Careers in Clinical Research Obstacles and Opportunities (1994) / Chapter Skim
Currently Skimming:
Clinical Research Funding and Infrastructure
Clinical Research Funding and Infrastructure
Pages 63-122
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From page 63... ...
Of the remainder, private nonprofit organizations supported about 4 to 5 percent, and state and local governments supported a small amount of health research. Although less well appreciated, the contributions by the academic health centers themselves cover many of the costs of performing research (Commonwealth Fund, 1985~.
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From page 64... ...
When possible, however, the trends in funding for patient-related research are elaborated. Since academic research careers are closely intertwined win He investigator-initiated, peer-reviewed grant system in the Public Health Service, including the National Institutes of Health ~ (and previously the Alcohol, Drug Abuse and Mental Health Administration [ADAMHA]
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From page 65... ...
This approach became the cornerstone of the peerreviewed, academically based system now in place for federally sponsored, competitive extramural research grant programs. From the end of the war to the mid-1960s, the federal government invested heavily in health research and allocated resources to build health research facilities and to create programs to train health researchers (Institute of Medicine, 1990~.
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From page 66... ...
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From page 67... ...
Even Bough some agencies have only a minimal role in sponsoring clinical research, Hey may require highly talented clinical investigators to carry out their mission, such as investigators at FDA and CDC. Thus, the committee sought to determine the fraction of federally sponsored research that involved human subjects.
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From page 68... ...
68 TIC o In E— ~ V C _ — C ho ~ {D o— o ~ _ {D ~ ~ ~ C: O I .
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From page 69... ...
. Most of these extramural research funds are allocated through peer review processes for research grants and cooperative agreements.
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From page 70... ...
translation of research findings into more effective medical care, the committee was most concerned about the research activities and training at the Warren Grant Magnuson Clinical Center. The clinical center was established in 1953 on the Bethesda, Maryland, campus of NIH to facilitate research using human subjects that could not be conducted at academic medical centers for various reasons (Ahrens, 1992~.
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From page 71... ...
The clinical center has accredited training programs in some fields, increasing the teaching requirements of the staff physician-scientists. Although the NIH campus served as a primary training ground for health scientists in the 1950s and 1960s, there were signs in the 1980s that NIH was beginning to have difficulty attracting and retaining scientists, including clinical investigators.
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From page 72... ...
Although a medical board composed of the clinical directors from each institute help guide policy at the clinical center, some believe that an external advisory board should be constituted along the lines of the institute advisory councils to review protocols to ensure appropriate allocation of clinical center resources and an appropriate level of research activity for each institute. Although the committee understands that there are problems with the physical infrastructure of the clinical center and intramural clinical investigators share the same career obstacles, the committee did not feel that it had enough information or insight to make recommendations concerning the intramural program.
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From page 73... ...
Funding for research project grants grew from $2.5 billion in 1977 to $3.9 billion by 1989, when measured in constant l9XS dollars. Along with this grown, He expectation of funding may have encourged scientists to submit more grant applications, which increased from 14,142 in 19X0 to 20,154 by 1990 (Figure 3-6)
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From page 74... ...
as well as the amounts paid to new and competing awards in what is commonly referred to as "downward negotiation" a recent practice for reconciling NIH and ADAMHA research grant commitments with annual appropriations by making across-e-board reductions in all grant awards. Although no negotiations between the scientist and NIH or ADAM actually occur, these budget "cuts" placed additional burdens on scientists; Hey were expected to perform the research outlined in their proposals with less than He recommended amount of funding.
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From page 75... ...
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From page 76... ...
The intended result of increasing award periods was to provide more stability in research activities and scientists' careers and, perhaps, to discourage the number of multiple grant applications by individual investigators. In addition, longer award periods were viewed as a way to reduce the administrative workload for NIH and ADAMHA study sections by reducing the number of competitive renewal applications processed each year.
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From page 77... ...
90— 80— 70 _ At 60— <) 5040_ 30 _ 20 10 _ O_ 77 C_ _ _ _ l T ~TT7 T T 80 81 82 83 84 85 86 87 88 :89 90 91 92 YEAR New Awards Competing Renewal Awards Noncompeting Continuing Awards FIGURE 3-7 Percentage of amount awarded by NIH for competing and noncompeting grant awards from 1980 to 1992.
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From page 78... ...
obtaining grant support in the 1950s and 1960s. More than 50 percent of all current research project grant applications for studies using human subjects or materials are led by a Ph.D.
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From page 79... ...
Costs of Human Studies The costs of performing clinical research are higher than those for performing preclinical research (Kimes et al., 1991~. Whatever He reasons, grant awards that indicate He use of human materials or human subjects are consistency larger Han other grants (Figure 3-10~.
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From page 80... ...
grant applications indicating the use of human materials (top panel) or human subjects compared to those not using human materials or subjects (bottom panel)
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From page 81... ...
250_ CO 7 ~ 200o I CO or 100 ~: 150O 50— o— 81 . 1- ~ I_ 80 81 82 83 84 85 86 87 88 89 90 91 92 YEAR No Human Subject or Human Matenals Human Subjects or Human Matenals C FIGURE 3-10 Average award size of NIH research project grants comparing awards for studies using human materials or human subjects with those awards for studies not using human materials or subjects.
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From page 82... ...
With minor exceptions, the study sections are suitably constituted to review basic science grant applications. Few, however, focus specifically on human biology or studies involving human subjects.
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From page 83... ...
applications comparing those indicating the use of human materials or subjects (top panel) with those applications not indicating use of humans or human materials (bottom panel)
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From page 84... ...
Although these estimates can be used as surrogate measures of clinical research activities, the committee was concerned that such measures do not accurately portray the amount of clinical research activity that directly involves interactions win human subjects. As indicated in Chapter 1, clinical research can have various meanings to different audiences.
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From page 85... ...
research and presents the committee's analysis of a sample of R01 grants indicating use of human subjects or materials. IMPAC Data As indicated previously, the number of new and competing research project grant applications submitted to NIH grew from 14,142 in 1980 to 20,154 in 1990.
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From page 86... ...
However, grant applications from M.D.s for studies not involving humans have a slightly better success rate than grant applications for studies involving humans (Figure 3-16~. Again, these data include all IRB reviewed clinical research.
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From page 87... ...
~ M.D. · T- = 1- ~-_1 Am- ~ 80 81 82 83 84 85 86 87 88 89 90 91 To 92 YEAR FIGURE 3-14 Success rates of traditional research project grant (ROT)
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From page 88... ...
(Source: National Institutes of Health, Division of Research Grants.) Ahrens' Analysis Ahrens reported on his longitudinal analysis of abstracts from a random sample of 557 RO1 grant awards selected from the years 1977, 1982, and 1987 (Ahrens, 1992~.
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From page 90... ...
be expected, most of me research projects are from N1H (and formerly ADAMHA) including some information on intramural research.
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From page 91... ...
There were 114 regular and ad hoc IRGs that reviewed IRB-positive grants that year. Many of these IRGs infrequency review grant applications for studies involving humans, that is, less Han 25 percent of grant awards resulting from a respective study section review are IRB positive.
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From page 92... ...
Thus, the IRGs were placed into four quartiles as shown in Table 3-3. The denominator of interest for this analysis was the 4,2X4 grants that indicated the use of human subjects or materials.
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From page 93... ...
Interestingly, 186, or 41.6 percent, of these grants were for fundamental research, as described above in the first category fundamental research. Of these, 46 did not involve human subjects or materials at all, and another 85 had more or equal amounts of nonhuman research than human materials research.
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From page 94... ...
Thus, the committee concluded that 1,504, or 10.4 percent, of the 14,535 RO1 grants active in 1991 were purely for studies involving human subjects; an additional 657, or 4.5 percent, had combined fundamental (human and nonhuman) and human subject research; and less than 2 percent involved human epidemiology.
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From page 95... ...
For example, it could be argued that most of the RO1 grants for studies involving human subject are reviewed by panels convened by the respective institute rather than IRGs in the Division of Research Grants. Indeed, about 1,800 RO1 grants active in 1991 were reviewed by IRGs convened by the institutes; nearly 800 RO1 grant awardees indicated Me use of human subjects or materials.
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From page 96... ...
Thus, the program was perceived as an extension of the Warren Grant Magnuson Clinical Center located on the NIH campus in Bethesda, Maryland. To this end, a typical GCRC is rather like a miniclinical center that occupies an area in a hospital through a contractual agreement (Ross, 1985~.
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From page 97... ...
. Although commonly a designated pad of a hospital, each GCRC is designed to support areas within academic medical centers dedicated to patient-related research.
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From page 98... ...
Much controversy has surrounded the support of centers over the past several years, in part because of the difficulties in obtaining individual investigator-initiated grants. Although this commmittee also places the highest value on investigator-initiated grants, it also believes that the conduct of human research requires infrastructure and resources that can be efficiently provided through centers.
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From page 99... ...
was established in 1989 as a focal point for health services research in the PHS. Whereas its predecessor, the National Center for Heals Services Research, focused on general
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From page 100... ...
Although the research portfolio of AHCPR spans a broad spectrum of health services research, the committee focused on the portion that involves patient interactions that lead to improved medical practice. AHCPR's Medical Treatment Effectiveness Program (MEDTEP)
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From page 101... ...
Of the 12 PORTs, 10 are run by clinicians, 1 is run by an economist, and 1 is run by a mathematical statistician. Eventually, AHCPR will support Medical Treatment Effectiveness Research Centers on Minority Populations and a pharmaceutical outcomes program.
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From page 102... ...
Department of Veterans Affairs, 1991~. Nevertheless, over the past few years the rehabilitation research component has shown a gradual increase, and heals services research has shown a tremendous surge in funding.
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From page 103... ...
Department of Veterans Affairs, 1992) Although the VA research budget is not very large when compared win that of NIH, it should be noted that salaries for clinical investigators, facility support, and so form are derived from other portions of the VA budget.
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From page 104... ...
Department of Veterans Affairs, 1980~1990. (Source: U.S.
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From page 105... ...
the Life Sciences Programs Directorate of the Office of Naval Research (Institute of Medicine, 1990~. While the three branches conduct a significant amount of health sciences research, there is no reliable estimate of how much is performed on human subjects.
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From page 106... ...
The 1990 budget had only slight increases for the biological and medical sciences to $25.3 million—and an increase $13.7 million for the cognitive and neural sciences. Although the committee is aware that the armed services may not be heavily involved in medical research on human subjects, some research areas may fall into the purview of the armed services.
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From page 107... ...
Private foundations currently provide a great variety of support mechanisms for health sciences research and use their resources to support new areas of investigation or to augment federal funding. Common categories of foundation support include individual research project grants, predoctoral and postdoctoral fellowships, equipment grants, payment of publication expenses, special library collections grants, and sponsorship of conferences or workshops.
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From page 108... ...
Because these organizations rely on voluntary contributions, they often are unable to make long-term commitments to research efforts such as multiyear clinical studies. They are effective, however, in responding rapidly to new research initiatives and providing resources to scientists to develop new lines of investigation.
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From page 109... ...
Physicians supported by EN may have clinical interests and may conduct clinical investigations, but the research portfolio of He institute is directed at preclinical research. Furthermore, although HHMI is sufficiently large to make major contributions in its selected areas of research, it does not seek to replace the central role of NIH in any field.
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From page 110... ...
Some of these unique relationships between industry and academic scientists are elucidated in Chapter 5. The shifting policies of the health insurance industry and Medicare is another problem confronting manufacturing industries that require human testing to bring their products to market.
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From page 111... ...
CLINICAL RESEARCH FUNDING TABLE 3-7 Distribution of U.S. R&D Expenditures for Ethical Pharmaceuticals by Function, 1991 111 Function Amount ($ million)
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From page 112... ...
The sad irony is that the 35 million or more people who have no health care coverage have more freedom to enroll in clinical studies or receive experimental therapy because they have no stake in who pays, and no Bird party questions their decision. Unfortunately, very little is known about the amount of support actually contributed by third-party payers.
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From page 113... ...
. An unwritten understanding previously promoted, or at least did not discourage, the participation of patients in clinical studies or trials in which third parties contributed patient care costs, whether or not they were cognizant of it.
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From page 114... ...
Patients, however, are suing their insurers to allow them to enroll in clinical studies and receive coverage for both the standard care and the experimental therapy, especially when standard therapies are not much improved over no treatment. Although this puts pressure on third-party payers to cover the costs associated with the standard care and those associated with the experimental therapy, moving these controversies into the courts may not be the best way to encourage participation in clinical research.
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From page 115... ...
This may signal a new paradigm for sharing the costs of clinical research in which payers, clinical investigators, and patients all cooperate to further understanding of novel and innovative therapies. Third-Party Payers' Perspective It has become increasingly necessary for plans to serve their subscribers while striving for access to quality health care at an affordable price.
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From page 116... ...
By He time one gets through compromising with 5 or 10 very aggressive investigators, each one altering the study design in his or her own way, a study may be misguided and not answer the originial question, or perhaps answer questions Hat were not very germane about the disease in question to society as a whole. These difficulties are not very appealing to insurers and make Hem disinclined to sponsor clinical studies.
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From page 117... ...
In the appropriate conduct of randomized clinical trials, however, the study is blinded and the codes cannot be broken until the statistical considerations are met. Other types of clinical studies may warrant other arrangements of data sharing.
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From page 118... ...
Meaningful partnerships and coalitions need to be created. These coalitions could include not only university academic health centers but also private foundations, federal and state agencies, the pharmaceutical and biomedical technological industry, and those in the health insurance industry.
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From page 119... ...
Previously, the separation of who should pay for what was of little concern because of plentiful resources and fairly well-established areas of responsibility. Simplistically, NIH and other federal agencies funded investigator-initiated human studies and other clinical studies deemed necessary by advisory bodies or Congress to fill gaps in certain areas, industry has been motivated by the potential for profits and clinical studies are driven by regulatory concerns, the insurance industry may or may not cover certain aspects of investigational care, and academic health centers and hospitals have underwritten significant portions of unrecovered clinical research expenses out of their own reserves.
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From page 120... ...
One proposal would be to form an alliance or consortia of all parties, similar to SEMATECH, so that critical, fundamental human research can be supported to the benefit of all parties and, most importantly, improve the health of the U.S public. Thus, funds from government, industry, dlird-party payers, nonprofit organizations, special interest groups, and academia could be pooled and available for peer-reviewed competition to close gaps of knowledge in particular areas or provide special emphasis in others deemed appropriate or urgent.
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From page 121... ...
economic competitiveness. Foundations, voluntary health agencies, and other nonprofit organizations have played a very important role in sponsoring health research.
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From page 122... ...
To facilitate cooperation to uncover new knowledge about human disease and improve health care, the committee recommends He formation of an alliance that will bring all panties with a vested interest to the table in support of patientoriented clinical research. New paradigms of cooperation are warranted to continue to improve the health of the U.S.
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