PARTNERSHIPS FOR VACCINE AND DIAGNOSTIC DEVELOPMENT RELEASE DATE: June 9, 2003 (see clarification NOT-AI-03-050) RFA: AI-03-028 National Institute of Allergy and Infectious Diseases (NIAID) ( CATALOGUE OF FEDERAL DOMESTIC ASSISTANCE NUMBERS: No. 93.855, Immunology, Allergy, and Transplantation Research No. 93.856, Microbiology and Infectious Diseases Research LETTER OF INTENT RECEIPT DATE: August 23, 2003 APPLICATION RECEIPT DATE: September 24, 2003 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 Research of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, strives to understand, treat and ultimately prevent the myriad infectious, immunologic, and allergic diseases that threaten millions of human lives. The NIAID Division of Microbiology and Infectious Diseases (DMID) supports extramural research to control and prevent diseases caused by virtually all infectious agents. This includes basic biomedical research, such as studies of microbial physiology and antigenic structure; applied research, including the development of diagnostic tests; and clinical trials to evaluate experimental drugs and vaccines. This Partnership program will use the cooperative agreement (U01) funding mechanism to support the development and testing of products for selected human infectious diseases of public health importance. A key component of the Partnership initiatives is the development of appropriate partnerships among government, academia, and the biotechnology, chemical or pharmaceutical industries. This RFA is specifically focused on: A) Development of vaccines against group A streptococci (GAS); B) Development of vaccines against group B streptococci (GBS); C) Development of vaccines against Helicobacter pylori; D) Development of point of care diagnostics for GAS; and E) Development of point of care diagnostics for GBS. PARTNERSHIPS A key component of this initiative is the development of appropriate partnerships between the government and industry. For the purpose of this RFA, "industry" is defined as large and small, domestic or foreign, pharmaceutical, biotechnology, bioengineering, and chemical companies. Since academic organizations are often the source of new candidate products, this RFA can also support a partnership between industry and a collaborator(s) as necessary from academic or non-profit research organizations. The involvement of an academic or non-profit research organization is NOT a requirement; therefore industry does not need a collaborator to submit an application to this program. All projects must demonstrate substantive involvement by the industry partner. For the purpose of this RFA, "substantive involvement" is defined as the commitment of any one or more of the following resources: funds; personnel; or in-kind contributions of materials and/or reagents, including but not limited to chemical libraries, GMP chemical synthesis or recombinant protein production, provision of animal or other laboratory models and assays, subcontracts, data management resources and regulatory support. The Principal Investigator of the project may be affiliated with either industry or academic organization (if academia is part of a partnership with industry). See information under Eligible Institutions below. The Partnership Program is intended to support all phases of development of a candidate product or platform technology including, but not limited to, early validation, pre-clinical stages, pilot lot production, regulatory requirements, and, where appropriate, limited clinical evaluation. The NIAID recognizes that the inherent nature and demands of the product development process may require funding large, complex grants with interdependent specific aims. Furthermore, some aspects of the product development process (e.g., production of GLP and cGMP product) are inherently not innovative. Recognizing that product development is often an iterative and sequential process, and that steps early in the process may not be successful and may need to be modified or reworked, NIAID staff, through the cooperative agreement grant mechanism, will be actively involved in evaluating the milestones of awardees and determining whether additional investment in the development is warranted. RESEARCH OBJECTIVES Background In late 2000, the NIAID convened a panel of experts to discuss the role and nature of NIAID/industry collaborations in antimicrobial drug development for public health needs and to learn how NIAID could better facilitate and engage industry and academia in these endeavors ("Summit on Drug Development for Infectious Diseases."). One of the recommendations from this meeting was a continued pursuit of innovative opportunities to form partnerships with the private sector for the control of a number of infectious diseases with public health importance. A report of this meeting is available at Since 2002, NIAID has identified a diverse set of priority areas for partnership solicitations that have included Partnerships for Novel Therapeutic, Diagnostic and Vector Control Strategies in Infectious Diseases (PAR-02-026, files/PAR-02-026.html) and Partnerships: Hepatitis B and Vector Borne Diseases Control (RFA-AI-03-003, files/RFA-AI-03-003.html). NIAID is also using this mechanism to solicit applications related to biodefense. The need to support the research specified by the current RFA has been emphasized by the NIAID-convened review of its Group A Streptococcal Program in 1998 and the Analysis and Action Plan for the National Vaccine Advisory Committee that was prepared in response to the Institute of Medicine's report, "Vaccines for the 21st Century". This plan is available at (November 2002) and includes information related to the development of vaccines for GAS, GBS and H. pylori. Investment by industry in the commercialization of products for the control of a number of infectious diseases of public health importance remains limited. This initiative is meant to help stimulate industry participation in decreasing the medical impact of these targeted important diseases for which effective new control measures and diagnostics are lacking. This program is seeking applications that propose to: A. Development of a vaccine against GAS GAS cause a broad spectrum of disease that ranges from uncomplicated pharyngitis and skin infections to life threatening invasive illnesses that includes pneumonia, bacteremia, necrotizing fasciitis, streptococcal toxic shock syndrome (STSS) and nonsuppurative sequelae consisting of acute rheumatic fever (ARF) and post streptococcal glomerulonephritis (PSGN). Streptococcal pharyngitis has been and continues to be one of the most common childhood illnesses throughout the world. Skin infections caused by GAS are a particular problem in tropical and subtropical climates and summer months of temperate or northern climates. Outbreaks of necrotizing fasciitis and STSS with significant rates of morbidity and mortality among otherwise healthy individuals were first reported in the 1980's in the U.S., Europe and Japan and have continued into the 21st century. Although the incidence of ARF has varied in the U.S.- decreasing in the 70's, reappearing in the 80's and limited to Utah and occasional outbreaks in the 90's-this disease continues to be a serious public health problem in developing countries. Recurrent infections with GAS following ARF result in rheumatic fever and rheumatic heart disease (RF/RHD), requiring costly resources for medical and surgical treatment. RF/RHD is the major cause of heart disease in children around the world. Post infectious glomerulonephritis (GN) is the most common form of GN in children and GAS are the most frequent infectious etiology. The frequency and severity of PSGN seems to be diminishing in the U.S. and epidemics have been rare since 1965. However, sporadic outbreaks of PSGN continue to be reported in developing countries and close communities with poor hygiene. Although penicillin is the treatment of choice for GAS infections, macrolides are used for patients who are hypersensitive to penicillin. In recent years, resistance to macrolides among group A streptococci is an increasing problem worldwide The high burden of disease from streptococcal infections and the emergence of antibiotic resistance emphasizes the need for a safe and efficacious vaccine. B. Development of a vaccine against GBS In the 1970's Group B Streptococci (GBS) emerged as the most important infectious cause of neonatal morbidity and mortality and pregnancy-related morbidity. Two syndromes in infants had been recognized: early onset disease (primarily sepsis, pneumonia and bacteremia within the first 7 days of life) and late onset disease (primarily meningitis between 7 and 90 days of age). GBS are vertically transferred from a colonized mother during delivery and can cause invasive disease. Neonatal disease prevention strategies in the United States have focused on the identification of vaginal and rectal colonization in pregnant women and the use of antibiotics during labor and delivery in those women who are colonized. Although there has been a decrease in the incidence of early onset neonatal infections (65%) and invasive GBS infections in pregnant girls and women (21%), the incidence of late onset GBS disease in infants has not changed. While this strategy is effective, it is an interim solution. It has not been able to eliminate GBS disease and encourages the widespread use of antibiotics with related concerns that include emergence of drug resistance in GBS. Recent data indicate that 15% of GBS isolates are resistant to clindamycin and 21% to erythromycin. Although the incidence of invasive GBS disease has recently decreased in the neonates, there has been an increase in the incidence of invasive GBS disease in non-pregnant adults. The majority of these cases occur in adults with significant underlying conditions such as diabetes, neurological impairment, breast cancer and cirrhosis. Common clinical manifestations of GBS disease in adults include skin and soft tissue infections, bone and joint infections, and pneumonia. Meningitis and endocarditis are less common but when present are associated with serious morbidity and mortality. The case fatality rate is higher in adults than in neonates and adults over the age of 65 are at the highest risk of dying from invasive GBS disease. A GBS vaccine would benefit pregnant women, neonates, and adults with underlying medical conditions. C. Development of a vaccine against H. pylori Helicobacter pylori infects the stomach of more than 50% of the human population worldwide. It is now firmly established that persistent infection can cause chronic gastritis, peptic ulcer disease, and in some individuals, gastric adenocarinoma and gastric B cell lymphoma. Neither the mechanism of transmission nor the relative susceptibility factors are known. Infection is usually acquired during childhood, especially in people living in developing countries and in low socioeconomic populations. Current treatment is based on the use of a proton-pump inhibitor and relatively long-term antibiotic therapy. Although this treatment is efficacious, its limitations include problems with patient compliance and antibiotic resistance. A vaccine against H. pylori has the potential to significantly reduce the morbidity and mortality associated with chronic H. pylori infection. A vaccine with both prophylactic and therapeutic potential would be enormously valuable. However, the specific immune responses that mediate either protection or cure in humans are incompletely characterized and thus whether a single vaccine could deliver both prophylactic and therapeutic protection is still in question. In addition, no investigational vaccine has yet achieved sterilizing immunity in humans. Bacterial colonization has been reduced but it is not known whether that end point will be sufficient to have a significant impact on the clinical course of infection. The high incidence of H. pylori infection in the developing world and the eventual adoption of a protective vaccine suggests the need for a low cost product that will meet the demands of use in developing countries. D. Development of point of care diagnostics for GAS Many point of care diagnostics for detection of GAS have been commercialized over the years. Experience in the medical community demonstrates variability in the sensitivity and specificity of currently used methodologies . As GAS vaccines are being developed, it is important to have burden of disease data at a field site to determine the sample size for clinical trials. Point of care diagnostics would be helpful in obtaining these data in field sites where bacterial culture is not routinely performed. Additionally, the public health community would benefit from improved, accurate, and rapid tests for GAS diagnostics. E. Development of point of care diagnostics for GBS Although there is a need for point of care diagnostics for detection of GBS, development has been affected by Center for Disease Control and Prevention guidelines for prenatal GBS disease prevention. These guidelines demonstrated the need to test both vaginal and rectal specimens and use selective growth media for optimal detection of GBS. Most of the commercially available direct antigen tests were not validated using selective media and none were validated using rectal specimens. A Safety Alert was issued in 1997 by the FDA for use of direct antigen tests. The impact on point of care diagnostics was that some products were discontinued, effectively removing them from the marketplace. Only one new product has been commercialized that meets the CDC guidelines for sensitivity. This diagnostic product was only recently approved and its performance in the community over time will need to be assessed. Research Goals and Objectives Applications should address research that will advance the development vaccines against GAS, GBS or H. pylori or development of point of care diagnostics for GAS or GBS. Research is not required to result in a "final" product but must advance the development of a candidate product. One objective of this RFA is to stimulate scientifically sound, original, and innovative research requiring comprehensive team and multidisciplinary effort that is likely to advance promising candidate products through the product development pathway. All applications should define the proposed project goal, interim objectives (development milestones), a general description of the potential ultimate product (a specific product profile that is defined by licensing indication is not requested), and provide a schedule or timeline for milestone and goal attainment. When appropriate, research plans should include an awareness of guidelines that govern GLP (as defined by 21 CFR(58)) and GMP (as defined by 21 CFR(211)) manufacturing and/or IND enabling studies that will be performed with this award as they would be applicable to eventual product licensure in the U.S. VACCINES It is the purpose of this RFA to fund research that addresses key issues related to the development of vaccines against GAS, GBS or H. pylori. These issues may include, but are not limited to, research focused on: o The identification and validation of protective immune responses, including antigen and/or epitope identification and characterization of the immune effector cells; o Delivery systems that target appropriate immune responses and stimulate active immunity without inducing undesirable inflammatory responses; o Evaluation of the safety, toxicity, immunogenicity and protective immunity in animal models; o Process development for the production of specified vaccine components, including QA/QC methods for product recovery, characterization, purification, identity, stability i.e. all the benchmarks required for successful submission and review of an Investigational New Drug application by the Food and Drug Administration (FDA) (; o Optimization of dose and route of delivery in preclinical evaluation; o Optimization of formulation with adjuvant (and justification for use of adjuvant) or specific delivery system; o Manufacture of pilot lots (GLP or cGMP) for preclinical and early clinical evaluation; o Optimization of safety and immunogenicity in Phase I clinical trials; o Evaluation of dose-ranging and dosing intervals in Phase II clinical trials; and o For vaccines against H. pylori, both prophylactic and/or therapeutic applications are acceptable. o A research and development plan that defines the proposed project goal, interim objectives (development milestones) and potential ultimate product, and provides a schedule or timeline for milestone and goal attainment. DIAGNOSTICS There is need for point-of-care rapid diagnostics for detection of GAS and GBS. All applications should include: o Preliminary data to support the basis of the diagnostic method; o Description of the capabilities of the method, technology, or assay, and advantages over currently available diagnostics; o Plans for determining performance characteristics including - sensitivity - false positive and false negative rates in the population of diagnostic interest - specificity - reproducibility - minimum turnaround time for results - validation of the technology, assay, and diagnostic; o Methods for rapid sample preparation and processing; o Feasibility of specimen collection and detecting organism in that specimen; o Process development for the manufacturing of diagnostic components, including QA/QC methods for reagent production, characterization, purification, identity, stability etc.; o Appropriateness of release criteria; o Appropriateness of internal controls; o Applicability in a clinical setting, and evaluation in human clinical studies; and o A research and development plan that defines the proposed project goal, interim objectives (development milestones) and potential ultimate product, and provides a schedule or timeline for milestone and goal attainment. Tests for use on human samples may consider benchmarks required for FDA approval ( MECHANISM OF SUPPORT This RFA will use NIH U01 award mechanism(s). 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. 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 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 The NIH (U01) is a cooperative agreement award mechanism in which the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the section "Cooperative Agreement Terms and Conditions of Award" The total project period for applications submitted in response to this RFA may not exceed five years. FUNDS AVAILABLE The NIAID intends to commit approximately $4 million in FY 2004 to fund approximately 6 to 10 new grants in response to this RFA. An applicant may request a project period of up to 5 years and a budget for direct costs must be less than $ 500,000 per year. Applications greater than $500,000 in direct costs per year will not be accepted. 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. ELIGIBLE INSTITUTIONS The applicant may submit (an) application(s) if the 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 Both domestic and foreign organizations are eligible. Institutions must be in compliance with U.S. laws and regulations and DHHS and NIH policies in effect at the time of grant award and during the period of performance of the research. FOREIGN ORGANIZATIONS Several special provisions apply to applications submitted by foreign organizations. o Funds for alterations or renovations cannot be requested. o Charge back of customs and import fees is not allowed. o Format: every effort should be made to comply with the format specifications, which are based upon a standard US paper size of 8.5" x 11." o Funds for up to 8% administrative costs can now be requested, ( o Organizations must comply with federal/NIH policies on human subjects, animals, and biohazards. o Organizations must comply with federal/NIH biosafety and biosecurity regulations o Proposed research should provide a unique research opportunity, not available in the U.S. 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 Depending upon the scientific area, each application must propose a research and development project whose ultimate goal is to develop a vaccine against GAS, GBS or H. pylori or to develop a point of care diagnostic for GAS or GBS. The application must document substantive involvement by the industry partner. Applications must propose clear project goal(s), including a final product or stage of development to be completed during the award period. The applicant must clearly state the interim objectives (developmental milestones) to be achieved during the project, identify impediments or critical decision points that could require a revision in the work plan or milestones, and provide a detailed schedule or timeline for the attainment of each milestone and/or goal. For applications that contain a clinical study, a mandatory milestone that must be included is the approval of the final clinical protocol by NIAID. Applicants must build this milestone into their application. Intellectual Property Intellectual property rights are likely to play an important role in achieving the goals of this program. To this end, the NIAID requires that at the time of the application all applicants must provide a letter ("Proprietary Rights Assurance Letter") containing the following assurances, which is signed by a representative who is duly authorized to provide such assurances on behalf of the applicant organization: o Applicant is solely responsible for the timely acquisition of all proprietary rights, including intellectual property rights, and all materials needed for applicant to perform the project o Applicant acknowledges that prior to, during, and subsequent to the award, the U.S. Government is not required to obtain for applicant any proprietary rights, including intellectual property rights, or any materials needed by applicant to perform the project. o Applicant acknowledges the requirement to report to the U.S. Government all inventions made in the performance of the project, as specified at 35 U.S.C. Sect. 202. Apart from the Proprietary Rights Assurance Letter, applicants are expected to exercise their Bayh-Dole rights in a manner that does not conflict with the goals of this award or the intent of the Bayh-Dole Act to promote the utilization, commercialization and availability of the U.S. Government-funded inventions for public benefit. In addition, applicants are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, and reports to the NIAID or other mechanisms. Mandatory Meetings The Principal Investigator, one or two key personnel designated by the Principal Investigator and NIAID program staff will meet once a year to review progress, aid program development, and foster collaborations among the programs. This meeting will likely be held at the NIH in Bethesda, MD and applicants should include requests for travel funds (airfare, and per diem) specifically for this meeting. COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator as well as the institutional official at the time of award. These special Terms of Award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR part 74 and 92, and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the research will be shared among the awardees and the NIAID Scientific Coordinator. 1. Monitoring Clinical Studies 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. AN UPDATED NIAID policy was published in the NIH Guide on July 8, 2002 and is available at: 02-032.html. The full policy, including terms and conditions of award, is available at: 2. Awardee Rights and Responsibilities Awardees will have primary responsibility for defining the research objectives, approaches and details of the projects within the guidelines of the RFA and for performing the scientific activity. Specifically, awardees have primary responsibility as described below. The Principal Investigator retains primary responsibility for the performance of the scientific activity, and agrees to accept close assistance in coordination, cooperation and participation of NIAID staff in scientific and technical management of the project in accordance with the terms formally and mutually agreed upon prior to the award. The responsibility for the planning, direction, and execution of the proposed project will be solely that of the Principal Investigator. o Publications: The Principal Investigator will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by members of the grant and supported in part or in total under this Agreement. The Principal Investigator and Project Leaders are requested to submit manuscripts to NIAID program staff within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained and joint press conferences prepared. Publications or oral presentation of work done under this Agreement is the responsibility of the Principal Investigator and appropriate Project Leaders and will require appropriate acknowledgement of NIAID support. Timely publication of major findings is encouraged. o Data: While the NIAID Scientific Coordinator and program staff have a right of access to the data (see NIAID staff responsibilities below) the applicant will retain custody of and right to the data. The awardee must have an approved data-sharing plan in place (see 3. NIAID Staff Responsibilities Dr. Fran Rubin will serve as NIAID's Scientific Coordinator and will have substantial scientific/programmatic involvement during the conduct of awarded activities through technical assistance, advice and coordination above and beyond normal program stewardship for this award, as described below. Other appropriate NIAID program staff assistance will be coordinated by the Scientific Coordinator. During performance of the award, the NIAID Scientific Coordinator may provide appropriate assistance, advice, and guidance by: participating in the design of the activities; advising in the selection of sources or resources (e.g., determining where a particular reagent can be found); coordinating or participating in the collection and/or analysis of data; advising in management and technical performance; or participating in the preparation of publications. The Scientific Coordinator will serve as a liaison/facilitator between the awardee, pharmaceutical and biotech industries, and other government agencies (e.g., FDA, USDA, CDC), and will serve as a resource of scientific and policy information related to the goals of the awardee's research. However, the role of NIAID will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus and the NIAID program staff will be given the opportunity to offer input into this process. The manner of reaching this consensus and the final decision-making authority will rest with the Principal Investigator. An NIAID Program Official will be responsible for the normal program stewardship of this award. For clinical studies, a mandatory milestone is the approval of the final clinical protocol by NIAID. The Program Official may also serve as the Scientific Coordinator. 4. Collaborative Responsibilities The specific timelines, interim objectives and funding levels agreed to by the Principal Investigator and the NIAID shall be included in the terms and conditions of award. Given the nature of product development, it is recognized that timelines and interim objectives may require revision and renegotiation during the course of the project period. The Principal Investigator and NIAID must agree to all such revisions. Release of each funding increment by NIAID will be based on a NIAID review of progress towards achieving the previously agreed upon interim objective. Where scientifically appropriate NIAID may ask recipients to collaborate or cooperate with other NIAID funded projects and/or US government agencies, for example CDC, FDA and USDA. 5. Arbitration Any disagreement that may arise on scientific or programmatic matters (within the scope of the award), between award recipients and the NIAID may be brought to arbitration. An arbitration panel will be composed of three members - one selected by the Steering Committee (with the NIAID representation not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by NIAID, and the third member selected by the two prior selected members. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16. 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 questions about scientific/research issues related to GAS and GBS vaccines and diagnostics to: Dr. Fran Rubin Division of Microbiology & Infectious Diseases National Institute of Allergy and Infectious Diseases Room Number 5055, MSC-6603 6610 Rockledge Drive Bethesda, MD 20892-6603 Telephone: (301) 496-5305 FAX: (301) 496-8030 Email: o Direct questions about scientific/research issues related to: Helicobacter pylori vaccines to: Dr. Katherine Taylor Division of Microbiology & Infectious Diseases National Institute of Allergy and Infectious Diseases Room Number 4011, MSC-6603 6610 Rockledge Drive Bethesda, MD 20892-6603 Telephone: (301) 451-5068 FAX: (301) 402-1456 Email: o Direct questions about peer review issues to: Madelon Halula, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 2150, MSC-7614 6700-B Rockledge Drive Bethesda, MD 20892-7614 Telephone: (301) 496-2550 FAX: (301) 402-2638 Email: o Direct questions about financial or grants management matters to: Ms. Donna M. Scarsciotti Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 3223, MSC-7614 6700-B Rockledge Drive Bethesda, MD 20892-7614 (20817 for courier) Telephone: (301) 451-9892 FAX: (301) 493-0597 Email: 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: Madelon Halula, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 2150, MSC-7614 6700-B Rockledge Drive Bethesda, MD 20892-7614 Telephone: (301) 496-2550 FAX: (301) 402-263 Email: 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 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: SUPPLEMENTAL INSTRUCTIONS: See "Research Goals and Objectives" and "SPECIAL REQUIREMENTS" sections above for additional application instructions. SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package by commercial carrier 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: Madelon Halula, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 2150, MSC-7614 6700-B Rockledge Drive Bethesda, MD 20892-7614 (20817 for express mail or courier service) Telephone: (301) 496-2550 FAX: (301) 402-263 Email: Applications must be received on or before September 24, 2003. Applications that are not received on the receipt date 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). 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. 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. 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. PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the (IC). Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications submitted by an academic institution alone without an industrial partner will be considered non-responsive and will be returned without review. 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 (IC) 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 Advisory Allergy and Infectious Diseases 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 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. INTERIM OBJECTIVES (DEVELOMENTAL MILESTONES): Are the interim objectives (developmental milestones) appropriate and feasible? STAFF: Are the scientific and technical staff (other than the principal investigator) appropriate and qualified? ORGANIZATIONAL AND MANAGEMENT APPROACH: Are the project management and administrative staff appropriate and qualified? ADDITIONAL CONSIDERATIONS DATA SHARING: The adequacy of the proposed plan to share data. 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: August 23, 2003 Application Receipt Date: September 24, 2003 Peer Review Date: February 2, 2004 Council Review: May 2004 Earliest Anticipated Start Date: June 1, 2004 AWARD CRITERIA Award criteria that will be used to make award decisions include: o Scientific merit of the proposed project 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. 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 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 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. This policy announcement is in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at 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 PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule," on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR). Those who must comply with the Privacy Rule (classified under the Rule as "covered entities") must do so by April 14, 2003 (with the exception of small health plans which have an extra year to comply). Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website ( 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 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 Catalog of Federal Domestic Assistance at 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. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. 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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