ASTHMA AND ALLERGIC DISEASES RESEARCH CENTERS RELEASE DATE: April 11, 2002 RFA: AI-02-007 (This RFA has been reissued, see RFA-AI-05-027) National Institute of Allergy and Infectious Diseases (NIAID) ( LETTER OF INTENT RECEIPT DATE: October 11, 2002 APPLICATION RECEIPT DATE: November 13, 2002 APPLICATIONS IN RESPONSE TO THIS REQUEST FOR APPLICATIONS (RFA) MUST BE PREPARED USING A MULTI-PROJECT GRANT APPLICATION FORMAT; SPECIFIC INSTRUCTIONS FOR COMPLETING THE APPLICATION ARE IN THE NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS" WHICH IS AVAILABLE AT THE FOLLOWING LINK: 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 NIAID Asthma and Allergic Diseases Research Centers (AADRC) program was established nearly three decades ago to promote innovative, multidisciplinary basic and clinical research on asthma and allergic diseases. NIAID currently supports 13 extramural AADRCs, two of which are co-funded by the National Institute of Environmental Health Sciences. Four of the NIAID centers will expire in FY 2003, and the purpose of this RFA is to solicit new and competitive continuation applications for AADRCs. The program is intended to provide support for integrated basic and clinical research centers to conduct studies on the mechanisms underlying the onset and progression of asthma and allergic diseases. The overarching goal of the program is to improve the diagnosis and treatment of asthma and allergic diseases and to provide a rational foundation for the development of effective prevention strategies. Applications must be structured around a central scientific theme that is clearly relevant to asthma and/or allergic diseases. A minimum of three research projects must be recommended for funding by the Internal Review Group (IRG), and at least one of those recommended projects must focus on immunologic aspects of asthma and/or allergic diseases in humans. All applicants must comply with this stipulation and the others described in the section of this RFA entitled "SPECIAL REQUIREMENTS." RESEARCH OBJECTIVES Background Asthma affects more than 11 million Americans, resulting in more than 130 million days of restricted activity, approximately 500,000 hospitalizations and over 5000 deaths each year. Allergic rhinitis and chronic sinusitis, two of the most commonly reported chronic diseases, together affect approximately 75 million Americans, and chronic sinus disease is frequently associated with asthma. The morbidity and mortality associated with asthma are disproportionately high among children, particularly those who reside in the inner city. African Americans are hospitalized for asthma three times more often than other Americans, and African Americans and Hispanic Americans living in inner cities are two to six times more likely to die from asthma. Although the mortality associated with asthma and allergic diseases is low, the economic burden is high, with an estimated cost for asthma in the United States of $12.7 billion in 1998 and more than $5.8 billion for sinusitis in 1996. In spite of recent advances in understanding the mechanisms underlying asthma and allergic diseases, and improvements in medications used to treat these diseases, the adverse impact on public health continues to grow. For example, the prevalence of asthma has increased by more than 80% in all age and ethnic groups over the past two decades. In order to reverse this trend, it will be necessary to continue to improve our understanding of the cellular and molecular events that lead to the onset of asthma and allergic diseases and the mechanisms involved in disease progression. This new knowledge is required for the development of novel approaches to treat and, eventually, prevent these diseases. Research during the past two decades has led to significant advances in understanding the mechanisms involved in the pathogenesis of asthma and allergic diseases but has had only a modest impact on therapy. Currently, the management of asthma is complex and treatment regimens for rhinitis and sinusitis are aimed at controlling inflammation and alleviating symptoms. Effective control of asthma is difficult to maintain because patients are required to comply with daily, multi-drug regimens, and severe asthma is often difficult to control, even with an optimal management plan. In addition, most of the drugs currently used to treat asthma have a number of undesirable side effects and, in some cases, overuse can actually lead to worsening of the disease. A growing body of evidence suggests that abnormal function of the immune system is central to the pathogenesis of asthma, as is the case with allergic diseases. Recent studies have suggested that perturbations of immune function during gestation and infancy "prime" for the development of asthma and allergy, and that expression of the diseases occurs as a result of exposure to environmental factors, including airborne allergens. Basic research in this area has largely focused on chronic respiratory tract inflammation, which is an important clinical feature of asthma and allergic rhinitis; however, much of this work has been limited to studies involving animal models. This body of research has begun to reveal the complex cellular and molecular interactions that contribute to inflammation in these diseases and has led to the identification of several promising targets for intervention, including IgE antibody and the pro-inflammatory cytokines IL-4, IL-5 and IL-13. In fact, clinical trials are now being conducted to evaluate the efficacy of anti- IgE in asthma and allergen-conjugated immunostimulatory DNA sequences in allergic rhinitis. Many of these clinical leads are the direct result of research funded through the AADRC program. Such therapeutic approaches that target discrete molecules or pathways promise to be effective and specific, without the side effects and limitations of current treatments. Nevertheless, significant gaps in knowledge persist. For example, little is known about the cellular and molecular immune mechanisms that contribute to the acute airway obstruction characteristic of an asthma exacerbation, which requires patients to use beta-adrenergic rescue medications and/or seek emergency medical treatment. Although it is likely that the contraction of airway smooth muscle is involved, the specific immune pathways, chemical mediators and/or neuroimmune mechanisms that trigger and regulate the process in humans are poorly understood. Furthermore, airway obstruction may be complicated by mucus hypersecretion, airway wall edema and changes in the mechanical properties of the airways, and research in these areas is in the early stages of development. Finally, a plethora of recent discoveries concerning the role of immune mechanisms in asthma and allergic diseases have originated in animal models or in vitro systems. These must be confirmed in human studies, which will require a coordinated multidisciplinary effort involving basic scientists and clinical researchers. Recent advances in technology, ranging from genomic and proteomic tools to high-resolution imaging, are available to support such studies. Innovative research in these important areas is essential to further elucidate the molecular and cellular immune mechanisms involved in the pathogenesis of asthma and allergic diseases and will lead to the development of the next generation of therapeutic agents and prevention strategies. Research Objectives and Scope The purpose of the AADRC program is to accelerate the development and application of fundamental knowledge of the immune system to investigations of asthma and allergic diseases. The AADRCs provide an infrastructure and a collaborative environment that make it possible to investigate complex clinical problems. The major goals of the program are to: 1) advance understanding of the etiology and pathogenic mechanisms of asthma and allergic diseases, and 2) apply an expanded knowledge base to the development of improved methods of diagnosis, treatment, and prevention of asthma and allergic diseases. Examples of research areas to be supported under this RFA include, but are not limited to: o the natural history of asthma and allergic diseases, including the identification of genetic and environmental risk factors for the development of these diseases; o studies of pre- and postnatal alterations in immune function that contribute to the onset or progression of asthma and allergic diseases; o studies of cellular and molecular mechanisms that contribute to airway inflammation and acute airway obstruction and their role in the pathophysiology of asthma; o identification of asthma phenotypes and the characterization of asthma expression in relation to underlying mechanisms that distinguish distinct subsets of asthma patients; o the role of the innate immune system in the pathogenesis of asthma and allergic diseases; o characterization of the pulmonary and systemic immune response to aeroallergens, including mechanisms that result in immune tolerance; o cellular and molecular mechanisms involved in food allergy and other severe allergic reactions, with an emphasis on novel therapeutic or prevention strategies such as DNA vaccines; o translational research, from animal models or in vitro systems to humans, particularly focused on new immune therapies for asthma and allergic diseases, including proof of concept studies in humans. Autoimmunity, immune deficiency, and Demonstration and Education Research Projects are not within the scope of this RFA. MECHANISM OF SUPPORT This RFA will use the NIH program project (P01) award mechanism. As an applicant you will be solely responsible for planning, directing, and executing the proposed project. This type of award supports broadly based multidisciplinary research programs that have a well-defined central research focus or objective. An important feature is that the interrelationships among the individual scientifically meritorious projects will result in a greater contribution to the overall program goals than if each project was pursued individually. The program project grant consists of a minimum of three interrelated individual research projects that contribute to the program objective. The award also can provide support for certain common resources termed cores. Such resources should be utilized by two or more projects within the award. Applications may include investigators from more than one institution, if that enhances the scientific strength of the application. In addition, applicants are strongly encouraged to include one or more investigators who are not currently involved in studies of asthma and allergic diseases. 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. FUNDS AVAILABLE The NIAID intends to commit approximately $4.8 million in FY 2003 to fund approximately 4 new and/or competitive continuation grants in response to this RFA. An applicant may request a project period of up to 5 years and a budget for total costs (direct and facility and administrative) of up to $1.2 million per year. Under exceptional circumstances applicants may propose budgets that exceed this amount, but will require prior approval of the project officer. 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 NIAID 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. At this time, it is not known if this RFA will be reissued. 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 Foreign organizations 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 The goal of this RFA is to support multidisciplinary research programs focused on studies of immunologic and other mechanisms underlying human asthma and allergic diseases. The AADRCs provide an infrastructure and a collaborative environment that make it possible to investigate complex clinical problems. Applications must propose a minimum of three research projects organized around a central scientific theme. The application should include an appropriate balance of basic and clinical research but with a significant emphasis on human studies. Among the projects recommended for funding: o A minimum of one project must focus on immunologic aspects of asthma and/or allergic diseases in humans, including advancing our understanding of the etiology and pathogenic mechanisms of asthma and allergic diseases and/or applying the expanded knowledge base to the development of improved methods of diagnosis, treatment, and prevention. This project may involve clinical studies of patients with asthma and/or other allergic diseases or in vitro investigations of patients' blood, fluid and/or tissue samples, immune cells and DNA/RNA. o Studies of relevant animal models may be included in the other research projects. When clinical studies or trials are a component of the research proposed, NIAID policy requires that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. Terms and Conditions of Award will be included with awards. NIAID policy was announced in the NIH Guide on February 24, 2000 and is available at: The full policy including terms and conditions of award are available at: 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: Direct your questions about scientific/research issues to: Ken Adams, Ph.D. Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases Room 5147, MSC-7640 6700-B Rockledge Drive Bethesda, MD 20892-7640 Telephone: (301) 402-8179 FAX: (301) 402-0175 E-Mail: Direct your questions about peer review issues; address the letter of intent; mail two copies of the application and all five sets of appendices to: Edward W. Schroder, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 2156, MSC-7616 6700-B Rockledge Drive Bethesda, MD 20892-7616 Telephone: (301) 435-8537 FAX: (301) 402-2638 E-Mail: Direct your questions about financial or grants management matters to: Jaqueline Johnson Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 2127, MSC-7614 6700-B Rockledge Drive Bethesda, MD 20892-7614 Telephone: (301) 402-5936 Fax: (301) 480-3780 E-mail: 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: Edward W. Schroder, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 2156, MSC-7616 6700-B Rockledge Drive Bethesda, MD 20892-7616 Telephone: (301) 435-8537 FAX: (301) 402-2638 E-Mail: SUBMITTING AN APPLICATION APPLICANTS FOR P01 GRANTS MUST FOLLOW SPECIAL APPLICATION GUIDELINES IN THE NIAID BROCHURE ENTITLED INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS; THIS BROCHURE IS AVAILABLE VIA THE WWW AT: Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). The PHS 398 is available at in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: 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: 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 exact copies of the grant application and all five sets of any appendix material must be sent to: Edward W. Schroder, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 2156, MSC-7616 6700-B Rockledge Drive Bethesda, MD 20892-7616 BETHESDA, MD 20817 (for express mail or courier service) Applications must be received by November 13, 2002. Applications that are not received as a single package on the receipt date or that do not conform to the instructions contained in PHS 398 (rev. 5/01) Application Kit (as modified in, and superseded by, the NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS"), will be judged non-responsive and will be returned to the applicant. It is highly recommended that the appropriate NIAID program contact be consulted before submitting the letter of intent and during the early stages of preparation of the application. (See program contact under INQUIRIES). SPECIAL INSTRUCTIONS FOR COMPLETION OF APPLICATIONS IN RESPONSE TO THIS RFA: APPLICANTS FOR P01 GRANTS MUST FOLLOW SPECIAL APPLICATION GUIDELINES IN THE NIAID BROCHURE ENTITLED INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS; THIS BROCHURE IS AVAILABLE VIA THE WWW AT: The brochure presents specific instructions for sections of the PHS 398 (rev. 5/01) application form that should be completed differently than usual. For all other items in the application, follow the usual instructions in the PHS 398. APPLICATION PROCESSING: Applications must be received by 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. 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. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an Introduction addressing the previous critique. Concurrent submission of an R01 and a Component Project of a Multi-project Application: Current NIH policy permits a component research project of a multi-project grant application to be concurrently submitted as a traditional individual research project (R01) application. If, following review, both the multi-project application and the R01 application are found to be in the fundable range, the investigator must relinquish the R01 and will not have the option to withdraw from the multi-project grant. This is an NIH policy intended to preserve the scientific integrity of a multi-project grant, which may be seriously compromised if a strong component project(s) is removed from the program. Investigators wishing to participate in a multi-project grant must be aware of this policy before making a commitment to the Principal Investigator and awarding institution. PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NIAID. Incomplete and/or non-responsive 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 NIAID 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 selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score o Receive a second level review by the National Institute of Allergy and Infectious Diseases Council REVIEW CRITERIA The general review criteria for P01 grant applications are presented in the NIAID brochure entitled "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS" at ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your application will also be reviewed with respect to the following: o PROTECTIONS: The adequacy of the proposed protection for humans, animals, or the environment, to the extent they may be adversely affected by the project proposed in the application. o INCLUSION: 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 included in the section on Federal Citations, below) o 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: October 11, 2002 Application Receipt Date: November 13, 2002 Scientific Peer Review Date: March 15, 2003 Advisory Council Review: June 2, 2003 Earliest Anticipated Start Date: September 1, 2003 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 MONITORING PLAN AND DATA SAFETY AND 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 Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: 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 AMENDMENT "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 ( files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are available at 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 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 HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at and at Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see It is the responsibility of the applicant to provide 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 Applicants may wish to place data collected under this RFA 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 AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Domestic Assistance in the following citations: No. 93.855, Immunology, Allergy, and Transplantation Research and No. 93.856, Microbiology and Infectious Diseases Research. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The NIH Grants Policy Statement is available at This document includes general information about the grant application and review process; information on the terms and conditions that apply to NIH Grants and cooperative agreements; and a listing of pertinent offices and officials at the NIH. 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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