Full Text DK-94-014 PROGRESSION OF RENAL DISEASE: IgA NEPHROPATHY IN CHILDREN AND YOUNG ADULTS NIH GUIDE, Volume 23, Number 1, January 7, 1994 RFA: DK-94-014 P.T. 34 Keywords: 0715133 Nephrology Etiology 0705048 Treatment, Medical+ National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: March 15, 1994 Application Receipt Date: April 12, 1994 PURPOSE The Division of Kidney, Urologic and Hematologic Diseases (DKUHD) of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites investigators to submit: (1) innovative research grant applications that could provide a critical insight into fundamental factors and/or mechanisms leading to progression of renal disease, such as IgA nephropathy in childhood, and (2) clinical research applications for pilot studies in IgA nephropathy. The latter will assess the efficacy and safety of innovative therapeutic strategies aimed at preventing and/or controlling renal disease progression in children, adolescents, and young adults with IgA nephropathy. HEALTHY PEOPLE 2000 The PHS is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications addressing the fundamental research aspects of this solicitation may be submitted by domestic and foreign for-profit or nonprofit organizations, whether public or private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal Government. Applications addressing the clinical pilot aspect of this solicitation may be submitted only by domestic for-profit and nonprofit organizations, as described above. Minority individuals and women are encouraged to submit as Principal Investigators. Note: Foreign institutions are ineligible for the R29 award. MECHANISM OF SUPPORT Support of this program will be through the NIH grant-in-aid research project (R01) and FIRST (R29) grant awards. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Awards will be administered under Public Health Service (PHS) grants policy as stated in the PHS Grants Policy Statement. This RFA is a one-time solicitation for applications for new awards. Generally, future unsolicited competing continuation applications for either the fundamental research or the clinical component of this solicitation will compete with all investigator-initiated applications and will be reviewed according to the customary peer review procedures. The total requested project period for applications submitted in response to this RFA, addressing either the fundamental research aspects of this solicitation or the clinical aspect of this RFA, may not exceed a total of five years. A maximum of three years may be requested for foreign awards. The earliest possible award date will be September 30, 1994. FUNDS AVAILABLE For FY 1994, $2,000,000 will be committed to fund applications submitted in response to this RFA; however, this funding level is dependent upon the receipt of a sufficient number of applications of high scientific merit. It is anticipated that 5-6 awards will be made to support applications addressing the fundamental research aspects of this solicitation, and 3-4 awards will be made to support applications addressing the clinical aspect. Applications must limit their requests to not more than $160,000 direct costs for the initial budget period. Although this program is provided for in the financial plans of the NIDDK, the award of grants pursuant to this RFA is also contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES This comprehensive research initiative is intended to (a) stimulate innovative fundamental research work utilizing state-of-the-art methodology including molecular and cell biology and genetic approaches that could provide critical insights into fundamental factors/mechanisms leading to renal disease progression in general, and to the establishment of IgA nephropathy in particular, in children and young adults; (b) identify and pilot test possible treatment intervention protocols that should result in control of renal disease progression in IgA nephropathy, once the diagnosis has been made. The pilot protocols will test the efficacy and safety of innovative therapeutic interventions aimed at preventing and/or controlling disease progression in children, adolescents and young adults affected with IgA nephropathy. Background Chronic renal insufficiency and end-stage renal disease (ESRD) in the pediatric patient represent a significant problem. This constitutes a unique pathophysiologic entity in which the multi-system effects of uremia adversely affect the growth and development of most organ systems and the individual. There is universal agreement that there are renal disorders unique to the pediatric age group that are clearly different in pathogenesis, management, and prognosis from renal disorders in adults. It is also recognized that, even though renal failure is more frequent in adults, the majority of the disorders observed in adults have their onset in childhood. Therefore, a reduction in the major causes of kidney diseases that start in infancy or childhood and efforts directed at the understanding of the most basic mechanisms underlying renal disease progression, minimizing complications and improving clinical outcome, constitute the mainstay of the long-range research plan for pediatric nephrology within the NIDDK. IgA nephropathy was first described over 20 years ago and is considered to be the most common primary glomerular disease throughout the world. In southern Europe, Asia and Australia the incidence is calculated at 30-40 percent; in northern Europe and the United States it is calculated at 20 percent of all primary glomerular diseases. The different estimates may reflect differences in screening practices and in indications for renal biopsy. The diagnostic hallmark of IgA nephropathy is the finding of mesangial deposition of IgA by immuno-fluorescence microscopy of biopsy specimens. This test is, therefore, essential for the correct diagnosis of the disease. There are strong suggestions that IgA nephropathy has a genetic predisposition; nevertheless, the pathogenesis remains an enigma, and different mechanisms have been ascribed. It affects the pediatric as well as the adult patient population, and the clinical course and prognosis varies greatly. The course of IgA nephropathy ranges from a small percentage of cases (estimated at 4 percent) with a benign course and with regression of symptoms without any treatment intervention, or a clinically progressive course with frequent recurrence of gross hematuria and a continuous deterioration of renal function (estimated at 50 percent), to a pathological deterioration in renal function leading to ESRD or death. There is no proven treatment for IgA nephropathy. Some regimens involve steroids with varying doses, varying schedules (daily vs. alternate days), and varying length of treatment. Other protocols involve azathioprine/chlorambucil, Cyclosporine, plasma exchange and antiplatelet agents alone or in combination. These different treatment regimens have been proposed and tested in small series; however, as of today, the results are openly controversial. Therefore, there is a need to learn more about the pathogenesis, genetics, natural history, true epidemiology, and effective treatment interventions for IgA nephropathy before ESRD ensues. STUDY POPULATIONS It is NIH policy that women and minorities must be included in clinical study populations unless there is a good reason to exclude them. The study design must seek to identify any pertinent gender or minority population differences. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample and must be appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (Rev. 9/91) in Item 4 (Research Design and Methods) of the Research Plan AND summarized in Item 5, Human Subjects. Applicants/offerors are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations; i.e., Native Americans [including AmeriCan Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics. The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention [and preventive strategies], diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned without review. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by March 15, 1994, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NIDDK staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to: Chief, Review Branch Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 605 Bethesda, MD 20892 Telephone: (301) 594-7515 FAX: (301) 594-7503 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) must be used in applying for these grants. The grant application kits are available from most institutional business offices or may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/435-0714. The RFA label available in the 9/91 revision of form PHS 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and check the YES box. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892 At time of submission, two additional copies of the application should also be sent under separate cover to: Chief, Review Branch Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 605 Bethesda, MD 20892 Applications must be received by April 12, 1994. If an application is received after that date, it will be returned to the applicant. The DRG will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, it is allowable to submit the same project as both an R01 and as a component project of a program project (P01). The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications previously reviewed. Such applications must not only include an introduction addressing the previous critique but also be responsive to this RFA. Applicants from institutions which have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so a letter of agreement from either the GCRC program director or principal investigator could be included with the application. For investigators applying for support through the FIRST award mechanisms (R29), three letters of references must be submitted with the application. An applicant submitting a revised application in response to this RFA must again submit reference letters. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the Division of Research Grants (DRG) for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the program requirements and criteria stated in the RFA is an NIDDK staff function. If the application is not responsive to the RFA, NIDDK staff will contact the applicant to determine whether it should be returned to the applicant or held until the next regular receipt date and reviewed in competition with all other applications. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by the appropriate peer review group convened by the NIDDK. If the number of applications is large compared to the number of awards to be made, a triage of the applications may be conducted. Applications judged to be not competitive for the award will be withdrawn from further review. The NIDDK will notify the applicant and institutional official of this action. Those applications judged to be competitive will be reviewed for scientific and technical merit in accordance with the NIH peer review procedures by an initial review group specifically convened for this RFA. Following this review, the applications will be given a secondary review by the National Diabetes and Digestive and Kidney Diseases Advisory Council unless not recommended for further consideration by the initial review group. Review Criteria Review criteria for RFAs are generally the same as those for unsolicited research grant applications. o scientific, technical, or medical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly but not exclusively in the area of the proposed research; o availability of resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; and o if an application involves and could have an adverse effect upon humans, animals, or the environment, the adequacy of the proposed means for protecting against or minimizing such effects. Additional Criteria for Review of Applications from Foreign Institutions Include: o uniqueness of research such that it can only be performed outside of the United States. Additional Criteria for Review of Pilot Clinical Study Applications include: o familiarity with and experience in recruiting participants for participation in clinical studies; o documentation of access to IgA patients. AWARD CRITERIA The anticipated date of award is September 30, 1994. Applications will compete for available funds with all other approved applications submitted in response to this RFA. The following will be considered in making funding decisions: o quality of the proposed work as determined by peer review; o availability of funds; o program balance among research areas of the RFA; and o how the proposed research relates to, or integrates with, ongoing research activities included in collaborator's laboratories; INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Inquiries regarding programmatic issues should be directed to: Gladys H. Hirschman, M.D. Chronic Renal Diseases Program and Pediatric Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A-07 Bethesda, MD 20892 Telephone: (301) 594 7584 FAX: (301) 594 7501 Inquiries regarding fiscal matters should be directed to: Aretina D. Perry Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 639 Bethesda, MD 20892 Telephone: (301) 594-7543 Schedule: Letter of Intent: March 15, 1994 Application Receipt: April 12, 1994 Initial Review: June-July, 1994 Second Level Review: September 20-21, 1994 Anticipated Award: September 30, 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.849. Awards are under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. .
Return to NIH Guide Main Index
![]() |
Office of Extramural Research (OER) |
![]() |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
![]() |
Department of Health and Human Services (HHS) |
![]() |
||||
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, RealPlayer, Video or Flash files, see Help Downloading Files. |