RFP No. NIH-NIAID-DMID-96-07 Title: "MUCOSAL PATHOGENS RESEARCH UNITS" Issued by: Rosemary McCabe Hamill Contracting Officer NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20982-7610 DATE ISSUED: DECEMBER 22, 1994 PROPOSAL DATE DUE: APRIL 14, 1995, 4:00 P.M. (EST) Ladies and Gentlemen: The National Institute of Allergy and Infectious Diseases (NIAID) invites interested parties to submit competitive offers for evaluation leading to multiple contract awards for "Mucosal Pathogens Research Units" (MPRUs). The Government contemplates the award of two (2), seven (7) year, cost-reimbursement, level of effort type contracts as a result of this RFP. Of these two expected awards, one (1) award is anticipated for an MPRU focusing on enteric pathogens, and one (1) award is anticipated for an MPRU focusing on respiratory pathogens. Offerors may submit proposals for either the enteric portion or the respiratory portion. If an offeror elects to submit proposals for both portions, the proposal for each portion shall be separate and complete. Listed below are the four attachments of this Electronic RFP package. These documents represent all the necessary information required for the submission of a proposal for this acquisition. Following proposal submission and review, additional information (e.g., Representations and Certifications) will be requested by the Contracting Officer from all offerors intended to comprise the competitive range. Although these documents contain sufficient information for you or your organization to submit a proposal, if you or your organization intend to submit a proposal in response to this RFP, IT IS ESSENTIAL THAT YOU IMMEDIATELY NOTIFY SARA SOUTHARD OF THE NIAID CONTRACTING OFFICE AT THE FOLLOWING INTERNET ADDRESS: ss63e@nih.gov IF YOU DO NOT NOTIFY THE CONTRACTING OFFICE INDICATED IN THIS DOCUMENT YOU WILL NOT RECEIVE AMENDMENTS TO THE RFP WHICH COULD IMPACT YOUR PROPOSAL PREPARATION. The documents included with this electronic RFP package are as follows: 1. Introduction, Background and Work Statements (Enteric and Respiratory), dated November 23, 1994 (Attachment A). 2. Reporting Requirements, dated November 23, 1994 (Attachment B). 3. Evaluation Factors for Award, dated November 23, 1994 (Attachment C). 4. Proposal Instructions and Information, dated December 22, 1994 (Attachment D) In addition to the information listed above, a listing of the applicable Government clauses/provisions, sample contract format, and terms and conditions which will be incorporated into the eventual contract document may be obtained either through accessing the NIH Gopher system or by sending a request to Sara Southard, Contract Specialist, using the internet electronic mail address listed above. The original and twenty (20) copies of your technical proposal and the original and five (5) copies of your business proposal must be received by the Contracting Officer no later than April 14, 1995, at 4:00 p.m. local time at the address listed in Attachment D, Item 7. You are reminded that the "Technical Proposal Cover Sheet" must be completed in full detail and used as the cover sheet for each copy of your technical proposal (A copy of this form is contained in this NIH Gopher under the directory entitled "Instructions for Proposal Submission".). New policies require submission of more detailed information than has been previously required. It is important that you list all professional personnel and organizations named in the proposal who have any role in the proposed work, including: staff of the primary organization (offeror), subcontractors, and collaborating organizations; and consultants. Organizational affiliation(s) must be indicated for every person named. You may use additional sheets, as needed, following the format shown in the Technical Proposal Cover Sheet. This information will be used to ensure that there will be no conflict of interest when selecting review committee members. Your attention is further directed to the "Proposal Intent" form contained in the Gopher sub-directory entitled "Forms Required for Proposal Submission". Please complete this form and return it to this office on or before March 29, 1995. Funds are not presently available for this requirement. The Government's obligation under a resulting contract is contingent upon availability of appropriated funds from which payment for contract purposes can be made. If you have any additional questions regarding this RFP, please contact Sara M. Southard through the internet using the electronic mail address listed above or phone 301/402-6289, fax 301/480-5253. Sincerely, \s\ Rosemary McCabe Hamill Chief, IADCS Contract Management Branch National Institute of Allergy and Infectious Diseases Attachments: A-D ***************************************************************** ***************************************************************** RFP-NIH-NIAID-DMID-96-07 ATTACHMENT A 11/23/94 MUCOSAL PATHOGEN RESEARCH UNITS WORK STATEMENT ______________ INTRODUCTION ------------ The objective of this acquisition is to support interactive research consortia focused on understanding the host/pathogen interaction at mucosal surfaces and developing prevention strategies that maximize protective mucosal immune responses in humans. To achieve this goal, the NIAID will support two (2) Mucosal Pathogen Research Units (MPRUs) which will conduct collaborative, interactive, multifaceted basic and clinical research. One of these Units will study enteric diseases, while the other will study respiratory diseases. Each Unit will consist of a basic research component composed of individuals with expertise in immunology and pathogenesis of microbial infections, and a clinical component composed of individuals with expertise in infectious disease and clinical research and evaluation. Both components will focus on understanding the pathogenesis and immune responsiveness in humans to either enteric or respiratory agents. In order to assemble the strongest proposal possible, the establishment of subcontracts among multiple institutions is both encouraged and expected. BACKGROUND ---------- Developing and testing new vaccine strategies is an essential component of efforts supported by the Division of Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious Diseases (NIAID). Since many pathogens either colonize mucosal surfaces or gain entrance to the host through such sites, the DMID has an interest in research focused on inducing significant and long lasting protective mucosal immune responses. To date, these efforts have included research on intranasally administered influenza vaccines as well as on orally administered vaccines against enteric diseases, such as cholera, typhoid fever, and rotavirus diarrhea. The DMID's interest in this regard receives additional impetus from the Children's Vaccine Initiative which seeks to develop new vaccines that will decrease the number of contacts between the health care system and the child in order to achieve adequate immunization against a variety of human enteric and respiratory diseases. Because enteric and respiratory diseases share the mucosal surface as the tissue for colonization or entry, it is likely that they will also share characteristics of pathogenesis and immune response, and that there will be similarities in the areas of vaccine design and delivery that can be exploited. Therefore, creating interactive research groups that will share data and approaches focused on the goals of defining the essential aspects of pathogenesis and the immune response as well as the development and testing of preventive strategies is expected to be synergistic. The enteric group should bring expertise in studying organisms such as Vibrio cholera, rotavirus, Salmonella sp., Shigella sp., Helicobacter sp., as well as pathogenic E. coli and Campylobacter. The group should also be well positioned to respond quickly to emerging infectious agents. As a group, the enteric pathogens produce an extraordinary number of infections and deaths worldwide. Rotavirus is the leading cause of infantile diarrhea both in the U.S. and worldwide. In the U.S. alone, it results in about 100,000 hospitalizations and costs approach $1 billion per year. Strains of enterotoxigenic E. coli are the most frequent cause of bacterial dehydrating diarrhea and were estimated by the Institute of Medicine (1986) to cause 400 million cases and 700,000 deaths per year worldwide in children under the age of five. For U.S. citizens, it is the leading cause of travelers diarrhea. Typhoid fever produced by Salmonella typhi, remains a serious public health problem throughout the world, with an estimated total incidence of 33 million cases and 500,000 deaths annually. Chronic gastritis, as well as duodenal and gastric ulcers, are now recognized to be caused by infection with Helicobacter pylori. In the U.S. it is estimated that 30% of our population is infected, that 10% will develop ulcers, that there will be 300,000 new cases and 3 million recurrences and 300 deaths per year. The financial burden imposed on our health care system by this infection is enormous. The respiratory group should provide expertise in a diversity of pathogens, such as influenza, respiratory syncytial virus, Streptococcus pneumoniae, Bordetella pertussis, and non-typable Haemophilus influenzae. Respiratory infections are the major cause of acute illness in the U.S. and of infectious disease morbidity and mortality worldwide. The economic burden associated with these diseases is staggering. For example, the common cold alone accounts for approximately 20% of all acute illness in the U.S. and direct costs estimated to be $500 million per year. Otitis media also represents a significant health burden in terms of costs, morbidity, and long term effects on speech and language development in children. The recent World Development Report ranked respiratory infections as the number one disease of female children under five in the developing world. It is estimated that pneumonia causes about 4 million deaths per year in children worldwide. In addition, infections with respiratory pathogens such as H. influenzae type b (Hib), group B streptococcus (GBS), and Neisseria meningitidis can lead to diseases not usually considered to be respiratory in nature, such as meningitis. The use of interactive research units focused on a specific need has proven to be a successful model that serves as both a responsive infrastructure capable of rapidly implementing new approaches and a mechanism to provide cross-fertilization of ideas. This RFP was designed around this model. The requirement to include studies of mucosal immunity by both the enteric and respiratory disease units, will provide further opportunities for collaboration and are expected to be synergistic. The work proposed under this RFP represents a restructuring of the work currently being performed under two existing contracts, N01-AI-15128 (Mucosal Immunology Research Group, University of Alabama, Birmingham, AL) and N01-AI-15103 (Acute Viral Respiratory Disease Unit, Baylor College of Medicine, Houston, TX) as well as aspects of the work previously supported by N01- AI-15096 (An Enteric Diseases Vaccine Evaluation and Treatment Unit, University of Maryland, Baltimore, MD). WORK STATEMENT -------------- {GENERAL NOTES TO OFFERORS: 1.These contracts are intended to form the basis of a coordinated, interactive, multi-disciplinary investigation on a subset of infectious agents, whose major portal of entry and primary defense involves the mucosal surface. It is the intent of this "Request for Proposals" (RFP) to award two contracts, one of which will focus on enteric pathogens and the other of which will focus on respiratory pathogens. The Government recognizes that one institution may not be able to perform all aspects of the Work Statement and welcomes offerors who propose the use of subcontractor(s). OFFERORS MAY SUBMIT PROPOSALS FOR EITHER THE ENTERIC PORTION OR THE RESPIRATORY PORTION. IF AN OFFEROR ELECTS TO SUBMIT PROPOSALS FOR BOTH PORTIONS, THE PROPOSAL FOR EACH PORTION SHALL BE SEPARATE AND COMPLETE. All Offerors should note that both the enteric and respiratory Work Statements contain three (3) parts and are presented as distinct packages. Parts I. and II., while similar, contain components specific to either enteric OR respiratory pathogens; therefore, Offerors should ensure that they are responding to the requirements of the correct section. Part III. is identical in both the enteric and respiratory sections but has been included in both for clarity. 2. To further describe the Government's requirements, approximate levels of effort for each of the three (3) parts are provided for both the enteric and the respiratory Work Statements. The Offeror is free to propose alternative levels of effort. Additional information regarding the Government's overall level of effort estimate for this requirement please see Attachment D, Item 4., of this RFP document. 3. For contracts dealing with clinical research, it is the policy of the NIH to include woman and minorities in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study. Special emphasis should be placed on the inclusion of minorities and women in studies of diseases, disorders and conditions that disproportionately affect them. This policy applies to males and females of all ages. Racial/ethnic minorities include Native American, Asian or Pacific Islander, Black and Hispanic groups. Clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventative strategies), diagnosis and treatment of diseases, disorders and conditions, including but not limited to clinical trials. The composition of the proposed study population must be described in terms of gender and racial/ethnic group, together with the rationale for its choice. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. Offerors are urged to assess carefully the feasibility of including the broadest possible representation of minority groups.} ENTERIC DISEASES ---------------- {NOTE TO OFFEROR: 1. Diseases or pathogens of interest include, but are not limited to, rotavirus, pathogenic Escherichia coli, Salmonella, Shigella, Vibrio cholera, Helicobacter pylori, and Campylobacter. The Institute is also interested in the development of new or improved attenuated vaccine vectors such as Salmonella, Bacille Calmette-Guerin (BCG), poliovirus, adenovirus, etc. capable of delivering relevant foreign antigens to the gut mucosa. Also of interest, is the use of adjuvants and delivery systems designed to stimulate mucosal immunity. The use of "naked DNA" vaccines designed to induce a protective gut immunity to the above organisms is also of interest.} Independently and not as an agent of the Government, the Contractor shall exert its best efforts to furnish services, qualified professional and technical personnel, materials, populations, equipment, and facilities not otherwise provided by the Government under the terms of this contract as needed to perform the work set forth below. Specifically the contractor shall: I. Establish and/or maintain a focused and coordinated basic research group with expertise in microbial pathogenesis, mucosal immunology and clinical studies. Such group shall develop and execute strategies that include but are not limited to: A. Basic studies of pathogenesis, host/pathogen interaction, and immune correlates of protection; B. Optimization of immune response using vaccines, adjuvants or delivery methods, with particular emphasis on the mucosal immune response; C. Development of new assays to ensure adequate assessment of immune responses in humans, particularly the mucosal immune response; D. Use of animal models to demonstrate proof of concept relating to pathogenesis, new vaccine strategies, adjuvants, delivery vehicles, assays, etc. {NOTES TO OFFEROR: 2. The Government estimates that the contractor will expend approximately 45% of its overall effort to complete Part I. 3. Offerors should demonstrate the capability to construct and evaluate any proposed antigen delivery vectors or systems and how he/she would evaluate these preparations before immunization of humans. For evaluation purposes the Offeror should present up to 2 approaches to each of the requirements identified above (Part I.A.; Part I.B., Part I.C, Part I.D.). 4. Animal studies should ONLY be used in experiments designed to demonstrate feasibility and safety of new methodologies. Offeror should document previous experience with such animal models and adequately justify their use for this purpose. 5. Although the focus of this request is targeted to immune responses at the mucosal surface, it is recognized that the relationship between the mucosal, systemic and cellular immune response is complex and inter-related and, as such, systemic and cellular immune responses should also be considered, where appropriate, as a necessary part of the evaluation.} II. Perform clinical studies to validate and apply information obtained in Part I. Specifically the contractor shall: A. Conduct Phase I/II clinical studies of potential new vaccine candidates or vaccination strategies using technology or information developed under Part 1. Such an approach shall include, but not be limited to the ability to: i. Optimize the delivery and release of protective immunogens to the mucosal surface. ii. Accurately and effectively measure the immune response induced by vaccine candidates targeted for delivery to mucosal surfaces. iii. Enhance the protective immune response to specific immunogens delivered to mucosal surfaces by the use of adjuvants, delivery vehicles, or vaccination schedules. {NOTES TO OFFEROR: 6. The Government estimates that the contractor will expend approximately 45% of its overall effort to complete Part II. 7. FOR EVALUATION PURPOSES ONLY, provide two sample protocols and consent forms which demonstrate the integration of Part 1 information into human subject evaluation. Performance of actual protocols will be done in consultation with and after approval by the Project Officer. Offerors should describe previous experience with the conduct of human Phase I/II trials. 8. Offerors should assume that volunteers will need to be studied as inpatients, and a detailed outline of the design of such a study including a description of patient isolation facilities, the time required for completion, types of specimens to be collected, assays to be conducted to determine immunogenicity, assessment of safety and efficacy, and the follow-up of patients should be included. 9. It is estimated that a minimum of 100 subjects/year will be required for initial studies aimed at examining comparability with animal data. For these preliminary studies, assume 10 subjects would be needed for each of 10 vaccine/delivery system evaluation. 10. Following preliminary evaluation, expanded capability to conduct placebo controlled studies will require at least 100 subjects/year, minimum. Assume that 20 patients will be enrolled as vaccinees or controls to test safety and immunogenicity of 5 vaccines or delivery systems per year. It is likely that some of these trials will also need to be performed as inpatient studies. 11. Depending on the vaccine candidate, evaluation of safety and immune response may also include the need to measure reactogenicity, infectivity, degree of virulence or attenuation, transmissibility, antibiotic resistance, optimal dose/schedule, genetic stability, interference with other vaccines, effect of pre-existing or maternal antibodies, and booster response.} B. Conduct challenge studies in human volunteers immunized with those vaccine candidates or delivery systems that, in the preliminary studies carried out above, are sufficiently immunogenic and non-reactogenic. Both vaccinees and controls shall be challenged with wild- type pathogens to assess protection. C. Conduct clinical studies in human volunteers providing expertise, facilities, and staff necessary to: i. Recruit appropriate number and type of volunteers as required for all approved studies; ii. Prepare protocols, consent forms, and data collection forms for clinical trials proposed. Submit for Project Officer's and local Institutional Review Board approvals. Amend as necessary after comments by approving authorities; iii. Collect and store sera and other clinical specimens from study participants; iv. Determine the safety, immunogenicity, and efficacy of vaccine candidates or prevention strategies; v. Perform assays on sera and other clinical specimens to evaluate the immune response to vaccine candidates, carrier molecules, live vaccine vectors, etc. Special attention shall be given to protective mucosal immune responses. {NOTE TO OFFEROR: 12. The NIAID will assume responsibility for filing all INDs. All protocol submissions are co-ordinated through the Project Officer. FDA and NIAID guidelines for the conduct of clinical trials will be implemented. Final determination of clinical trial studies to be performed shall be made by the Project Officer.} III. Develop and implement an organizational and administrative plan. A. Assume responsibility for: i. The detailed planning, conduct, and reporting of the proposed clinical studies and associated basic research and pre-clinical studies. This shall include developing the specifics of experimental design, collection and storage of clinical samples, coding/randomization of patients, vaccines, adjuvants, or other samples, and coordinating all of the subcontractors' activities. ii. The data management, including transmission, storage, confidentiality, retrieval, validation, statistical analysis, and publication. B. Establish and manage laboratory facility(ies) to support the various studies. C. Supervise, coordinate, and perform the tasks outlined in the Work Statement. D. Conduct at least two meetings per year to discuss results and future plans with all subcontractors within the study consortia. E. Attend and participate in one 3 day meeting per year in Bethesda to discuss results, future plans, protocol development, and regulatory issues with members of both respiratory and enteric study consortia. The purpose of these meetings will be to share data and allow the transmittal of encouraging approaches to the members of the other Study Unit. F. Report to the DMID Clinical and Regulatory Affairs Branch and to the Project Officer all adverse reactions to comply with FDA regulations. {NOTES TO OFFEROR: 13. The Government estimates that the contractor will expend approximately 10% of its overall effort to complete Part III. 14. Costs for travel to these meetings should be included in the business proposal. 15. As a multi-center (hence sub-contractor) approach is anticipated for response to this RFP, the organizational and administrative plan should clearly identify the role of subcontractors and provide for a clear plan of communication and project interactions. Letters of willingness to participate/collaborate must accompany the proposal. Potential subcontractors may submit such letters to more than one offeror. Although other government agencies are excluded from receiving funds either directly or indirectly from this contract activity they are not excluded from collaborating in any project at their own expense. Subcontractors may be added or deleted during the contract award period with the prior approval of the Project Officer and Contracting Officer. A two page Biosketch of all proposed professional personnel shall be included in the proposal.} RESPIRATORY DISEASES -------------------- {NOTE TO OFFEROR: 1. Diseases or pathogens of interest include, but are not limited to, pneumonia, influenza, respiratory syncytial virus, Streptococcus pneumonia, and Bordetella pertussis.} Independently and not as an agent of the Government, the Contractor shall exert its best efforts to furnish services, qualified professional and technical personnel, material, populations, equipment, and facilities not otherwise provided by the Government under the terms of this contract as needed to perform the work set forth below. Specifically the contractor shall: I. Establish and/or maintain a focused and coordinated basic research group that will bring expertise in microbial pathogenesis, immunology and clinical studies. Such group shall develop and execute strategies that include but are not limited to: A. Basic and mechanistic studies of pathogenesis, host/pathogen interaction, and immune correlates of protection including, but not limited to: i. bacterial carriage ii. progression to lower respiratory tract disease iii. mixed viral/bacterial infection B. Optimization of immune response using vaccines, adjuvants or delivery methods, with particular emphasis on the mucosal immune response; C. Development of new assays to ensure adequate assessment of immune responses in humans, Particularly the mucosal immune response; D. Use of animal models to demonstrate proof of concept relating to pathogenesis, new vaccine strategies, adjuvants, delivery vehicles, assays, diagnostics, etc; E. Development of approaches for the more effective diagnosis of pneumonia. {NOTES TO OFFEROR: 2. The Government estimates that the contractor will expend approximately 55% of its overall effort to complete Part I. 3. Offerors should identify the key issues and opportunity associated with each of the requirements under Part 1. For evaluation purposes the Offeror shall present up to 2 approaches to each of the requirements identified above (Part I.A.i, I.A.ii, I.A.iii, Part I.B., Part I.C, Part I.D., and Part I.E.). 4. Offerors should document previous experience with animal models and adequately justify their use for this purpose. 5. These strategies should be directly applicable to, and testable in, humans. Animal studies should be proposed only to demonstrate feasibility and safety of new methodologies. 6. Although the focus of this request is targeted to immune responses at the mucosal surface, it is recognized that the relationship between the mucosal, systemic and cellular immune response is complex and inter-related and, as such, systemic and cellular immune responses should also be considered, where appropriate, as a necessary part of the evaluation.} II. Perform clinical studies to validate and apply information obtained in Part I. Specifically the contractor shall: A. Conduct Phase I/II clinical studies of potential new vaccine candidates or prevention strategies which interfere with: i. bacterial carriage ii. progression to lower respiratory tract disease iii. mixed viral/bacterial infections B. Perform focused surveillance and epidemiology studies to evaluate new diagnostic approaches for pneumonia. C. Conduct clinical studies in human volunteers providing expertise, facilities, and staff necessary to: i. Recruit appropriate number and type of volunteers as required for all approved studies; ii. Prepare protocols, consent forms, and data collection forms for clinical trials proposed. Submit for Project Officer's and local Institutional Review Board approvals. Amend as necessary after comments by approving authorities; iii. Collect and store sera and other clinical specimens from study participants; iv. Determine the safety, immunogenicity, and efficacy of vaccine candidates or prevention strategies; v. Perform assays on sera and other clinical specimens to evaluate the immune responses. Special attention shall be given to protective mucosal immunity. {NOTES TO OFFEROR: 7. The Government estimates that the contractor will expend approximately 35% of its overall effort to complete Part II. 8. FOR EVALUATION PURPOSES ONLY, provide two sample protocols and consent forms which demonstrate the integration of Part 1 information into human subject evaluation. One sample protocol should demonstrate understanding of issues, opportunities, and capability focused on the requirement for Part II.A and one sample protocol should focus on strategies needed for Part II.B. Performance of actual protocols will be done in consultation with and after approval by the Project Officer. 9. It is anticipated that a minimum of 100 subjects/year will be required. 10. The NIAID will assume responsibility for filing all INDs. All protocol submissions are co-ordinated through the Project Officer. FDA and NIAID guidelines for the conduct of clinical trials will be implemented. Final determination of clinical trial studies to be performed shall be made by the Project Officer.} III. Develop and implement an organizational and administrative plan. A. Assume responsibility for: i. The detailed planning, conduct, and reporting of the proposed clinical studies and associated basic research and pre-clinical studies. This shall include developing the specifics of experimental design, collection and storage of clinical samples, coding/randomization of patients, vaccines, adjuvants, or other samples, and coordinating all of the subcontractors' activities. ii. The data management, including transmission, storage, confidentiality, retrieval, validation, statistical analysis, and publication. B. Establish and manage laboratory facility(ies) to support the various studies. C. Supervise, coordinate, and perform the tasks outlined in the Work Statement. D. Conduct at least two meetings per year to discuss results and future plans with all subcontractors of the study consortia. E. Attend and participate in one 3 day meeting per year in Bethesda to discuss results, future plans, protocol development, and regulatory issues, with members of both respiratory and enteric study consortia. The purpose of these meetings will be to share data and allow the transmittal of encouraging approaches to the members of the other Study Unit. F. Report to the DMID Clinical and Regulatory Affairs Branch and to the Project Officer all adverse reactions to comply with FDA regulations. {NOTES TO OFFEROR: 11. The Government estimates that the contractor will expend approximately 10% of its overall effort to complete Part III. 12. Costs for travel to these meetings should be included in the business proposal. 13. As a multi-center (hence sub-contractor) approach is anticipated for response to this RFP, the organizational and administrative plan should clearly identify the role of subcontractors and provide for a clear plan of communication and project interactions. Letters of willingness to participate/collaborate must accompany the proposal. Potential subcontractors may submit such letters to more than one offeror. Although other government agencies are excluded from receiving funds either directly or indirectly from this contract activity they are not excluded from collaborating in any project at their own expense. Subcontractors may be added or deleted during the contract award period with the prior approval of the Project Officer and Contracting Officer. A two page Biosketch of all proposed professional personnel shall be included in the proposal.} ***************************************************************** ***************************************************************** RFP-NIH-NIAID-DMID-96-07 ATTACHMENT B 11/23/94 REPORTING REQUIREMENTS ______________________ The Contractor shall submit to the Contracting Officer and to the Project Officer technical progress reports covering the work accomplished during each reporting period. These reports are subject to the technical inspection and requests for clarification by the Project Officer. These shall be brief and factual and prepared in accordance with the following format: A. Technical Reports In addition to those reports required by SECTION I and other terms of this contract, the Contractor shall prepare and submit the following reports in the manner stated below: (1) Semi-Annual Technical Progress Reports - by the fifteenth working day of the month following the end of each six month period, the Contractor shall submit five (5) copies of a semi-annual Technical Progress Report, comprising four (4) copies to the Project Officer and one (1) copy to the Contracting Officer. Such reports shall include the following specific information: a. A cover page that lists the contract number and title, the period of performance being reported, the contractor's names and address, the author(s), and the date of submission; b. SECTION I - An introduction covering the purpose and scope of the contract effort; c. SECTION II - A description of overall progress plus a separate description for each task or other logical segment of work on which effort was expended during the report period. The description shall include pertinent data and/or graphs in sufficient detail to explain any significant results achieved and preliminary conclusions resulting from analysis and scientific evaluation of data accumulated to date under the project; d. SECTION III - Substantive performance; a description of current technical or substantive performance and any problems encountered and/or which may exist along with proposed corrective action. Each clinical study should be reported separately according to the number assigned by the Project Officer. An explanation of any difference between planned progress and actual progress, why the differences have occurred, and if behind planned progress what corrective steps are planned. e. An anticipated work plan for the following six months. f. Preprints, reprints, and abstracts shall be submitted along with the report. Semi-annual Technical Progress Reports are not due for periods in which an annual or final report is due. (2) Annual Reports - On the anniversary date of the contract, the Contractor shall submit five (5) copies of an Annual Technical Progress Report, as above, comprising four (4) copies to the Project Officer and one (1) copy to the Contracting Officer. Such reports shall detail, document, and summarize the results of the entire contract work for the period covered. These reports shall be in sufficient detail to explain comprehensively the results achieved. Also to be included in the report is a summary of work proposed for the next reporting period. Specific requirements, if any, are set forth in the Work Statement. A one page summary of each ongoing and completed protocol shall be submitted at this time. An annual report will not be required for the period when the final report is due. Preprints and reprints of papers and abstracts not submitted in the semi-annual report shall be submitted. (3) Final Report - By the expiration date of the contract, the Contractor shall submit five (5) copies of a comprehensive Final Report, as above, comprising four (4) copies to the Project Officer and one (1) copy to the Contracting Officer. This final report shall detail, document and summarize the results of the entire contract work for the period covered. This report shall be in sufficient detail to explain comprehensively the results achieved. Additional specific requirements are set forth in the Work Statement. Preprints and reprints not included previously submitted shall be submitted. (4) Summary of Salient Results - With the annual/final reports the Contractor shall submit a summary (not to exceed 200 words) of salient results achieved during the performance of the contract. (5) Other Reports - The Contractor shall submit five (5) copies of: a) a one page summary of each ongoing and completed protocol one year and thirty days after an individual IND goes into effect and b) yearly IRB approvals and supporting documents. B. If the Contractor becomes unable to deliver the reports specified hereunder within the period of performance because of unforeseen difficulties, notwithstanding the exercise of good faith and diligent efforts in performance of the work, the Contractor shall give the Contracting Officer immediate written notice of anticipated delays with reasons, therefore. C. Technical Report Distribution Copies of the technical reports shall be submitted as follows: Type of # of Report Copies Addressee Due Dates ______ ______ _________ _________ Semi- 4 Project Officer Semi-Annually Annual DMID, NIAID, NIH (Dates to be Progress Solar Building, Room ____ specified 6003 Executive Blvd. MSC 7630 in contract) Bethesda, MD 20892-7630 Semi- 1 Contracting Officer Same as above Annual CMB, NIAID, NIH Progress Solar Building, Room 3C07 6003 Executive Blvd. MSC 7610 Bethesda, MD 20892-7610 Annual 4 Same as P.O. above Annually (Dates to be specified in contract) Annual 1 Same as C.O. above Same as above Final 4 Same as P.O. above Expiration date Final 1 Same as C.O. above Same as above ***************************************************************** ***************************************************************** RFP-NIH-NIAID-DMID-96-07 ATTACHMENT C 11/23/94 EVALUATION FACTORS FOR AWARD ____________________________ A. GENERAL The technical proposal will receive paramount consideration in the selection of the Contractor(s) for this acquisition. The evaluation will be based on the demonstrated capabilities of the prospective contractors in relation to the needs of the project as set forth in the RFP. The merit of each proposal will be evaluated carefully, based on responsiveness to the RFP and thoroughness and feasibility of the technical approach taken. Offerors must submit information sufficient to evaluate their proposals based on the detailed criteria listed below. Failure to provide the information required to evaluate the proposal may result in rejection of that proposal without further consideration. B. COMPARATIVE IMPORTANCE OF PROPOSALS You are advised that paramount consideration shall be given to the evaluation of the technical proposals, but not to the exclusion of cost considerations. In the event that the technical evaluation reveals that two or more offerors are approximately equal in technical ability, then the estimated cost of performance may become the determining factor. While high competence is sought, capabilities that exceed those needed for successful performance of the contract work/statement are not requested. Proposals submitted in response to the enteric diseases and respiratory diseases Work Statements will be ranked separately. The NIAID intends to make one award to an offeror responding to the enteric diseases Work Statement and one award to an offeror responding to the respiratory diseases Work Statement. In any event, the Government reserves the right to make an award to the best advantage of the Government, cost and other factors considered. C. MANDATORY QUALIFICATIONS FOR FACILITIES Prior to award the offeror must document the adequacy and suitability of facilities for performing all of the requirements of the Work Statement. D. TECHNICAL EVALUATION CRITERIA Proposals submitted in response to this RFP will be evaluated based on the following factors which are listed and weighted in order of their relative importance. Proposals will be judged solely on the written material provided by the offeror. Criterion Element Weight 1. TECHNICAL APPROACH ..................................... 80 Documented technical excellence and feasibility of the proposed plans for the basic and pre-clinical, and clinical research proposed, demonstration of innovative and novel thinking in proposed experimental design, integration of basic and clinical approaches, capability in performance of assays and laboratory procedures, adequacy, suitability and availability of necessary populations, including women and minorities as documented in the proposal. a) Basic research: This includes the proposed methods and approaches for studying microbial pathogenesis, host/pathogen interactions at mucosal surfaces, creating and evaluating new vaccines or vaccination strategies designed to deliver immunogens to maximally stimulate mucosal immunity, measuring the immune response (especially the mucosal immune response), and the proposed animal models to evaluate new vaccine or diagnostic approaches................................... .......................... 30 b) Clinical studies: This includes the application of basic and clinical methods and proposed approaches for evaluating bacterial or viral vaccines or prevention strategies, suitability and originality of the sample clinical approaches and protocols, appropriateness of consent forms, plans for storage and analysis of data, methods proposed for performing assays on sera and other body fluids, and plans for other relevant laboratory procedures.............................................. .......................... 30 c) Population: Offeror should demonstrate access to, and the ability to recruit, retain, and follow appropriate study volunteers. Strategies for follow-up of vaccinees should be presented. The recruitment plan should describe specific experience, plans and abilities to include minorities and women in clinical studies..... .......................... 10 d) Administration: Proposed plans for managing the clinical and basic research activities to ensure a cooperative, integrated focused scientific effort...... .......................... 10 2. PERSONNEL.............................................. 20 Documented adequacy and relevance of expertise, experience, education, and availability of personnel for performing all the requirements of the Work Statement. The PI should have an M.D. and/or Ph.D. degree and should provide documented evidence of experience in microbial pathogenesis, immunology, and/or clinical studies involving appropriate populations. Investigators heading sub-contract groups should bring expertise in complementary areas as needed. The team of professional personnel (including the nursing personnel) should have composite expertise in infectious diseases, immunology, clinical trials, and immunodiagnostics. The technical personnel should have documented training and experience to perform the assay and laboratory procedures. The administrative staff should possess the requisite experience to perform their duties related to program administration. TOTAL POSSIBLE POINTS.................................... 100 E. EVALUATION OF MINORITY GROUP AND GENDER REPRESENTATION (NIH 3185) (JUL 1994) This research project involves human subjects. NIH Policy requires that woman and members of minority groups and their subpopulations must be included in the study population of research involving human subjects, unless a clear and compelling rationale and justification is provided with respect to the health of the subjects or the purpose of the research. Where inclusion of women and minority populations is not feasible, a detailed rationale and justification for exclusion of one or both groups from the study population must be submitted with the technical proposal. The NIH will review the exclusion rationale to determine if it is appropriate with respect to the health of the subjects and/or the purpose of the research. If the rationale is not considered acceptable by the Government and you are included in the competitive range, you will be afforded the opportunity to further discuss and/or clarify your position during discussions or include women and minorities in your best and final (BAFO). If your exclusion position is still considered unacceptable by the Government after discussions, your proposal may not be considered further for award. ***************************************************************** ***************************************************************** RFP-NIH-NIAID-DMID-96-07 ATTACHMENT D 12/22/94 PROPOSAL INSTRUCTIONS AND INFORMATION _____________________________________ NOTICE TO OFFERORS: This attachment contains proposal instructions and information which is specifically related to this acquisition. The information provided below is only a portion of the instructions and notices required for the submission of a proposal. Additional, more general, information and forms regarding proposal preparation are contained in the NIH Gopher directory entitled "Instructions for Proposal Submission". 1. 52.216-1 TYPE OF CONTRACT (APR 1984) The Government contemplates award of a cost-reimbursement contract resulting from this solicitation. 2. SIC CODE AND SMALL BUSINESS SIZE STANDARD (NIH 3150) (JUN 1988) (a) The standard industrial classification (SIC) code for this acquisition is 8733. (b) (1) The small business size standard is $5.0 million dollars. (2) The small business size standard for a concern which submits an offer in its own name, other than on a construction or service contract, but which proposes to furnish a product which it did not itself manufacture, is 500 employees. (c) This requirement is NOT Set-Aside for Small Business. However, the Federal Acquisition Regulation (FAR) requires in every solicitation (except for foreign acquisitions) the inclusion of the Standard Industrial Classification (SIC) Code and corresponding size standard which best describes the nature of the requirement in the solicitation. 3. NUMBER AND TYPE OF AWARD(S) (NIH 2980) (APR 1984) It is anticipated that 2 awards will be made from this solicitation and that award will be made on or about December 1, 1995. It is anticipated that the awards from this solicitation will be multiple-year cost reimbursement type contracts with a term of 7 years, and that incremental funding will be used. (Also, see Incremental Funding Provision in this Section.) 4. ESTIMATE OF EFFORT (NIH 2985) (APR 1984) To assist you in the preparation of your proposal, the Government considers the total effort to perform this contract to be approximately 97.3 person years. This number is furnished for your information only and is not to be considered restrictive for proposal purposes. As further assistance, it is estimated that the above total labor effort is constituted as follows: Labor Percentages of Effort Category Yr1 Yr2 Yr3 Yr4 Yr5 Yr6 Yr7 -------- --- --- --- --- --- --- --- Prin. Invest. 40% 40% 40% 40% 40% 40% 40% Investigators 300% 300% 300% 300% 300% 300% 300% RNs, Techs 1000% 1000% 1000% 1000% 1000% 1000% 1000% Administrative 50% 50% 50% 50% 50% 50% 50% _____ _____ _____ _____ _____ _____ _____ Subtotal 1390% 1390% 1390% 1390% 1390% 1390% 1390% (Based on a 12-month work year) 5. COMPARATIVE IMPORTANCE OF PROPOSALS (NIH 3171) (JUL 1994) You are advised that paramount consideration shall be given to the evaluation of technical proposals. However, the Government reserves the right to make an award to the best advantage of the Government, cost and other factors considered. 6. 52.233-2 SERVICE OF PROTEST (NOV 1988) (a) Protests, as defined in Section 33.101 of the Federal Acquisition Regulation, that are filed directly with an agency, and copies of any protests that are filed with the General Accounting Office (GAO) or the General Services Administration Board of Contract Appeals (GSBCA), shall be served on the Contracting Officer (addressed as follows) by obtaining written and dated acknowledgement of receipt from: Mr. Lewis Pollack Hand-Carried Address: NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard Rockville, Maryland 20852 Mailing Address: NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 (b) The copy of any protest shall be received in the office designated above on the same day a protest is filed with the GSBCA or within one day of filing a protest with the GAO. 7. PACKAGING AND DELIVERY OF THE PROPOSAL (NIH 2995) (JUL 1994) Your proposal shall be organized as specified in this Section (III-V below). Shipment and marking shall be as indicated below: External Package Marking: _________________________ In addition to the address cited below, mark each package as follows: "RFP No. NIH-NIAID-DMID-96-07" "TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY" PLEASE READ THE FOLLOWING INFORMATION CAREFULLY: Number of Copies: ________________ Technical Proposal: Original and 20 copies. Business Proposal: Original and 5 copies. If hand delivered or delivery service ------------------------------------- NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard Rockville, Maryland 20852 If using U.S. Postal Service ---------------------------- NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20982-7610 * THE ORIGINALS MUST BE READILY ACCESSIBLE FOR DATE STAMPING PURPOSES NOTE: The U.S. Postal Service's "Express Mail" does not deliver to the Rockville, Maryland address. Any package sent to the Rockville address via this service will be held at a local post office for pick-up. THE GOVERNMENT IS NOT RESPONSIBLE FOR PICKING UP ANY MAIL AT A LOCAL POST OFFICE. If a proposal is not received at the place, date, and time specified herein, it will be considered a "late proposal". 8. EVALUATION OF PROPOSALS (NIH 3125) (JUL 1986) The Government will evaluate Proposals in accordance with the evaluation criteria set forth in Attachment C (Proposal Evaluation Criteria) of this RFP document. 9. PHSAR 352.280-1(a) NOTICE TO OFFERORS OF REQUIREMENTS OF 45 CFR PART 46, PROTECTION OF HUMAN SUBJECTS (SEP 1985) (a) Copies of the Department of Health and Human Services (Department) regulations for the protection of human subjects, 45 CFR Part 46, are available from the Office for Protection from Research Risks (OPRR), National Institutes of Health, Bethesda, Maryland 20892. The regulations provide a systematic means, based on established ethical principles, to safeguard the rights and welfare of individuals who participate as subjects in research activities supported or conducted by the Department. (b) The regulations define a human subject as a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention of interaction with the individual, or (2) identifiable private information. The regulations extend to the use of human organ, tissue, and body fluids from individually identifiable human subjects as well as to graphic, written, or recorded information derived from individually identifiable human subjects. The use of autopsy materials is governed by applicable State and local law and is not directly regulated by 45 CFR Part 46. (c) Activities in which the only involvement of human subjects will be in one or more of the categories set forth in 45 CFR 46.101(b)(1-6) are exempt from coverage. (d) Inappropriate designations of the non-involvement of human subjects or of exempt categories of research in a project may result in delays in the review of a proposal. The Public Health Service will make a final determination of whether the proposed activities are covered by the regulations or are in an exempt category, based on the information provided in the proposal. In doubtful cases, prior consultation with OPRR, (telephone: 301-496-7163), is recommended. (e) In accordance with 45 CFR Part 46, prospective Contractors being considered for award shall be required to file with OPRR an acceptable Assurance of Compliance with the regulations, specifying review procedures and assigning responsibilities for the protection of human subjects. The initial and continuing review of a research project by an institutional review board shall assure that the rights and welfare of the human subjects involved are adequately protected, that the risks to the subjects are reasonable in relation to the potential benefits, if any, to the subjects and the importance of the knowledge to be gained, and that informed consent will be obtained by methods that are adequate and appropriate. Prospective Contractors proposing research that involves human subjects shall be contacted by OPRR and given detailed instructions for establishing an institutional review board and filing and Assurance of Compliance. (f) It is recommended that OPRR be consulted for advice or guidance concerning either regulatory requirements or ethical issues pertaining to research involving human subjects. 10. PHSAR 352.280-2(a) NOTICE TO OFFERORS OF REQUIREMENT FOR ADEQUATE ASSURANCE OF PROTECTION OF VERTEBRATE ANIMAL SUBJECTS (SEP 1985) The PHS Policy on Humane Care and Use of Laboratory Animals by Awardee Institutions establishes a number of requirements for research activities involving animals. Before a PHS award may be made to an applicant organization, the organization shall file, with the Office for Protection from Research Risks (OPRR), National Institutes of Health (NIH), PHS, a written Animal Welfare Assurance which commits the organization to comply with the provisions of the PHS Policy on Humane Care and use of Laboratory Animals by Awardee Institutions, the Animal Welfare Act, and the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources. In accordance with the PHS Policy on Humane Care and Use of Laboratory Animals by Awardee Institutions, applicant organizations must establish a committee, qualified through the experience and expertise of its members, to oversee the institution's animal program, facilities and procedures. No PHS award involving the use of animals shall be made unless the Animal Welfare Assurance has been approved by OPRR. Prior to award, the contracting officer will notify Contractor(s) selected for projects that involve live vertebrate animals that an Animal Welfare Assurance is required. The contracting officer will request that OPRR negotiate an acceptable Animal Welfare Assurance with those Contractor(s). For further information, OPRR may be contacted at NIH, Bethesda, Maryland 20892 (301-496-7163). 11. PRIVACY ACT (NIH 3131) (JUL 1994) The Privacy Act of 1974 (P.L. 93-579) requires that a Federal agency advise each individual whom it asks to supply information, the authority which authorizes the solicitation, whether disclosure is voluntary or mandatory, the principal purpose or purposes for which the information is intended to be used, the uses outside the agency which may be made of the information, and the effects on the individual, if any, of not providing all or any part of the requested information. The NIH is requesting the information called for in this RFP pursuant to the authority provided by Sec. 301(g) of the Public Health Services Act, as amended, and P.L. 92-218, as amended. Providing the information requested is entirely voluntary. The collection of this information is for the purposes of conducting an accurate, fair, and adequate review prior to a discussion as to whether to award a contract. Failure to provide any or all of the requested information may result in a less than adequate review. In addition, the Privacy Act of 1974 (P.L. 93-579, Sec. 7) requires that the following information be provided when individuals are requested to disclose their social security number. Provision of the social security number is voluntary. Social security numbers are requested for the purpose of accurate and efficient identification, referral, review and management of NIH contracting programs. Authority for requesting this information is provided by Section 305 and Title IV of the PHS Act, as amended. The information provided by you may be routinely disclosed for the following purposes: - to the cognizant audit agency and the General Accounting Office for auditing. - to the Department of Justice as required for litigation. - to respond to congressional inquiries. - to qualified experts, not within the definition of Department employees, for opinions as a part of the review process. 12. INCLUSION OF MINORITIES AND WOMEN AS SUBJECTS IN RESEARCH PROPOSAL INSTRUCTIONS (NIH 3475) (JUL 1994) It is the policy of NIH that woman and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations) which have been in effect since 1990. The new policy contains some new provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research" which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513), [(this was reprinted to correct typesetting errors from the Federal Register dated March 9, 1994 (FR 59 11146-11151)], and reprinted in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. Offerors may obtain copies from these sources or from the contact person listed in the RFP. Unless otherwise specified in this solicitation, the Government has determined that the work set forth herein does not involve a gender specific study or a single or limited number of minority population groups. Therefore, the NIH believes that the inclusion of women an minority population is appropriate for this project. (See Attachment C of this RFP for more information about evaluation factors for award.) The format for the Annual Technical Progress Report (See Technical Reporting Requirements contained in Attachment B of this RFP) shall be used in proposal preparation. 13. ADDITIONAL PROPOSAL INSTRUCTIONS A listing of additional instructions and notices required for proposal preparation is provided below. The full text versions of these provisions are contained in the NIH Gopher directory entitled "Instructions for Proposal Submission". - NOTICE LISTING SOLICITATION PROVISIONS INCORPORATED BY REFERENCE - 52.227-6 ROYALTY INFORMATION (APR 1984) - 52.252-1 SOLICITATION PROVISIONS INCORPORATED BY REFERENCE (JUN 1988) - COMMITMENT OF PUBLIC FUNDS (NIH 2455) (JUL 1986) - COMMUNICATIONS PRIOR TO CONTRACT AWARD (NIH 2345) (FEB 1990) - RELEASE OF INFORMATION (NIH 3170) (JUL 1994) - PREPARATION COSTS (NIH 3173) (JUL 1994) - PHSAR 352.215-10 LATE PROPOSALS, MODIFICATIONS OF PROPOSALS AND WITHDRAWALS OF PROPOSALS (NOV 1986) - CONTRACT CLAUSES (NIH 3120) (JUN 1986) - FORMAT AND CONTENT OF PROPOSALS (NIH 3121) (JUL 1994) - SEPARATION OF TECHNICAL AND BUSINESS PROPOSALS (NIH 3122) (JUL 1994) - ALTERNATE PROPOSALS (NIH 3123) (JUL 1994) - CONFIDENTIALITY OF PROPOSALS (NIH 3124) (JUL 1994) - USE OF THE METRIC SYSTEM OF MEASUREMENT (NIH 3126) (JUL 1994) - SELECTION OF OFFERORS (NIH 3130) (JUL 1986) - SMALL BUSINESS AND SMALL DISADVANTAGED BUSINESS SUBCONTRACTING PLAN (NIH 3135) (JUL 1986) - REIMBURSEMENT OF COSTS FOR INDEPENDENT RESEARCH AND DEVELOPMENT PROJECTS (NIH 3165) (JUL 1994) - SALARY RATE LIMITATION INFORMATION FOR OFFERORS (NIH 3101) (OCT 1994) - TECHNICAL PROPOSAL INSTRUCTIONS (NIH 3500) (JUL 1994) - TECHNICAL DISCUSSIONS (NIH 3505) (JUL 1994) - TECHNICAL EVALUATION (NIH 3510) (JUL 1994) - ADDITIONAL TECHNICAL PROPOSAL INFORMATION (NIH 3165) (JUL 1994) - OTHER CONSIDERATIONS (NIH 3520) (JUL 1994) - COST AND PRICING DATA (NIH 3600) (JUL 1994) - QUALIFICATIONS OF THE OFFEROR (NIH 3615) (JUL 1994) - PROPERTY/EQUIPMENT/FACILITIES (NIH 3620) (JUL 1994) - ROYALTIES (NIH 3625) (JUL 1994) - FINANCIAL CAPACITY (NIH 3630) (JUL 1994) - SUBCONTRACTORS (NIH 3635) (JUL 1994) - INCREMENTAL FUNDING (NIH 3640) (JUL 1994) - REPRESENTATIONS AND CERTIFICATIONS (NIH 3645) (JUL 1994) - NOTICE TO OFFERORS - FORMS/FORMATS/ATTACHMENTS (NIH 3145) (JUL 1986)