HIGH THROUGHPUT GENOTYPING CENTERS FOR HUMAN AND ANIMAL DNA RELEASE DATE: September 24, 2003 (see addendum NOT-RR-04-002) RFA Number: RFA-RR-03-012 Department of Health and Human Services (DHHS) PARTICIPATING ORGANIZATIONS: National Institutes of Health (NIH) (http://www.nih.gov) COMPONENT OF PARTICIPATING ORGANIZATIONS: National Center for Research Resources (NCRR) (http://www.ncrr.nih.gov) National Cancer Institute (NCI) (http://www.nci.nih.gov) CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBERS: 93.389, 93.393, 93.394, 93.399 LETTER OF INTENT RECEIPT DATE: November 18, 2003 APPLICATION RECEIPT DATE: December 18, 2003 THIS RFA CONTAINS THE FOLLOWING INFORMATION o Purpose of this RFA o Research Objectives o Mechanism of Support o Funds Available o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Letter of Intent o Submitting an Application o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE OF THIS RFA The National Center for Research Resources (NCRR) invites applications to develop and operate High Throughput Genotyping Centers. The purpose of this Request for Applications (RFA) is to increase the research resource capacity that provides for the genotyping of polymorphic markers in human and animal DNA. The research proposed under this RFA will expand the nation's resources for high-throughput genotyping under conditions that allow for economies of scale, quality assurance and data sharing. The program should facilitate identification of biomarkers for disease risk, disease severity/activity, and clinical outcome as well as animal genetic loci related to human disease, and should encourage development of new approaches to diagnosis, prevention, and treatment of human diseases. RESEARCH OBJECTIVES Background Many disorders are known to occur in families but lack the simple inheritance pattern that allows a single gene to be identified as the causative agent. The identification, two decades ago, of polymorphic markers spanning all 24 human chromosomes made linkage studies possible, and led to the conclusion that multiple genes could act together to increase or reduce the risk of numerous common disorders. The cost to society of these diseases, whether assessed in economic terms or as burden of care, is enormous and justifies research that will lead to strategies for prevention or cure. Genotyping describes the characterization of inheritable characteristics and is widely used for studies that seek to identify genes that contribute to disease. The contribution is generally in the form of susceptibility to a disorder or, conversely, to protection. Genotyping studies play an increasingly important role in our understanding of the pathogenesis of a wide range of diseases, encompassing immune as well as vascular, neuropsychiatric, metabolic, malignant and gastrointestinal etiologies. Studies of siblings who differ in disease expression have pointed to susceptibility genes in many disorders (such as histocompatibility antigens for type 1 diabetes). The identification of genes contributing to other common disorders (such as multiple sclerosis) will likely require comparisons between unrelated individuals with and without the disorder (association studies) in order to understand the familial trends. When multiple human genes that contribute to a disease phenotype are identified, it is likely that animal models will be required to understand the separate contribution that each gene makes and to identify points at which a medical intervention might serve to prevent the disorder. In addition, animal models have proven useful for identifying Quantitative Trait Loci (QTLs), regions of the genome containing genes that contribute to a disease phenotype. Identification of candidate genes within animal QTLs can then be used to identify the cognate human genes that contribute to the particular condition. This process should be enhanced with the completion of whole genome sequences, e.g., for humans, mice and rats. Human genotyping studies in recent years have identified chromosomal regions that associate with susceptibility to common (and therefore economically important) disorders such as autism, schizophrenia and celiac disease. Many animal QTLS influencing, for example, body weight, cholesterol metabolism and cardiovascular physiology, have been identified. The methods currently in widest use do not identify individual genes often large numbers of subjects must be studied before this critical step can be reached. With the increasing refinement of genotyping methods it seems likely that some common disorders will be separated into sub-types, for which different approaches may be required for prevention. The need for genotyping will grow through the foreseeable future as investigators come to prioritize potential targets for treatment interventions and as the members of afflicted families wish to estimate their risk for a particular condition. The use of association studies themselves will enormously strain presently available genotyping facilities as the number of subjects to be tested increases exponentially. In terms of technologies, whole genome scans of polymorphic microsatellite markers have been the mainstay of human linkage studies in the past decade. The higher resolution afforded by single nucleotide polymorphism (SNP) typing seems likely to dominate the demands of clinical investigators in the future while, for many animal species, microsatellite-based techniques will be needed. However, SNP maps will probably also be expanded for the most commonly studied animals, particularly the mouse. The considerations discussed above are the impetus to this initiative by the Divisions of Clinical Research (DCR) and Comparative Medicine (DCM) at the National Center for Research Resources that will increase capacity for genotyping. Research Objectives Applicants will be expected to meet the following objectives: o Equip and run a facility that can accession bar coded DNA samples that will be supplied by investigators approved by the Steering Committee. The accession database must be web accessible and, where appropriate, compliant with the Privacy Rule of the Health Insurance Portability and Accountability Act (HIPAA). In addition to testing these samples for polymorphic markers, the scope of activity shall extend to the organization of the polymorphic markers identified into a user-interpretable format and to the posting of de-identified data on a web server in a form compatible with the requirements of the NIH Data Sharing plan http://grants.nih.gov/grants/policy/data_sharing/). For animal studies, applicants will be expected to genotype samples using existing markers, to develop new markers, as needed, and to integrate new markers into extant maps. Components of these activities are described in the following paragraphs. o Implement and support a Laboratory Information Management System along with other database platforms that will allow for the input, storage and retrieval of clinical, genotypic, laboratory, and phenotypic data. The laboratory will employ electronic worksheets with on line and bar-coded data entry. Facilities for secure storage of data prior to establishing HIPAA-compliance and/or web posting are required along with the generation of anonymized unique patient numbers to allow clinical and phenotypic data to be cross-referenced to any DNA samples and genotype data. o Develop a web site on which they publish their standard operating procedures for the collection, processing and storage of DNA by investigators whose projects are approved by the Steering Committee (defined below) for Center Resources. They will advise approved investigators concerning the quality control of samples to be accessioned for testing, written procedural manuals for collecting, transporting and storing biological specimens together with protocols for extracting DNA and troubleshooting common problems. o Develop a web site to include additional resources for education of the lay public, patients, basic and clinical researchers and clinicians. Examples include but are not limited to: contacts for advice concerning animal genotyping together with links to relevant genetic resources; registries; education materials; and/or diagnostic flow charts. The actual design and implementation of the site will be a collaborative activity of the Genotyping Center, the Steering Committee and the NCRR. o Test accessioned DNA samples for quality and notify investigators of failures. Subject variables must be accessioned and stored in a HIPAA- compliant format such that the results of genotyping can be made available to the requestors in a web-compliant form. Current estimates are that over 6,000 samples will be accessioned in year 1, increasing to about 20,000/year in subsequent years. o State the approach they will take to type for polymorphisms (for example, micro-satellite typing, SNP typing or any combinations of the two) and the internal review mechanisms that will operate to determine what approaches to genotyping should be available to approved investigators. Applicants should describe their approaches and laboratory methods in sufficient detail for their review. o 10-20% of the budget should be committed to the research and development components of genotyping. These components might, for example, encompass the development of high-throughput chip approaches to SNP typing or alternative methodologic advances. Progress with the HapMap and characterization of different block sizes will, for example, likely accelerate the use of SNP-based genotyping. Other possible areas for research and development include the refinement of polymorphic markers for non-human primates and other animal models, and/or the enhancement of statistical methods for analyzing clinical and epidemiological data and their relationship to co-inheritance of DNA markers and complex traits. A Steering Committee (see below) will meet twice-yearly, and travel and per diem funds for the Center Director and two external members should be included in the budget. MECHANISM OF SUPPORT This RFA will use the NIH U54 award mechanism. As an applicant you will be solely responsible for planning, directing, and executing the proposed project. This RFA is a one-time solicitation. Future unsolicited, competing-continuation applications based on this project will compete with all investigator-initiated applications and will be reviewed according to the customary peer review procedures. The anticipated award date is July 28, 2004. The NIH U54 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the section "Cooperative Agreement Terms and Conditions of Award." Plans for possible continuation of the cooperative agreement project beyond the initially awarded period of performance, or reissue an RFA or other announcement beyond the current RFA, are indefinite. FUNDS AVAILABLE NCRR intends to commit approximately $3.5 M in direct costs in FY 2004 to equip and support one or two Genotyping Centers. An applicant may request a project period of up to five years and a budget for direct costs of up to $2M per year in years 2-5. Although the financial plans of the NCRR and NCI provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of meritorious applications. ELIGIBLE INSTITUTIONS You may submit an application if your institution has any of the following characteristics: o For-profit or non-profit organizations o Public or private institutions, such as universities, colleges, hospitals, and laboratories o Units of State and local governments o Eligible agencies of the Federal government o Domestic institutions/organizations o Foreign institutions are not eligible to apply. INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. SPECIAL REQUIREMENTS Cooperative Agreement Terms and Conditions of Award The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator as well as the institutional official at the time of award. 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 92, and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is the multiproject cooperative agreement (U54), an "assistance" mechanism rather than an "acquisition" mechanism, in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in 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 dominant role and prime responsibility for the activity resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the research will be shared among the awardees and the NIH Research Coordinators. 1. Awardee Rights and Responsibilities Awardees will have primary responsibility for defining the details of the project within the guidelines of the RFA RR-03-012 and for performing the scientific activity, and agree to accept close coordination, cooperation, and participation of the NIH staff in those aspects of the scientific and technical management of the project described below. Awardees will accept the role of the Steering Committee as described below. Specifically, awardees have primary responsibility as described below. Genotyping Center Director. The Genotyping Center Director should commit at least 20% time to this project. The Genotyping Center Director will be a member of the Steering Committee. Publication and Presentation of Study Findings Early publication of major findings is encouraged. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of the NCRR. Awardees will retain custody of and have primary rights to all data developed under these awards; the NIH will have access as described below. Federally Mandated Regulatory Requirements All institutions participating in the High Throughput Genotyping Center must meet DHHS regulations for the protection of human subjects and their confidentiality as well as any applicable FDA requirements. These include assuring that each institution from which DNA is received has registered with the Office of Human Research Protections (OHRP; http://www.hhs.gov/ohrp/) and has a Federalwide Assurance; that study protocols are reviewed and approved by the responsible Institutional Review Board (IRB) prior to patient entry; that active protocols are reviewed at least annually by the IRB, and that amendments are approved by the IRB. OHRP guidance for repositories may be found at http://www.hhs.gov/ohrp/humansubjects/guidance/reposit.htm and additional NIH guidance is available from the NIH Brochure on Research Involving Human Specimens at http://www.cdp.ims.nci.nih.gov/policy.html Where animal samples are used, they must have been collected under the contributing institution's IACUC-approved protocols. 2. NIH Staff Responsibilities NIH staff assistance will be provided by the NCRR Program Coordinator, who shall represent the DCR, NCRR and also by a representative of the DCM, NCRR. The Program Coordinator will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for grants, as described below. The NCRR Program Coordinator will serve as a voting member of the Steering Committee, will attend all SC meetings, and will participate in other Committee activities, including, but not limited to, conference calls, subcommittees, and special committees. The DCM representative will also attend all SC Meetings and will provide advice to the center regarding animal studies. He/she will not be a voting member of the Committee. The NCRR Program Coordinator will assist the Steering Committee in the development of procedures for monitoring the performance of the clinical studies. This includes participation in periodic on-site monitoring with respect to compliance with protocol specifications, quality control and accuracy of data recording, and accrual. The NIH will also provide assistance in identifying technology resources, provide oversight of activities, including security and privacy issues. The NCRR, via Program Coordinator, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports consistent with current DHHS, PHS and NIH policies. Information obtained from the data may be used by NIH staff for the preparation of internal reports on the activities of the clinical studies. However, awardees will retain custody of and have primary rights to all data developed under these awards. The NCRR will assign a program director that is responsible for normal program monitoring and stewardship of the award. The program director may also serve as the NCRR Program Coordinator. 3. Collaborative Responsibilities Steering Committee. The Genotyping Center in collaboration with the NCRR will establish an independent Steering Committee (SC) to review and approve requests for access to the resources of the high throughput genotyping center. The SC shall comprise one member each from the Divisions of Clinical Research and Comparative Medicine at NCRR and the Genotyping Center Director. These three individuals shall select two additional and appropriately qualified members from outside the recipient institution. The SC shall be responsible for scheduling the time and location of meetings that shall be held at least twice yearly. The SC will establish the procedures for the function of the Center. Requests for access that are approved by the SC will be prioritized on the basis of their scientific merit. 4. Arbitration Any disagreement that may arise on scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An arbitration panel will be formed to review any scientific or programmatic issue that is significantly restricting progress. This panel will be composed of three members -- one selected by the Steering Committee (with the NIH members not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by the NIH, and a third member with expertise in the relevant area and selected by the two prior members. While the decisions of the Arbitration Panel are binding, these special arbitration procedures will in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, subpart D, and HHS regulations at 45 CFR Part 16. PRE-APPLICATION MEETING NCRR anticipates holding a pre-application meeting with videoconference in October 2003 to which all interested prospective applicants are invited. Program staff will make presentations that explain their goals and objectives for the High Throughput Genotyping Center and answer questions from the attendees. A Grants Management Specialist will be available to answer financial questions. Prospective applicants are urged to monitor the NIH Guide Notice for the date and time of the meeting at http://grants.nih.gov/grants/guide/index.html. WHERE TO SEND INQUIRIES We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues: o Direct your questions about scientific/research issues to: Anthony R. Hayward, M.D., Ph.D. Division of Clinical Research National Center for Research Resources 6701 Democracy Boulevard Room 906 MSC 4874 Bethesda, MD 20892-4874 Telephone: (301) 435-0790 FAX: (301) 480-3661 Email: haywarda@mail.nih.gov Or John Harding Ph.D. Division of Comparative Medicine National Center for Research Resources 6701 Democracy Boulevard Room 906 MSC 4874 Bethesda, MD 20892-4874 Telephone: (301) 435-0776 Fax: (301) 480-3819 Email: hardingj@mail.nih.gov Or Wendy Wang, Ph.D. M.Sc. Cancer Biomarkers Research Group Division of Cancer Prevention National Cancer Institute 6130 Executive Boulevard, EPN 3138 Rockville, MD 20852 Telephone: (301) 594-7607 Fax: (301) 402-8990 E-mail: wangw@mail.nih.gov o Direct your questions about peer review issues to: Sheryl Brining Ph.D. National Center for Research Resources 6701 Democracy Blvd, Room 1074 MSV 4874 Bethesda MD 20892-4874 Telephone: (301) 435-0809 Fax: (301) 480-3660 Email: brinings@mail.nih.gov o Direct your questions about financial or grants management matters to: Judy Musgrave Office of Grants Management, NCRR 6701 Democracy Blvd., Room 1048 MSC 4874 Bethesda, MD 20892 Telephone: (301) 435-0841 Fax: (301) 480-3777 Email: musgravj@mail.nih.gov LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes the following information: o Descriptive title of the proposed research o Name, address, and telephone number of the Principal Investigator o Names of other key personnel o Participating institutions o Number and title of this RFA Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. The letter of intent is to be sent by the date listed at the beginning of this document. The letter of intent should be sent to: Anthony R. Hayward, M.D., Ph.D. Division of Clinical Research National Center for Research Resources 6701 Democracy Boulevard Room 906 MSC 4874 Bethesda, MD 20892-4874 SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). Applications must have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number can be obtained by calling (866) 705-5711 or through the web site at http://www.dunandbradstreet.com/. The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: GrantsInfo@nih.gov. SUPPLEMENTARY INSTRUCTIONS. See the Research Objectives section for additional application instructions. USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. 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 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf. SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package, to: Center For Scientific Review National Institutes Of Health 6701 Rockledge Drive, Room 1040, MSC 7710 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to: Anthony R. Hayward, M.D., Ph.D. Division of Clinical Research National Center for Research Resources 6701 Democracy Boulevard Room 906 MSC 4874 Bethesda, MD 20892-4874 APPLICATION PROCESSING: Applications must be received on or before the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to an RFA, it is to be prepared as a NEW application. That is, the application for the RFA must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application. PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by NCRR. Incomplete and/or unresponsive applications will not be reviewed. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCRR in accordance with the review criteria stated below. As part of the initial merit review, all applications will: o Undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed and assigned a priority score o Receive a written critique o Receive a second level review by the NCRR National Advisory Council. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to evaluate the application in order to judge the likelihood that the proposed research resource will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of the following criteria in assigning the application's overall score, weighting them as appropriate for each application. o Significance o Approach o Innovation o Investigator o Environment The application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. SIGNIFICANCE: Does the Genotyping Center provide a cost efficient resource for human and animal samples? Do the research and development components of the application address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? APPROACH: Are the conceptual framework, design, methods, and data handling components adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? INNOVATION: Does the project extend currently available genotyping resources or employ novel concepts, approaches or methods to increase capacity? Does the project develop new methodologies or technologies? INVESTIGATOR: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? ENVIRONMENT: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, responsiveness to the Research Objectives listed in that section of this RFA will be considered in the determination of scientific merit and the priority score. PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. (See criteria included in the section on Federal Citations, below). INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. (See Inclusion Criteria in the sections on Federal Citations, below). CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to be used in the project, the five items described under Section f of the PHS 398 research grant application instructions (rev. 5/2001) will be assessed. ADDITIONAL REVIEW CONSIDERATIONS Sharing Research Data Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a data sharing plan in their application. The reviewers will assess the reasonableness of the data sharing plan or the rationale for not sharing research data. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or priority score. Details of the NIH data sharing requirements may be found at: http://grants.nih.gov/grants/policy/data_sharing/). BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt Date: November 18, 2003 Application Receipt Date: December 18, 2003 Peer Review Date: March 2004 Council Review: May 2004 Earliest Anticipated Start Date: July 28, 2004 AWARD CRITERIA Award criteria that will be used to make award decisions include: o Scientific merit (as determined by peer review) o Availability of funds o Programmatic priorities. REQUIRED FEDERAL CITATIONS HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose-finding studies (phase I); efficacy studies (phase II); efficacy, effectiveness and comparative trials (phase III). The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risk to the participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html). SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, investigators submitting an NIH application seeking more than $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible. http://grants.nih.gov/grants/policy/data_sharing Investigators should seek guidance from their institutions, on issues related to institutional policies, local IRB rules, as well as local, state and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score. INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of the NIH that women and members of minority groups and their sub- populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH- defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at http://grants.nih.gov/grants/funding/children/children.htm REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see http://escr.nih.gov). It is the responsibility of the applicant to provide, in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule," on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR). Those who must comply with the Privacy Rule (classified under the Rule as "covered entities") must do so by April 14, 2003 (with the exception of small health plans which have an extra year to comply). Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html. URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.healthypeople.gov/. AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm The PHS strongly encourages all grant recipients to provide a smoke- free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices



NIH Office of Extramural Research Logo
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®



Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.