Funding Biomedical Research Programs: Contributions of the Markey Trust (2006)

In order to understand how best to make significant contributions to the advance of biomedical research, the Markey Trustees held a series of meetings with experts in the biomedical sciences. The first meeting took place in Menlo Park, California, in April 1984 and was quickly followed by a similar meeting in New York City in May 1984. A third meeting was held in Dallas, Texas, in February 1989. The information collected from these meetings was used to focus and guide the three primary funding activities of the Trust. The first two meetings were especially important in identifying potential targets for Trust funding. The California conference was concerned primarily with what would emerge as the Markey Scholars program, and nine target areas were identified as appropriate for Markey funding (Lucille P. Markey Charitable Trust Records, 1984). These target areas included the following:

1. Research training

2. Support for young promising investigators

3. Support for established investigators

4. Funds for laboratory equipment

5. Discretionary funds to support promising research opportunities and fields of investigation

6. Identification and support of small groups of investigators already established and recognized for outstanding biomedical research

7. Support of promising fields of investigation

8. Funds for important but not popular research fields

9. Long-term support for ongoing research endeavors where the current track record presages future payoffs. Such as support provided by the Medical Research Council, University of Cambridge.

The Markey Predoctoral Fellows, the General Organizational Grants, and Markey Scholars programs addressed the first two targets. All of the remaining targets were addressed through the Research Program Grants. The Trustees wanted the Research Program Grants to have a major impact on biomedical sciences and used input from meeting participants to direct funding. Participants concluded that the flexibility to change directions in basic research to pursue new leads and ideas was vital. Although the level of private sector funding in biomedical sciences was lower than federal funding in an absolute sense, this greater flexibility would complement and augment federal funding. In addition, the support for equipment, construction, and renovation—which are generally not covered by federal funding—would provide infrastructure not generally available from other funding sources that was essential to establish or grow new programs. Finally, the relatively large grants would provide sufficient funding for bold efforts and usually represented a significant portion of the recipient’s basic research portfolio (Lucille P. Markey Charitable Trust Records, 1984).

A consensus emerged among experts who advised the Markey Trustees that the focus of the Research Program Grants should be to fund research and infrastructure that would ordinarily not be funded by NIH or NSF. Rather, awards should be directed to proven, able individuals or to small groups working in areas that seemed promising, but might not have preliminary data nor show immediate applied results. The Trustees desired “to encourage the development of programs in biomedical research going beyond the reach of others—things that otherwise might not be done, but should be done” (Lucille P. Markey Charitable Trust Records, 1984). The experts recommended funding long-term support for ongoing research endeavors in which the track record of the individuals in a leadership position predicted major payoffs. They urged the Trustees to emulate a model based on the Medical Research Council Laboratory of Molecular Biology at Cambridge that had provided such support with extraordinary results.

Consequently, the Trustees identified a set of elements to guide the selection of awardees that might predict success and maximize the impact of Markey Research Program Grants. Although all tenets were not applicable to Research Program Grants, they provided guidelines for the selection of grantees by the Markey Trust (Lucille P. Markey Charitable Trust Records, 1989). By the third meeting in Dallas, these characteristics were crystallized into six basic tenets:

1. Investigators were encouraged to eschew conservatism in the choice of research topics, to take risks, and to pursue longer-term objectives than is the rule under conventional grant support.

2. Research environments were strengthened and enhanced by the establishment of new state-of-the-art laboratories and sophisticated multiuser resources.

3. Intellectual capital was made available for new ventures and for exploring emergent and unexpected research opportunities.

4. New faculty were given start-up funds for carrying out pilot research, gathering data, and positioning themselves to compete effectively for external funds from other sources.

5. Financial incentives were provided for dissolving departmental barriers, creating joint programs, and sharing graduate students. Indeed, it is difficult to exaggerate the catalytic effect of the Markey mode of support in fostering interaction and interdisciplinary research.

6. Investigators were encouraged to propose their best ideas for funding rather than having the Trustees specify program themes for grant awards.

Ninety-two Research Program Grants were awarded between fiscal years 1986 and 1995. These grants varied in terms of size, duration, and approach. This diversity is described in Appendix A, which presents brief descriptions of each of the programs. The following material reviews the selection process and provides a history of events that occurred.

Early in its tenure, the Trustees recognized that they needed to establish a systematic procedure to rationalize the selection of Research Programs Grants that underwent a thorough review process. They quickly came to the conclusion that a considerable number of applications could not be funded either because the applicants were not legally qualified or because the purpose of the application was clearly outside the purposed of the Trust. The Trustees decided that such applications should be denied as promptly as possible by the staff in Miami.

Additional consideration was given to applications that were broadly within the field of biomedical research but which were not basic biomedical research. In some cases this discrepancy may have been apparent to the Miami staff, but in some instances professional judgment would be required. The Trustees decided that, in such cases, decisions would be made either by conference call with the Director for Medical Science or by

forwarding the application to him. Notification of denials would be made by the Miami staff except for a few denials that would require a letter from the Director for Medical Science.

Moreover, the Trust received some applications that were within the field of basic biomedical research, but were not in accordance with the policies established by the trustees. These applications included requests from re-grant organizations, requests for conference travel, requests for endowments, and requests for construction and renovation unconnected with a funded project. The Trustees decided that such applications should be denied by the Miami staff with a proviso that the Director for Medical Science, and if necessary, the Trustee Executive Committee be consulted in advance in cases in which the application of the policy might be unclear.

The goal of this screening process was to eliminate as many applications as possible without requiring review by the Director for Medical Science and expert consults. Nevertheless, the Trust received a large number of proposals for basic biomedical research that did not violate any of the previously established Trustee policies. The Executive Committee concluded that such applications could be denied by the Director for Medical Science, with appropriate advice from the expert consultants, or any one or more of the following general policy reasons:

• The National Institutes of Health would normally fund the proposal, but the proposal had not been submitted to NIH or had been submitted and had not been approved.

• The proposal substantially duplicated other research projects that appeared to have greater prospects of success.

• The proposal appeared to have no real expectation of important results.

In summary, the Trustees identified 16 denial codes classified into three categories. These included:

1. Denials under the provisions of Mrs. Markey’s Will

   • Requests from an individual

   • Requests from a for-profit organization

   • Requests from an organization not in the United States

   • Requests for other than biomedical research

   • Requests for biomedical research that is not basic

2. Denials by policy established by the Trustees

   • Requests from re-grant organizations

   • Requests from private foundations

• Requests for support of travel to a conference

• Requests for endowment unconnected with a project

• Requests for construction/renovation funds unconnected with a project

• Requests for fellowships, scholarships, or similar programs

3. Denials as a result of review

   • Request denied, but a revised proposal requested

   • Request denied on merit

   • Request denied as the proposal would be funded by NIH

   • Request denied as the proposal substantially duplicates other research

   • Request denied as the proposal has no realistic expectations of significant or important results

The Markey Trustees never prepared a formal solicitation for Research Program Grants. Applicants were required to submit a preliminary letter of not more than four pages, briefly outlining the plans and objectives of the program for which support was sought and an estimate of the required budget. Curriculum vitae and a listing of current research support for investigators from NIH, NSF, and other funding agencies were also required. (Lucille P. Markey Charitable Trust Records, 1989). These guidelines were published by the Trust in 1991 as program information and guidelines (see below) but not as a formal solicitation:

If the application survived the previous screens, Trustees reviewed the preliminary letter, and if they found that the proposal met the requirements for a Research Program Grant, additional information was requested. Following receipt and approval of the additional information, arrangements were made for the applicant to meet with the Trust’s director for medical science. In some cases a site visit was also scheduled. At this point, the Trustees turned to five senior consultants to judge the merit of an application. These senior consultants, utilized throughout the duration of awards, included the following:

• Michael S. Brown, M.D., University of Texas Southwestern Medical Center

• Joseph M. Davie, M.D., Ph.D., Biogen, Inc.

• Arno G. Motulsky, M.D., University of Washington School of Medicine

• Elizabeth F. Neufeld, Ph.D., University of California, Los Angeles, School of Medicine

• Eric M. Shooter, Ph.D., Stanford University School of Medicine

Based on the advice of the senior consultants and the director for medical science, the initial Research Program Grants were made in August of 1985 to Carnegie Mellon University and the University of Texas Southwestern Medical Center and in November 1985 to the University of Chicago, Stanford University, and the California Institute of Technology. These five grantees were competitively selected from more than 100 proposals submitted. Because of problems associated with the natural gas pricing litigation, Trustees restricted the number of awards made in the fall of 1985 to those that could be funded from available funds. No awards were made in 1986 and 1987. After favorable resolution of the litigation, Research Program Grants awards resumed in 1988. In that year, 21 awards were made for a total of $105,120,402.

At the end of fiscal year 1988, the Trustees realized that there was an expectation at biomedical research institutions that grant activity by the Trust would continue at the 1988 level. The Trustees knew, however, that this level of annual funding would be reduced sharply because declines in oil and gas revenues had reduced the Markey Trust dollars. Consequently, a large number of meritorious proposals were unable to receive funding. The Trust calculated it could make approximately $25 million in new Research Program Grants awards annually for the next six years. In fact, over the next four years, 29 awards were made for a total of $118,590,000, an average of $30 million per year.

By 1992, the Trustees recognized that they needed to change their focus from Research Program Grants awards to General Organizational Grant awards. Consequently, in fiscal year 1993, the Trust made only five Research Program Grants awards to proposals that had been received and approved earlier for a total of $14,000,000.

From 1993 on, the focus of the Research Program Grants changed. The Trustees were increasingly aware that the Trust would have to close out its activities and considered two alternatives. First, the Trust could restrict the remaining funds to institutions that had not received support or could allocate remaining funds to previous grant recipients who had made exemplary use of funds. Second, the Trust could make awards to

new applicants—either relatively few grants in the $3 million to $6 million range or a larger number of grants in the in the $1 million to $2 million range. Contemplation of these strategies was tempered by the uncertain market for the remaining oil and gas revenues, which meant that the Trustees had only estimates of funds available for distribution.

After careful consideration, the Trustees had concluded that the best use of the remaining funding would be to award a larger number of Research Program Grants in the $1 million to $2 million dollar range. The Trustees reasoned that grants in this range were large enough to have an impact, particularly given the Trust’s willingness to permit flexibility in the use of awards. Recent experiences indicated that established investigators were successful in targeting funds to high-priority areas so as to enhance the impact of relatively smaller awards. Therefore, the Trust sent a letter to a number of Research Program Grants applicants explaining the new program of smaller awards and requesting updated proposals in the $1 million to $2 million dollar range. In the fall of 1993, it budgeted $32 million for these smaller Research Program Grants and gave preliminary approval to the first batch. The Trustees’ strategy was to make a large number of smaller awards in fiscal year 1995 and then to determine a strategy for any remaining funds. During the 1995 fiscal year, they made awards to 26 institutions for a total of $31,400,000.

As the Trust neared its closing date, the Trustees began planning for the final distribution of funds. In the spring of 1994, Louis Hector recommended that the Trust complete the funding of the $1 million to $2 million smaller Research Program Grants applications; pause for a while, saying nothing about the potential for extra funds being available; and then late in 1995 or early in 1996 announce one final round of grants—whether new, continuation, or otherwise. The Trustees were not sure exactly how much funding would be available for distribution and did not wish to make any announcements until they had a good estimate of funds available to distribute.

In the fall of 1995, the Trustees concluded that the best utilization of funds would be to (1) create a series of endowment grants to endow chairs and (2) develop continuation/special consideration awards to previously funded Research Program Grants awardees that had exhibited outstanding progress addressing important problems in biomedical science. These awards would be for $500,000 each. The Director for Medical Science and Eric Shooter, a special advisor to the Director for Medical Science, identified 22 previous Research Program Grants awardees worthy of consideration for these continuation/special consideration awards. In February of 1996, the Trustees awarded continuation/special consideration awards to 12 institutions. In September 1996, sufficient funds were

available to award an additional six continuation/special consideration awards. With these awards, the funding for Research Program Grants came to an end.

Because of the extensive review process, the Markey Trustees were less concerned about the supervision of grantee awards. Continuation of funding in subsequent years was dependent upon the receipt of an annual progress report, but the level of monitoring and evaluation was minimal. All Markey Research Program Grants awardees received second- and additional-year funding following receipt of an annual report. The Trustees allowed a great deal of flexibility in the timing of distribution of funds, and budget lines could be moved without returning for Trust approval. Many grantees were able to extend the period of funding beyond the initial tenure of the grant. This changing nature of program emphasis and lack of an evaluation plan make it difficult to assess the impact of the program.