$$XID RFA HD9301 HD-93-01 P1O1 ***************************************** MENTAL RETARDATION RESEARCH CENTERS NIH GUIDE, Volume 21, Number 10, March 13, 1992 RFA: HD-93-01 P.T. 04; K.W. 0715130, 0745020, 0745027, 0404000, 0404004, 0710030 National Institute of Child Health and Human Development Letter of Intent Receipt Date: April 17, 1992 Application Receipt Date: July 17, 1992 PURPOSE The National Institute of Child Health and Human Development (NICHD), through the Mental Retardation and Developmental Disabilities Branch (MRDD), Center for Research for Mothers and Children (CRMC), invites research center core grant applications as part of the NICHD Mental Retardation Research Program to develop new knowledge in the field of diagnosis, prevention, treatment, and amelioration of mental retardation and developmental disabilities. A Mental Retardation Research Center (MRRC) is a center to facilitate, through organization and operation, a program of biomedical and/or behavioral research related to mental retardation. MRRC core grants support multidisciplinary research in areas that may lead to diagnosis, prevention, treatment, and/or amelioration of mental retardation and developmental disabilities. These grants fund core support services, administration, and development of a limited number of new research programs. The primary objective of the NICHD Mental Retardation Research Centers Program is to provide support and facilities for a cohesive, interdisciplinary program of research and research training in mental retardation and related aspects of human development. Public Law 88-164, Title I, Part A authorized construction of mental retardation research centers. The NICHD has provided partial support for a limited number of these centers through the provision of core grants, which facilitate program coordination and support central research facilities. Funds for the research projects using these core facilities come from independent sources including Federal, State, and private organizations. This announcement seeks applications not only from these constructed centers, but also from other comparable institutions that meet the qualifications for a program of mental retardation research. A major goal of the MRDD's Mental Retardation Research Centers Program is to prevent and/or ameliorate mental retardation. The degree of impairment associated with mental retardation varies in relation to the cause. Moderate and more severe mental retardation often results from problems that produce profound alterations in brain development and/or function. Diminished intellectual and adaptive capacity can often be traced to defective genes, teratogenic agents, toxic substances, infections, nutritional deficits, accidents, diseases, and other disorders causing brain damage. A larger proportion of cases of mental retardation is related to environmental conditions and disorders of unknown etiology. These complex problems require integrated, multidisciplinary approaches involving biomedical and behavioral sciences in a variety of settings. More than 400 mental retardation syndromes have been identified and new ones are being discovered. Each requires fundamental research into the underlying processes, and studies designed to meet the unique needs of the afflicted children. Therefore, one of the missions of the MRDD is to support research on the etiology, pathophysiology, epidemiology, diagnosis and evaluation, and prevention or amelioration of mental retardation. The purpose of an MRRC is to provide a research environment which facilitates interdisciplinary collaboration among investigators who are working in areas of relevance to the prevention and amelioration of mental retardation. Such research will cover a broad spectrum of scientific approaches ranging from laboratory research on fundamental processes of normal and abnormal development, to clinical and behavioral research in which persons with mental retardation are studied. It is thought that major solutions to the problems of mental retardation may be found as a result of multidisciplinary collaboration involving a variety of approaches in the MRRC. As a result of the administrative and scientific organization within a MRRC and across the network of MRRCs, opportunities for breakthroughs will be enhanced. 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), Mental Retardation Research Centers, is related to several priority areas including nutrition, alcohol and other drugs, mental health and mental disorders, environmental health, maternal and fetal health, HIV infection, immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-011-00474-0) 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, and units of State and local governments. As stated in the NICHD Center Guidelines, the NICHD will not support more than one center grant (P30 or P50) in a given department or specialty unit. To be eligible for award as an MRRC, the Center must provide core support for a minimum of 10 projects funded from non-university sources. MECHANISM OF SUPPORT MRRC grants will be supported through the Center Core (P30) grant. Awards will be made for a period of five years. The total direct costs requested for the first year of a new Center Core Grant (P30) may not exceed $500,000. Competing renewal applications from existing P30 Centers may not request initial year direct costs exceeding 120 percent of the Notice of Grant Award level of direct costs for the final year of the preceding project period, or $500,000 direct costs, whichever is greater. Budget increments for subsequent years generally will be limited to four percent. Budgets of new and renewal applications will be stringently reviewed within these guidelines. An application with a budget request exceeding these guidelines will be administratively withdrawn by NICHD and returned to the applicant. The anticipated date of award is August 1, 1993. FUNDS AVAILABLE This is the fifth in a series of annual announcements. Plans are to make four awards in fiscal year 1993. The estimated funds available for the first year of support related to this RFA is $3.1 million total costs. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NICHD, awards pursuant to this RFA are also contingent upon the availability of funds for this purpose. RESEARCH SCOPE MRRC core grants are intended to bring together in a center scientists from a variety of disciplines to work on the common problems of mental retardation. Consequently, applications for MRRCs must include investigators studying a range of topics in basic and clinical or applied research. Applicants are encouraged, but are not required, to include both biomedical and behavioral components among the topics addressed within the center. Center grant applications must include at least five of the following topics: o Developmental neurobiological studies relevant to MRDD: neurophysiological, neuroanatomical, neurochemical, and neuropharmacological. o Inborn errors of metabolism relevant to MRDD: pathophysiology, recombinant DNA technology, screening, and applied clinical and experimental studies including treatment. o Genetic/cytogenetic disorders associated with MRDD: antenatal diagnosis research, particularly non-invasive methods during the early stages of pregnancy, on prevalent genetic causes of mental retardation, such as Down's syndrome or Fragile X syndrome; research on rare genetic disorders associated with mental retardation. o Molecular biology: gene localization, structure, function and organization; gene mapping; gene therapy; and development of animal models. o Toxicology and physical environmental factors in the etiology, treatment, and prevention of MRDD including lead, mercury, and alcohol; developmental and behavioral teratology; and subclinical levels of toxic agents and their effects on morphological and behavioral changes associated with mental retardation. o Effects of malnutrition (protein, calorie, micronutrients) on intellectual, behavioral, social, and physical development and the intergenerational effects of malnutrition. o Developmental pharmacology and psychopharmacology: medication used with MRDD populations. o Infectious diseases in the etiology, prevention, and treatment of MRDD; neurological, neuropathological, behavioral, and intellectual consequences of AIDS in children. o Diagnosis: development and application of biomedical and behavioral methods and measures; identification of children and infants at risk for MRDD. Predictive and developmental studies of perinatal problems associated with MRDD: developmental studies of low-birth weight, small for gestational age, preterm, and neonatally sick infants. o Psychobiological processes in MRDD of conditions such as autism and Rett syndrome using methods of behavioral genetics, embryology, and teratology, and developmental neuroscience and psychophysiology. o Psychological processes in MRDD: studies of cognitive and information processing; attention and perception; sensory and motor development; family, social, and affective behavior; and motivation and personality. o Early interventions for infants at risk to develop MRDD: research into the process of early intervention strategies. o Behavioral analyses: manipulations of interaction between behavior and environments of individuals with MRDD to reduce problem behaviors, facilitate vocational training, improve social and self-help skills, and increase acquisition of adaptive behaviors. o Family and community studies: parent-child and family interactions; sexual behaviors; family structure and demographic variables; family and community factors influencing developmental outcomes and adjustment; community resources; caregiver behavior; social support networks; and the effects of children with MRDD on family life in different ethnic groups. o Language and communication of MRDD populations: studies on development of alternative communication systems; ontogeny of linguistic processes. o Learning disabilities, dyslexia, and attention deficit disorder. o Residential and educational setting: effects on behavior and adjustment of MRDD individuals; learning and social behavior in educational settings; adaptation to residential environments; aberrant behavior, e.g., self-injury. o Socioeconomic status, ethnicity, and ecological processes: interaction of MRDD individuals in multiple settings (naturalistic observation); ethnographic research; life history reporting; systematic observation of specific activities. o Epidemiology of MRDD: analytic and case-control studies of etiology, prevalence, follow-up of outcomes. STUDY POPULATIONS NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy requires applicants for NIH grants that include clinical research 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 in section 2, 1-4 of the Research Plan and summarized in Section 2, E, 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). In that case, 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 the 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 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. In addition, NIH funding components will not award grants or cooperative agreements that do not comply with these policies. Because P30 funds do not directly support research projects, the issue of minority/gender representation will need to be addressed at the individual project level (i.e., R01 level). However, the application will specifically need to address these issues for any new program development projects or core units that focus on subject recruitment. LETTER OF INTENT Prospective applicants are asked to submit, by April 17, 1992, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the names of other key personnel and participating institutions, the core unit directors and principal investigators of the research projects that would use the core units, 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 NICHD staff to estimate the potential review workload and to avoid possible conflict of interest in the review. The letter of intent is to be sent to: MRDD Branch, CRMC National Institute of Child Health and Human Development Room 631, Executive Plaza North 6130 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-1383 APPLICATION PROCEDURES The applicant is to submit the application using PHS 398 (rev. 9/91). Application kits containing this form and the necessary instructions are available in most institutional business offices and may be obtained 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 program administrator named below. The NICHD recommends that the application be developed in consultation with the MRDD Program staff, CRMC, who will provide appropriate guidance in relation to both scientific and administrative issues. The application must be prepared in a manner consistent with the general guidelines presented in the publication titled P30 CENTER CORE GRANT GUIDELINES that are available form the MRDD Branch office listed below. Applicants for the MRRC grants must propose a program with a theme relevant to the mission of the MRDD as outlined above. The program must consist of at least 10 externally funded research projects grouped according to relevant topics. These projects must be of high quality, providing a multidisciplinary approach to the problem(s) being investigated. Each project is to be summarized in accordance with the NICHD P30 Center Core Grant Guidelines. The MRRC Director must be a scientist or science administrator who can provide effective administrative and scientific leadership. The Director will be responsible for the organization and operation of the MRRC and for communication with the NICHD on scientific and operational matters. Scientific personnel and institutional resources capable of providing a strong research base in the fields specified must be available. In addition, the institution and pertinent departments have to show a strong commitment to the center's support. Such commitment may be provided as dedicated space, salary support for investigators, dedicated equipment, or other financial support for the proposed MRRC. Each core unit proposed for funding under the MRRC grant must be utilized by at least three Federally funded research projects, one of which is NIH funded, exclusive of research contracts, interagency agreements, and NIH-supplemental projects funded by other agencies. Subprojects within a program project (P01) will be considered as individual projects comparable to an R01. A detailed description of each core unit proposed as part of the center must be provided with detailed budget and budget justification. A scientist must be named as responsible for each core unit proposed. The description of the core units proposed must include a rationale to show how they will support the research effort in a cost-effective manner. Facilities must be available for the primary needs of the MRRC Program and require no more than modest alteration and/or renovation. Funds for new construction will not be provided. Promoting interdisciplinary collaboration among scientists working within a Center is a major goal of the MRRC Program. Each MRRC applicant must submit a plan, as part of the application, to ensure continuing interaction among participating scientists from different disciplines. Another goal of the MRRC Program is to attract scientists to the field of mental retardation research. Therefore, where appropriate, the applicant may request "New Program Development" funds for direct research support of one or more projects not to exceed a total of $50,000 per year or 10 percent of total direct cost, whichever is less. Such funds might serve to attract new investigators to the Center, to develop a new area or program of research, or to facilitate the development of research programs for newly trained investigators. Descriptions of New Program Development projects should be comparable to R01 research applications in the amount of detail and development. Each such project can provide support for only two years for any one investigator. It is a major goal of the NICHD to promote active collaboration among MRRCs. To accomplish this goal, the successful applicants will be encouraged to participate in the collaborative efforts of established MRRC programs. Some consideration should be given, in planning the program, to potential collaborative studies and projects that might be proposed for the MRRC network. 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. Applications must be identified by checking the YES box in item number 2a on the face page of the application and typing in RFA HD-93-01, Mental Retardation Research Centers, and then insert P30 in Item Number 2b. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: DIVISION OF RESEARCH GRANTS National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Acting Director, Division of Scientific Review National Institute of Child Health and Human Development Executive Plaza North, Room 520 6130 Executive Boulevard Bethesda, MD 20892 Applications must be received on or before July 17, 1992. If an application is received after that date, it will be returned to the applicant. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by NIH staff for completeness and responsiveness to the RFA. Incomplete applications will be returned to the applicant without further consideration. Under certain circumstances, applications may be triaged by a peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Applications judged to be competitive will undergo further scientific merit review. Applications that are complete and responsive will then be evaluated for scientific and technical merit by the NICHD Mental Retardation Research Committee at its March 1993 meeting, in accordance with the criteria stated below. Because a site visit is not a prerequisite for MRRC consideration, each application should be thorough and complete enough to stand on its own. The second-level review will be made by the National Advisory Child Health and Human Development Council at its June 1993 meeting. Review Criteria Criteria for the initial review of applications include: o scientific, technical, or medical significance of the application; o qualifications and research experience of the Principal Investigator and staff; o scientific and administrative leadership of the Principal Investigator; o quality of proposed core facilities; o availability and quality of resources and research environment; o appropriateness of the proposed budget; o adequacy of plans for the protection of human subjects; o adequacy of plans to protect against or minimize adverse effects on animals; o inclusion of women and minority subjects in research; o quality and relevance to mental retardation of research projects that will be using the core facilities; o plans for interdisciplinary/multidisciplinary collaboration; o cost-effectiveness of the proposed MRRC; o institutional commitment. AWARD CRITERIA In addition to the scientific and technical merit of the application, the following factors will be considered in making awards: o centers addressing research areas of high programmatic interest to the MRDD, the CRMC, and NICHD; and areas targeted by Congress; o availability and quality of resources, especially institutional commitment and support; o access to unique study populations o potential to increase productivity and quality of research within the center, and stimulate interdisciplinary/multidisciplinary collaborations; o providing unique resources for the use of other Centers, and the greater research community; and o cost-effectiveness of the core facilities INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Direct inquiries regarding programmatic issues to: Felix F. de la Cruz, M.D., M.P.H. Chief, MRDD Branch, CRMC National Institute of Child Health and Human Development Executive Plaza North, Room 631 6130 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-1383 Direct inquiries regarding fiscal matters to: Mr. Edgar D. Shawver Supervisory Grants Management Specialist Office of Grants and Contracts National Institute of Child Health and Human Development Executive Plaza North, Room 505 6130 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-1303 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.865 Research for Mothers and Children. Awards will be 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 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review.