Experiments in International Benchmarking of US Research Fields (2000) / Chapter Skim
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Attachment III: International Benchmarking of US Immunology Research
Attachment III: International Benchmarking of US Immunology Research
Pages 249-306
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From page 249... ...
ATTACHMENT 3 INTERNATIONAL BENCHMARKING OF US IMMUNOLOGY RESEARCH Pane! on international Benchmarking of US immunology Research Committee on Science, Engineering, and Public Policy
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This report is dedicated to Marian (Bunny) Koshiand a pioneer in thefield of molecular immunology and afriend to young immunologists
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ALT, Howard Hughes Medical Investigator and Professor, Children's Hospital, Harvard Medical School, Cambridge, Massachusetts HAROLD VON BOEHMER, Professor, Faculte de Medicine NeckerEnfants Malades, Institut Necker, Institut National de la Sante et de la Recherche Medicale, Paris, France MAX D COOPER, Howard Hughes Medical Investigator and Professor of Medicine, Pediatrics, Pathology, and Microbiology, University of Alabama, Birmingham IRWIN FELLER, Director, Institute for Policy Research and Evaluation and Professor of Economics, Pennsylvania State University, University Park LAURIE H
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, Professor of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley ENRIQUETA C BOND, President, The Burroughs Wellcome Fund, Durham, NC RUBY B
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In that report, COSEPUP suggested that the United States adopt the principle of being among the world leaders in all major fields of science so that it can quickly apply and extend advances in science whenever and wherever they occur. The report also recommended that the United States maintain clear leadership in fields that are tied to national objectives, that capture the imagination of society, or that have multiplicative effects on other scientific advances.
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In addition, while US dominance is evident in the major sub-fields: cellular immunology, molecular immunology, immunogenetics, and clinical aspects of immunology, and among the world leaders in some parts of subfields, the panel found that US leadership in immunology depends on being able to generate and pursue innovative research ideas. Sufficient funding from both government and private sources, talented researchers, and key infrastructure support mechanisms are instrumental in maintaining US leadership.
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Seaver Laboratory, Department of Medicine, Cornell University Medical College Joseph Newhouse, John D MacArthur Professor of Health Policy and Management, Harvard University Philippa Marrack, Howard Hughes Medical Institute, National Jewish Medical and Research Center Edward Penhoet, Vice Chairman and CEO, Chiron Corporation Klaus Rajewsky, Institute for Genetics, University of Cologne Martin Weigert, Department of Molecular Biology, Princeton University Arthur Weiss, Howard Hughes Medical Institute, University of California Although those just listed have provided many constructive comments and suggestions, responsibility for the final content of this report rests solely with the author panel and COSEPUP.
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3-6 1.5 What Are Some Caveats? 3-6 1.6 Panel Charge and Rationale 3-6 BENCHMARKING RESULTS 2.1 Methods, 3-8 2.1.1 Reputation Survey, 3-9 2.1.2 Citation Analysis, 3-11 2.1.3 Journal Publication Analysis, 3-12 Results, 3-12 2.2.1 Reputation Survey, 3-12 2.2.2 Citation Analysis, 3-13 2.2.3 Journal Publication Analysis, 3-16 Summary, 3-18 KEY FACTORS 3.1 Funding, 3-19 3.2 Human Resources, 3-22 3.3 Infrastructure, 3-23 3-3 3-8 3-19 ~ ~5-IX
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In Addition, Increasing Dominance of Managed Care Means That Fewer Patients Are Available to Academic Institutions for Clinical Trials, 3-37 5.5 Shifting Federal and Industry Priorities, a Potential Reduction in Access to Domestic and Foreign Talent, and the Increasing Cost of Maintaining Mouse Facilities Could Curtail US Ability To Capitalize on Leadership Opportunities, 3-37 6 REFERENCES 7 3-39 APPENDIX: PANELAND STAFF BIOGRAPHICAL 3-40 INFORMATION Tables ant! Graphs Figure 2.1: Contribution of United States and other nations to immunology papers in 1981-1996, 3-9 Figure 2.2: Percentage of world's papers in immunology from 19811996, by country, 3-10 3-x
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Contents Figure 2.3: Contribution of United States and other nations to immunology citations in 1981-1997,3-11 Figure 2.4: Percentage of world's citations in immunology in 1981-1997, by country, 3-15 Figure 3.1: U.S. net trade balance: biotechnology, 1990-1996,3-27 Figure 4.1: Number of PhD students in immunology in the United States, 1977-1996,3-31 Figure 4.2: Percentage of US citizen and permanent-resident PhD students in immunology supported by National Institutes of Health, 1977-1996, 3-31 Table 2.1: Immunology International Reputation Survey Results, 3-14 Table 2.2: Relative Citation Impact of high-impact papers in immunology, by country, 1981-1997,3-16 Table 2.3: Authorship of Immunology Papers in Blood, 1995-1997,3-17 Table 2.4: Authorship of Immunology Papers in Cell, 1995-1997,3-17 Table 2.5: Authorship of Immunology Papers in Immunity, 1995-1997, 3-17 Table 2.6: Authorship of Immunology Papers inNature, 1995-1997, 3-17 Table 2.7: Authorship of Immunology Papers in Science, 1995-1997,3-18 Table 2.8 Authorship of Immunology Papers in the Journal of E'cperimental Medicine, February 1996-July 1996,3-18 Table 3.1: Analysis of Nobel Prizes Presented for Immunology Research, 3-22 Table 3.2: Biotechnology Industry Comparable Metrics (Ecu in Millions)
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The panel was not able to assess this question in an objective way, but it used the expertise and judgment of its members and the limited information available to conclude that the United States is the world leader in immunology. US dominance is also evident in the major subfields of immunologycellular immunology, molecular immunology, immunogenetics, and clinical aspects of immunology.
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In addition, increasing dominance of managed care means that fewer patients are available to academic institutions for clinical trials. · Shifting federal and industry priorities, a potential reduction in access to domestic and foreign talent, and the increasing cost of maintaining mouse facilities could curtail US ability to capitalize on leadership opportunities.
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in Immunology Research? Immunology encompasses fundamental scientific discovery at all levels of biological organization.
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Long after an infection (or vaccination) , the expanded number of memory cells guarantees that a second exposure to the same virus will be met by an expanded response which develops more rapidly, providing effective immunity before serious consequences of the infection develop.
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The multidisciplinary nature of immunology research is probably a major reason that immunology is so well connected with the more traditional subjects (such as biochemistry, genetics, and microbiology) , whose approaches define their disciplines.
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Immunology is an essentially multidisciplinary field, and immunological research overlaps with many other disciplines, including molecular and cellular biology, genetics, and biochemistry. Immunology serves as a foundation for the design and testing of varied biologic hypotheses.
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The determinants of leadership that have influenced US advancement in the field are discussed in Chapter 3. Chapter 4 assimilates past leadership determinants and current benchmarking results to predict future US leadership status in the field.
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In addition, in the case of this panel's operations, budget and time constraints effectively ruled out any major undertakings to generate new data sets. Within those constraints, the panel's strategy was to use three mainstream performance measures: reputation survey, citation analysis, and journal publication analysis, it then relied on the convergence of findings to compensate for the specific shortcomings of each measure.
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2.1.1 Reputation Survey To estimate reputation, the panel conceived a virtual congress in which leading experts in immunology were asked to identify potential participants. Specifically, the field was divided into four major subfieldscellular immunology, molecular immunology, immunogenetics, and clinical aspects of immunology and each was subdivided into four to 10 sub-subfields.
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disadvantages are multiple: variable modes of polling, a variable sample size that was usually too small to allow statistical treatment of the data, lack of objective criteria, and nonproportionate sampling of researchers in countries outside the United States.
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The ISI database was scanned over the years 1990-1997. For each year, the 200 most-cited papers in journals relevant to the field of immunology were listed.
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In addition, the list of authors is truncated after the first 15 names, possibly excluding authors who participated in large clinical trials. An additional limitation imposed by the database was that there was no breakdown according to subfield and sub-subfield of immunology.
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ciency. In clinical aspects of immunology, the sub-subfields of tumor immunology and transplantation and immunosuppressive drugs.
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The discrepancy can probably be attributed to flaws in the two approaches, in particular such defects in the ISI database as the exclusion of critical journals such as Cell and the Journal of Experimental Medicine.
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The subfield of cellular immunology and clinical aspects were dominated by US-based researchers in all journals examined except Blood. Because of its extensiveness, only 6 months of the Journal of Experimental Medicine was analyzed, as shown in Table 2.8.
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1(100) 1 Clinical aspects 12(75.0)
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2(13 3) 15 Clinical aspects 37(64 9)
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Many foreign countries, US universities, medical schools, and research institutes are either privately supported or supported by individual state governments-separate administrative units, under the federal system in 3-19 3-19
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Another major source of funding of immunology (and other biomedical subjects) is the Howard Hughes Medical Institute (HHMI)
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Additional private sources of immunology funding in the United States are the American Cancer Society, the Juvenile Diabetes Foundation, the Arthritis Foundation, and the Multiple Sclerosis Society. Funding for training grants for predoctoral fellows and postdoctoral fellows also comes from a wide variety of institutes of NIH and from private sources.
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This has given US research institutions a greater ability than foreign institutions to attract graduate students and postdoctoral fellows from other countries. The flexibility of funding based primarily on peer review and the merit of applications have made the United States a more attractive country for talented researchers at higher ranks to settle and pursue their research careers.
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3.4 Biotechnology anc! Pharmaceutical Firms Because of the nature of the venture-capital industry in the United States, the greater flexibility of this industry, and its willingness to fund ~ All data in this paragraph is from special analysis conducted by NRC Office of Scientific and Engineering Personnel of Survey of Earned Doctorates database for this study.
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. This financing of research and the use of many academic researchers for consultation in biotech firms and large pharmaceutical firms have provided relatively direct avenues for postdoctoral immunologists to obtain employment, to move across disciplines, and to capitalize rapidly on technology developments that are fostered primarily in biotech firms.
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Key Factors TABLE 3.2 Biotechnology Industry Comparable Metrics (Ecu in Millions) European Companies Market Profit/ R&D Biotech Company Cap Turnover Loss Costs Employees British Biotech 1,015 29.1 -42.6 54.2 454 Qiagen 699 68.2 8.1 7.6 650 Innogenetics 552 25.9 -0.9 12.6 380 Biocompatibles International 544 16.4 -27.6 12.2 393 Shire Pharmaceuticals 531 34.4 -0.2 16.1 390 Cortecs 412 11.5 -17.5 17.2 258 Genset 392 14.9 -17.1 23.1 355 Chiroscience 358 17.2 -27.9 33.2 320 NeuroSearch 357 2.7 -8.9 10.1 110 Celltech Group 340 6.4 -17.9 31.2 220 Scotia Holding 309 42.1 -30.8 34.3 420 Market Profit/ R&D Multinational Company Cap Turnover Loss Costs Employees Novartis 99,554 19,590.4 3,274 2,320.3 87,239 Glaxo Welcome 76,153 11,915.7 4,011 1,714.2 52.501 Smithkline Beecham 52,447 11,639.5 2,464 1,255.8 55,400 Zeneca 303,312 7,749 1,120 975.1 31,100 Astra 25,425 5,074.2 1,153 988.3 22,206 Baver Group 24,741 27,912 1,498 2,011.7 144,600 Hoechst Marion Roussel 18,590 7,091 838 1,206 40,500 US Companies Market Profit/ R&D Biotech Company Cap Turnover Loss Costs Employees AmAen 14,144 2,115.8 624.7 485.1 4,646 Chiron 3,588 1,206.3 50.5 340.8 7,434 Genentech 2,469 888.4 108.4 432.7 3,071 Biogen 2,300 254.5 37.7 121.3 675 Alza 2,264 428.1 84.5 130.5 1,652 Genzyme 1,938 488.7 -67.1 194.8 3,516 Immunex 1,319 140.6 -49.6 89.1 808 Market Profit/ R&D Multinational Company Cap Turnover Loss Costs Employees Merck 114,894 18,216.9 3,566 1,366.1 49,100 Johnson & Johnson 78,847 19,531.6 2,652 1,750.1 89,300 Bristol-Myers Squibb 74,174 13,840.2 2,618 1,172.3 51,200 Eli Lilly 55,517 6,749.7 1,400 1,093.3 29,200 Pfizer 35,479 10,386.8 1,772 1,547.1 46,500 Source: Ernst & Young, 1998a.
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INTERNATIONAL BENCHMARKING OF US IMMUNOLOGY RESEARCH TABLE 3.3 Entrepreneurial Life Science Highlights (Ecu in Millions) Europe Public Companies Industry Total Current Prior Percent Current Prior Percent Year Year Change Year Year Change Financial Revenues 648 433 50% 2,725 1,721 58% R&D expense 534 243 120% 1,910 1,508 27% Net loss 347 73 375% 2,020 1,113 81% Industry Number of Companies 61 49 24% 1,036 716 45% Employees 8,418 5,315 58% 39,045 27,500 42% USA Public Companies Industry Total Current Prior Percent Current Prior Percent Year Year Change Year Year Change Financial Revenues 12,862 10,565 22% 15,985 13,413 19% R&D expense 5,145 4,226 22% 8,268 7,258 14% Net loss 1,654 2,021 -18% 3,767 4,134 -9% Industry Number of companies 317 294 8% 1,274 1,287 -1% Employees 94,000 73,000 29% 140,000 118,000 19% Source: Ernst & Young, 1998a.
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Key Factors 1 000 900 to o ~ 800 .
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It must be recognized, however, that this could change. A return to the funding situation of the late 1980s and early l990s, with low pay grades and administrative cuts in funded-grant applications, could possibly harm the US leadership position by driving investigators and students away from biomedical research in general.
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The increasing cost of maintaining mouse facilities has raised serious concern among academic researchers. Although the cost of the mice is reasonable, as is the cost of the component of their care that includes husbandry, housing, feeding, and cleaning, as long as the charges match the costs on a species-specific basis, very large increases in charges often result for the following reasons: specialized veterinary care, which for all species is usually distributed in a species-nonspecific fashion, as are administrative and staff costs; the increased personnel efforts that are required to meet regulatory-compliance needs; and Office of Management and Budget (OMB)
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4.4 Training of US Students Panel members perceive the quality of US graduate students and postdoctoral fellows in immunology to be declining. Several factors Z Data in this paragraph from special analysis by NRC Office of Scientific and Engineering Personnel of data from the survey of Doctorate Recipients and the Survey of Earned Doctorates for this study.
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50 45 40 I 35 Q in 30 <~, 25 20 15 10 / \ / \J Y l 1977 1 979 1 981 1 983 1 985 1 987 1 989 1 991 1 993 1995 Years FIGURE 4.2 Percentage of US citizen and permanent-resident PhD students in immunology supported by National Institutes of Health, 1977-1996. Source: Analysis conducted by National Research Council's Office of Scientific and Engineering Personnel of Survey of Earned Doctorates for this study.
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of Resident Supported Resident Doctorates Supported Year Doctorates Doctorates byNIH Supported byNIH ByNIH 1977 101 90 39 39 43% 1978 94 86 43 43 50% 1979 134 131 56 55 42% 1980 125 119 49 49 41% 1981 148 141 61 60 43% 1982 151 136 66 66 49% 1983 154 137 58 58 42% 1984 133 121 43 42 35% 1985 124 113 42 42 37% 1986 146 129 54 53 41% 1987 136 113 45 44 39% 1988 179 164 43 43 26% 1989 152 136 49 49 36% 1990 153 129 46 46 36% 1991 177 140 47 46 33% 1992 181 155 60 60 39% 1993 169 131 47 46 35% 1994 161 143 51 51 36% 1995 190 171 62 62 36% 1996 238 198 81 80 40% Source: Analysis conducted by National Research Council's Office of Scientific and Engineering Personnel of Survey of Earned Doctorates for this study. might contribute to a decline in quality.
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o o E ._ CO o o CO Cal Al o Cal U)
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3 Data in this paragraph from special analysis by NRC Office of Scientific and Engineering Personnel of data from the Survey of Doctorate Recipients for this study.
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On the basis of the results of three benchmarking methods a virtual-congress survey, citation analysis, and publication counts the United States appears to be preeminent in immunology. Furthermore, it leads in all four of the subfields examined: cellular immunology, molecular immunology, immunogenetics, and clinical aspects of immunology.
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Critically, it is the individual investigator rather than the department chair or other research colleagues, as it often is in many European countries that has the authority and autonomy to pursue a specific research interest. Unlike many foreign countries, the United States supports research institutions and medical schools through state governments and private foundations, and this allows the freedom and flexibility to develop innovative research programs.
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The expense of a large-scale clinical trial often proves prohibitive, especially when there is fierce competition among institutions and between research interests for limited funding dollars. European countries, because of their centralized government control of medical schools and research institutions have been able to support large-scale clinical trials more successfully than the United States.
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Because much immunology research involves the use of mice, this resource is critical to the development of the field.
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Stanford Medical School, 1998. Conversation Between Irving Weissman and Michael Hindery, Associate Dean, Stanford Medical School regarding Cost of Animal Care Facilities.
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Dr. Allison is professor of immunology, director of the Cancer Research Laboratory, and a Howard Hughes Medical Investigator at the University of California, Berkeley.
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In 1982, he joined the faculty of the College of Physicians and Surgeons of Columbia University in New York, where he became professor of biochemistry and molecular biophysics and, professor of microbiology. In 1987, he became a Howard Hughes Medical Investigator at Columbia University.
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Dr. Cooper is professor of medicine, pediatrics, pathology, and microbiology at the University of Alabama at Birmingham; senior scientist at the University of Alabama Comprehensive Cancer Center; professor of medicine and director of the Division of Developmental and Clinical Immunology at the University of Alabama; and a Howard Hughes Medical Investigator.
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He has received the 3M Life Sciences Award, the Paul Erlich Prize, and Outstanding Investigator Award from NCI and NIH, the Barbara Davis Diabetes Award, and the Paul Klemperer Award from the New York Academy of Sciences. He became a member of the National Academy of Sciences in 1977, of the Institute of Medicine in 1983, and of the Royal Society of London in 1994.
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Dr. Thompson is a professor in the Department of Medicine and Molecular Genetics and Cell Biology at the University of Chicago and a Howard Hughes Medical Investigator.
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, where she is researching the risk factors for the progression of low-grade cervical disease to cervical cancer. She is also participating in analyzing data from the ASCUS/LSIL Triage Study, which is an NCI-sponsored clinical trial designed to determine the optimal management plan for low-grade cervical cytologic abnormalities.
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