MYELODYSPLASTIC SYNDROME (MDS): SEEKING CURE THROUGH DISCOVERY ON PATHOGENESIS AND DISEASE PROGRESSION RELEASE DATE: May 21, 2004 RFA Number: RFA-HL-04-033 EXPIRATION DATE: February 17, 2005 Department of Health and Human Services (DHHS) PARTICIPATING ORGANIZATION: National Institutes of Health (NIH) (http://www.nih.gov) COMPONENT OF PARTICIPATING ORGANIZATION: National Heart, Lung, and Blood Institute (NHLBI) (http://www.nhlbi.nih.gov) CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S) 93.839 LETTER OF INTENT RECEIPT DATE: January 16, 2005 APPLICATION RECEIPT DATE: February 16, 2005 THIS RFA CONTAINS THE FOLLOWING INFORMATION o Purpose of this RFA o Research Objectives o Mechanism(s) 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 Supplementary Instructions o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE OF THIS RFA This Request for Applications solicits applications that seek new discoveries in the etiology and pathophysiology of myelodysplastic syndromes (MDS) with the aim to develop new and curative treatment options in the future. A separate RFA HL-04-034 (please see https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-04-034.html) is directed towards myeloproliferative disorders. Applicants are directed to apply to one or the other but not both RFAs. BACKGROUND The frequency and incidence of MDS is increasing in the US population and is thought to be influenced by factors such as advancing age, the use of cytotoxic and mutagenic therapies for cancer, and greater exposure to environmental toxins. While some patients have an insidious onset of the disease that can even be remitting, others experience dramatic presentations including marrow failure or acute hematologic malignancy, which rapidly becomes fatal. The highly variable nature of MDS creates difficulties in the characterization and study of the syndromes and/or diseases that constitute evolving dysplasia of the hematopoietic system and transformation into malignancy. The etiology and pathophysiology of myelodysplasia is poorly understood. The conditions may arise or evolve from fundamental defective stem cell biology or later disrupted and/or disordered cell lineage differentiation, maturation and proliferation of the hematopoietic system. In some patients the diagnosis is associated with genetic constitutional abnormalities. The occurrence of these blood disorders is also increasingly identified in patients following successful cancer therapy and/or transplantation procedures and presents as a secondary malignancy. Myelodysplastic syndromes are considered clonal stem cell diseases that are characterized by peripheral cytopenias in the setting of a normocellular or hypercellular bone marrow that morphologically shows bilineage or trilineage dysplasia. Mechanisms of disease include pluripotent stem cell damage, abnormalities in proliferation, differentiation, and apoptosis leading to an ineffective hematopoiesis. The most common diagnosis include refractory anemia (RA), refractory anemia with ringed sideroblast (RARS), refractory anemia with excess blast (RAEB), and refractory anemia with excess blast in transformation (RAEB-T). MDS has a high propensity for transformation to myeloid leukemia but can transform into acute leukemia of other hematopoietic lineage. Overlapping features of MDS with aplastic anemia, T-cell large granular lymphocyte lymphoproliferative disorder, and paroxysmal nocturnal hemoglobinuria suggest a shared pathophysiologic mechanism of marrow failure. A category of secondary MDS is used when typical biologic characteristics of MDS occur after known constitutional or acquired abnormalities (e.g. association with genetic disorders or anti-neoplastic therapy). In addition, some clinical entities are being reclassified into "mixed" myeloproliferative and myelodysplastic disorders, such as chronic myelomonocytic leukemia, atypical myeloid leukemia, and juvenile myelomonocytic leukemia. However, diagnostic criteria can be imprecise and treatment empiric until malignant transformation is evident. Other than hematopoietic stem cell transplantation (HSCT), no curative therapies are available. Many patients do not have access to nor are appropriate candidates for intensive HSCT therapy. Furthermore, successful outcome following transplant is limited by associated toxicities and complications. Otherwise, traditional chemotherapy, radiation, immunotherapy, biologic modifiers, growth factors, and transfusion support have been used with limited success and are primarily palliative. Therefore, new and improved therapies that will be acceptable for an older patient population are needed. RESEARCH OBJECTIVES Research that uncovers critical genetic, biochemical and molecular pathways that operate in the emergence and progression of MDS is needed. Through basic stem cell biologic experimentation, the mechanisms of disease mutagenesis, evolution, and progression can be studied. The use of gene expression analysis and identification of relevant gene products and cellular molecular profiles may be instrumental in discovering key features of disease pathogenesis. Animal models may be required for hypothesis testing and pre-clinical therapeutic exploration. Identifying biologic markers of MDS should improve disease characterization, earlier diagnosis, and identification of targets that can be exploited for either preventative or therapeutic intervention. SCOPE OF RESEARCH This RFA intends to encourage basic research on the pathogenesis and disease progression of MDS. Applications focused on understanding the genetic and cellular processes associated with MDS are responsive to this RFA. Interventional clinical trials will be considered unresponsive. Examples of research on MDS that would be of interest would include but not be exclusive to: 1.) detection of early diagnostic biologic markers of MDS, 2.) cellular and molecular profiles for defining stages of MDS evolution, 3.) correlation of molecular profiles with chromosomal and gene specific alterations or mutations associated with MDS, 4.) cytometric characterization of premalignant clones and subpopulations in MDS, 5.) identification of mechanisms for induction of MDS through environmental or specific toxin exposure, and 6.) stem cell biologic and animal disease models specific to MDS in order to explore etiologic hypothesis and therapeutic interventions. Laboratory and clinical correlative studies may be used to define meaningful disease characteristics to improve early diagnosis and serve as basis for the development of novel, safer, and more effective therapy. The following examples illustrate patient groups that are of interest. o patients with refractory anemia (RA), refractory anemia with ringed sideroblast (RARS), refractory anemia with excess blast (RAEB), refractory anemia with excess blast in transformation (RAEB-T), and transformation to acute leukemia with pre- existing MDS characteristics. o patients with dysplastic features associated with peripheral cytopenias, aplastic anemia, T-cell large granular lymphocyte lymphoproliferative disorder, paroxysmal nocturnal hemoglobinuria, and marrow failure. o patients with secondary MDS who demonstrate typical biologic characteristics of MDS occurring after known constitutional or acquired abnormalities (e.g. association with genetic disorders or anti-neoplastic therapy). o patients with a diagnosis reclassified as having mixed myelo-proliferative and myelodysplastic features including chronic myelomonocytic leukemia, atypical myeloid leukemia, and juvenile myelomonocytic leukemia. (An application that includes the study of these diseases that are not specific to either MPD or MDS must be submitted to either HL-04-033 or to HL-04-034 and can not be submitted to both RFAs.) MECHANISM OF SUPPORT This RFA will use the NIH RO1 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 September 2005. Applications that are not funded in the competition described in this RFA may be resubmitted as NEW investigator-initiated applications using the standard receipt dates for NEW applications described in the instructions to the PHS 398 application. This RFA uses just-in-time concepts. It also uses the modular budgeting as well as the non-modular budgeting formats (see https://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format. Otherwise follow the instructions for non-modular budget research grant applications. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm. FUNDS AVAILABLE The NHLBI intends to commit approximately $ 3,000,000 (total costs) in FY 2005 to fund up to 10 new grants in response to this RFA. An applicant may request a project period of up to four years and a budget for direct costs (excluding Fiscal and Administrative costs) of up to $350,000 per year. Please see https://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-040.html for more information on the exclusion of the facilities and administrative (F&A) costs requested by consortium participants or contact the Grants Management Specialist listed under "Where to Send Inquiries", below. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NHLBI provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. ELIGIBLE INSTITUTIONS You may submit (an) application(s) 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 or foreign institutions/organizations o Faith-based or community-based organizations 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 An individual principal investigator who submits an application to HL-04-033 RFA titled "Myelodysplastic Syndrome (MDS): Seeking Cure through Discovery on Pathogenesis and Disease Progression" will not be eligible to submit an identical application to HL-04-034 RFA entitled "Genetic and Cellular Discovery Toward Curative Therapy in Myeloproliferative Disorders (MPD)". This restriction does not apply to institutions (as described above) providing the two applications are from different principal investigators. There can be no over lap in research funding between two grants submitted from the same institution in response to HL-04-034 and HL-03-033. Further, each application to this RFA must clearly demonstrate a sole focus of research on myelodysplastic syndrome as described in this document. Applicants are referred to the NIH suggested strategic plan described in the report of the March 3, 2003 State of the Science (SOTS) Implementation Working Group Meeting for Myeloproliferative, Myelodysplastic, and Marrow Failure Syndromes (http://www.webtie.org/SOTS/Meetings/Leukemia/FnlRep703.pdf). The lack of public databases on patients with MDS is considered to be a major barrier in generating new hypotheses that can advance knowledge and improve treatment. A requirement in this RFA is that grantees, who create genomics or proteomics data, are required to enter the information into a public database (at least five samples). The data should meet MIAME standards (http://www.mged.org/Workgroups/MIAME/miame.html), and be accompanied by adequate phenotype information to characterize the cell types and clinical stages in a multi-step process of disease transformation. Such databases include the Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo) at the NCBI, or ArrayExpress (http://www.ebi.ac.uk/arrayexpress/) at the EBI. Alternatively, applicants may wish to establish collaborations with experts in genomics or proteomics funded by the NIH to generate and release genomics/proteomics data into the public domain quickly. These collaborations should be documented in a letter included in the application. A minimum requirement in this regard is for applicants to describe plans to share and analyze independently at least five duplicate or split samples by the applicant and the genomics/proteomics collaborator. The analysis may be complementary or overlapping, but differences in the grantee's and collaborating genomics/proteomics center's results should be resolved between them in order to improve the quality of the public database. Again, data should be accompanied by adequate phenotype information to characterize the cell types and clinical stages in a multi-step process of disease transformation. Public databases available for reporting include the Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo) at the NCBI, or ArrayExpress (http://www.ebi.ac.uk/arrayexpress/) at the EBI. Examples of genomics/proteomic centers which could provide suitable collaborators include, but are not limited to, existing NIH programs, such as: the NCI Director's Challenge (http://dc.nci.nih.gov/organization/principalInvestigators); the Cancer Genome Anatomy Project (http://cgap.nci.nih.gov/) or contact Dr. Greg Riggins at griggin1@jhmi.edu; the NHLBI shared microarray facilities, contact to Dr. Jane Ye at yej@nhlbi.nih.gov; and the NHLBI Proteomics Initiative (http://www.nhlbi.nih.gov/resources/medres/proteomics/index_contacts.htm). Applicants may specifically request in their budgets up to $10,000 direct cost per sample per year ($50,000 over the grant period) to support independent genomic/proteomic analyses of the split samples as described above. In the event that collaborations are not possible, the attempts should be documented, and applicants must describe plans to make their data available to the wider scientific community in a timely fashion. Comparable funds may be requested to convert existing private databases into public ones. Investigators should budget for and be prepared to come to a yearly meeting in Bethesda for up to two days. These meetings will be for the sharing of scientific information and planning activates of wider interest to the research and clinical communities. One expectation is that investigators will determine codification of phenotypes for clinical, cellular, genetic, and proteomic investigations. An NHLBI repository is available for materials and samples that the investigators agree should be preserved as a wider resource (http://www.nhlbi.nih.gov/resources/medres/reposit/contents.htm). Applicants should also include a statement in the applications indicating their willingness to participate in these meetings and activities. 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 or research issues to: Jean Henslee-Downey, M.D. Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 10042 Bethesda, MD 20892 Telephone: (301) 435-0078 FAX: (301) 480-1060 Email: downeyj@nhlbi.nih.gov o Direct your questions about peer review issues to: Valerie L. Prenger, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7178 (MSC 7924) Bethesda, MD 20892-7924 (20817 for Courier) Telephone: (301) 435-0270 Fax: (301) 480-0730 E-mail: prengerv@nhlbi.nih.gov Direct your questions about financial or grants management matters to: Robert Vinson, Jr. DEA-GOB/NHLBI/NIH Rockledge II, Room 7158 Bethesda, MD 20892 - 7950 (20817 for overnight couriers) Telephone: (301) 435-0169 FAX: (301) 480-3310 Email: vinsonr@nhlbi.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 Chief, NHLBI Review Branch at the address listed under WHERE TO SEND INQUIRES. 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 document is available at https://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. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting up to $250,000 per year in direct costs must be submitted in a modular grant format. The modular grant format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 (rev. 5/2001) at https://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular grants. Additional information on modular grants is available at https://grants.nih.gov/grants/funding/modular/modular.htm. 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: https://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 as well as all five sets of the appendix material must be sent to: Valerie L. Prenger, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute 6701 Rockledge Drive, Room 7178 (MSC 7924) Bethesda, MD 20892-7924 (20817 for Courier) Telephone: (301) 435-0270 Fax: (301) 480-0730 E-mail: prengerv@nhlbi.nih.gov 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 the NHBLI. Incomplete and/or nonresponsive 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 NHLBI 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 National Heart, Lung and Blood 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 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. Applications that include research plans for a clinical interventional study will be considered unresponsive to this RFA. SIGNIFICANCE: Does this study 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 analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? Does the research plan meet the data sharing requirements of the RFA? INNOVATION: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or 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? 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. 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: January 16, 2005 Application Receipt Date: February 16, 2005 Peer Review Date: May/June 2005 Council Review: September 2005 Earliest Anticipated Start Date: September 30, 2005 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: https://grants.nih.gov/grants/guide/notice-files/not98-084.html). 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 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are available at https://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. 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 https://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 https://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 https://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 https://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). 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 https://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 https://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.
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