Change
Fig. 1. Recommended career development schedule by NIH. Mechanism of support refers to the types of grant one may seek through the Institutes. (Used with permission) N I H research project grants. It is ideal for young investigators to apply for this support before they apply for R01 grants FIRST Awards are made for a period of 5 years. These awards are not renewable. The total direct costs awarded must not exceed $350,000 for the 5 years, with no more than $100,000 for any i year. Principal investigators must make a maly significant commitment of time and effort, at least 50%, to the proposed research project. The Research Career Development Programs. There are several types of awards designed for research career development for potential investigators. All these awards are selected by national competition.
Research Career Development Award (K04). Candidates must have at least 3 years of postdoctoral experience and the award is for 5 years and is nonrenewable. The salary support is about $50,000 per year plus fringe benefits. Clinical Investigator Award (K08). The Clinical Investigator Award is designed to encourage newly trained clinicians to develop dinical and basic research interests and skills in the area of cardiovascular disease. In addition to salary support of up to $40,000 a year with fringe benefits, up to $10,000 a year will be provided for research support. The K08 grant is a 5-year grant that requires the applicant to commit 75% of his or her time to clinical or basic research.
Physician Scientist Award (Kll). The Physician Scientist Award is designed to encourage individuals with clinical training to develop research skills in a fimdamental science. Minority SchoolFaculty DevelopmentAward (K14). The Minority School Faculty Development Award is reserved for faculty of minority schools. Preventive Cardiology Academic Award (K07). As the name Preventive Cardiology Academic Award indicates, this is strictly for the development of ventive cardiology. Academic Research Enhancement Award (R15) . To avoid the tendency of the rich getting richer, the Academic Research Enhancement Award is reserved for those schools that have not been major participants in N I H programs. SBIR Program (R43, R44). The objective of the SBIR is to promote technologic innovation within the American small business community. Surgeons who have innovative ideas about developing new devices, instruments, and procedures with small companies are encouraged to apply. Phase I (R43) es-, tablishes the technical merit and feasibility of the proposal. Awards are for a maximum of $50,000 total costs (direct plus indirect costs) for a period not to exceed 6 months. Phase II (R44) continues the research and development efforts initiated in phase I, which are likely to result in commercial prod-
Volume 12 Number 1 July ~!990
ucts. Phase II awards are for a maximum of $500,000 total cost for a period nornaally not to exceed 2 years. National Research Service Awards. National Research Service Awards include postdoctoral fellowships (F32), senior fellowships (F33), and institutional training grants (T32). Support of scientific meetings (R13). The objective of the R13 grant is to assist in the support of scientific ~eetings or conferences (either domestic or international) that are directed toward areas of Public Health Service scientific program missions. Requests for applications. Periodically, N I H invites applications for a focused project on a specific topic. For instance, in 1987 the requests for applications on "Vascular Heating: Cell and Rheological Factors" was released and generated a response of 40 applic, ions. A special review committee is set up to review these grants. Grants that are not fimded may be resubmitted for an R01 grant through the usual process.
The above-mentioned grants or awards are open to vascular surgeons. However, it is important to take into consideration the stage of one's career before applying for these grants. Fig. 1 illustrates the recommendations by NIH. All grant applications to N I H are subjected to peer review. Most grants are reviewed by a panel of experts referred to as initial review groups. In the ~Division of Research Grants, the panels are usually called study sections. For applications related to vascular surgery, the main review body is the Surgery and Bioengineering Study Section. This study section consists of 18 members) ~ The composition of ~ s section includes general surgeons, cardiac surgeons, vascular surgeons, biomedical engineers, and basic scientists with expertise in such areas as biomaterials, pathology, hematology, and vascular biology. The section is headed by an executive secretary ~who will assign each proposal to a primary and secondary reviewer who are members of the study -group. Recently a reader or tertiary reviewer who does not prepare a report has been added to augument the discussion. The study section meets three times a year for 2 days. During the meeting the assigned reviewers lead the discussion of the application for which they prepared written critiques. In ~most instances a concensus is reached by the group and a recommendation of approval, disapproval, or deferral is made by majority vote. For each favorably recommended application, each member of the study section records a numeric rating that reflects his or her opinion of the scientific merit of the application. The rating scale ranges from 1.0 to 5.0, with 1.0
Research and researchfinding 87 being the best (outstanding, 1.0 to 1.5; excellent, 1.5 to 2.0; good, 2.0 to 2.5; satisfactory, 2.5 to 3.0; adequate, 3.0 to 3.5; fair, 3.5 to 4.0; and acceptable, 4.0 to 5.0). After the meeting the executive secretary averages the individual reviewers' ratings for each favorably recommended application and multiplies by 100 to provide a three-digit rating that is the priority score. The score is added to the "pink sheet" or summary statement, which is prepared by the executive secretary and sent to the grant applicant and the National Advisory Council of the N I H for approval. In addition to the priority score, a percentile figure is calculated. The percentile represents the relative position or rank of each priority score among the scores assigned by the particular study section at its last three meetings. The lower the numeric value of the priority score or percentile, the better the application. The percentile also appears on the pink sheet. The council's recommendations are forwarded to the director of the NIH, and he or she makes the final decision on funding. However, the director of the N I H can fund only a proposal that has been approved by the Advisory Council, and it is this restriction that prevents political interference. Once the investigator receives the pink sheet, which contains the critique and priority score, the applicant may submit a letter of rebuttal or alternatively withdraw the proposal or resubmit it. For the beginning applicant, if funding is not forthcoming (approved but not funded) it is advisable to resubmit the proposal incorporating changes according to the critique on the pink sheet. The applicant must be sure to indicate changes made within the body of the application by underlining them or using different print and explaining these changes in the introduction section. Resubmission is common and about one quarter of the grant applications are resubmissions. Success in applying for a research grant depends on the soundness of the design of the study. Several publications are now available to advise investigators how to prepare for a research grant. ~2-17In an article on how to apply for a research grant, Howie ~8 states that success depends on producing clear evidence of good questions that need to be answered, a capacity to make a promising attempt at finding the answer, reasonable opportunity to do the work in good conditions and within a defined period, and the need for specified financial support for the stated purpose. Brevity and organization are also important to the success of the application. 16 To be a successful applicant, one must understand the review process and what the reviewers are looking for. For reviewers the principal criteria for the initial
88
Journal of VASCULAR SURGF~Y
Ya0
Table II. Shortcomings of grant applications not approved or poorly rated by NIH
Table III. Numbers of grants in vascular surgery funded by NIH
Grants showing that shortcoming Shortcoming
Hypothesis: ill-defined, lacking, faulty, diffuse, unwarranted Research problems: significance unimportant, unimaginative, unlikely to provide new information Experimental design: study group or controls: inappropriate composition, number, or characteristics Experimental design: technical methodology: questionable, unsuited, defective Experimental design: data collection procedures: confused design, inappropriate instrumentation, timing, or conditions Experimental design: data management and analysis: vague Investigator: inadequate expertise or familiarity with literature in the research area, poor past performance, insufficient time to be devoted to project Resources: inadequate institutional se~ing, support staff, laboratory facilities, equipment, or personnel; restricted access to appropriate population; insufficient involvement or collaboration of colleagues and coinvestigators
No. %
120
47
77
30
103
40
168
66
104
41
80
31
43
17
9
4
Modified from Smith R. Br Med J 1988;296:691-5.
review of applications for research project grants include (1) scientific, technical, or medical significance and originality of the proposed research, (2) appropriateness and adequacy of the experimental approach and methods to be used, (3) qualifications and experience of the principal investigator and staff in the area of the proposed research, (4) reasonable availability of resources necessary to the proposed research, (5) reasonableness at the proposed budget and duration in relation to the proposed research, and, (6) where an application involves activities that could have an adverse effect on humans, animals, or the environment, the adequacy of the proposed means for protecting effects)° In addition to these criteria, the reviewer will also pay special attention to the hypothesis, the preliminary data demonstrating feasibility of the study, and the statistical design. The support staff is also especially important when complex basic science methods are involved in the proposal.
Grant
No.
Endovascular Cerebrovascular Vascular graft Ultrasonography Venous thrombosis Peripheral arterial disease Raynaud's syndrome Intestinal ischemia Renal artery disease Portal hypertension Total
19 7 7 3 11 13 10 2 2 6 80
Obviously not all proposals are successful. Applicants are encouraged to know the most comm~,~ shortcomings in failed proposals) 9 Table II outlines a survey by Cuca, 2° who reviewed 256 proposals that had been either disapproved or given a low priority score. Of the eight shortcomings listed, deficiency i~ methodology was the most common shortcoming (66%) followed by a poor hypothesis (47%). How good is peer review? The process of peer review has come under critical examination and is a subject of endless debate) 8,21 Nevertheless, the process is a fair system and is summarized superbly by Stephen Lock in his Rock Carling lecture. He stated, 'q~his instrument is fallible but it is the best we" have. "22 Who is a peer for peer-reviewed surgical research? The recent editorial by Jaffe23 has answered the question clearly, that is "another surgeon, of course." It is hoped that continuous participation of vascular surgeons in the study section will give surgeons a fair hearing of their research proposals. N I H - f u n d e d research in vascular surgery. Because of the broad scope of vascular surgery, NIHfunded research in this area is provided through several institutes and divisions; the assignment of the, source of ftmding depends on the relevance of the research to a particular organ, tissue, or disease. 24Ar present there is no information available regarding NIH-supported research under the disease category of vascular surgery. To survey the level of support in vascular surgery, an inquiry was made to the NIH for all grants funded under the category of vascular disease and surgery. A total of 3654 funded projects or grants with the tittle and abstracts of each project or grant was received (unpublished data). Unfortunately, the classification of vascular disease and surgery by NIH is too diffuse, with inclusion of nephritis, chronic renal failure, and various cardiac disorders that are unrelated to vascular surgery.
Volume 12 Number 1 Iulv 1990
Research and research finding
Table IV. N I H support for research career development (KO-4) and clinical ~investigator (KO-8) awards KO-4 No: applications No. approved Awarded (n/%) KO-8 No. applications No. approved Awarded (n/%)
89
Table V. Specialized Center for Research (P50) awards
1987
1988
43 42 14/32
25 24 7/29
29 20 18'/90
I5 12.
2/17
second request was then made with categories related to vascular disease and surgery, and 1066 abfacts were available for detailed analysis. The total funding for these 1066 grants and contracts was $204,319,127. The title and abstract of each project were then analyzed and categorized. These 1066 funded projects were derived from a wide variety of grants and support mechanisms. These include ROI, K04, K08, R29, P0I (program project), P50 (specialized center), P60 (National Research and Demonstration Center), and M 0 I (Clinical Research Center) Grants. Table III shows the number of grants =classified by the traditional terms in vascular ddisease or surgery. Eighty grants related to vascular surgery .....were awarded in 1988. It is of great interest to note the lack of funding in research on aortic aneurysm despite being ranked as the fifteenth most common cause of death in this country and the tenth leading cause of death among those above the age o f 55 years. 2s On the contrary, a rather nonfatal disease 2,ch as Raynaud's disease received strong support, and a total of i0 grants were awarded in this eate, gory. New technology such as endovascular surgery has also received satisfactory support. N I H funding for K04 and K08 is: less optimal. Only seven K08 and two K04 grants were awarded in i988, and in-formation on how many of these awards are assigned to vascular research is unavailable (Table IV) (unpublished data). However, it must be emphasized that vascular surgery and disease embraces a rather broad field. Thrombosis, hemodynamic phenomenon, biochemical factors, and recent interest in molecular biotogy, especially endothelial ceil research, are related to vascular disease. Many of these areas of interest are supported by intense research by specialized center or national demonstration centers~ Table V lists the targets of disease supported by N I H through the specialized centers for research. As stated clearly by
Disease
No.
Atherosclerosis Hypertension Ischemic heart disease Cerebrovascular disease Thrombosis
5 6 10 ~ 14t 4
¢Indudcs seven in ischemi¢ heart disease, one in peripheral vascular disease, one congential heart disease, and one in heart failure: tCerebrox.ascular Disease Research Centers under P50 and PO1 mechanisms.
Didisheim 24 in his presentation on National Heart, Lung and Blood Institute-funded research in vascular surgery at the Research Initiatives Meeting, NIH-supported research in vascular surgery is much better than it was I 0 years ago. Within the Division of Heart and Vascular Diseases of the National Heart, Lung and Blood Institute, a grant dealing with vascular surgery may be assigned to the Lipid Metabolism and Atherosderosis, Cardiac Disease, or Devices and Technology Branches depending on its focus. In Didisheim's analysis it is gratifying to note the increase of participation of vascular surgeons in NIH-funded research. O f the 28 grants on vascular grafts and vascular healing, 12 of the principal investigators, 3 of the coprincipal investigators, 17 of the coinvestigators, and 3 of the consultants are vascular surgeons. The recent award of a Specialized Center on Research program in vascular disease to University of Washington is also a welcome addition to the endeavor by members of the Society. SUMMARY The presentation summarized thc current status of funding available for vascular surgeons. In spite of the shrinking support for research by the federal government, there are oppommities for young investigators to pursue an academic career. Success of a grant application depends on preparation, design, and hypothesis. Potential applicants are encouraged to pay special attention to the many publications on how to prepare a research g r a n t ) 2"17 Although there is an increase in participation by vascular surgeons in NIH-supported research, the funding support and focus on vascular surgery remains unsatisfactory. Despite the high ranking of death from aortic aneurysm, there is virtually no funded project on aortic aneurysm in either basic or clinical study. New technology such as laser has received some support, but clinical trial comparing this modality with standard treat-
90
Journal of VASCULAR SURGERY
Ya0
ment is lacking and not forthcoming. The participation by vascular surgeons in the American Heart Association-ftmded research activities remains unknown, even though the American Heart Association claims to have spent millions on research in heart and vascular diseases. To promote the study of and research in vascular disease, the members of this distinguished Society need to guide young vascular surgeons to submit grant proposals to various organizations.
L
11.
12. 13.
14. 15.
REFERENCES 1. Shumacker HB Jr. The Society for Vascular Surgery: a history: 1945-1983. Society for Vascular Surgery, 1984. 2. Thompson JC. The role of research in the surgery of tomorrow. Am J Surg 1984;147:2-8. 3. Wyngaardeum JB. The support of clinical research and training by the National Institutes of Health: Introduction to the symposium. Arch Intern Med 1985;145:1241-4. 4. Lenfant C, Moskowitz J. The National Heart, Lung and Blood Institute: a plan for the eighties. Circulation 1983; 68:1141-4. 5. Healy B. Biomedical research: inlook and outlook. Cleve Clin J Med 1987;54:143-9. 6. Glickman RM. The future of the physician. Sci J Clin Invest 1985;76:1293-6. 7. Information for members of scientific review groups. Department of Veterans Affairs, Medical Research Service, 1989. 8. American Heart Association. Annual report, 1988. 9. NIH peer review notes. Division of Research Grants, Febmary 1989.
10. Orientation handbook for members of scientific review
16. 17.
18. 19. 20. 21. 22. 23. 24.
25.
groups. US Department of Health and Human Services, Public Health Service, National Institutes of Health, June 1989. NIH advisory committees. US Department of Health and Human Services, Public Health Service, National Institutes of Health, April 1989. SultzHA, SherwinFS. Grant writing for health professionals. Boston: Little, Brown and Co. 1981. Marks RG. Designing a research project: the basics of biomedical research methodology. Belmont, CA: Lifetime Learning Publications, 1982. Reif-Lehrer L. Going for the gold: some dos and don'ts f o r grant seekers. Scientist 1989;3:15-9. Pollock R, Balch CM. The NIH investigator award: how to write a training grant application. J Surg Res 1988;46:1-3. Niederhuber JE. Writing a successful grant application. J Surg Res 1985;39:277-81. Gordon SL. Ingredients of a successful grant application to the National Institutes of Health. J Orthop Res 1989;7:13841. Howie J. Apply for a research grant. Br Med J 1978;~ 1553-4. Smith R. Glimpses of the National Institutes of Health: review system and evaluation. Br Med J 1988;296:691-5. CucaJM. NIi-Igrant applications for clinical research: reasons for poor ratings or disapproval. Clin Res 1983;31:453-63. Relman AS, Angell M. How good is peer review? N Engl J Med 1989;321:827-9. Lock S. A difficult balance: editorial peer review in medicine. Philadelphia: ISI Press, 1986. Iaffe BM. Editorial: who is a peer for peer-reviewed surgical research? Surg Rounds 1989;2:11-2. Didisheim P. National Heart, Lung, and Blood Institutefimded research in vascular surgery. J VASC SUWG 1989; 10:563. Mortality for leading causes of death, United States-i986. Cancer Stat i990;40:12-5.
