RFA-HL-04-005: INFLAMMATION AND THROMBOSIS

Department of Health
and Human Services (HHS)

NIH... Turning Discovery Into Health^®

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

INFLAMMATION AND THROMBOSIS RELEASE DATE: August 5, 2003 RFA Number: RFA-HL-04-005 National Heart, Lung, and Blood Institute (NHLBI) (http://www.nhlbi.nih.gov) Institute of Circulatory and Respiratory Health (ICRH), Canadian Institutes of Health Research (CIHR) (http://www.cihr-irsc.gc.ca) CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.837, 93.838, 93.839 LETTER OF INTENT RECEIPT DATE: December 22, 2003 APPLICATION RECEIPT DATE: January 22, 2004 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 Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE OF THIS RFA The processes of inflammation and thrombosis interact at multiple points and there is abundant evidence to suggest that there are mechanisms common to both these processes. The possibility exists that anti-inflammatory agents could be utilized to manage thrombotic processes underlying disease. The goal of this initiative is to identify molecular targets and develop novel therapeutic agents towards better management of thrombotic disorders. Thus, NHLBI and the Institute of Circulatory and Respiratory Health (ICRH) invite applications that utilize innovative research approaches to the molecular and cellular interactions between the hemostatic and inflammatory systems to identify novel therapeutic agents and that translate this knowledge to preclinical research. RESEARCH OBJECTIVES Formation of a blood clot resulting in ischemia may precipitate cardiovascular diseases and stroke, which are the leading causes of morbidity and mortality in the United States and Canada. Rapid response and early intervention with thrombolytic, antiplatelet, and anticoagulant drugs have contributed to reduce the mortality of these patients. However, the anticoagulants in use are decades old and there is a need to apply new scientific knowledge and improve therapy of thrombotic disorders. The proteins of the coagulation cascade and the inflammatory molecules work in concert to mediate the adhesion of leukocytes, platelets, and the endothelium that occurs during thrombotic and inflammatory complications. In addition to their well established role in hemostasis and thrombosis, it is now recognized that platelets play a pivotal role in orchestrating the process of inflammation. Activated platelets shed CD40 ligand (CD40L) that directly activates the inflammatory process on the endothelium. The concentration of soluble CD40L in serum increases in acute coronary thrombosis and induces tissue factor expression on monocytes. Not only do platelets contain about 90 percent of the CD40L in the body, they also produce key inflammatory mediators such as platelet-derived growth factors, thrombospondin, P selectin and interleukins. CD40L can also activate platelets through the integrin, GP IIb/IIIa, and appears to be necessary for stabilizing the arterial thrombi. Similarly, activated protein C (APC), traditionally considered to be an anticoagulant protein, has now been shown to have antiinflammatory and antiapoptotic properties and was demonstrated to be neuroprotective in an animal model of stroke. Thus platelets and clotting proteins which are essential in hemostasis/ thrombosis have indeed a dual role as initiators and modulators of the inflammatory process. The selectin family of receptors is now known to mediate the critical cell-cell interactions involved in leukocyte trafficking, thrombosis, and inflammation. The rolling of leukocytes is thought to be mediated by P-selectin and its ligand, P-selectin glycoprotein ligand 1 (PSGL-1), but extravasation probably involves the integrins. This is a complex process that seems to be regulated by internalization of the ligand - receptor molecules and signaling events in leukocytes. Monocytes also rapidly bind activated platelets that display P-selectin on their surface. An emerging area of critical importance is the role of blood tissue factor (TF) in thrombosis. An alternatively spliced soluble TF in humans has recently been reported. Monocyte tissue factor in the form of microparticles may be transferred to activated platelets at the site of injury and P-selectin has been proposed as the TF binding protein or receptor. Thus, P-selectin plays an important role in coagulation as well as in inflammation. Over expression of soluble P-selectin in an animal model creates a hypercoagulable state. Infusion of PSGL-Ig, an inhibitor of P-selectin, reversed this procoagulant state. Moreover, PSGL-1 mimetics, in the absence of anticoagulants, showed therapeutic benefits in reducing hypercoagulation and vein wall inflammation in animal models in thromboembolic disorders. A role for E-selectin in thrombosis has been suggested but not confirmed. These observations show that thrombosis and inflammation are biologically inseparable processes. P-selectin may no longer be considered only as a marker of platelet activation or inflammation, but also a direct inducer of procoagulant activity related to vascular and thrombotic diseases. It is known that TF Factor VIIa complex can activate Factor X which is an important step in the initiation of blood coagulation. Recent observations suggest that the complex, TF FVIIa or TF-FVIIa - FXa, can also initiate the inflammatory pathway by cleaving the protease activated receptors, PAR -1 and PAR-2, thereby activating endothelial cells. Thus, the initiation of coagulation and the initiation of inflammation are kinetically coupled events. This is further supported by the observation that tissue factor pathway inhibitor (TFPI) reduces inflammatory responses as well as antithrombotic effects. PARs are known to mediate the biological actions of thrombin and other proteases released during tissue injury. PARs coordinate the hemostatic and inflammatory responses in endothelial and other cells. Activation of the coagulation cascade in Gram-negative septicemia is known to trigger thrombotic and inflammatory events. Recently, recombinant APC, a major regulator of the anticoagulant pathway, has been observed to be effective in the treatment of sepsis. Sepsis is also the major risk factor for acute lung injury (ALI) / acute respiratory distress syndrome (ARDS) and this finding needs to be extended to non-septic ARDS. Like tissue factor, APC also has cell receptor mediated anti-inflammatory properties. It is now reported that APC also directly prevents cell death and improves cell survival that involves p53 and PAR on the endothelial cells. APC has been shown to be beneficial in experimental stroke in animal models and provides a potential treatment option in any ischemic injury. There is evidence linking inflammation, atherosclerosis, and thrombosis. Circulatory inflammatory mediators, in particular, C-reactive protein, has emerged as a marker of coronary risk and seems to be associated with increased cardiovascular events. The interaction between inflammation and thrombosis may involve a series of biochemical and cellular events, and the severity of the clinical outcome may depend on other risk factors and genetic predisposition. Thus, anti-inflammatory therapy may limit thrombosis and antithrombotic therapy may reduce vascular inflammation. The recent scientific developments described above have important therapeutic implications. Thrombotic diseases such as myocardial infarction, stroke, and thromboembolism are major public health problems with significant mortality and morbidity. It has been considered to be primarily a disorder of the coagulation and platelet function. Accordingly, the mainstay of its therapy has been the anticoagulant and platelet aggregation inhibitors. The carbohydrate specificity of PSGL-1 in its interaction with P-selectin has been defined and several mimetics have been developed. In experimental models of venous thrombosis, these inhibitors of P-selectin produced encouraging results without the use of anticoagulants. Another pertinent example is the possible early use of aspirin after bypass surgery. The beneficial effects in averting some of the ischemic complications by early aspirin use are likely to relate to its antiinflammatory properties. Recognition of the basic molecular processes involved and the interplay between inflammation and thrombosis provide opportunities to develop novel therapeutics to combat thrombotic and thromboembolic diseases. Examples of Research Areas The goal of this RFA is to identify new targets and develop novel therapy for thrombotic disorders such as heart attack, stroke, deep vein thrombosis (DVT), and pulmonary embolism in preclinical studies. These are examples of thrombotic disorders to study but applicants are encouraged to develop their own ideas. MECHANISM OF SUPPORT This RFA will use NIH Research Project Grant (R01) award mechanism. Applications submitted in response to this RFA may have a project period of up to four years. 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 30, 2004. 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 format. (see http://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 format. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm. Applications submitted by foreign institutions can request facilities and administrative (F&A) costs up to a maximum of eight percent. Please see the web site HTTP://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html for more information on allowable F&A costs for foreign grants and domestic grants with foreign components. FUNDS AVAILABLE The NHLBI intends to commit approximately $3,000,000 in FY 2004 to fund about 10 to 12 new grants in response to this RFA. The ICRH intends to commit approximately $1,200,000 to fund meritorious applications, relevant to their mission, involving Canadian institutions. ICRH will make the award of grants for meritorious applications of interest to them. Applicants who wish to have their projects considered for funding by ICRH should include with their application a letter stating that their application and summary statement may be shared with ICRH. An applicant may request a project period of up to four years and a budget for direct costs of up to $200,000 per year. 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 and ICRH 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 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 The goal of this initiative is to develop new targets for therapy of thrombosis by focusing on translational research at the interface of thrombosis and inflammation. In order to be responsive to the RFA, studies must propose specific approaches to identify novel therapeutic agents in preclinical studies. Studies purely on either inflammation or thrombosis will not be considered responsive to this RFA. In addition studies on currently established agents such as aspirin will not be considered responsive. The expectation is that the results from studies supported under this RFA will contribute to the development of novel therapeutic agents for thrombotic disorders. General Clinical Research Centers Applications from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources (NCRR) may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or the principal investigator should be included with the application. Meetings Principal investigators will be required to attend an annual meeting organized by the NHLBI/ICRH. Please include travel to Bethesda, MD area as part of the budget request. 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: Ahmed A.K. Hasan, M.D., Ph.D. Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute Building RKL II, Room 10180 Bethesda, MD 20892 Telephone: (301) 435-0070 Email: hasana@nhlbi.nih.gov Stephen Goldman, Ph.D. Division of Heart and Vascular Diseases National Heart, Lung, and Blood Diseases Building RKL II, Room 10192 Bethesda, MD 20892 Telephone: 301-435-0565 E-mail: goldmanS@nhlbi.nih.gov Andrea Harabin, Ph.D. Division of Lung Diseases National Heart, Lung, and Blood Disease Building RKL II, Room 10120 Bethesda, MD 20892 Telephone: 301-435-0233 E-mail: vreimC@nhlbi.nih.gov Teri Manolio, M.D. Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute Building RKL II, Room 8160 Bethesda, MD 20892 Telephone 301-435-0708 E-mail: manolioT@nhlbi.nih.gov o Direct your questions about peer review issues to: Anne P. Clark, Ph.D. Chief, Review Branch Division of Extramural Affairs National Heart, Lung, and Blood Institute Building RKL II, Room 7214 Bethesda, MD 20892 Bethesda, MD 20817 (for express/courier service) Telephone: (301) 435-0270 FAX: 301-480-0730 Email: ClarkA@nhlbi.nih.gov o Direct your questions about financial or grants management matters to: Robert Vinson Division of Extramural Affairs National Heart, Lung, and Blood Institute Building RKL II, Room 7156 Bethesda, MD 20892 - 7926 Telephone: (301) 435-0166 FAX: 301-480-0166 Email: VinsonR@nhlbi.nih.gov Direct any questions directed to ICRH, please contact: Elissa Hines Reimer Senior Associate Institute of Circulatory and Respiratory Health Telephone: (613) 954-0544 Email: ehinesreimer@cihr.gc.ca 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 Dr. Anne Clark at the address listed under WHERE TO SEND INQUIRIES. In addition, for this RFA, principal investigators located in Canada are requested to notify ICRH of their intent to apply by sending an email to by 12/22/2003. SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). 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. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget grant format. The modular budget 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 http://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 http://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: http://grants.nih.gov/grants/funding/phs398/label-bk.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 plus all five collated sets of appendix material must be sent to Dr. Anne Clark at the address listed under WHERE TO SEND INQUIRIES. 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. While the investigator may still benefit from the previous review, the RFA application is not to state explicitly how. PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NHLBI and ICRH. Incomplete applications will be returned to the applicant without further consideration. 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 consultation with ICRH, and in accordance with the review criteria stated below. As part of the initial merit review, all applications will: o Receive a written critique 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 second level review by the NHLBI 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 discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals: o Significance o Approach o Innovation o Investigator o Environment The scientific review group will address and consider each of these criteria in assigning the application's overall score, weighting them as appropriate for each application. 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 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? 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? ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following items 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 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 CONSIDERATIONS 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: December 22, 2003 Application Receipt Date: January 22, 2004 Peer Review Date: June, 2004 Council Review: September, 2004 Earliest Anticipated Start Date: September 30, 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 MONITORING PLAN AND DATA AND SAFETY MONITORING BOARD: Research components involving Phase I and II clinical trials must include provisions for assessment of patient eligibility and status, rigorous data management, quality assurance, and auditing procedures. In addition, it is NIH policy that all clinical trials require data and safety monitoring, with the method and degree of monitoring being commensurate with the risks (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). 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. 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/Default.htm. ICRH WEBSITE: Applicants are encouraged to visit the ICRH website, accessible through the Canadian Institutes of Health Research homepage () for information concerning the ICRH mandate, current research initiatives and publications such as the ICRH Strategic Plan (available in English and French). 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