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HEPATOLOGY and hepatology: The good, the bad, and the ugly
Editorials HEPATOLOGY and Hepatology: The Good, the Bad, and the Ugly This issue of HEPATOLOGY is the 72nd published since the Editorial Office was transferred from San Antonio to New York 6 years ago. By the end of 1996, we will have received a projected total of 5,844 manuscripts, and filled 21,823 pages in publishing 2,253 of them. The cohort of 1,138 manuscripts submitted in 1996 is the largest in any year since the founding of the journal, as is the collection of 445 articles published. Both figures continue long-established growth trends described in previous Editorials.1-3 Control over growth in the number of pages published, and therefore, subscription prices, was achieved by the introduction this past July of slightly smaller type faces and narrower page margins. Over time, this will permit the publication of roughly 10% more material without an increase in pages published. The change seems to have gone largely unnoticed except among a few incipient senior citizens who were at last driven to accept the need for bifocals. I have expressed my view that the growth in HEPATOLOGY largely reflects the growth of hepatology as a vibrant, independent, clinical subspecialty and equally vibrant scientific discipline.2,3 Liver transplantation, the recognition of new hepatitis viruses and the gradual evolution of antiviral therapies for them, a better understanding of portal hypertension with pharmacological and interventional approaches to its management, the potential of bioartificial devices to support the acutely failing liver, new information about hepatic growth and regeneration, oncogenesis, transport, cytokines, and a host of other areas are all attracting more and more people to the field, to the annual meeting of the American Association for the Study of Liver Diseases (AASLD) and its sister organizations abroad, and to the ranks of those who contribute (and subscribe) to these pages. Even the pharmaceutical industry has recognized that hepatology and hepatologists have an identity that, while clearly related, is separate from the broader field of general gastroenterology. HEPATOLOGY will include well over 100 pages of pharmaceutical advertising in 1996. Comparing the past 6 years with those that came before, the rate of growth of advertising in these pages has been infinite (the pre-1991 denominator having been virtually zero). Only the American Board of Internal Medicine has yet to recognize the uniqueness and independence of hepatology as a discipline. HEPATOLOGY was launched with some trepidation. There was concern by the AASLD Council, which, in the late 1970s, was considering the creation of this journal, that a publication restricted to the liver would not succesfully compete for what was considered to be a limited number of quality, publishable articles, and that such a journal would be a financial burden on the Association. This trepidation led to delay, during which the preferred title, Liver, was preempted by our less reticent European colleagues who launched another distinguished journal by that name. Nevertheless, the decision to proceed was finally made in 1980, and the first issue of HEPATOLOGY appeared in 1981. Since then, both fears have proven unfounded. Manuscripts have flowed in from the beginning, and, by 1990, revenues from HEPATOLOGY had become a major engine driving the dramatic expansion of the activities of the AASLD as a whole. If the field itself was burgeoning and generating a rapidly expanding volume of publishable data, was the success of HEPATOLOGY inevitable? Put another way, can one identify in some way a value added by the efforts of those who have toiled in various Editorial positions over the past 17 years? By comparing the early growth of HEPATOLOGY with that of other fledgling journals, even within the same field, it is
clear that major credit for HEPATOLOGY’s ability to hit the ground running belongs to our Founding Editor, Win Arias. In the journal’s first editorial, ‘‘HEPATOLOGY: A New Adventure in Liverland,’’ which appeared in Volume 1, Number 1, he laid down the principles that have guided the journal ever since.4 ‘‘A major long range objective of HEPATOLOGY,’’ he said in 1981, ‘‘is to bridge the ever-increasing gap between the amazing advances in biology and their application to liver physiology and disease.’’ These latter disciplines ‘‘are only beginning to experience the effect of modern cellular and molecular biology, immunology, genetics, and pharmacology. It requires little imagination to realize that the future will see direct applications of cloning, molecular hybridization, genetic engineering, advanced technology, membrane and receptor biology, collagen and biomatrix physiology, and other advances of the scientific revolution we are fortunate enough to be witnessing.’’ In his forward-looking view, it was ‘‘clear that these advances will profoundly change our discipline, alter our teaching and research, and underlie advances in pathophysiology, diagnosis, and treatment. HEPATOLOGY will not be a basic science journal but will hopefully constitute a scientific home for biologists who use the liver and thereby serve to enlighten us regarding the exciting new paths that are unfolding before our eyes. We will strive to have HEPATOLOGY reflect all dimensions of the remarkable organ which attracts our interests.’’ And so we have. This ab initio definition of HEPATOLOGY’s persona has continued to guide this journal through the tenures of Professor Arias’ successors, Steven Schenker and myself. It is clear from the pages of any recent issue of HEPATOLOGY that many aspects of the scientific revolution predicted by Arias have ceased being revolutionary, and are now the daily staples of high-quality, contemporary biomedical research. HEPATOLOGY’s Editors have extended every effort to make these pages hospitable to quality science across the entire spectrum, from molecular to clinical. The emphasis is, and always has been, on quality. The fundamental questions here are: What is quality and how can it be measured? The ‘‘quality’’ of a manuscript may reside, e.g., in a truly novel or provocative idea, even if presented with little or no experimental verification; in the presentation of a new method that permits important questions to be addressed for the first time or at a new level of sophistication; or in the elegant experimental confirmation of a previously elusive hypothesis. Some of the benchmarks for judgment are clear: the use of appropriate controls, proper statistical analysis, and the use of analytical methods capable of the precision required in the particular ciurcumstance. It is clear, however, that despite pretensions of objectivity, reviewers’ opinions and editorial decisions are inherently subjective. Nevertheless, the passage of time permits a retrospective assessment of the quality of scientific papers. It can be presumed that papers of quality are those that make an impact on their field, and are therefore frequently cited in subsequent publications. Therefore, at least a crude estimate of the quality of published papers, and of the perceptiveness of those subjective editorial decisions, can be obtained by an examination of the citation history of published articles. Similar examinations may also say something about the comparative vigor of different fields. Using data supplied by the Institute for Scientific Information, we have examined the citation history of the 22,132 papers in the field of gastroenterology and hepatology published in specialty journals between 1991 and 1995. Approximately one
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HEPATOLOGY Vol. 24, No. 6, 1996
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FIG. 3. Source, by journal, of the 100 most frequently cited articles about the liver and biliary tract, published in the gastroenterology and hepatology specialty literature, 1991 through 1995. Articles are ranked from 1 to 100 according to how frequently they were cited. FIG. 1. Subject matter of the 100 most frequently cited articles in the gastroenterology and hepatology specialty literature, 1991 through 1995. Articles are ranked from 1 to 100 according to how frequently they were cited.
quarter of these papers were never subsequently cited. When the data base was restricted to papers that had been cited at least 25 times after publication, and therefore likely to represent papers that had made an appreciable impact on their respective fields, a total of 582 papers were identified. Seven of the 10 most cited articles, 19 of the top 25 (76%), and 64 of the top 100 dealt with the liver, its biology, pathobiology, and diseases (Fig. 1). Thus, among the most widely cited papers published in the broad field of gastroenterology and hepatology over the past 5 years, papers about the liver represented a very solid majority. Hepatology, the discipline, is thriving! Where were these important papers published? In the broad field of gastroenterology and hepatology, 6 of the 10 most frequently cited articles, 15 of the top 25, 26 of the top 50, and 44 of the top 100 papers were published in HEPATOLOGY (Fig. 2). Within each of these four categories of citation frequency, Gastroenterology ranked second, accounting for 24% to 34% of the articles. Together, HEPATOLOGY and Gastroenterology accounted for 78% to 90% of these often cited papers within this subject category. Among the 100 most frequently cited papers that dealt specifically with the liver and biliary tract (Fig. 3), 8 of the top 10, 20 of the top 25, 37 of the top 50, and 68 of the top 100 appeared in this journal. Gastroenterology was the source of 3 of the top 25, 7 of the top 50, and 21 of the top 100. All other journals combined accounted for 11 of the 100 most frequently cited articles.
FIG. 2. Source, by journal, of the 100 most frequently cited articles from the gastroenterology and hepatology specialty literature, 1991 through 1995. Articles are ranked from 1 to 100 according to how frequently they were cited.
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Although science is a discipline that prides itself on precision, quantification, standards, and controls, there is no absolute gold standard for the quality of scientific publications. Even citation frequency can be analyzed by several models. Moreover, as noted above, editorial decisions are inherently subjective. Nevertheless, the results presented above suggest that the Editors of HEPATOLOGY over the past 5 years have exercised good judgment and have chosen well. For this, the community owes a debt of gratitude to D. Montgomery Bissell, Andres T. Blei, Henry C. Bodenheimer, Jr., Herbert L. Bonkovsky, Adrian M. DiBisceglie, Lawrence S. Friedman, Michael A. Gerber, Robert M. Glickman, Jorge J. Gumucio, Jay H. Hoofnagle, Ann L. Hubbard, Albert Jones, Raymond S. Koff, T. Jake Liang, Willis C. Maddrey, Esteban Mezey, Kunio Okuda, Gustav Paumgartner, Ju¨rg Reichen, Nicola Tavoloni, and Allan W. Wolkoff, who have served as Associate Editors during the past 6 years; to the more than 200 colleagues who have served terms on the Editorial Board; and to the more than 1,500 who have served as reviewers. HEPATOLOGY would not be what it is today without their efforts. Nor, in a very real sense, would hepatology. Joan Blumberg, Nancy Mullins, Michael Miller, and others at W. B. Saunders make their own, distinctive contributions to our journal, for which we are most grateful. If both HEPATOLOGY and hepatology are thriving, why the mixed message implied by the title of this editorial? The answer reflects, in part, a bit of chauvinism on the part of this Editor. Hepatology is a uniquely international discipline, and HEPATOLOGY, nominally the official publication of the AASLD, has become de facto an international journal. For these reasons, the very success of hepatology and HEPATOLOGY tends to obscure the hard times currently being experienced by the American biomedical science community. These hard times are reflected by the static, or, in some disciplines, declining, research output of American biomedical research programs. We received 259 American manuscripts in 1995. At the time of this editorial’s writing, October 4, 1996, we project receiving 261 original manuscripts from American contributors by the end of the 1996 calendar year. This represents a decline of 2.2% from the 267 received in 1991, the first year that HEPATOLOGY was edited in New York. Over the same period, foreign submissions have increased by 76%, from 497 to a projected 876. If this trend were unique to HEPATOLOGY, one could excuse it in many ways. Perhaps, for example, American authors simply prefer to send their papers elsewhere. However, the trend is equally visible in submissions to Gastroenterology,5 and, as summarized in a recent editorial in The New England Journal of Medicine,6 in many of the most outstanding American biomedical publications.
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HEPATOLOGY December 1996
It seems most unlikely that an epidemic of acute and chronic stupidity has swept through this country’s scientific community. The very breadth of the stagnation in biomedical research output argues that community-wide structural forces are at work. It is not difficult to identify at least some of these forces. In a variety of different guises, however, they can all be summarized in a single word: money. The plight of basic investigators dependent on grant support, especially from the National Institutes of Health (NIH), has been addressed many times, both in these pages3 and elsewhere.7 In fact, the situation is in some respects improving. Effective public education campaigns and old-fashioned political lobbying by a number of academic organizations protected the NIH budget from the draconian cuts that threatened 2 years ago, and the budget has actually risen slightly since. Funding paylines, which had plunged to record lows, appear to be recovering somewhat. Nevertheless, substantial damage has been done, both to the recruitment of America’s most talented students into biomedical research careers7 and to the productivity of established programs. It is not unusual for an investigator to spend the better part of 3 months preparing an NIH grant application. Over the past several years, the proportion of both new and competing renewal applications funded on the first submission seems also to have been at an all-time low,8 so that a second, or, all too often, a third application was required to obtain support. In personal discussions, one NIH administrator compared the large number of talented, established investigators caught in a cycle of repetitive re-applications with airliners stacked up over a fog-bound airport, ‘‘just waiting their turn.’’ Several years of budgets supporting paylines at better than the 20th percentile will be necessary just to eliminate the backlog of deserving but unfunded proposals. In consequence of the funding situation, many established programs have experienced an interruption in financial support. These have come at a time when their own departments or institutions were increasingly unable to provide adequate bridging funds during the intervals between grants. Even if the principal investigator’s salary was not at risk, which was by no means the universal situation, it was often impossible to support technicians and other valuable, experienced members of a research team through the funding hiatus. Thus, when funding finally was obtained, it was often necessary to start by training a new staff, resulting in an inevitable loss of momentum in the research effort and in the government’s return on its investment of research dollars. Simultaneously, as the effort expended in obtaining grant support has increased, various pressures have reduced the average duration of funding, throwing investigators back into the application cycle more frequently. Although the United States spends a higher proportion of its gross domestic product on biomedical research than any other nation, the consequences of the imbalance between the large and still-expanding pool of highly trained investigators and a finite budget that is unlikely to expand in real terms in the forseeable future are disappointment, frustration, and inefficiency. These, in turn, are reflected in the diminishing proportion of American research reports in America’s most prestigious journals. Beyond the limited supply of NIH support, clinical investigators face special problems, which illustrate more specifically the extent to which the funding of biomedical investigation has become inextricably interwoven with ‘‘the health care financing mess.’’9 More and more American institutions are requiring that members of their clinical faculties support themselves entirely through their clinical practice revenues. Because the growing shift to managed care has meant less return for greater clinical effort, the time available for planning, writing, and execution of clinical research protocols, not to mention thoughtful analysis of data, is increasingly squeezed by the need to generate one’s salary elsewhere. The continuing tension between American clinical investigators
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and insurers of health care, including the federal government itself, over who should pay the costs of actual care rendered in the course of clinical trials has often made the costs of such trials prohibitively expensive to prospective pharmaceutical sponsors. This is particularly true of trials to be performed in traditional academic medical centers, which almost universally have high patient care costs. In an age when the costs of any delay in bringing a drug to market are estimated at $20 per second, the inevitable bureaucratic delays in obtaining Institutional Review Board approval at most academic medical centers are a further factor discouraging the conduct of sponsored clinical research at many institutions. These issues have fostered the growth of for-profit Contract Research Organizations, which contract with sponsors to perform clinical trials in nonacademic settings with lower costs and far less bureaucracy. Because the raison d’eˆtre of these organizations is profit, not academic productivity, much of their research is likely to be unpublished, at least in traditional channels, and therefore not subject to the scrutiny of peer review. Finally, the recent decision that the Food and Drug Administration can use the results of clinical studies abroad in the process of evaluating new drugs for approval in the United States—while a boon both to patients and the pharmaceutical industry—will almost certainly be a further blow to the American clinical research community. Particularly because most major pharmaceutical houses are now multinational enterprises, this rule change, while both logical and desirable in most regards, will likely stimulate a further major shift in sponsored clinical research sponsorship to sites abroad. Even more worrisome than these trends themselves is the difficulty experienced by the academic community in mounting a strong and constructive response. American biomedical institutions are all embattled with various manifestations of the managed care health maintenance organization onslaught, and their leadership is increasingly focused on economic survival. Even at highly successful academic institutions, annual research budgets of, e.g., $100 million are likely to be dwarfed by hospital revenues measured in billions. Accordingly, faculty development and support for science too often appear to receive a proportionately small share of attention. Even at the departmental level, faculty practice issues and revenues, rather than research activities, are likely to dominate the agendas. Hepatology and HEPATOLOGY both verge on the start of a potential golden age. As measured by papers published in this journal, American participation is decreasing by about 1% annually. Unless the American biomedical research enterprise is assigned a higher national priority and considered and supported as an integrated system, our participation in this golden age extrapolates to zero in 2023. PAUL D. BERK, M.D. Editor-in-Chief REFERENCES 1. Schenker S, Khan SA. HEPATOLOGY: What a difference a decade makes. HEPATOLOGY 1990;12:1436-1439. 2. Berk PD. HEPATOLOGY and hepatology: a midterm status report. HEPATOLOGY 1993;18:454-456. 3. Berk PD. HEPATOLOGY and hepatology: the trends continue. HEPATOLOGY 1995;21:875-878. 4. Arias IM. Hepatology: a new adventure in liverland. HEPATOLOGY 1981;1:84. 5. LaRusso NF, Link AM. Gastroenterology—an international journal. Gastroenterology 1995;108:625-626. 6. Kassirer JP. My years at the journal—so far. N Engl J Med 1995;333:654655. 7. National Research Council. The funding of young investigators in the biological and biomedical sciences. Washington, DC: National Academy Press, 1994:1-117. 8. Mandel HG. Funding of NIH grant applications: update. Science 1995;269: 13-14. 9. Berk PD. Restructuring American health care financing: first of all do no harm! HEPATOLOGY 1993;18:206-215.
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WBS: Hepatology
clear that major credit for HEPATOLOGY’s ability to hit the ground running belongs to our Founding Editor, Win Arias. In the journal’s first editorial, ‘‘HEPATOLOGY: A New Adventure in Liverland,’’ which appeared in Volume 1, Number 1, he laid down the principles that have guided the journal ever since.4 ‘‘A major long range objective of HEPATOLOGY,’’ he said in 1981, ‘‘is to bridge the ever-increasing gap between the amazing advances in biology and their application to liver physiology and disease.’’ These latter disciplines ‘‘are only beginning to experience the effect of modern cellular and molecular biology, immunology, genetics, and pharmacology. It requires little imagination to realize that the future will see direct applications of cloning, molecular hybridization, genetic engineering, advanced technology, membrane and receptor biology, collagen and biomatrix physiology, and other advances of the scientific revolution we are fortunate enough to be witnessing.’’ In his forward-looking view, it was ‘‘clear that these advances will profoundly change our discipline, alter our teaching and research, and underlie advances in pathophysiology, diagnosis, and treatment. HEPATOLOGY will not be a basic science journal but will hopefully constitute a scientific home for biologists who use the liver and thereby serve to enlighten us regarding the exciting new paths that are unfolding before our eyes. We will strive to have HEPATOLOGY reflect all dimensions of the remarkable organ which attracts our interests.’’ And so we have. This ab initio definition of HEPATOLOGY’s persona has continued to guide this journal through the tenures of Professor Arias’ successors, Steven Schenker and myself. It is clear from the pages of any recent issue of HEPATOLOGY that many aspects of the scientific revolution predicted by Arias have ceased being revolutionary, and are now the daily staples of high-quality, contemporary biomedical research. HEPATOLOGY’s Editors have extended every effort to make these pages hospitable to quality science across the entire spectrum, from molecular to clinical. The emphasis is, and always has been, on quality. The fundamental questions here are: What is quality and how can it be measured? The ‘‘quality’’ of a manuscript may reside, e.g., in a truly novel or provocative idea, even if presented with little or no experimental verification; in the presentation of a new method that permits important questions to be addressed for the first time or at a new level of sophistication; or in the elegant experimental confirmation of a previously elusive hypothesis. Some of the benchmarks for judgment are clear: the use of appropriate controls, proper statistical analysis, and the use of analytical methods capable of the precision required in the particular ciurcumstance. It is clear, however, that despite pretensions of objectivity, reviewers’ opinions and editorial decisions are inherently subjective. Nevertheless, the passage of time permits a retrospective assessment of the quality of scientific papers. It can be presumed that papers of quality are those that make an impact on their field, and are therefore frequently cited in subsequent publications. Therefore, at least a crude estimate of the quality of published papers, and of the perceptiveness of those subjective editorial decisions, can be obtained by an examination of the citation history of published articles. Similar examinations may also say something about the comparative vigor of different fields. Using data supplied by the Institute for Scientific Information, we have examined the citation history of the 22,132 papers in the field of gastroenterology and hepatology published in specialty journals between 1991 and 1995. Approximately one
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HEPATOLOGY Vol. 24, No. 6, 1996
BERK
1531
FIG. 3. Source, by journal, of the 100 most frequently cited articles about the liver and biliary tract, published in the gastroenterology and hepatology specialty literature, 1991 through 1995. Articles are ranked from 1 to 100 according to how frequently they were cited. FIG. 1. Subject matter of the 100 most frequently cited articles in the gastroenterology and hepatology specialty literature, 1991 through 1995. Articles are ranked from 1 to 100 according to how frequently they were cited.
quarter of these papers were never subsequently cited. When the data base was restricted to papers that had been cited at least 25 times after publication, and therefore likely to represent papers that had made an appreciable impact on their respective fields, a total of 582 papers were identified. Seven of the 10 most cited articles, 19 of the top 25 (76%), and 64 of the top 100 dealt with the liver, its biology, pathobiology, and diseases (Fig. 1). Thus, among the most widely cited papers published in the broad field of gastroenterology and hepatology over the past 5 years, papers about the liver represented a very solid majority. Hepatology, the discipline, is thriving! Where were these important papers published? In the broad field of gastroenterology and hepatology, 6 of the 10 most frequently cited articles, 15 of the top 25, 26 of the top 50, and 44 of the top 100 papers were published in HEPATOLOGY (Fig. 2). Within each of these four categories of citation frequency, Gastroenterology ranked second, accounting for 24% to 34% of the articles. Together, HEPATOLOGY and Gastroenterology accounted for 78% to 90% of these often cited papers within this subject category. Among the 100 most frequently cited papers that dealt specifically with the liver and biliary tract (Fig. 3), 8 of the top 10, 20 of the top 25, 37 of the top 50, and 68 of the top 100 appeared in this journal. Gastroenterology was the source of 3 of the top 25, 7 of the top 50, and 21 of the top 100. All other journals combined accounted for 11 of the 100 most frequently cited articles.
FIG. 2. Source, by journal, of the 100 most frequently cited articles from the gastroenterology and hepatology specialty literature, 1991 through 1995. Articles are ranked from 1 to 100 according to how frequently they were cited.
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5p19$$$881
11-04-96 20:36:31
Although science is a discipline that prides itself on precision, quantification, standards, and controls, there is no absolute gold standard for the quality of scientific publications. Even citation frequency can be analyzed by several models. Moreover, as noted above, editorial decisions are inherently subjective. Nevertheless, the results presented above suggest that the Editors of HEPATOLOGY over the past 5 years have exercised good judgment and have chosen well. For this, the community owes a debt of gratitude to D. Montgomery Bissell, Andres T. Blei, Henry C. Bodenheimer, Jr., Herbert L. Bonkovsky, Adrian M. DiBisceglie, Lawrence S. Friedman, Michael A. Gerber, Robert M. Glickman, Jorge J. Gumucio, Jay H. Hoofnagle, Ann L. Hubbard, Albert Jones, Raymond S. Koff, T. Jake Liang, Willis C. Maddrey, Esteban Mezey, Kunio Okuda, Gustav Paumgartner, Ju¨rg Reichen, Nicola Tavoloni, and Allan W. Wolkoff, who have served as Associate Editors during the past 6 years; to the more than 200 colleagues who have served terms on the Editorial Board; and to the more than 1,500 who have served as reviewers. HEPATOLOGY would not be what it is today without their efforts. Nor, in a very real sense, would hepatology. Joan Blumberg, Nancy Mullins, Michael Miller, and others at W. B. Saunders make their own, distinctive contributions to our journal, for which we are most grateful. If both HEPATOLOGY and hepatology are thriving, why the mixed message implied by the title of this editorial? The answer reflects, in part, a bit of chauvinism on the part of this Editor. Hepatology is a uniquely international discipline, and HEPATOLOGY, nominally the official publication of the AASLD, has become de facto an international journal. For these reasons, the very success of hepatology and HEPATOLOGY tends to obscure the hard times currently being experienced by the American biomedical science community. These hard times are reflected by the static, or, in some disciplines, declining, research output of American biomedical research programs. We received 259 American manuscripts in 1995. At the time of this editorial’s writing, October 4, 1996, we project receiving 261 original manuscripts from American contributors by the end of the 1996 calendar year. This represents a decline of 2.2% from the 267 received in 1991, the first year that HEPATOLOGY was edited in New York. Over the same period, foreign submissions have increased by 76%, from 497 to a projected 876. If this trend were unique to HEPATOLOGY, one could excuse it in many ways. Perhaps, for example, American authors simply prefer to send their papers elsewhere. However, the trend is equally visible in submissions to Gastroenterology,5 and, as summarized in a recent editorial in The New England Journal of Medicine,6 in many of the most outstanding American biomedical publications.
hpta
WBS: Hepatology
1532
BERK
HEPATOLOGY December 1996
It seems most unlikely that an epidemic of acute and chronic stupidity has swept through this country’s scientific community. The very breadth of the stagnation in biomedical research output argues that community-wide structural forces are at work. It is not difficult to identify at least some of these forces. In a variety of different guises, however, they can all be summarized in a single word: money. The plight of basic investigators dependent on grant support, especially from the National Institutes of Health (NIH), has been addressed many times, both in these pages3 and elsewhere.7 In fact, the situation is in some respects improving. Effective public education campaigns and old-fashioned political lobbying by a number of academic organizations protected the NIH budget from the draconian cuts that threatened 2 years ago, and the budget has actually risen slightly since. Funding paylines, which had plunged to record lows, appear to be recovering somewhat. Nevertheless, substantial damage has been done, both to the recruitment of America’s most talented students into biomedical research careers7 and to the productivity of established programs. It is not unusual for an investigator to spend the better part of 3 months preparing an NIH grant application. Over the past several years, the proportion of both new and competing renewal applications funded on the first submission seems also to have been at an all-time low,8 so that a second, or, all too often, a third application was required to obtain support. In personal discussions, one NIH administrator compared the large number of talented, established investigators caught in a cycle of repetitive re-applications with airliners stacked up over a fog-bound airport, ‘‘just waiting their turn.’’ Several years of budgets supporting paylines at better than the 20th percentile will be necessary just to eliminate the backlog of deserving but unfunded proposals. In consequence of the funding situation, many established programs have experienced an interruption in financial support. These have come at a time when their own departments or institutions were increasingly unable to provide adequate bridging funds during the intervals between grants. Even if the principal investigator’s salary was not at risk, which was by no means the universal situation, it was often impossible to support technicians and other valuable, experienced members of a research team through the funding hiatus. Thus, when funding finally was obtained, it was often necessary to start by training a new staff, resulting in an inevitable loss of momentum in the research effort and in the government’s return on its investment of research dollars. Simultaneously, as the effort expended in obtaining grant support has increased, various pressures have reduced the average duration of funding, throwing investigators back into the application cycle more frequently. Although the United States spends a higher proportion of its gross domestic product on biomedical research than any other nation, the consequences of the imbalance between the large and still-expanding pool of highly trained investigators and a finite budget that is unlikely to expand in real terms in the forseeable future are disappointment, frustration, and inefficiency. These, in turn, are reflected in the diminishing proportion of American research reports in America’s most prestigious journals. Beyond the limited supply of NIH support, clinical investigators face special problems, which illustrate more specifically the extent to which the funding of biomedical investigation has become inextricably interwoven with ‘‘the health care financing mess.’’9 More and more American institutions are requiring that members of their clinical faculties support themselves entirely through their clinical practice revenues. Because the growing shift to managed care has meant less return for greater clinical effort, the time available for planning, writing, and execution of clinical research protocols, not to mention thoughtful analysis of data, is increasingly squeezed by the need to generate one’s salary elsewhere. The continuing tension between American clinical investigators
AID
Hepa 0045
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5p19$$$881
11-04-96 20:36:31
and insurers of health care, including the federal government itself, over who should pay the costs of actual care rendered in the course of clinical trials has often made the costs of such trials prohibitively expensive to prospective pharmaceutical sponsors. This is particularly true of trials to be performed in traditional academic medical centers, which almost universally have high patient care costs. In an age when the costs of any delay in bringing a drug to market are estimated at $20 per second, the inevitable bureaucratic delays in obtaining Institutional Review Board approval at most academic medical centers are a further factor discouraging the conduct of sponsored clinical research at many institutions. These issues have fostered the growth of for-profit Contract Research Organizations, which contract with sponsors to perform clinical trials in nonacademic settings with lower costs and far less bureaucracy. Because the raison d’eˆtre of these organizations is profit, not academic productivity, much of their research is likely to be unpublished, at least in traditional channels, and therefore not subject to the scrutiny of peer review. Finally, the recent decision that the Food and Drug Administration can use the results of clinical studies abroad in the process of evaluating new drugs for approval in the United States—while a boon both to patients and the pharmaceutical industry—will almost certainly be a further blow to the American clinical research community. Particularly because most major pharmaceutical houses are now multinational enterprises, this rule change, while both logical and desirable in most regards, will likely stimulate a further major shift in sponsored clinical research sponsorship to sites abroad. Even more worrisome than these trends themselves is the difficulty experienced by the academic community in mounting a strong and constructive response. American biomedical institutions are all embattled with various manifestations of the managed care health maintenance organization onslaught, and their leadership is increasingly focused on economic survival. Even at highly successful academic institutions, annual research budgets of, e.g., $100 million are likely to be dwarfed by hospital revenues measured in billions. Accordingly, faculty development and support for science too often appear to receive a proportionately small share of attention. Even at the departmental level, faculty practice issues and revenues, rather than research activities, are likely to dominate the agendas. Hepatology and HEPATOLOGY both verge on the start of a potential golden age. As measured by papers published in this journal, American participation is decreasing by about 1% annually. Unless the American biomedical research enterprise is assigned a higher national priority and considered and supported as an integrated system, our participation in this golden age extrapolates to zero in 2023. PAUL D. BERK, M.D. Editor-in-Chief REFERENCES 1. Schenker S, Khan SA. HEPATOLOGY: What a difference a decade makes. HEPATOLOGY 1990;12:1436-1439. 2. Berk PD. HEPATOLOGY and hepatology: a midterm status report. HEPATOLOGY 1993;18:454-456. 3. Berk PD. HEPATOLOGY and hepatology: the trends continue. HEPATOLOGY 1995;21:875-878. 4. Arias IM. Hepatology: a new adventure in liverland. HEPATOLOGY 1981;1:84. 5. LaRusso NF, Link AM. Gastroenterology—an international journal. Gastroenterology 1995;108:625-626. 6. Kassirer JP. My years at the journal—so far. N Engl J Med 1995;333:654655. 7. National Research Council. The funding of young investigators in the biological and biomedical sciences. Washington, DC: National Academy Press, 1994:1-117. 8. Mandel HG. Funding of NIH grant applications: update. Science 1995;269: 13-14. 9. Berk PD. Restructuring American health care financing: first of all do no harm! HEPATOLOGY 1993;18:206-215.
hpta
WBS: Hepatology