Full Text DK-93-008 NIDDM PRIMARY PREVENTION TRIAL: DATA COORDINATING CENTER NIH Guide, Volume 22, Number 18, May 7, 1993 RFA: DK-93-008 - (Reissued as RFA-DK-08-504) P.T. 34 Keywords: Clinical Trial Disease Prevention+ Data Management/Analysis+ National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: September 17, 1993 Application Receipt Date: October 19, 1993 PURPOSE The Division of Diabetes, Endocrinology and Metabolic Diseases (DDEMD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), invites cooperative agreement applications for the Data Coordinating Center in a multicenter, randomized clinical trial to evaluate the efficacy of interventions designed to delay or prevent onset of non-insulin dependent diabetes mellitus (NIDDM) in individuals at increased risk for NIDDM. The Data Coordinating Center will participate with the NIDDK and fifteen to twenty Clinical Centers in all phases of this trial. A separate request for the Clinical Centers has been issued (RFA DK-93-007). The Data Coordinating Center and a participating Clinical Center may be located in the same institution; however, each must be administratively and fiscally distinct from the other. HEALTHY PEOPLE 2000 The Public Health Service (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. This Request for Applications (RFA), NIDDM Primary Prevention Trial, is related to the priority area of diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock Number 017-001-00474-0 or Summary Report: Stock Number 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325, telephone 202/783-3238. ELIGIBILITY REQUIREMENTS Applications may be submitted by for-profit and non-profit domestic organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Minority individuals and women are encouraged to submit as Principal Investigators. Applications from minority institutions are especially encouraged. Applications from foreign institutions will not be considered. The expertise appropriate for this research program includes statistical knowledge of the clinical and epidemiological aspects of diabetes and expertise in data coordination for clinical trials. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to undertake this program will be a cooperative agreement (U01), which is an assistance mechanism, rather than an acquisition mechanism. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by collaborating and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships and governance of a study funded under a cooperative agreement are discussed later in this document under the section "Terms and Conditions of Award." FUNDS AVAILABLE It is anticipated that an award for one new Data Coordinating Center will be made under this RFA. Support during the planning phase (Phase 1) of this trial in FY 1994 is expected to be approximately $1,000,000 (direct and indirect costs). The levels of effort are expected to remain at this amount during the remainder of the study. However, funding will be provided by the NIDDK to support subcontracts for centralized laboratory and clinical resources reflecting the start of the full scale trial and described in greater detail under SPECIAL REQUIREMENTS. Funds for the subcontract(s) will be approximately five million dollars (total costs) during Phase 2 to support adherence and end point analyses. Additional funds in the first year of Phase 2 will be provided to cover the costs of screening. The nature and extent of the screening will be established by the outcome of the protocol development. Funds to support the subcontract aspects of the Trial will largely cease during Phase 3 reflecting the final period of data analysis and reporting. Although this program is provided for in the financial plans of the NIDDK, an award in response to the RFA is contingent on the availability of funds for this purpose. The total project period for applications submitted in response to the present RFA will be seven years. This is due, in part, to the necessity to screen large numbers of potential participants to identify individuals with sufficient risk to answer the study question discussed under RESEARCH OBJECTIVES. The anticipated award date is July 1994. At this time the NIDDK anticipates that there will not be a renewed competition after seven years. If the NIDDK does not continue the program, awardees may submit grant applications through the usual investigator-initiated grants program. RESEARCH OBJECTIVES Background A family history of diabetes, obesity, insulin resistance, hyperinsulinemia, a history of gestational diabetes, and impaired glucose tolerance (IGT) are risk factors for NIDDM (1). Based on the NHANES II survey data, IGT is present in 16 percent of adults aged 40 to 74 in the US and in 23 percent of this age group who have a family history of diabetes and body weight greater than 120 percent of desirable weight (2). Minority populations have even higher rates of IGT (3). For high risk individuals the rate of progression to NIDDM is 5 to 10 percent per year (4). Importantly, screening for IGT can identify individuals at increased risk for development of NIDDM (5,7,7). In addition, obesity and gestational diabetes (GDM), an apparently temporary condition of pregnancy, are important independent risk factors for the subsequent development of NIDDM. African, Hispanic and Native American women have significantly increased prevalence of both of these conditions. It appears that excessive weight gain during pregnancy may play a role in the appearance of GDM and the documented lack of weight loss to pre-pregnancy levels following delivery may conspire to magnify the risk of future NIDDM in these groups of minority women. There is currently no accepted standard of care for patients with IGT or a history of GDM. Screening for IGT, which is undiagnosed in most affected individuals, is not widely recommended or practiced, nor are there accepted interventions for patients with IGT. No large scale, randomized, prospective, controlled clinical trials have determined whether or not progression of IGT to NIDDM can be prevented. Insulin resistance is the earliest abnormality detected in individuals who will develop NIDDM and appears to have a genetic component (8). However, it is not known whether reversing insulin resistance will prevent or delay onset of NIDDM. Insulin resistance can be reduced through weight reduction and exercise (9). Corresponding to these findings, epidemiological data indicate an association between exercise frequency and significant lowering of risk for NIDDM (10,11). Results of another study performed in Sweden suggest that moderate weight reduction of two to four percent of initial weight and increased maximal oxygen uptake of 10 to 14 percent could be maintained for a period of five years. This was associated with improvement in glucose tolerance, blood pressure, lipids, and hyperinsulinemia, and reduced mortality (12). Sustained intervention appears to be necessary to achieve these lifestyle changes (13) but importantly, such changes have the potential to slow the deterioration of glucose tolerance in IGT, thereby delaying the onset of diabetes. Pharmacologic agents also can potentially prevent or delay onset of NIDDM. Biguanides are suggested to reduce insulin resistance and improve glycemia and hyperinsulinemia, while sulfonylurea agents appear to improve glycemia by increasing insulin secretion and through extra-pancreatic effects. Data in the literature are inconclusive with respect to the ability of these agents to prevent or delay onset of NIDDM. One study using the biguanide metformin showed no effect on prevention or delay of onset (14). In contrast, studies with sulfonylureas have shown decreased rates of diabetes and of mortality in patients treated with modest doses for IGT (15,16) but are inconclusive. Nonetheless, these interventions could slow the deterioration of glucose tolerance in patients with IGT. In so doing, diabetic complications, including atherosclerosis, may also be delayed reducing morbidity and mortality due to diabetes. Methods are available for potentially reducing insulin resistance and improving glucose tolerance. Based on this and the high rates of IGT in the United States, the NIDDK has determined that a randomized controlled clinical trial is necessary. Such a trial would define the effectiveness of interventions for delaying or preventing NIDDM in high risk persons with glucose intolerance. Since the estimated population prevalence of undiagnosed NIDDM is six percent, screening for IGT will detect individuals with previously undiagnosed NIDDM, most of whom do not have fasting hyperglycemia (2). The NIDDK also believes that those with newly diagnosed NIDDM should be treated in a randomized, prospective fashion to determine whether early detection and treatment of NIDDM can reverse the disease process or have favorable effects on the deterioration of glucose tolerance that is characteristic of NIDDM. Goal of the Activity The purpose of this RFA is to invite applications for the Data Coordinating Center in a multicenter collaborative study of interventions to prevent NIDDM in people with IGT or a history of GDM and to prevent the worsening of glucose tolerance in people with newly diagnosed NIDDM. The study will determine whether onset of NIDDM can be delayed and whether interventions in newly diagnosed NIDDM can favorably influence glucose tolerance and progression to fasting hyperglycemia. The objectives of this RFA are to select a Data Coordinating Center to participate in the following: o A full-scale trial with the Clinical Centers and the NIDDK o Design of the study protocol and writing of the manual of operations o Development of the operational plans for the trial in close collaboration with the communities they serve. These plans must include racially and ethnically sensitive strategies for recruitment, screening, enrollment and adherence to the study protocol. o The establishment of clinical and laboratory subcontracts to serve as centrally supported resources for the Clinical Centers. Additional clinical centers will be recruited through a follow-up RFA if necessary to achieve adequate numbers of subjects. The collaborative protocol will be developed by a Steering Committee composed of the awardees, a Chairperson appointed by the voting members of the Steering Committee from among the Committee members or from experts in the field of diabetes and clinical trials not participating directly in the study, the Principal Investigator of the Data Coordinating Center, and the NIDDK Project Coordinator. The protocol and manual of operations will be subject to review by an uninvolved expert group (Policy and Data Monitoring Committee), and the NIDDK. The study will move into its operational phase only with the concurrence of the awardees, the Policy and Data Monitoring Committee, and the Institute. Scope of the Activity It is expected that the study will take place in fifteen to twenty Clinical Centers over a period of seven years. Each clinical center will randomize an average of 200 study participants over a 12 month period of recruitment. The entire collaborative clinical trial will consist of the following three phases: Phase 1 (12 months): Planning phase, collaborative development of the protocol and manual of operations which includes procedures for data collection and pretesting of these procedures. There must also be included in the manual well-defined procedures for the training and certification of clinic personnel in study procedures. Phase 2 (60 months): Conduct of the full-scale collaborative clinical trial including patient recruitment and followup. Phase 3 (12 months): Close out, analysis of data, and reporting of results. The Data Coordinating Center will participate during Phase 1 in the planning phase of the Trial including protocol development, preparation of the manuals of operations, sample size determination, estimates of event rates and full statistical oversight. Centralized laboratories and centralized clinical support facilities will also be developed during this period for use during Phase 2 supported through subcontracts. During Phases 2 and 3 the Data Coordinating Center will analyze the cumulative data from the study with appropriate participation of the Clinical Centers and the NIDDK. Participation in Phase 1 will require staff of the Data Coordinating Center to travel to meetings in a location such as Bethesda where the protocols, manuals, and forms will be developed. Phase 2 will require, in addition to data processing and analysis, qualified personnel to travel to the Clinical Centers to monitor quality control procedures, to attend meetings with Clinical Center personnel and NIDDK staff, and to conduct training programs for clinic staff. Phase 3 will require staff qualified to analyze data from large-scale clinical trials. Additionally, the Data Coordinating Center will be required to assist in managing the logistics of committee and sub-committee meetings during the course of the trial and be responsible for taking minutes of the various meetings. It will also provide the support and guidance necessary to maintain the scientific integrity of the trial through Coordinating Center staff or procurement of consultants. The Data Coordinating Center will be responsible for acquiring and administering subcontracts for central laboratory and clinical resources. The applicant for the Coordinating Center must identify and prepare budgets for the central laboratories and facilities proposed to carry out the centralized activities dictated by the trial protocol. The specific centralized facilities and the budgets to be supported through subcontracts will depend on the final protocol developed cooperatively by the Steering Committee. The applicant should address the requirements of the Trial with a description of the tasks to be performed and provide corresponding budgets as presented later under "Budget Preparation by Study Phase." It should, however, be understood that the final budgets will be determined following the design of the study protocol and writing of the manual of operations. Examples of the types of centralized laboratory functions that may be required include analyses such as blood glucose determinations, blood lipid and lipoprotein subtypes, and determination of drug treatment levels. Endpoint analyses may include measures conducted at centralized reading centers for electrocardiograms, reading of fundus photography, non invasive vascular determinations and renal and cardiovascular biochemistry. For a central laboratory supported by a subcontract from the Data Coordinating Center, all NIH policies and procedures governing consortium grants must be adhered to. The Data Coordinating Center will process and review all data transmitted on standard forms and prepare periodic reports to participating clinics on outstanding, incomplete, and delinquent forms or other missing information. The Coordinating Center will also prepare reports to the NIDDK and the Steering and the Policy and Data Monitoring Committees at regular intervals and as dictated by the study needs. The NIDDK Project Director will serve as a liaison between the Data Coordinating Center and the Clinical Centers. During Phase 3, the Data Coordinating Center will complete all analyses of the data from the clinical trial. Final reports will be submitted to the Steering Committee and the Policy and Data Monitoring Committee. The Coordinating Center, after final analyses, will collaborate with the investigators and the NIDDK to prepare reports of the study for publication. SPECIAL REQUIREMENTS The Data Coordinating Center will be closely involved with all facets of the trial from the initiation of Phase 1 to Phase 3 final data analysis and reporting. The following minimum number of issues should accordingly be addressed: o The participation of the Coordinating Center in the design and refinement of all protocols and the Coordinating Center's function as central point for assembling the Manuals of Operation and Forms Manuals; o The Data Coordinating Center's primary responsibility in developing and implementing systems necessary for intra-study communications. o The primary responsibility of the Data Coordinating Center for data collection, editing, processing, analysis and reporting. o The responsibility for monitoring both the quality of the data and the performance of each clinical center in the performance of the protocols. o Documentation for experience in utilizing procedures that insure the safety and confidentiality of all records. Personnel A Director and Deputy Director for the Data Coordinating Center must be designated. The Director of the Data Coordinating Center should be an experienced biostatistician, epidemiologist, physician, or other professional with experience in directing a coordinating center for a large scale collaborative clinical trial or other large scale epidemiological research project. A physician with professional interests in diabetes as part of the management team is highly desirable. Staff needs may be modified as the trial progresses; however, statisticians, systems analysts, programmers, statistical assistants, clerks, and administrative assistants must be available. It is appropriate that funds for adequate support staff to manage routine tasks be requested. It is expected that senior statistical staff devote time to developing data analysis methods for use in the trial. Budget Preparation by Study Phase Applicants for the Data Coordinating Center should submit adequately justified budgets for the entire anticipated project period of 84 months. The budgets for each phase of the study should be clearly delineated. Final budgets, however, will be generated following the design of the study protocol and writing the manual of operations during Phase 1. The Phase 1 budget period will be for establishment of the Data Coordinating Center staff such as the PI, senior statistical advisor, biostatistician, senior data controller, and others as required to carry out the Coordinating Center's functions. During this phase the collaborating centralized laboratory functions and facilities and individuals to perform clinical determinations of outcome measures will be identified. These centralized functions will be supported by subcontracts provided through the Data Coordinating Center and are to be included in the overall Coordinating Center budget for Phase 2. The Phase 2 period will be for 60 months. Separate budgets for each 12-month budget period in Phase 2 should be submitted. Activities in this second period will include all data handling costs, reporting functions, meetings and the cost of the subcontracts necessary to carry out laboratory and other central functions. The Phase 3 budget period will be for 12 months. This budget period will be concerned with study close-out, analysis of study data, and reporting of results in collaboration with the centers. Budgets for both Phases 2 and 3 will be modified based on the final protocol developed collaboratively during Phase 1. Terms and Conditions of Award 1. Cooperative Activities. The administrative and funding mechanism to be used to undertake this project will be cooperative agreements (U01), which is an "assistance" mechanism, rather than and "acquisition" mechanism. Under the cooperative agreement, the NIDDK purpose is to support and/or stimulate the recipient's activity by collaborating and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity., Consistent with this concept, the tasks and activities in carrying out the studies will be shared among the awardees and the NIDDK Project Coordinator. 2. Awardees Activities. Awardees will have substantial and lead responsibilities in all tasks and activities. These include protocol development, patient recruitment and follow-up, data collection, quality control, final data analysis and interpretation, preparation of publications. The awardee agrees to work cooperatively with the Clinical Centers and agrees to follow the common protocol and manual of operations developed in Phase 1 of the study by the Steering Committee. Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government, e.g., NIDDK, NIH, or PHS, rights or access consistent with current HHS, PHS, and NIH policies. 3. NIDDK Activities. It is the intention of the NIDDK that the central resource units for the standardized assessment of key laboratory and clinical parameters will be established and utilized by all participating Clinical Centers. These central resources will function and be supported under the Data Coordinating Center award. The NIDDK will name the Director, Special Programs from within the Division of Diabetes, Endocrinology, and Metabolic Diseases to be the Project Coordinator whose function will be to assist the Steering Committee and Policy and Data Monitoring Committee in carrying out the study. The Project Coordinator will be a voting member of all key study group committees. The Project Coordinator will serve as executive secretary of the independent Policy and Data Monitoring Committee. The NIDDK Project Coordinator will assist in quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and coordination and performance monitoring. The NIDDK Project Coordinator will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The NIDDK reserves the right to terminate or curtail the study (or an individual award) in the event of (a) a major breach in the protocol or substantial changes in the agreed-upon protocol with which the Institute does not agree or (b) human subject ethical issues that may dictate a premature termination. 4. Governance. The primary governing body of the study will be the Steering Committee comprised of each of the Principal Investigators of the Clinical Centers and the Data Coordinating Center and the NIDDK Project Coordinator. The Steering Committee will have primary responsibility for developing common clinical protocols, facilitating the conduct and monitoring of the studies, and reporting the study results. Topics for the protocols will be proposed and prioritized by the steering Committee. Each member of the Steering Committee will have one vote. A chairperson will be appointed by the voting members of the Steering Committee from among the Steering Committee members but not including the Project Coordinator, or alternatively, from among experts in the field of diabetes and clinical trials who are not participating directly in the study. It is anticipated that the Steering Committee will meet on a monthly basis during protocol development (Phase 1), three times a year in Phase 2, and two times in Phase 3. Subcommittees of the Steering Committee may be established as necessary and will meet as necessary. The NIDDK Project Coordinator or designee and the Data Coordinating Center will be represented on each subcommittee. An independent Policy and Data Monitoring Committee supported by the NIDDK and composed of experts in relevant medical, psychological, statistical, operational, and bioethical fields who are not otherwise involved in the study will be established to review periodically the progress of the study. The committee will oversee participant safety, evaluate results, monitor data quality, and provide operational and policy advice to the Steering Committee and the NIDDK regarding the status of the study. The Principal Investigator of the Data Coordinating Center, the NIDDK Project Coordinator, and the Director of the Division of Diabetes, Endocrinology and Metabolism may participate as ex-officio, non-voting members of this Committee. Committee members will be appointed by the Director, NIDDK in consultation with members of the Steering Committee. The NIDDK named Project Coordinator will serve as executive secretary of the Policy and Data Monitoring Committee. 5. Arbitration. Any disagreement that may arise in scientific-programmatic matters between award recipients and NIDDK may be brought to arbitration. An arbitration panel will be composed of three members - one selected by the Steering Committee (with NIDDK member not voting) or by the individual awardees in the event of an individual disagreement, a second member selected by NIDDK and the third member selected by the preceding two members. This special arbitration procedure in no way affects the awardees' right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR part 50, subpart D and HHS regulations at 45 CFR part 16. These special terms of award described above are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR parts 74 and 92, and other HHS, PHS, and NIH grant administration policy statements. STUDY POPULATIONS 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 size 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 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. 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, but not required, to submit a letter of intent. This letter is to include the name, telephone number and mailing address of the Principal Investigator, the names of other key personnel, the name of the applicant institution, and the number and title of this RFA. Such a letter of intent is not binding and it will not enter into the review of any application subsequently submitted nor is it a necessary requirement for application. Letters of intent are requested solely for planning purposes. The information contained in these letters is helpful in planning for the review of applications. It allows NIDDK staff to estimate the potential review workload and to avoid possible conflicts of interest in the review. The NIDDK staff will not provide responses to such letters. Letters of intent are to be received no later than September 17, 1993, and are to be addressed to: Robert D. Hammond, Ph.D. 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 Submit applications on form PHS 398 (rev. 9/91), the application form for NIH research project grants. This form is available in the applicant institution's office of sponsored research and may be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7250. Use the conventional format for research project grant applications and ensure that the points identified in the SPECIAL REQUIREMENTS section above and in the "Review Criteria" section below are fulfilled. To identify the application as a response to the RFA, Check "YES" on item 2a of page 1 of the application and enter the title "NIDDM Primary Prevention Trial: Data Coordinating Center" and enter the RFA number DK-93-008 in the space provided. The RFA label found in the form PHS 398 application kit must be affixed to the bottom of the face page of the original completed application form. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. Send or deliver the completed, signed application and three complete photocopies to the following office, making sure that the original application with the RFA label attached is on top: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Send two additional copies of the application to Dr. Hammond at the address listed under LETTER OF INTENT. It is important to send these two copies at the same time as the original and three copies are sent to the Division of Research Grants, otherwise the NIDDK cannot guarantee that the application will be reviewed in competition for the RFA. Applications must be received by October 19, 1993. An application not received by this date will be returned to the applicant. REVIEW CONSIDERATIONS Upon receipt, the Division of Research Grants (DRG) will review applications for completeness. Applications will be reviewed by NIDDK staff for responsiveness to the objectives of this RFA. If an application is judged unresponsive or incomplete, the application will be returned. If the number of applications is large compared to the number of awards to be made, the NIDDK will conduct a preliminary scientific peer review and will withdraw from further competition those applications that are not competitive for award. The NIDDK will notify the applicant and institutional official of this action. Those applications judged to be both competitive and responsive will be evaluated further according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NIDDK. Subsequently, they will be reviewed by the National Advisory Diabetes and Digestive and Kidney Diseases Council. Review Criteria Specific criteria for review of applications will be as follows: o The scientific merit of the proposed approach to study design, data collection and management for interventions as outlined in the RFA o Documentation of the specific competence and previous experience of professional, technical, and administrative staff pertinent to the operation of a Data Coordinating Center for a collaborative clinical trial. Prior experience in the collection of data from multiple clinical sites, as well as experience in monitoring the quality of such data must be demonstrated. o The approach to developing a cooperative relationship among the participating clinical centers and exercising appropriate leadership in matters of study design, data acquisition, data management, and data analysis, o Suitability of the proposed data management and data analysis plans as well as the specific plans for central laboratories and clinical facilities, o Appropriateness of the proposed budget, o Ability to identify and enlist the cooperation of central laboratories and clinical facilities to carry out centralized biochemical and clinical support functions for the Clinical Centers. o The adequacy of the proposed facility, technical hardware, and space; o The organizational and administrative structure of the proposed Coordinating Center, o Evidence of the degree of commitment and support of the organization/institution for the proposed Coordinating Center including documentation of available space. Seminar for Prospective Applicants A special technical assistance workshop will be offered to assist potential applicants. The purpose of this seminar is to give background information and respond to any questions about the preparation of an application in response to this RFA. The workshop will be held in the Washington, DC metropolitan area approximately one month after the publication of this announcement. The NIH cannot support individuals who wish to attend the conference, but the conference will be open to any individual who wishes to attend. Interested persons may contact Dr. Sanford A. Garfield, at the address listed under INQUIRIES, for further information. AWARD CRITERIA The anticipated date of award is July 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. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Sanford Garfield, Ph.D. Division of Diabetes, Endocrinology, and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 626 Bethesda, MD 20892 Telephone: (301) 594-7535 FAX: (301) 594-9011 Inquiries regarding fiscal matters may be directed to: Linda Stecklein Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649B Bethesda, MD 20892 Telephone: (301) 594-7543 FAX: (301) 594-7594 Schedule Letter of Intent Receipt Date: September 17, 1993 Application Receipt Date: October 19, 1993 Initial Review: February/March 1994 Review by the NIDDK Council: May/June 1994 Anticipated Award Date: July 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.847. Awards are made under the authority 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 Part 52 and 45 CFR parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. References: 1. National Diabetes Data Group: Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28:1039-57, 1979 2. Harris MI, Hadden WC, Knowler WC, Bennett PH. Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20-74 yr. Diabetes 36:523-534;1987 3. Harris MI Epidemiological correlates of NIDDM in Hispanics, Whites, and Blacks in the U.S. population. Diabetes Care 14:639-648:1991 4. Saad MF, Knowler WC, Pettitt DJ, Nelson RG, Mott DM, Bennett PH. The natural history of impaired glucose tolerance in the Pima Indians. New Engl J Med 319:1500- 1506;1988 5. Yudkin JS, Alberti KGMM, Mclarty DG, Swai ABM Impaired glucose tolerance. Brit Med J 301:397-402;1990 6. Eriksson KF, Lindgarde F, Impaired glucose tolerance in a middle-aged male urban population: a new approach for identifying high risk cases. Diabetologia 33:526- 531;1990 7. Harris MI, Hadden WC, Knowler WC, Bennett PH: International criteria for the diagnosis of diabetes and impaired glucose tolerance. Diabetes Care 8:562-67, 1985 8. Lillioja S, Mott DM, Zawadzki JK, Young AA, Abbott WGH, Knowler WC, Bennett PH, Moll P, Bogardus C. In vivo insulin action is a familial characteristic in nondiabetic Pima Indians. Diabetes 36:1329;1987 9. Horton ES. Exercise and decreased risk of NIDDM. N Engl J Med 325:197;1991 (editorial) 10. Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS. Physical activity and reduced occurrence of non-insulin- dependent diabetes mellitus. N Engl J Med 325:147;1991 11. Manson JE, Nathan DM, Krowlewski AS, Stampfer MJ, Willett WC, Hennekens CH. A prospective study of exercise and incidence of diabetes among US male physicians. JAMA 268:63;1992 12. Eriksson KF, Lindgarde F. Prevention of Type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise: The 6-year Malmo feasibility study. Diabetologia 34:891-898;1991 13. Page RCL, Harnden KE, Cook JTE, Turner RC. Can life-styles of subjects with impaired glucose tolerance be changed? A feasibility study. Diabetic Medicine 9:562-566;1992 14. Jarrett RJ, Keen H, Fuller H, McCartney M. Worsening to diabetes in men with impaired glucose tolerance ("Borderline Diabetes"). Diabetologia 16:25- 30;1979 15. Sartor G, Schersten B, Carlstrom S, Melander A, Norden A, Persson G. Ten-year follow-up of subjects with impaired glucose tolerance. Diabetes 29:41;1980 16. Melander A, Bitzen P-O, Sartor G, Schersten B, Wahlin-Boll E. Will sulfonylurea treatment of impaired glucose tolerance delay development and complications of NIDDM? Diabetes Care 13:53-58;1990 .
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