The National Institute of Diabetes & Digestive & Kidney Diseases

May 1997 - Meeting Minutes

Department of Health and Human Services
Public Health Service
National Diabetes and Digestive and Kidney Diseases
Advisory Council
May 28-29, 1997

I. Call to Order

Dr. Gorden called to order the 144th NDDK Advisory Council meeting on May 28, 1997, at 8:40 a.m.

A. Attendance

Council Members Present (See Attachment A)

Dr. Phillip Gorden, Chairman (Ex officio)
Dr. Irwin M. Arias
Dr. Judith Bond
Dr. Richard J. Boxer
Dr. Jack E. Dixon
Dr. Thomas F. Ferris (Ad hoc)
Dr. James R. Gavin III
Dr. David M. Harlan (Ex officio)
Ms. Ruby R. Haughton
Dr. Barbara E. Hayes
Dr. Jules Hirsch (Ad hoc)
Dr. Robert S. Levine
Dr. Eric G. Neilson
Dr. Don W. Powell
Dr. Jerrold M. Olefsky
Dr. Barbara J. Rolls
Mrs. Suzanne Rosenthal
Dr. James Rothman
Dr. Joseph T. Spence (Ex officio)
Dr. George Stamatoyannopoulos
Dr. Joseph H. Szurszewski
Dr. Richard D. Williams

Council Members Absent

Dr. Saulo Klahr

B. Staff and Guests

In addition to Council members, others in attendance at the meeting included NIDDK staff members, NIH office of the Director (OD), Division of Research Grants (DRG), Scientific Review Administrators, and other NIH staff members. Guests were present during the open parts of the meeting. Attendees included the following:

Syed Amir, DRG David Badman, NIDDK Ralph Bain, NIDDK Pamela Belton, NIDDK Sharon Bourque, NIDDK Josephine Briggs, NIDDK Francisco Calvo, NIDDK Kim Chase, NIDDK Paul Coates, NIDDK Florence Cohen, NIDDK Catherine Cowie, NIDDK C. Robert Creveling, NIDDK Nancy Cummings, NIDDK Leslie Curtis, NIDDK Don Cyphers, NIDDK Charlenia Daniels, NIDDK Jane DeMouy, NIDDK Nancy Dixon, NIDDK Jacqueline Dobson, NIDDK Richard Eastman, NIDDK Linda Edgeman, NIDDK Donald Ellis, NIDDK William Elzinga, NIDDK James Everhart, NIDDK Ned Feder, NIDDK Carol Feld, NIDDK Willis Foster, NIDDK Judith Fradkin, NIDDK Joanne Gallivan, NIDDK Chhanda Ganguly, DRG John Garthune, NIDDK Sanford A. Garfield, NIDDK Mary Groesch, OD, NIH Judith Grover, OD, NIH Colleen Guay-Broder NIDDK Roberta Haber, NIDDK Ann Hagan, NIDDK Frank Hamilton, NIDDK Joan Harmon, NIDDK Mary Harris, NIDDK Maureen Harris, NIDDK Barbara Harrison, NIDDK Trudy Hillard, NIDDK Gladys Hirschman, NIDDK Terri Holmes, NIDDK Jay Hoofnagle, NIDDK Van S. Hubbard, NIDDK Donna Huggins, NIDDK Susan Hutson, NIDDK

Desiree Johnson, NIDDK Camille Jones, NIDDK Mohammed A. Khan, DRG Sooja Kim, DRG Thomas Kresina, NIDDK Krish Krishman, DRG John Kusek, NIDDK L. Earl Laurence, NIDDK Alec S. Liacouras, DRG Helen Ling, NIDDK Mimi Lising, NIDDK Billie Mackey, NIDDK Denise Manouelian, NIDDK Donita Marconi, NIDDK Ronald Margolis, NIDDK Dan E. Matsumoto, NIDDK Michael Ken May, NIDDK Daniel McDonald, DRG Ludlow McKay, NIDDK Catherine McKeon, NIDDK Pamela Moore, Capitol Publications Clifford Moss, NIDDK Diana Nguyen, NIDDK Scott Osborne, DRG Beth Paterson, NIDDK Denise Payne, NIDDK Sharee Pepper, NIDDK Aretina Perry, NIDDK Judith Podskalny, NIDDK Rose Pruitt, NIDDK Alice Robinson, NIDDK Carmen Robinson, NIDDK Ruth Robinson, NIDDK Charles Rodgers, NIDDK Lakshmanan Sankaran, NIDDK M. James Scherbenske, NIDDK Michael Showe, NIDDK Elizabeth Singer, NIDDK Philip F. Smith, NIDDK Gloria Snowden, NIDDK Walter Stewart, NIDDK Walter Stolz, NIDDK Tommie S. Tralka, NIDDK George Tucker, NIDDK Charles A. Wells, NIDDK Jennifer Wilkinson, NIDDK Danita Woodley, NIDDK Susan Yanovski, NIDDK Rita Yeager, NIDDK Charles Zellers, NIDDK

C. Conflict of Interest Statement (See Attachment B)

Dr. Gorden called to the attention of the Council the Confidentiality and Conflict of Interest Statements. After discussing the scope of confidentiality and conflict of interest, he requested that Council members comply with the requirements. He reminded Council members to avoid a conflict of interest by leaving the room when the Council discussed individual applications in which an actual or perceived conflict of interest might occur. Members were asked to sign a statement to this effect. This did not apply to "en bloc" actions.

Dr. Gorden announced that the Council meeting would be open to the public in accordance with the provisions of Public Law 92-463 on Wednesday, May 28, 1997, from 8:40 a.m. to 1:00 p.m., closed from 2:00 p.m. until 5:00 p.m., closed on Thursday, May 29, 1997, from 8:30 a.m. to 11:00 a.m. for review, Discussion, and evaluation of grant applications, and open from 11:00 a.m. to 12 Noon.

II. Consideration of the Summary Minutes of the Previous Meeting

The NDDK Advisory Council Summary Minutes of the last Council meeting were accepted unanimously by mail by the Council members present.

III. Future Meeting Dates

Dr. Gorden reviewed with the Council the meeting dates for future NDDK Advisory Council meetings:

• September 17-18, 1997
• February 4-5, 1998
• May 27-28, 1998
• September 14-15, 1998
• February 17-18, 1999
• June 16-17, 1999
• September 8-9, 1999
  

IV. Director's Report (See Attachment C and D)

Dr. Gorden began his report by introducing Ad Hoc Council members Drs. Jules Hirsch and Thomas F. Ferris. New staff members he introduced included Dr. Josephine Briggs, the new Director of the Kidney, Urologic, and Hematological Diseases Division and Dr. Susan Hutson who had joined the Metabolism Program of the Division of Diabetes, Endocrinology, and Metabolism. He announced that Ms. Nancy Dixon had been named Grants Management officer of the Institute.

Dr. Gorden announced that Congressional hearings had been held on the NIH Budget, but the Congress had not passed a Budget bill.

Dr. Gorden reported that the NIDDK planned to revise its projection of the number of competing research project grants that would be funded in FY 1997 from its previous projection of 603 to 615. He announced that the payline would be raised from the 23rd percentile for new awards and the 25th percentile for competing renewal awards to the 25th percentile for new awards and the 27th percentile for renewal awards. He also announced that the average grant size would be allowed to grow by 2-3 percent.

Dr. Gorden discussed issues brought forth at the last Council meeting by the ad hoc subcommittee of Council chaired by Dr. Richard Williams. He said the issues for Discussion at this Council were peer review concerns, streamlining Subcouncils' review of grants, and priority setting. He reported that the NIDDK had not been able to effect a change in NIH policy regarding the cap on the FIRST Awards (R29), but he announced that the NIDDK had gained consent from the office of the Director, NIH, to increase the size of R29 awards on a case by case basis and then fund the increased awards as R01s. He said the Council members would be reviewing all R29 awards coming to this Council as well as those funded to date from this fiscal year's funds, and Council members would be asked to decide how much to raise the awards on each grant, if at all. He said that there would be a tracking mechanism put in place to indicate that these were originally R29 grants and to follow their progress.

Another issue he discussed was streamlining Subcouncils' review of grants. He said this involved decisions about what actions the Council felt comfortable in delegating to the staff.

The third issue was priority setting. Dr. Gorden described how this issue would be addressed in each Subcouncil, and he reviewed some of the preparatory steps that had been taken to inform the Subcouncil members about the portfolios of the Divisions in preparation for these Discussions.

Discussion

Council members said that, with little increase in the Budget, there were few funds for new initiatives, and they asked how more funds could be raised. Dr. Gorden responded by briefly describing the developmental stages the NIH Budget went through. He pointed out the importance of special emphasis areas in the Budget allocation that NIDDK received.

Council members expressed concern about opportunities that would not be funded and urged that funds be found to pursue these opportunities.

Dr. Gorden indicated that the Institute was planning a major workshop to assess the status of research opportunities in diabetes to be held September 4 and 5, 1997. The workshop will be sponsored by NIDDK along with several other institutes.

Reports and Discussions

A. Increasing Budgets on FIRST Awards

Dr. Walter Stolz reported on plans to increase First Independent Research Support and Transition (FIRST) Award Budgets. Dr. Stolz said that each FIRST Award application would have to be reviewed individually, with Council members recommending any increase in each Budget. He gave criteria for Council members to use in making this determination: the apparent cost of doing the research recommended by the initial review group, and (2) the scientific merit of the application. He said that those projects recommended for funding above the R29 cap would be converted to R01s for funding, but would be tracked as R29s.

Discussion

Council members pointed out that in the cases of some FIRST Awards, even though they had good priority scores, the study sections questioned the independence of the Prinicpal Investigator. Council members recommended that this should also be considered in awarding more funds. A Council member pointed out that the independence issue had to do with the investigator staying in the same laboratory where the post doctoral work had been done and not moving on to a different laboratory or mentor.

They asked if clinical investigation would be encouraged by the possibility of increased funds. Dr. Stolz expressed the belief that very few clinical investigations could be supported with annual Budgets of $100,000, so this program would probably not serve as a major factor in encouraging clinical investigators to apply for FIRST Awards. He described a proposal now circulating within NIH to establish a "modular grant" program and that such a grant could serve to increase the Budget flexibility a new investigator would have in applying for support of clinical research.

Council members were concerned about the awards being changed to R01 awards. Dr. Stolz said that it was necessary because when the Council members increased the awards, the grants no longer conformed to the NIH definition of an R29. He said by changing the award to an R01, NIDDK was not bound by the $350,000/5-year cap.

Council members asked if the R29 applicants could apply for the higher amounts, if there was going to be a general announcement about increased funding by NIDDK, and how new investigators would learn about this changed policy. Dr. Stolz responded that applicants could not apply for the higher amounts and still have their applications considered as R29s. He said that the new procedure for increasing Budgets would be announced to the community.

Council members were concerned about how the added funds would be used. Some were concerned that the funds would somehow end up supporting the R29 PI's department or mentor rather than his/her own research program.

Council members pointed out that when the R29 grant was first designed, it was adequate to support half of the researcher's salary with enough left over to support at least some of their research, but over the years the award had not kept up with inflation, so the grant was no longer adequate to be used both for the PI's salary and research expenses. Council members pointed out that the NIH could not expect the institutions to support research that the NIH was supposed to support in these times of fiscal restraint.

A Council member pointed out that the NIDDK staff would have to make decisions about how the additional funds would be used. Dr. Gorden assured the Council members that the staff would share their experiences and decisions with the Council at the next meeting.

Council members recommended that the procedure for raising the cap on the FIRST Awards be reviewed at the end of 1 year and that the numbers of these awards that had the cap raised be monitored closely.

B. Streamlining Subcouncil Procedures (See Attachment E)

Dr. Stolz said that Council members have often commented that they spend too much time in Subcouncil meetings discussing requests for relatively small changes in the Budgets of applications under review. This issue was discussed in some detail by the Williams Committee, and Dr. Stolz used that Discussion to formulate some specific recommendations for streamlining subcouncil procedures. Dr. Stolz then reviewed the current operating procedures whereby staff members make decisions on Budget increases of $15,000 or less, and he described the Williams committee recommendations of increasing the delegation to staff to $30,000 in 1 year and $100,000 over the life of the grant. Budget changes over those thresholds and increases in the project period of a grant would be given to one or two Council members to review and decide. Consideration of increased dollar amounts for FIRST Awards, and requests for deferral for re-review would require Discussion by the full Subcouncil (as is current procedure).

Discussion

Council members discussed whether it would be important to have two or only one Council member reviewing the items to be decided upon. Many Council members recommended that two Council members be contacted for decisions. Council members pointed out that such a procedure would not save Council members time except at the Subcouncil meeting.

Council members were unanimous that decisions regarding a change in the length of an award were important enough to mandate Discussion by the entire Subcouncil rather than by only one or two members.

A Council member pointed out that the Discussion during full Council was the only time all Subcouncils were aware of what the other Subcouncils were discussing.

Dr. Gorden said that they could bring any issue for Discussion at the Subcouncil about which they had concerns. He said that this would be a trial period and they would have the opportunity to change aspects they were uncomfortable with, and the issues would be reviewed again.

C. Report on Merit Awards (See Attachment F)

Dr. Paul Coates gave a report on MERIT (Method to Extend Research in Time) Awards. He described the background of how the program was started about 12 years ago and how various institutes were managing the program. He pointed out that the NCI and NIDDK were only extending the MERIT Awards for 3 years rather than 5. He gave the numbers of NIDDK MERIT awards (about 200), described the "life cycle" of these awards, and summarized the experiences to date of the PIs as they have finished their MERIT Awards and competed for continued support. He pointed out that over the past few years the numbers of new MERIT Awards given by NIDDK had stabilized such that there are about 10-15 new MERIT Awards each year. He pointed out that approximately 5 to 10 percent of the NIDDK research project grant Budget went to the MERIT Awards each year.

Dr. Coates gave statistics of the "success" rates of the MERIT awardees, both at the point of extension from 5 to 8 years, and at the point of recompetition after completion of the 8 years. He said that 95 percent had their MERIT Awards extended from 5 to 8 years; and in recompeting for grants after their MERIT Awards had completed the 8 years, he said that 57 percent were successful with the first application submitted. In addition, he said that if one included successful revised applications, then the success rate for former MERIT awardees was 78 percent within 1 year after the MERIT Award had finished. He said that MERIT awardees were more successful than a comparison group of applicants who had held their grants for the same amount of time as the MERIT awardees but who had not been granted MERIT status.

Discussion

Council members pointed out that a senior principal investigator with a past record of three consecutive excellent reviews who then had his application scored outside of the funding range perhaps was encountering an arbitrariness of the review process that was a concern. Dr. Coates pointed out that there were many reasons for the reviewers not to be enthusiastic. Council members pointed out that perhaps the MERIT awardee may not have put as much effort into writing the new grant application after receiving the MERIT Award.

Council members were concerned that the pool of good candidates for MERIT Awards often had the best candidates competing against each other. Dr. Gorden pointed out that some years back Council members were concerned that the MERIT Award program would grow too quickly and had put limitations on the numbers of MERIT Awards to be given each year. He said that the Council members could reconsider that action at any time.

Council members were interested in whether the MERIT Awards had helped the investigators and whether there had been any measurement of impact on the field as measured by citations, by major awards, and by the fate and numbers of trainees. Dr. Coates pointed out that when the program began there was no evaluation program in place to determine the impact on the field.

Dr. Gorden said that it was essential for NIDDK to have the MERIT Award program in order to be competitive with other institutes, and he invited any suggestions for changes from Council members.

D. Task Force on the Prevention and Treatment of Obesity (See Attachment G)

Council member Dr. Barbara Rolls gave a report on the activities of the Task Force on the Prevention and Treatment of Obesity. She pointed out that since obesity is such a complex issue, it required a membership with a wide variety of expertise. She described the membership as balanced between basic scientists and clinicians and that it included clinical nutritionists, endocrinologists, metabolic specialists, exercise physiologists, gastroenterologists, psychologists, childhood obesity specialists, health communicators, and eating disorder specialists. She said that it also had liaison members from other Government agencies and non-Federal groups such as sports medicine organizations and lay advocacy groups. She said the mission of the Task Force was to synthesize current scientifically-based information about the prevention and treatment of obesity. She gave several examples of topics that had been developed, and described an article titled "Towards Prevention of Obesity: Research Directions in 1994." She reported other Task Force activities such as sponsoring workshops and working with the Weight Information Network.

E. Annual Report on the NIDDK Intramural Program

Dr. Allen Spiegel reported on the Intramural Research Program of the NIDDK. He said that, in his report to the Council last year, he had described each of the intramural laboratories and sections. This year he said he would focus on laboratory personnel, some of the scientific accomplishments, and the revitalization of research in NIDDK. He said that several laboratories recently had been closed or were being closed because the Laboratory Chiefs were leaving government service. He reported that three scientists had accepted tenured positions with NIDDK, and he described some of the research advances that had been accomplished over the past year.

He described steps being taken to revitalize clinical research in NIDDK and the NIH as a whole, including plans for the new Clinical Center and a program to include second and third year medical students in a formal 1-year clinical research course to interest young physicians in clinical research.

Discussion

Council members asked about their role in the review of laboratories and intramural research. Dr. Spiegel responded that Council members had an open invitation to become involved as observers, and some Council members in the past had attended meetings of the Board of Scientific Counselors (BSC), the panel of outside experts that regularly reviews all of the Intramural Division's programs and scientists.

Council members asked what happened to scientists that were no longer on the cutting edge of science. Dr. Spiegel pointed out that as the director of a Government research organization, it was his responsibility to expand or contract the laboratories and branches in the Division according to the reviews performed by the BSC, but that there were many factors to be considered when responding to such reviews, including the tenure system and the fact that there were relatively few non-research jobs within the Institute to which a scientist could be productively reassigned.

Council members asked whether the Council had been asked to review and comment upon the reports of the BSC. Dr. Spiegel responded that the Council members had not needed a mandate to make comments, and he said that he was always open to suggestions.

V. Scientific Presentation: Identification of the Gene for Multiple Endocrine Neoplasia Type 1

Dr. Stephen Marx, Chief, Genetics and Endocrinology Section, Metabolic Diseases Branch, Division of Intramural Research, summarized research leading to the identification of the tumor suppressor gene that is responsible, when it mutates, for a major subgroup of parathyroid hyperplasias called Multiple Endocrine Neoplasia Type 1 (MEN-1). He said that this autosomal dominant gene, located on chromosome 11, caused hormone secreting tumors in many of the important endocrine glands. He described three basic approaches to finding the gene which included (1) protein sequencing, (2) the positional candidate approach, and (3) positional cloning. He described and gave examples of all three approaches for cloning genes, and said that the approach they took was positional, because there had not been any positional candidates that were successful in their region of interest. He described two methods of narrowing the candidate interval; first by looking at recombinants in patients in kindreds with unusual recombinations, and second, by looking at tumors with losses of heterozygosity that might have useful boundaries that could be informative in their case. He said that the research group had to find all candidate genes in their interval of interest on chromosome 11, and then they had to narrow their search to the one gene that was the culprit. He described the resources with which they had to work, which included 65 unrelated MEN-1 families, many sporadic cases of MEN-1, and many tumors, both hereditary and non-hereditary, that had been accumulated over the years.

VI. Division Directors' Reports

A. Division of Diabetes, Endocrinology, and Metabolic Diseases

Dr. Richard Eastman began the Division report by describing how a group of advisors had been convened the day before the Council meeting in order to meet with the Council members and program directors of the Division to advise them on the formulation of initiatives for the Division. He reported that the meeting was successful.

He announced several future meetings, including a workshop on progenitor cells and a meeting on the brain and the adipocyte that would focus on the interaction between the two systems. He described a meeting held on AIDS and the wasting syndrome which resulted in a program announcement to encourage research in this area.

B. Division of Digestive Diseases and Nutrition

Ms. Tommie Sue Tralka gave the Division report and began by describing two recently published journal articles. The first was on hepatic drug delivery and gene therapy that appeared in the February issue of Hepatology, and the second was the proceedings of a meeting on liver tranplantation for chronic alcoholic liver disease which was published in the May issue of Hepatology. She announced a meeting planned for September on digestive diseases and AIDS, with the proceedings to be published in the Journal of Infectious Diseases. She asked Council member Dr. Don Powell to describe the Consensus Development Conference on "The Management of Hepatitis C" that had been held in March.

Dr. Powell gave an overview of the results of the conference which included the topics: diagnostic criteria; which patients should be treated; what therapies should be used; recommendations to limit transmission of the disease; and future research directions.

C. Division of Kidney, Urologic, and Hematologic Diseases

Dr. Josephine Briggs, Director of the Division, gave the report. She began by describing some newly published insights into the mechanisms of polycystic kidney disease (PKD). She described PKD as a disease in which patients develop many cysts in the kidney nephrons. She reported that when the DNA from different cysts was analyzed, it appeared that the cysts had lost a good copy of the PKD gene. The defective copy of the gene would cause a somatic copy to be developed and this second defective copy would cause uncontrolled growth and cyst formation. She pointed out that these mutations must occur in immature and young kidneys during nephrogenesis rather than in the mature kidney. She said that the significance of this finding was that this process was well established in malignant diseases, but that this was the first example where this process had been demonstrated in a non-malignant disease. She reported that the Division was sponsoring a PKD symposium scheduled for September 10-11, 1997.

D. Division of Extramural Activities

Dr. Stolz gave the Division report and introduced the new committee management officer for the NIDDK, Denise Manouelian.

VII. Consideration of Review of Grant Applications

Summary Table 1

* Includes both DK primary and secondary
of these applications, 2 were received from institutions outside the U.S.A.

Summary Table 2

Council did not concur with Initial Review Group recommendations on 15 applications.

Summary Table 3

VIII. Adjournment

Dr. Gorden thanked the Council members for their attendance and advice. There being no other business, Dr. Gorden adjourned the 144th meeting of the NDDK Advisory Council on May 29, 1997, at 12:10 p.m.

I hereby certify that, to the best of my knowledge, the foregoing summary minutes and attachments are accurate and complete.

Phillip Gorden, M.D.

Director, National Institute of Diabetes and Digestive and Kidney Diseases and
Chairman, National Diabetes and Digestive and Kidney Diseases Advisory Council