Full Text NIH-92-HL-08-P OBESITY PREVENTION IN AMERICAN INDIANS/ALASKA NATIVES: FIELD CENTER NIH GUIDE, Volume 21, Number 31, August 28, 1992 RFA: NIH-92-HL-08-P P.T. 34, FE Keywords: Obesity Disease Prevention+ National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: October 15, 1992 Application Receipt Date: December 18, 1992 PURPOSE The Division of Epidemiology and Clinical Applications (DECA) invites cooperative agreement applications for an estimated five Field Centers to participate [with the Coordinating Center, to be solicited under a separate Request for Applications (RFA) RFA: NIH-92-HL-09-P, and with the assistance of the National Heart, Lung, and Blood Institute (NHLBI)] in a collaborative study to assess the effectiveness of school-based intervention to prevent obesity in young American Indians/ Alaska Natives (hereafter referred to as Native Americans). The solicitation is for the initial three-year planning and feasibility study of a planned nine-year effort. The purpose of this planning and feasibility study is to test the acceptability and efficacy of school-based interventions focused on the primary prevention of obesity in pre-adolescent Native Americans. The intervention is envisioned to include elementary school curricula that may incorporate a variety of nutrition and physical education methods, inter-generational components, skill-building and behavioral activities, and strong family or home-based components. The intervention may also include environmental changes related to food consumption and physical activity as well as development of supporting community programs. The planning and feasibility phase will include collaboratively establishing the study's design and organizational structure; developing the study protocol; selecting and pilot testing all measurement instruments and methods; and developing and pilot testing all intervention protocols, materials, and methods. 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 RFA, Obesity Prevention in American Indians/Alaska Natives, is related to the priority areas of nutrition, physical activity fitness, educational and community- based programs, heart disease and stroke, and diabetes and chronic disabling diseases. The Healthy People 2000 objectives specify a reduction in overweight to a prevalence of no more than 30 percent among American Indian/Alaska Native adolescents aged 12 through 19. 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 may be submitted by domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. Foreign organizations are not eligible to apply and domestic applications may not include international components. Applications from minority individuals, especially American Indians/Alaska Natives, and women are encouraged. Awards for Field Centers under this RFA and a Coordinating Center under a separate RFA will not be made to the same Principal Investigator (PI); this is to ensure that data analysis is done independently of data acquisition. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to undertake this project will be a cooperative agreement (U01), an assistance mechanism. Under the cooperative agreement, the NIH assists, supports, and/or stimulates and is involved substantially with recipients in conducting a study by facilitating performance of the effort in a "partner" role. Details of the responsibilities, relationships and governance of a study funded under a cooperative agreement are discussed later in this document under the sections entitled STUDY ORGANIZATION and TERMS AND CONDITIONS OF AWARD. FUNDS AVAILABLE An estimated five awards for Field Centers will be made under this RFA. A maximum of $6.3 million (including direct and indirect costs) over a three-year period will be awarded for Field Centers and the Coordinating Center with at least two-thirds for Field Centers. Approximately $2.0 million will be available for the first year to be allocated among the Field Centers and Coordinating Center. The level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this project is provided for in the financial plans of the NHLBI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. At the end of the three-year planning and feasibility study, two possible options will be available to awardees: (1) the NHLBI hopes to invite competitive renewals under the Cooperative Agreement mechanism for the six-year full-scale study, if feasibility is shown, or (2) the awardees may submit grant applications through the usual investigator-initiated grants program. RESEARCH OBJECTIVES Background The Native American population, including American Indians and Alaska Natives, totals nearly 1.5 million from over 500 tribes and nearly 300 reservations and Alaska Native villages. Earlier in this century, heart disease was rarely noted in Native Americans, but in the last decade cardiovascular disease has become the leading cause of death in Native Americans. Several factors may be responsible for this increase: a decreasing incidence of infectious disease, an increasing incidence of diabetes mellitus, and an increasing incidence of obesity. Previous research on non-Indian populations indicates that obesity is an independent risk factor for cardiovascular disease and that it is associated with increases in other cardiovascular disease risk factors such as high blood pressure, diabetes, and low HDL-cholesterol levels. The high prevalence of obesity among Native Americans, coupled with its role as a risk factor for hypertension, coronary heart disease, and diabetes, suggests that a reduction in the average weight of young Native Americans would improve their health. Reduction of the prevalence of obesity in Native Americans has been designated as a goal for improving the health of this minority population. Healthy People 2000 states that this objective should be achieved through emphasis on physical activity accompanied by properly balanced dietary intake so that growth is not impaired. This RFA attempts to address these issues with a project on primary prevention of obesity in young Native Americans. A more detailed scientific background may be found in the appendix of this RFA. Successful respondents to this RFA are likely to have a thorough knowledge of the history, customs and culture of the Native American population to be studied, and administrative skills and experience needed to design and implement collaborative intervention studies. A multi-disciplinary approach to this study is appropriate for the Field Centers. Disciplines and expertise of staff members may include health promotion, obesity and weight management programs, physical fitness, nutrition, behavioral modification, pediatric medicine, cardiovascular epidemiology, educational technology, and instructional design. Objectives and Scope This study is envisioned as a nine-year effort to develop and test interventions to reduce the rate of weight gain in schoolchildren of the Native American community. To provide a common understanding of factors necessary for a collaborative effort, it is important for applicants to understand at the outset certain common temporal goals and features, e.g., study magnitude, phases, and handling of certain central functions. A number of possible components are listed purely for illustrative purposes. This is necessary so that the applicants can address some similar fundamental topics in their applications. When the recipients are convened, they can work together to develop the common protocol, with the assistance of the two NHLBI Project Scientists (an epidemiologist and a nutritionist). The collaborative protocol will be developed by the Project Steering Committee (see below) and will be subject to peer review by an uninvolved expert group. The study will move into its second (or full-scale) phase only with the concurrence of both the award recipients and the NHLBI. The study consists of two phases. Feasibility of the concept will be determined during the first three years of the study. If it is shown to be feasible, the full-scale study will be implemented during the next six years. The planning and feasibility study is expected to be completed over approximately a three-year period. During this period, investigators from the Field Centers, Coordinating Center, and the NHLBI will collaboratively develop the study design, materials, forms, protocol, and manual of operations to be cooperatively followed by all Field Centers and Coordinating Center in the pilot test and subsequent full-scale study if it is approved. Some aspects of the protocol may vary by Center to meet local conditions and needs. The expertise of the investigators will be fully utilized to collaboratively determine the most appropriate approach to prevent obesity among young Native Americans. The objective of Phase II - not within the scope of the current awards, but relevant to the current RFA - will be to conduct a full-scale randomized intervention trial to prevent the development of obesity. It is envisioned that the intervention will be focussed on pre-adolescent elementary schoolchildren and that about 3000 Native American students study-wide will participate in intervention and control groups. Schools are expected to be the unit of randomization. An estimated six schools per center may be required in the full-scale study. The intervention is envisioned to last three to four years, depending on the time needed to show measurable difference in the selected obesity index between the intervention and control groups. (Note that this is not weight loss but a reduction in the rate of weight gain.) Data analysis and publication of study results will follow the completion of the intervention. Timetable The planning and feasibility study may be loosely divided into three subphases covering about a three-year period. There may be some overlap of functions within each of the subphases and time estimates are only approximations; the purpose of subphasing is to provide broad guidelines of the work to be accomplished in Phase I and Phase II. Phase I(a): Planning and Protocol Development - 1 year Phase I(b): Training and Pilot-testing - 1 year and 6 months Phase I(c): Post-Pilot-testing Assessment - 6 months The full-scale intervention study is expected to last six years and might include the following subphases: Phase II(a): Intervention Preparation - 8 months Phase II(b): Intervention - 4 school years Phase II(c): Analysis and Reporting - 16 months Objectives for Phase I The planning and feasibility study will attempt to answer questions related to political, intervention, and design issues. Examples of topics that need to be resolved and shown feasible include: (1) How receptive are Tribal governments and community members to various potential intervention strategies that may affect the school curriculum, community programs, food distribution systems, and traditional Native American attitudes and behaviors? (2) What impact will the concerns of other relevant government agencies, such as the Bureau of Indian Affairs (BIA), Centers for Disease Control (CDC), Indian Health Service (IHS), United States Department of Agriculture (USDA), and State and local boards of education, have on the objectives of this initiative? (3) Can a school curriculum focused on the prevention of obesity be implemented in schools serving Native Americans? (4) Can obesity prevention modifications in food service and food distribution systems be implemented in Native American communities? (5) Can a family-based component of the school curriculum be implemented and accepted by Native American families? (6) Can community programs be developed to support the prevention of obesity among pre-adolescents in the Native American community? (7) Can knowledge and attitudes related to obesity be changed in young Native Americans with a focused intervention effort? (8) Is a non-intervention arm acceptable as part of a controlled randomized trial on the primary prevention of obesity in Native Americans and, if not, what is an appropriate alternate intervention? (9) What kinds of schools (BIA, tribally operated, public, or private) are most appropriate as intervention sites? (10) What measure of obesity should be used as the end point for this study of obesity prevention in Native American elementary schoolchildren? Phase I(a) Possible objectives of Phase I(a) are to develop a complete study protocol, data forms, and a manual of operations, and to recruit and prepare for the work with the schools. The PIs, through the Steering Committee, will lead the planning effort. Other key Center staff may be involved in the planning. The primary issues to be considered by the Steering Committee during Phase I(a) include eligibility criteria, recruitment of schools, selection of baseline/follow-up measurements, and selection and design of the interventions. Subcommittees of the Steering Committee will likely be needed to address these issues. Phase I(b) The main activities of this phase are envisioned to include training of intervention personnel, conducting the pilot test of the study protocol which was developed in Phase I(a), and evaluating and cooperatively revising the study materials and methods. The Field Centers are likely to be responsible for assisting school personnel and community representatives in implementing the interventions, for collecting the evaluation data, and for transmitting the data to the Coordinating Center. Phase I(c) This Phase is expected to include refinement of the protocol, intervention and measurement manuals, and study materials as well as manuscript preparation. Analyses of the data will be completed. The goal of these analyses will be to evaluate acceptance of and adherence to interventions and the effects of the interventions. Results of these analyses will be used to address such questions as suggested under "Objectives for Phase I," determine the feasibility of Phase II, to plan Phase II, and as a basis for scientific papers and presentations. Phase II Phase II(a) is expected to include recruitment of schools; final production of protocol, manuals, materials, and forms; and training of additional personnel. Phase II(b) is envisioned to extend up to four years to provide time to complete the intervention. Support will be continued for the Field Centers for about 10 months during Phase II(c) to complete final entry of data, responses to edit queries, and orderly transmission of information about participants to school systems. It is anticipated that a main results paper will be prepared by the investigators and submitted for publication. The Coordinating Center will support the paper writing efforts of Field Center and Coordinating Center investigators with data analysis, statistical consultation, editorial and clerical tasks, and coordination of meetings. SPECIAL REQUIREMENTS Additional Material to Include in the Application To allow the development of a collaborative project among the award recipients, it will be necessary for applicants to address, at a minimum, a number of issues in the application. Applicants for Field Centers should discuss design considerations relevant to this plan and to the envisioned full-scale study, including the following: intervention methods, randomization methods, baseline and outcome measures, frequency of data collection, and mechanics of data collection. Applicants should discuss school eligibility criteria and describe the number and population characteristics of schools proposed for the study. Field Center applicants should discuss the advantages and disadvantages of various intervention methods for obesity prevention programs. Field Center applicants should propose a school-based project, possibly including a family or home-based component, and/or an environmental change program, each with a rationale based on current developments in the field. Attention should also be paid to the potential for contamination of control and intervention cohorts and provision for a non-obesity-related intervention program (e.g., accident prevention) in the control schools. All the intervention methods are likely to be considered since final decisions as to the specific content will be made collaboratively during Phase I. Field Center applicants should discuss the mechanics of data collection including: frequency of collection; how, where, and by whom data are collected. Additionally, Field Center applicants should discuss aspects of quality control, which is the responsibility jointly of the Field Center, Coordinating Center, and the NHLBI Project Scientists with the Coordinating Center taking a primary role. Field Center applicants must be able to interact effectively with the Coordinating Center to transmit and edit data. Field Center applicants should discuss their capability to participate in distributed data entry if this approach is selected. Study Organization The Steering Committee will be the main governing body of the study and, at a minimum, will be composed of the PIs of the Field Centers, the PI of the Coordinating Center and two NHLBI Project Scientists (an epidemiologist and a nutritionist). Unless otherwise explicitly provided, the non-NHLBI investigators will have the lead role in the Steering Committee. Each center and the NHLBI will have one vote. The Committee may meet as often as eight to ten times in the first 12 months of the study and three to four times a year thereafter. All major scientific decisions will be determined by majority vote of the Steering Committee. A chairperson (who will be other than an NHLBI staff member) shall be selected by the end of the second meeting of the Steering Committee. The first two meetings of the Steering Committee will be convened by the NHLBI Project Scientists. The Steering Committee will have primary responsibility for the development of the study protocol, facilitating the conduct of the study, and reporting of the study results. Subcommittees of the Steering Committee will be established as necessary. The NHLBI may have one representative on each subcommittee. With data submitted centrally, the protocol will define rules regarding access to data and publications. A Data and Safety Monitoring Board, to be appointed by the NHLBI, will review progress at least annually and report to the NHLBI. Terms and Conditions of Award The administrative and funding mechanism to be used to undertake this project will be cooperative agreements, an assistance mechanism. Under the cooperative agreement, the NIH assists, supports and/or stimulates and is involved substantially with recipients in conducting a study by facilitating performance of the effort in a "partner" role. Consistent with this concept, the tasks and activities in carrying out the studies will be shared among the awardees and the Institute Project Scientists. The tasks or activities in which awardees will have substantial responsibilities include protocol development, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, collaboration with other awardees, and collaboration with the NHLBI Project Scientists. The NHLBI Project Scientists will have substantial responsibilities in protocol development, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, collaboration with awardees, and coordination and performance monitoring. It is anticipated that awardees will have lead responsibilities in study design, protocol development, final data analysis and interpretation, and in the preparation of most publications. It is anticipated that the NHLBI Project Scientists will have lead role responsibilities in quality control and interim data and safety monitoring, and in the preparation of some publications. The NHLBI Project Scientists will have membership on the Steering Committee and, as appropriate, its subcommittees. Awards resulting in response to this RFA are for three years only. It is anticipated that Phase II will be undertaken if Phase I is completed successfully. Progression to Phase II will be undertaken only after external review and recommendation by the NHLBI. As noted earlier, at the end of the three-year planning and feasibility study, two possible options will be available to awardees: (1) the NHLBI hopes to invite competitive renewals under the Cooperative Agreement mechanism for the six-year full-scale study, if feasibility is shown, or (2) the awardees may submit grant applications through the usual investigator-initiated grants program. Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government, e.g., NHLBI, NIH, or PHS, rights of access consistent with current HHS, PHS, and NIH policies. Any disagreement that may arise in scientific matters between award recipients and the NHLBI may be brought to arbitration. An arbitration panel will be composed of three members---one selected by the Steering Committee (with the NHLBI member not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by NHLBI and the third member selected by the two prior 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 regulation at 45 CFR part 16. These special Terms of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR part 74, and other HHS, PHS, and NIH grant administration policy statements. The NHLBI reserves the right to terminate or curtail the study (or an individual award) in the event of a substantial shortfall in (a) participant recruitment, follow-up, data reporting, quality control or other major breech of the protocol, or (b) substantive changes in the agreed-upon protocol to which the Institute does not agree, or (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance, or (d) human subject ethical issues that may dictate a premature termination. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH and ADAMHA policy is that applicants for NIH/ADAMHA 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 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 disproportionally affect them. Because this RFA is directed to a single minority population, it is not restricted by the minority section of this policy statement. This policy is intended to apply to males and females of all ages. If women 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 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 in Sections 1-4 of the Research Plan and Summarized in Section 5, Human Subjects. For the purpose of this policy, clinical research includes 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 not subject to these policies. 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. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women 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 will be reflected in assigning the priority score to the application. 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 October 15, 1992, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the PI, 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 the NHLBI 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: C. James Scheirer, Ph.D. Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 548 5333 Westbard Avenue Bethesda, MD 20892 Telephone: (301) 496-7363 FAX: (301) 402-1660 APPLICATION PROCEDURES Applicants applying for both a Field and Coordinating Center must submit separate applications. A detailed budget page should be submitted for each of the three 12-month budgets periods. Costs relating to subphases I(a), I(b), and I(c) should be clearly designated on each budget page. The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these awards. These forms are available at most institutional business offices; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/496-7441; and from the NIH Project Scientists named below. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. 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. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Send or deliver the original signed application and three legible complete photocopies to: Division of Research Grants Westwood Building, Room 240 National Institutes of Health Bethesda, MD 20892** Send two additional copies of the application to: C. James Scheirer, Ph.D. Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 548 5333 Westbard Avenue Bethesda, MD 20892 Telephone: (301) 496-7363 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 NHLBI CANNOT GUARANTEE THAT THE APPLICATION WILL BE REVIEWED IN COMPETITION FOR THIS RFA. Applications must be received by December 18, 1992. An application not received by this date will be considered ineligible. REVIEW CONSIDERATIONS General Considerations All applicants will be judged on the basis of the scientific merit of their proposed study and their documented ability to conduct the essential study components as broadly outlined in the RESEARCH OBJECTIVES of this RFA. Review Method Upon receipt, applications will be reviewed by the NHLBI staff for their completeness and for their responsiveness to this RFA. Incomplete applications will be returned to the applicant without further consideration. If an application is unresponsive, the applicant will be contacted and given an opportunity to withdraw the application or to have it considered for the regular, investigator-initiated grant program of the NIH. If an application submitted in response to this RFA is identical to or substantially the same as one already submitted to the NIH for review by the NHLBI Council in the same cycle, the PI will be asked to withdraw the pending application before the new one is accepted. Simultaneous submission of identical applications will not be allowed. Applications judged to be responsive will be reviewed for scientific and technical merit by an initial peer review group, that will be convened by the Division of Extramural Affairs, NHLBI, solely to review these applications. The initial review will include a preliminary evaluation to determine scientific merit relative to the other applications received in response to this RFA (triage); the NIH will remove from further consideration applications judged to be noncompetitive and promptly notify the PI and the official signing for the applicant organization. Those applications judged to be competitive will be further evaluated for scientific/technical merit by the usual peer review procedures, including, if deemed appropriate, an applicant interview in or near Bethesda (a reverse site visit) at the applicant's expense. Subsequently, they will be reviewed by the National Heart, Lung, and Blood Advisory Council. Review Criteria Applicants are encouraged to submit and describe their own ideas on how best to meet the goals of the study, but they are expected to address issues identified under SPECIAL REQUIREMENTS of this RFA. Applications will be judged primarily on the scientific quality of the application, the availability of a study sample with adequate numbers of students, evidence of a commitment of the Native American community to the proposed study and study investigators, the discussion of considerations relevant to this RFA, expertise of the investigators, their capability to perform the work proposed, and a demonstrated willingness to work together with other Centers and the NHLBI Project Scientists. The review group will assess: 1. Scientific merit of the study including: o documenting the need for an obesity prevention effort in the proposed study population; o proposed study design and issues related to implementation; o rationale for the selection of interventions methods, implementation strategies and measurement strategies, and safety measures; and o methods to minimize contamination of control and intervention schools. 2. Plans to recruit schools and secure student, family and community participation including: o demonstration of Tribal/community support for an intervention study; o documentation of the availability of at least six elementary schools with adequate numbers of Native American students; o documentation providing evidence of school administrator support; o documentation supporting the likelihood of acceptable family participation rates; o documentation describing the student attrition rates; o stability of the school faculty at the available schools; and o description of the relevant facilities and equipment at the available schools. 3. Qualifications, experience, and commitment of key personnel including: o scientific and administrative abilities of the PI and coinvestigators; o experience of the investigators and other key personnel in conducting school-based, behavioral, and health education research and research related to obesity in children; o plans for key personnel to devote adequate time for the effective conduct of the study; o willingness to work collaboratively with other Field Centers, the Coordinating Center, and the NHLBI; o experience of the staff in working with Native American communities; o representation of Native Americans among the staff members; and o commitment to conduct the study in a way that promotes involvement of the Native American community being studied. 4. Facilities, equipment and organizational structure to effectively implement intervention and data collection procedures. 5. Appropriateness of the budget for the work proposed. AWARD CRITERIA Applications recommended by the National Heart, Lung, and Blood Advisory Council will be considered for award based upon (a) scientific and technical merit and the requirements explicitly stated in this RFA, (b) program balance, including in this instance, sufficient compatibility of features to make a successful collaborative program a reasonable likelihood, and (c) availability of funds. Timetable Letter of Intent: October 15, 1992 Application Receipt Date: December 18, 1992 Review by National Heart, Lung, and Blood Advisory Council: May 1993 Anticipated Award Date: July 1, 1993 INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding this announcement to: Richard R. Fabsitz Clinical and Genetic Epidemiology Branch Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute Federal Building, Room 3A17 7750 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-4333 or to the Deputy Project Scientist: Marguerite A. Evans Prevention and Demonstration Research Branch Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute Federal Building, Room 604 7550 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-3503 Direct fiscal and administrative matters to: Marie Willett Deputy Chief, Grants Operations Branch Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute Westwood Building, Room 4A12 5333 Westbard Avenue Bethesda, MD 20892 Telephone: (301) 496-7255 AUTHORITY AND REGULATIONS This project is described in the Catalog of Federal Domestic Assistance No. 93.837. Awards are made 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 74. This project is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. APPENDIX Scientific Background Prevalence of obesity in Native Americans: Because Native Americans are not represented in most national health and nutrition surveys, data on the prevalence of overweight among Native Americans are limited to smaller studies that are based on limited population surveys of specific tribes. However, they all indicate a greater proportion of overweight adults among American Indians compared to U.S. adults (Donato, Evans, Haines 1990). Broussard and colleagues (1991) used several different data sources to estimate the prevalence of overweight and obesity in Native Americans. The prevalence of overweight and obesity were assessed by using body mass index (BMI, in kg/m(2)). For adults the prevalence of overweight is defined as the percentage of adults with BMI >85th percentile of the NHANES II reference for men and women aged 20 to 29 years: BMI >27.8 for men and >27.3 for women. The prevalence of obesity is defined as the percentage of adults with BMI >95th percentile: BMI >31.1 for men and >32.3 for women. The estimated prevalence of overweight in Native American males >18 years was 33.7 percent (obesity 13.7 percent) compared with the U.S. rate of overweight of 24.1 percent (obesity 9.1 percent) for males and in Native American females >18 years 40.3 percent (obesity 16.5 percent), which is much greater than the U.S. rate of 25.0 percent (obesity 8.2 percent) for females. Data from the Strong Heart Study suggest that there is variability in obesity within the Indian population. There is evidence that the prevalence of obesity is high among Native Americans in various geographic areas for both men and women across all ages. Very early data from the three geographic areas of the Strong Heart Study, an area near Phoenix, Arizona, the southwestern area of Oklahoma, and the Aberdeen area of North and South Dakota, showed the mean BMI's in each respective area to be 33.6, 31.2, and 30.3 for women aged 45-74 years and 30.6, 30.6, and 28.8 for men aged 45-74 years (unpublished). Seventy percent of female Cree and Ojibwa Indians in northwestern Ontario between the ages of 35 and 64 had BMIs >25 (McIntyre and Shah 1986). In comparison, 87 percent of female Pima Indians aged 35 to 44 years had BMIs >27.3 decreasing to 74 percent in females aged 55 to 64 years (Knowler et al. 1991), suggesting that the problem may actually be increasing in younger Indians. Of greater concern, overweight and obesity rates in American Indian adolescents and preschool children are higher than the respective rates for U.S. all-races combined (Broussard et al. 1991). Most striking are the adolescents from Arizona (44.1 percent of boys and 51.8 percents of girls aged 14-17 are obese---74.6 and 78.3 percent respectively are overweight). For adolescents, overweight is defined as BMI >23.0 for males aged 12 through 14, and 24.3 for males aged 15 through 17; 23.4 for females aged 12 through 14, and 24.8 for females aged 15 through 17. Preliminary data (unpublished) from the CDC-IHS height/weight school survey (1991) for three locations, Phoenix, Billings and Navajo, show the mean BMIs for boys aged five are 16.4, 16.5 and 16.5 respectively, aged 12: 23.2, 21.6 and 19.6, and aged 17 mean BMIs are 25.2, 26.0 and 22.4 respectively. For girls aged five the mean BMIs are 16.2, 16.3 and 15.7 respectively, aged 12: 23.1, 21.5 and 21.0, and for aged 17 26.5, 23.9, and 24.5. At even younger ages the prevalence of obesity is also excessive. The prevalence rate of obesity in Native American children aged zero to four participating in public health programs was 11.2 percent, higher than the U.S. all-races rate of 8.1 percent (Broussard et al. 1991). Freedman et al. (1992) found that about 12 percent of American Indian preschool children were above the 95th percentile of weight-for-height, and American Indian preschool children had the highest mean age-adjusted Quetelet index compared to white, black, and Hispanic preschoolers. The data suggest that there has been a secular change in height, weight, overweight, and obesity among American Indian children and adolescents (Broussard et al. 1991). Over the past 35 years (Sugarman, White, Gilbert 1990) obesity has increased in Navajo schoolchildren; compared with data from 1955, mean weights increased 28.8 percent among boys and 18.7 percent among girls across all age groups. Similarly, there have been modest increases in age- and sex-specific mean BMIs of Pima Indians for the past 25 years (Knowler et al. 1991). Relationship of obesity to health outcomes: Many of the health problems of American Indians and Alaska Natives are related to obesity. Along with the increased prevalence of obesity, there has been an increase in cardiovascular disease. There has also been an epidemic of diabetes and an increase of other chronic diseases, including end-stage renal disease, gallbladder disease, uterine cancer, and perinatal mortality rates. Their precise magnitude is poorly defined (Broussard et al. 1991). Health implications of obesity vary greatly in the Indian Health Service areas. This variability reflects the co-existence of other risk factors, including smoking, hypertension, diabetes, and hypercholesterolemia, as well as differences in genetic predisposition for various diseases (Welty 1991; Young, Sevenhuysen 1989). Although Native Americans are not a homogeneous group with regard to health problems, they have all suffered adverse effects from the high prevalence of obesity. The degree to which obesity in childhood imposes a risk for obesity in adulthood is of great concern. Data from the Muscatine Study indicates that obesity acquired in adolescence has deleterious effects on adult cholesterol levels and lipoprotein fractions (Lauer et al. 1988). In addition, children who gain in ponderosity show a gain in their blood pressures which does not depend on the initial blood pressure (Clarke et al. 1986). Data from the Bogalusa Health Study indicate that children who are obese over consecutive examinations are likely to become obese adults (Freedman 1987). This is likely to occur in Native American children; however, these patterns have not yet been documented. Johnston (1985) has concluded that the relative risk for obese children becoming obese adults, compared with the risk for non-obese children, may be as high as 2.3 and this increases markedly with age. By pre-adolescence the relative risk is >6. Potential contributors: The causes of obesity are complex and include cultural, familial, and genetic factors. Studies of energy expenditure among the Pima Indians suggest that a low metabolic rate contributes to the familial aggregation of obesity in man (Bogardus, Lillioja, Ravussin 1990). In addition, there may be multiple metabolic differences between Indians and non-Indians that may predispose Native Americans to become obese when food is abundant. Neel's thrifty-gene hypothesis in 1962 suggested that obesity results from the introduction of a continuous and ample food supply to people who have evolved an ability to store energy efficiently, permitting survival through millennia of feast-famine cycles (Neel 1962). Since obesity may have multiple possible determinants, it is unclear whether the primary defect is genetic, environmental, or an interaction between the two (Howard et al. 1991). Sociodemographic and lifestyle determinants of obesity identified in some Native American groups are compatible with findings from surveys in other populations. Age, sex, marital status, smoking, alcohol use, employment, income, and education were significant predictors of BMI. The observations that there is more obesity/overweight in younger Native Americans suggest that the older adults have had less exposure to factors leading to obesity than have the younger adults (Knowler 1991). Also, not all tribes share the general American cultural ideal for slimness. Some believe that being somewhat heavy is advantageous and a sign that one is not suffering from a disease or subject to sorcery (Jackson, Broussard 1987; Joos 1980). On the other hand, the mainstream social ideals of thinness appear to have been internalized by Native American youths (The State of Native American Youth Health 1992); for example, about 44 percent of female adolescents worry a great deal about being overweight and about 28 percent are very dissatisfied with their weight. Stress due to acculturation may also influence eating behavior in Native Americans (Pine 1984, 1985). Racial differences among young non-Indians are currently being investigated in NHLBIs National Growth and Health Study. Over five years, this study will estimate the occurrence of obesity among black and white girls age nine to ten at baseline and assess the predictors of transition to the obese state, the correlates of this transition, and the relationship of this transition to other CHD risk factors. Baseline data revealed that black girls had higher BMI and greater skinfolds than white girls. They also reported consuming more calories and more grams of fat and watching considerably more television than white girls. Results from the psychosocial questionnaires showed that compared to white girls, black girls were more content with their present weight, more satisfied with their appearance, and more satisfied with their separate body parts. Although the exact mechanisms leading to obesity are unclear, the fact remains that for an individual to add fat to body stores requires taking in more energy than is expended. The increasing rate of obesity may be related to fairly recent changes in lifestyle among many Native American tribes (Jackson 1986; Jackson, Broussard 1987). As late as 1967 malnutrition was a serious health problem in a small Navajo community (Welty 1991). However, in the late 1960s feeding programs, which included commodity foods high in fat and calories, were made available to reach malnourished people. A variety of Federal food assistance programs are currently available. Not all programs are operating at each community, and no programs are operating in some communities. In addition to Federal assistance, many non-Federal organizations provide food to Native Americans (GAO 1989). However, the Family Food Distribution Program, USDA, and the Food Stamp Program contribute significantly to Native American diets. Food may also be purchased with vouchers distributed through the Special Supplemental Food Program for Women, Infants, and Children (WIC) program. Participation in particular programs varies with the economic restrictions and frequently involves periodic switching to meet family needs (USDA 1990). In the Pimas, 33 percent of the women participate in the commodity food distribution program, 13 percent in the Food Stamp Program, and 39 percent in the WIC program (Smith et al. unpublished). Commodity foods contributed 40 to 50 percent of the intake of most nutrients in Navajo diets surveyed. Hunting, gathering, and on-reservation farming contribute less to the total energy intake than commodity distribution programs, foods purchased on or off reservation, and/or restaurants. For example, 16 percent of Pima Indians indicated the use of desert animals or fish for food (Smith et al. unpublished). Native diets have changed from high fiber and low fat to diets high in refined and simple carbohydrates and fat, and low in fiber (Jackson, Broussard 1987). There is limited published research regarding food patterns of Native Americans; however, a number of investigators (Teufel et al. 1990; Simons-Morton et al. 1990; Owen et al. 1981; Toma and Curry 1980; Koehler et al. 1989; Smith et al. 1991) have identified dietary practices which may contribute to obesity including the wide use of butter, lard, whole milk, fry breads, and fried meats and vegetables, as well as the generous use of fats in the preparation of beans. Sweets and snacks, including alcoholic and non-alcoholic beverages, account for high caloric intakes in some groups. The diet of Alaska Native adults is higher in energy and fat than the general U.S. adult population with the major contributors of fat being fish, agutuk, beef, seal oil, whale blubber, chicken, butter, and margarine (Nobmann et al. 1992). At the same time, physical activity markedly decreased. Most Native American populations developed obesity in less than a generation. So it can be said that the cause of obesity in Native Americans is related to the relative abundance of high-fat foods accompanied by rapid changes from an active to a sedentary lifestyle. Obesity intervention programs: The diversity of the population, in addition to cultural and social differences, provide challenges for effective health programming. Many health professionals and researchers have advocated culturally sensitive and population- or community-based approaches to nutrition and cardiovascular health education with increased involvement by Native Americans to achieve a significant impact. Intervention trials are needed urgently in Native American communities to develop and test effective education, diet, and exercise strategies for weight reduction in overweight individuals, but the history of such efforts in the general population suggests that obesity prevention may have a greater impact. Because of the concern regarding the consequences later in life of overweight among Native American youths, effective intervention programs to encourage increased physical activity and healthful eating habits need to be developed. Weight-reduction programs in obese adults have been conducted and are ongoing, but the literature documents only a few Native American population-based programs specific to obesity. The Zuni Diabetes Project is a community-based exercise and weight-control program initiated in July 1983 to reduce rates of obesity and provide primary and secondary prevention of non-insulin-dependent diabetes mellitus (NIDDM). Two studies of the project's activities demonstrated that (1) participation in a community-based exercise program can produce significant weight loss and improvement in glycemic control in obese adult Zuni Indians with NIDDM, and (2) weight-loss competitions appear to be an important public health model for health-behavior change in communities similar to that of Zuni, New Mexico (Heath et al. 1991). Other projects (personal communications) for primary and secondary prevention of obesity in various stages of development and implementation include a point-of-purchase education program in a grocery chain and a school-based program targeting normal and overweight adolescents on the Navajo Reservation. A number of school-based weight control programs for obese children have met with successful results (Brownell, Kaye 1982; Epstein, Masek, Marshall 1978; Seltzer, Mayer 1970; Wolf, Cohen and Rosenfeld 1985). Their results indicate that an effective program consisting of increased physical activity, dietary education, and psychological support can be introduced in a school system. Much of the success is dependent on the degree of cooperation of the community, the school board, the staff of the school system, and available facilities. These studies also indicate that the lower grade the level at which the weight control program is instituted, the better for the obese, and they must be continuously available for the students throughout their academic careers. D'Arca et al. (1986) proved the efficacy of an obesity prevention program in elementary and nursery-school children. Obesity is a family matter whether it afflicts children or adult members. The family as a culture transmitter plays a role in the development of health maintenance practices and plays a pivotal role in the creation and control of obesity among both children and adults. Epstein et al. (1981) noted that similarities between parent and child behavior during treatment for obesity, but not the follow-up period suggest that different mechanisms are at work during acquisition and maintenance of eating and exercise for the parents and children. Whereas a parent may lose self-control and act as an inappropriate model, child behavior can be maintained by consistent parental support or child self-regulation. Epstein et al. (1990) and Stunkard and Berkowitz (1990) state that treatment of obesity in childhood can produce effects that persist into young adulthood, especially if behavioral, family-based treatment is initiated when the child is between the ages of six and twelve years (Epstein et al. 1990). More general school curricula have been adopted in a number of Native American communities in the last few years that incorporate a component of obesity control in the context of overall health. Various schools serving the Oglala Sioux in South Dakota and the Pima in Arizona have modified the Growing Healthy curriculum produced by the National Center for Health Education to improve the health of their school-age population. In New Mexico the Navajo people have received instruction in weight control as part of a program to prevent the development of diabetes. While each of these includes obesity control in the message, none provides a focus on obesity prevention. Related NHLBI Studies: The NHLBI is sponsoring a five-year project, the Southwestern Cardiovascular Curriculum Project, in predominantly Pueblo and Navaho elementary schools. This project is testing a cardiovascular curriculum developed from existing curricula during a feasibility study. The revised obesity unit changes the focus from obesity to nutrition. In addition to the curriculum content, the project employs outreach activities including family participation and involvement, community health days, and peer and inter-generational involvement and modeling. These supplemental activities are designed to reinforce the curriculum, to encourage diffusion of the project materials to families and community, and to maintain cultural relevance of the project. Preliminary results from the first two years show a change in knowledge and practices. For example, the intervention schools show a greater increase in knowledge of cardiovascular biology and disease risk factors and an increase in physical activity (self report) compared to the controls. The intervention schools also show a decrease in the percent using butter at the table. Another NHLBI-sponsored study directed to Native Americans is the Strong Heart Study, which is a longitudinal observational study of cardiovascular disease (CVD) in American Indian men and women ages 45-74 (Lee et al. 1990). It is designed to estimate CVD mortality and morbidity rates and the prevalence of known and suspected CVD risk factors in American Indians. The study population consists of 12 tribes in three geographic areas: an area near Phoenix, Arizona, the southwestern area of Oklahoma, and the Aberdeen area of North and South Dakota. The envisioned study design described in this RFA is similar to the NHLBI- sponsored study, Child and Adolescent Trial for Cardiovascular Health (CATCH) (Perry et al. 1990). CATCH is a multisite intervention targeting third to fifth grade students and focuses on multiple cardiovascular health behaviors. The study has three phases: Phase I deals with study design, intervention, and measurement development, Phase II involves the main trial in 96 schools in four states, and Phase III focuses on analysis. REFERENCES Donato KD, Evans MA, Haines CM. Obesity in Minority Populations: A Background Paper Prepared Under the Aegis of the NHLBI Ad Hoc Committee on Minority Populations. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health. Draft August 1990. Bogardus C, Lillioja S, Ravussin E. The pathogenesis of obesity in man: results of studies on Pima Indians. International Journal of Obesity 14:5-15, 1990. Broussard BA, Johnson A, Himes JH, et al. Prevalence of obesity in American Indians and Alaska Natives. American Journal of Clinical Nutrition 53:1535S-42S, 1991. Brownell KD, Kaye FS. A school-based behavior modification, nutrition education, and physical activity program for obese children. American Journal of Clinical Nutrition 35:277-283, 1982. Clarke WR, Woolson RF, Lauer RM. Changes in ponderosity and blood pressure in childhood: the Muscatine Study. American Journal of Epidemiology 124:195-206, 1986. D'Arca AS, Tarsitani G, Cairella M, Siani V., De Filippis S, Mancinelli S, Marazzi MC, Palombi L. Prevention of obesity in elementary and nursery school children. Public Health 100:166-173, 1986. Epstein LH, Wing, RR, Koeske R, Andrasik F, Ossip DJ. Child and parent weight loss in family-based behavior modification programs. Journal of Consulting and Clinical Psychology 49(5):674-685, 1981. Epstein LH, Valoski A, Wing RR, McCurley J. Ten-year follow-up of behavioral, family-based treatment for obese children. Journal of the American Medical Association 264(19):2519-2523, 1990. Epstein LH, Masek BJ, Marshall WR. A nutritionally based school program for control of eating in obese children. Behavior Therapy 9:766-778, 1978. Freedman DS. Persistence of juvenile-onset obesity over eight years; the Bogalusa Heart Study. American Journal of Public Health 77:588-92, 1987. Freedman DS, Lee SL, Byers T, Kuester S, Sell KI. Serum cholesterol levels in a multiracial sample of 7,439 preschool children from Arizona. Preventive Medicine 21:162-176, 1992. General Accounting Office. Food Assistance Programs - Nutritional Adequacy of Primary Food Programs on Four Indian Reservations. GAO/RCED-89-177. September 1989. Healthy People 2000: National Health Promotion and Disease Prevention Objectives. DHHS Publication No. (PHS) 91-50212. Heath GW, Wilson RH, Smith J, Leonard BE. Community-based exercise and weight control: diabetes risk reduction and glycemic control in Zuni Indians. American Journal of Clinical Nutrition 53:1642S-1646S, 1991. Howard BV, Bogardus C, Ravussin E, et al. Studies of the etiology of obesity in Pima Indians. American Journal of Clinical Nutrition 53:1577S- 85S, 1991. Jackson MY, Broussard BA. Cultural challenges in nutrition education among American Indians. Diabetes Educator 13:47-50, 1987. Jackson MY. Nutrition in American Indian health: past, present, and future. Journal of the American Dietetic Association 86:1561-5, 1986. Johnston FE. Health implications of childhood obesity. Annals of Internal Medicine 103:1068-72, 1985. Joos SK. Diet, obesity, and diabetes mellitus among the Florida Seminole Indians. Florida Science 43:148-52, 1980. Knowler WC, Pettitt DJ, Savage PJ, et al. Diabetes incidence in Pima Indians: contributions of obesity and parental diabetes. American Journal of Epidemiology 113:144-156, 1981. Knowler WC, Pettitt DJ, Mohammed FS, et al. Obesity in the Pima Indians: its magnitude and relationship with diabetes. American Journal of Clinical Nutrition 53:1543S-51S, 1991. Koehler KM, Harris MB, Davis SM. Core, secondary, and peripheral foods in the diets of Hispanic, Navajo, and Jemez Indian children. Journal of the American Dietetic Association 89:538-40, 1989. Lauer RM, Lee J, Clarke WR. Factors affecting the relationship between childhood and adult cholesterol levels: the Muscatine Study. Pediatrics 82:309-18, 1988. Lee ET, Welty TK, Fabsitz R, Cowan LD, Le N, Oopik AJ, Cucchiara AJ, Savage PJ, Howard BV. The Strong Heart Study, A study of Cardiovascular Disease in American Indians: Design and Methods. American Journal of Epidemiology 132(6):1141-1155, 1990. McIntyre L, Shah CP. Prevalence of hypertension, obesity and smoking in three Indian communities in northwestern Ontario. Canadian Medical Association Journal 134:345-349, 1986. Neel JV. Diabetes mellitus: a "thrifty" gene genotype rendered detrimental by "progress"? American Journal of Human Genetics 14:353-62, 1962. Nobmann ED, Byers T, Lanier AP, Hankin JH, Jackson MY. The diet of Alaska Native adults: 1987-1988. American Journal of Clinical Nutrition 55:1024- 32, 1992. Owen GM, Garry PJ, Seymoure RD, Harrison GG, Acosta PB. Nutrition studies with White Mountain Apache preschool children in 1976 and 1969. American Journal of Clinical Nutrition 34:266-77, 1981. PATCH. Planned Approach to Community Health. Program Summary, Cheyenne River Sioux Tribe, Aberdeen Area Indian Health Service, South Dakota Department of Health, August 1988. Perry CL, Stone EJ, Parcel GS, Ellison RC, Nader PR, Webber LS, Luepker RV. School-Based Cardiovascular Health Promotion: The Child and Adolescent Trial for Cardiovascular Health (CATCH). Journal of School Health 60(8):406-413, 1990. Pine CJ. Field-dependence factors in American Indian and Caucasian obesity. Journal of Clinical Psychology 40:205-209, 1984. Pine CJ. Anxiety and eating behavior in obese and nonobese American Indians and white Americans. Journal of Personality and Social Psychology 49:774-80, 1985. Seltzer CC, Mayer J. An effective weight control program in a public school system. American Journal of Public Health 60(4);679-689, 1970. Simons-Morton BG, Baranowski T, Parcel GS, O'Hara NM, Matteson RC. Children's frequency of consumption of foods high in fat and sodium. American Journal of Preventive Medicine 6:218-27, 1990. Smith CJ, Manahan EM, Pablo SG. Food habit and cultural changes among the Pima Indians. Culture Change, Diabetes, and Native Americans to be published by Mouton Press. Smith CJ, Schakel SF, Nelson, RG. Selected traditional and contemporary foods currently used by the Pima Indians. Journal of the American Dietetic Association 91:338-341, 1991. Stunkard AJ, Berkowitz RI. Treatment of obesity in children. Journal of the American Medical Association 264(19):2550-2551, 1990. Sugarman JR, White LL, Gilbert TJ. Evidence for a secular change in obesity, height, and weight among Navajo Indian schoolchildren. American Journal of Clinical Nutrition 52:9606, 1990. Teufel NI, Dufour DL. Patterns of food use and nutrient intake of obese and non-obese Hualapai Indian women of Arizona. Journal of the American Dietetic Association 90:1229-35, 1990. The State of Native American Youth Health. University of Minnesota, Division of General Pediatrics and Adolescent Health, 1992. Toma RB, Curry ML. North Dakota Indians' traditional foods. Journal of the American Dietetic Association 76:589-90, 1980. Unites States Department of Agriculture. Evaluation of the Food Distribution program on Indian Reservations Final Report June 15, 1990. Welty TK. Health implications of obesity in American Indians and Alaska Natives. American Journal of Clinical Nutrition 53:1616S-20S, 1991. Wolf MC, Cohen KR, Rosenfeld JG. School-based interventions for obesity: Current approaches and future prospects. Psychology in the Schools 22:187-200, 1985. Young TK, Sevenhuysen G. Obesity in northern Canadian Indians: patterns, determinants, and consequences. American Journal of Clinical Nutrition 49:786-93, 1989. .
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, Audio or Video files, see Help Downloading Files. |