RFP No. NIH-NIAID-DMID-98-19 Title: MALARIA: CLINICAL RESEARCH AND TRIAL PREPARATION SITES IN ENDEMIC AREAS Issued by: Carl R. Henn Contracting Officer NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard (MSC 7610) Rockville, Maryland 20892-7610 DATE ISSUED: OCTOBER 24, 1997 PROPOSAL DATE DUE: JANUARY 23, 1998, 4:00 P.M. (EST) Ladies and Gentlemen: You are invited to submit a proposal in accordance with the requirements of this RFP (NIH-NIAID-DMID-98-19) for "Malaria: Clinical Research and Trial Preparation Sites in Endemic Areas". The Government anticipates that three (3)to five (5) contracts will be awarded for a period of five (5) years as a result of this RFP. The documents included with this electronic RFP package are as follows: Attachments: A. Background and Work Statement, dated October 23, 1997 B. Deliverables and Reporting Requirements, dated October 23, 1997 C. Evaluation Factors for Award, dated October 23, 1997 D. Specific RFP Instructions and Provisions (includes page limitations, the Technical Proposal Format, and the proposal intent form) E. Applicable RFP References In addition to the directory in which you are currently located (i.e., the streamlined RFP), there are five (5) other Subdirectories in the Gopher System (under C, RFP References) which must be retrieved, in whole or in part, in order to submit a proposal (the applicable portions are explained in Attachment E). The Subdirectories are: STANDARD RFP INSTRUCTIONS AND PROVISIONS OPTIONAL RFP INSTRUCTIONS AND PROVISIONS FORMS, FORMATS AND ATTACHMENTS REPRESENTATIONS AND CERTIFICATIONS SAMPLE CONTRACT FORMAT-GENERAL If you are unable to download any of the applicable documents, please contact Carl Henn, Contracting Officer, by phone/fax/Internet (see contact numbers/addresses below). The attachments/documents listed above represent all the necessary information required for the submission of a proposal for this acquisition. Following proposal submission and review, additional information will be requested by the Contracting Officer from all offerors which comprise the Competitive Range. The Business and Technical proposals must be separate portions in the proposal package. The Business Proposal must be signed by an authorized official of your organization, and must contain a detailed breakdown of costs by year for each cost category/element; the basis for all costs must be explained, and the supporting documentation must be submitted with the proposal. See Standard RFP Instructions and Provisions, in the subdirectory C, RFP References, for more detail on the Business Proposal requirements. Also, please see Notes to Offeror in the Statement of Work (Attachment A) information which offerors are required to submit in the proposals. The Statement of Work is composed of two parts, the second of which, Part B, would expand the contract to perform safety, immunogenicity and efficacy testing of drugs or vaccines. The government will decide whether and when to go forward with Part B. All offerors must address both parts A and B in their proposal. It is recommended that any proposed annual increase in costs for inflation be limited to no more than 3% of total costs per year, which is also the maximum currently allowed by NIH for research projects. The format and content of your TECHNICAL PROPOSAL is detailed in the "Technical Proposal Table of Contents", in Attachment D. SEE SECTION D.5 FOR INFORMATION ON PAGE LIMITATIONS. Your attention is further directed to the "Proposal Intent" form contained in Attachment D, Item 6. Please complete this form and return it to this office on or before December 22, 1997. This will allow us to expedite preparations for the peer review of proposals. The original and nineteen (19) 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 January 23, 1998, at 4:00 p.m. local time at the address listed in Attachment D, item 4. If you have any additional questions regarding this RFP, please contact Mr. Carl Henn at the Internet electronic mail address ch24v@nih.gov, by phone at 301/496-0993, or by fax at 301/402- 5253. Collect calls will NOT be accepted. Amendments fo the RFP will be posted on the NIH homepage. If you wish to be notified of any amendments, please contact Mr. Henn. Sincerely, /s/ Rosemary McCabe Hamill Chief, Infectious and Allergic Diseases Contract Section Contract Management Branch National Institute of Allergy and Infectious Diseases Attachments: A - E ******************************************************************** RFP-NIH-NIAID-DMID-98-19 STREAMLINED RFP ATTACHMENT A (10/23/97) ---------------------------- INTRODUCTION The objective of these contracts is to implement clinical and field- based research on malaria at multidisciplinary field sites. This RFP details two different components, each with its own work statement, evaluation criteria, and budget. Part A solicits proposals for work that includes: characterization of patient populations in preparation for future clinical trials; provision of baseline data with respect to epidemiology, parasite populations, vector biology, immunity, and other factors influencing clinical presentation; training of local scientists in research and clinical trial methodology; development and validation of case-definitions and field-appropriate diagnostics which will be valuable for clinical trials; provision of research reagents to the NIAID Malaria Reagent Repository; and, undertaking research on malaria transmission and pathogenesis. It is anticipated that three to five completion type contracts will be awarded for Part A. Part B describes Optional Contract Activities (i.e. they are optional for the Government to support), and solicits proposals describing capacity for performance of safety, immunogenicity, and/or efficacy trials of new prevention/intervention strategies when the need arises. When the Government exercises the Optional Contract Activities in Part B, these will be accomplished under a completion type contract. Offerors submitting a proposal under this solicitation must prepare a proposal which includes the required work outlined above (Part A) AND the optional contract activities identified in Part B. Within the proposal, each part should be distinct as each will be subject to its own review criteria. PROPOSALS FOR PART A ALONE OR PART B ALONE SHALL NEITHER BE ACCEPTED NOR CONSIDERED FOR AWARD UNDER THIS SOLICITATION. BACKGROUND - PART A Malaria is an infectious disease caused by protozoan parasites of Plasmodium spp. (primarily P. falciparum and P. vivax), which claims an estimated 2 to 3 million lives annually and accounts for untold morbidity in the approximately 300 to 500 million people who develop clinical disease annually. There are no licensed vaccines for malaria. Currently available drugs are losing their utility as a result of the development of drug-resistant parasites. Malaria is considered a re-emerging disease, due largely to the spread of drug- resistant parasite strains, decay of the health-care infrastructure, and difficulties in implementing and maintaining vector control programs in many developing countries. Basic and applied research is needed to develop and implement new tools to control this deadly disease. Enhanced capacity to conduct collaborative/multicenter research was recognized as a critical need in the report from the International Conference on Malaria in Africa, held in Dakar, Senegal, in January, 1997. Consequently, one goal of this solicitation is to increase the number of sites within endemic regions that are capable of performing these types of studies. One important area for increased collaboration is that of pathogenesis research. As noted in the 1991 IOM report on "Malaria: Obstacles and Opportunities", even with current state-of-the-art care, some 25% of people presenting with the most severe form of malaria die. The IOM committee ranked improved understanding of the disease process as one of its highest priority recommendations. The pathogenesis of malaria is complex; current evidence, albeit limited, indicates that host genetic factors and host immunity (e.g. TNF-alpha polymorphisms, nitric oxide levels) are important, but the role of other influences having to do with exposure to the parasite (entomologic inoculation rate, seasonality of transmission, etc.) as well as parasite strain have not yet been systematically analyzed. Improved understanding of the pathogenesis of severe malaria can best be achieved by a multidisciplinary approach, combining clinical, immunologic, genetic, entomologic, and other related studies in endemic areas. This information will be important for improved case management of severe malaria, and for the development of potential immuno- or chemotherapies and/or anti- pathology vaccines, and will be central to overall vaccine development efforts in order to avoid induction of potentially immunopathologic responses. Evaluation of new prophylactic, therapeutic and diagnostic approaches to malaria requires an understanding of the epidemiology and transmission dynamics in locations in which statistical discriminatory power can be achieved and where the approach is likely to be implemented. While some such sites are currently supported by various agencies/institutions, the development of additional sites with appropriate baseline information, expertise, and infrastructure will broaden our understanding and ultimately allow for more efficient conduct of clinical trials. Studies carried out in these sites will contribute necessary field information that can assist investigators to develop factually based strategies for intervention and evaluation. Linking of these sites into a network will allow for greater comparability of malaria studies and trials in both similar and different epidemiologic settings. WORK STATEMENT - PART A Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities not otherwise provided by the Government as needed to perform the work described below. Specifically, the Contractor shall: 1. Establish a field-based research program on P. falciparum malaria, including access to appropriate academic, laboratory and clinical facilities, and necessary collaborative arrangements. (NOTE 1 TO OFFEROR: Offerors should submit a plan which includes documentation of access to patient populations and facilities which will be adequate and appropriate for the work to be performed under this contract. Offerors proposing to work in sites where both infections occur may include studies on P. vivax, as well as P. falciparum, in their plan. It is anticipated that at least 90% of the work performed under these contracts will be conducted at the overseas field site and that local scientists and physicians will be involved in all facets of this work. The plan should describe the anticipated involvement of local scientists in the project.) 2. Develop and implement a systematic longitudinal approach towards understanding malaria epidemiology in populations with substantial malaria morbidity and in a region with predictable parasite transmission. Under the terms of this task, the contractor shall: a. Collect data on the incidence, prevalence, and clinical presentation of malaria in areas where malaria is endemic, including but not limited to the relationship among groups with different clinical presentations (e.g. asymptomatic parasitemic, symptomatic parasitemic, severe and complicated malaria); b. Collect data with respect to entomologic parameters, including but not limited to identification of the species and population structure of vector mosquitoes, and the number of infective bites/person/year; c. Collect data on parasite population dynamics and heterogeneity, including but not limited to information on the expression of alleles of major antigens that may be used in subsequent vaccine trials; final determination of antigens to be characterized for allelic variation will be subject to the approval of the Project Officer. (NOTE 2 TO OFFEROR: For planning purposes, the offeror should describe screening for expression of allelic variants of MSP-1, CSP, and LSA-1 antigens.) d. Document and monitor the prevalence and use of available interventions (e.g. drugs, bednets, spraying of insecticides); e. Document and monitor the level of drug resistance in the local parasite population, and the clinical responsiveness of patients to antimalarials used in the community. 3. Develop and validate case-definitions and diagnostics which will be useful for subsequent clinical trials. Under this task the Contractor shall: a. Develop and/or validate rapid, specific, sensitive and field- appropriate diagnostics for subclinical infection and specific clinical manifestations; b. Develop and/or validate sensitive and specific case definitions of protection (e.g. reduction of parasitemia, reduction of pathologic complications, reduction of transmission) appropriate for the conduct of field trials in endemic areas, and identify relevant confounders. 4. Conduct a coordinated, multi-disciplinary, investigation of malaria pathogenesis and immunity within the context of the local epidemiologic conditions. Under this task, the Contractor shall address one or more of the following topics: a. Characterize host, parasite and vector factors, including genetic factors, associated with adverse clinical outcomes; b. Characterize the role of infection intensity and parasite transmission patterns (e.g. seasonality, inoculation rate, etc.) in development of severe disease as well as protective immunity; c. Characterize the relevance of the type and magnitude of human immune response in pathogenesis and resistance; Selection of projects to perform under this task will be subject to the approval of the Project Officer. d. Identify and/or validate surrogate markers for protection and pathology; e. Characterize the role of other host-related factors (e.g. behavioral, nutritional) in transmission and pathogenesis. (NOTE 3 TO OFFEROR: The offeror must submit a complete description of the specific aims to be addressed, experimental approach, and the methods to be utilized for analyzing the resulting data. It is anticipated that this research component shall comprise approximately 40% of the effort under the contract.) 5. Develop and implement mechanisms to facilitate linkage and coordination with other contract field sites, such as electronic computer-based networks, organization of joint workshops, and travel of scientists between sites, for purposes of developing collaborative protocols and compatible data management systems, providing peer review of proposed protocols, facilitating information exchange and transferring technology. The Contractor shall attend an initial planning meeting to ensure compatibility of clinical trial design and data management systems, as well as to develop an ongoing system for internal review of research ideas, concepts and proposals. In addition, the Contractor shall attend annual meetings with NIAID Program Staff in Bethesda, MD. (NOTE 4 TO OFFEROR: The offeror should anticipate participating in the annual meeting of the NIAID International Centers for Tropical Disease Research meeting. For purposes of developing a cost proposal, the offeror should include travel for the P.I. and other appropriate personnel to attend one four-day meeting per year, and an additional three-day planning meeting in the first year, to be held in the Bethesda, MD, area.) 6. Provide relevant research experience and training for local and U.S. scientists and physicians in order to will strengthen the capacity of the site to perform clinical trials. Specifically, the contractor shall: a. Within the scope of activities described in (1) - (4) above, provide training in malaria surveillance and research, including but not limited to entomological and parasitological surveillance, diagnosis, laboratory technical training, and graduate or post- graduate research training, to local scientists; b. Provide training in clinical trial methodology, management and support, including but not limited to trial design and methodology, data management, good laboratory practice, and good clinical practice, to local physicians and scientists; (NOTE 5 TO OFFEROR: Although it is likely that some of the specified training activities will ultimately be developed jointly among the several field sites to be established under these contracts, for purposes of developing a cost proposal the offeror should detail how training opportunities will be provided within his/her own program, and how these are reflected in the cost proposal.) c. Within the scope of activities described in (1) - (4) above, provide opportunities for U.S. graduate and medical students to obtain short-term (< 3 months) training experiences in tropical disease research. 7. Provide research reagents to the NIAID Malaria Research and Reference Reagent Repository (Malaria Reagent Repository) and to other researchers collaborating in comparative studies. Under this task the Contractor shall: a. Collect clinical materials from patients with different manifestations of P. falciparum infection (e.g. asymptomatic parasitemic, symptomatic parasitemic, severe and complicated malaria), as well as uninfected individuals residing in the same locations, including but not limited to leukocytes, sera/plasma, and parasite samples; the number of samples to be collected will be determined on an annual basis by the Project Officer, but will be no less than 200 serum and leukocyte samples; b. Collect specimens of local vector mosquitoes; c. Following approval of the Project Officer, arrange for these samples to be shipped under conditions appropriate to maintenance of viability/stability to the U.S.-based NIAID Malaria Reagent Repository and to collaborators within the network; d. Provide any information that has been obtained regarding the characterization of these reagents (e.g. clinical status of donor, genetic characteristics of cells, antibody content of sera/plasma, drug resistance or genetic characteristics of parasites) to the NIAID Malaria Reagent Repository or collaborators within the network. (NOTE 6 TO OFFEROR: The offeror should submit a plan for collection, on an annual basis, of 200 serum and leukocyte samples from malaria patients, comprised of those exhibiting a range of clinical syndromes including severe malaria. In addition, finger-prick filter paper blood samples from approximately 1000 individuals should be collected on an annual basis from malaria patients for submission to the repository. Minimum characterization required for these samples would include clinical history, physical findings, and appropriate laboratory results (both positive and negative). It is anticipated that these patients will be followed longitudinally over the period of this award, where possible.) 8. Coordinate the preparation of all manuscripts and presentations involving data from the project, for publication in a timely manner. All publications shall acknowledge NIAID support and be submitted to the Project Officer for review, prior to publication. The Project Officer shall have access to all data generated with the support of this contract. (GENERAL NOTES TO OFFEROR: Some activities carried out under this award may be governed by HHS Regulations for the Protection of Human Subjects in Research, Title 45 Code of Federal Regulations Part 46 (45 CFR 46). These regulations require awardees to establish procedures for the protection of subjects involved in any research activities. Prior to funding and upon request of the Office for Protection from Research Risks (OPRR), prospective awardees must file an Assurance of Compliance with OPRR and establish or identify an Institutional Review Board (IRB) to review and approve the procedures for carrying out any research activities occurring in conjunction with this award. A formal request for the required Assurance will be issued by OPRR at an appropriate point in the review process, and examples of required materials will be supplied at that time. However, applicants may wish to contact OPRR (301-496- 7041) to obtain preliminary guidance on human subjects issues. For contracts dealing with clinical research, it is the policy of the NIH that women 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 policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103- 43) 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) and the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994. This note applies to Part B as well as to Part A.) BACKGROUND - PART B The capacity to evaluate new and improved vaccine candidates or other interventions in an efficient and expeditious manner is an essential element of the NIAID Research Plan for Malaria Vaccine Development. As recommended at the International Conference on Malaria in Africa (Dakar, Senegal, 1997), "efficacy trials of malaria vaccines will require the identification and characterization of a number of field sites suitable for evaluating the expected number of vaccine candidates". The actual number of vaccines or other prevention/intervention methods developed during the period of this award that will require further evaluation under field conditions is difficult to anticipate. It is likely that these will include methods to prevent infection, decrease disease and/or reduce transmission of parasites. Under Part A of these contracts, patient contacts will be made and laboratory/clinical infrastructure will be developed that will be useful for clinical trials. When the need arises, these sites will be utilized to conduct safety, immunogenicity and/or efficacy trials in populations where malaria is endemic. The mechanism to be used is a priced Option to this contract. The tasks to be performed within the Optional Contract Activities will be consistent with the Work Statement below. The offeror must provide appropriate clinical populations, staff, expertise, and facilities to test the full range and number of candidate vaccines developed by industry and government/academic scientists. It is anticipated that the offeror may need to coordinate his/her response with other clinical sites and laboratories in which access to populations or demonstrated technical ability would complement the abilities and populations available to the primary contractor. WORK STATEMENT - PART B Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities not otherwise provided by the Government as needed to perform the work described below. 1. Provide facilities and staff necessary to conduct safety, immunogenicity and efficacy trials of prophylactic and therapeutic vaccines or drugs in human volunteers living in regions where malaria is endemic. 2. Provide patients from appropriate populations as required to conduct Phase I, II and/or III clinical evaluation of prophylactic or therapeutic methodologies. The target population for many of these studies will be children 1 to 6 years of age, although all vaccines/drugs will be tested at a minimum for safety in adults prior to extending evaluation to include children. (NOTE 1 TO OFFEROR: Any prophylactic or therapeutic method to be tested at the NIAID field sites will first have undergone safety testing on human volunteers within the U.S. It is anticipated that such initial testing will be conducted at the Vaccine and Treatment Evaluation Units supported by NIAID or at similar sites provided by other collaborators. ) 3. Determine safety, reactogenicity, immunogenicity, optimal dose and schedule, as specified by the Project Officer depending on the prophylactic or therapeutic method being assessed. Conduct appropriate assays to determine volunteer eligibility, baseline parameters upon entry into the study, and response to treatment. Collect sera, and other body fluids or blood cells, from study participants, and arrange for appropriate storage or shipment as directed by the Project Officer. Amounts and types of samples to be collected will depend on the study protocol. For prophylactic agents, the follow-up period required for assessment of efficacy under conditions of natural re-exposure to parasites is expected to vary according to the epidemiologic characteristics of the region, but should be no less than 6 months. (NOTE 2 TO OFFEROR: It is anticipated that most trials to be conducted under this option will involve assessment of candidate vaccines for safety and immunogenicity. Small scale efficacy trials may also be required at individual field sites. In the case that more extensive efficacy trials are called for, it is likely that multiple NIAID field sites will be required to carry out the trial under a common protocol, as directed by the Project Officer. Vaccine types will include, but are not limited to, those based on single or multiple epitopes from pre-erythrocytic, erythrocytic or sexual stages of the parasite, or combinations thereof. In addition, it is possible that the safety and efficacy of immuno- or chemotherapies may be evaluated. For immunologic assays to be performed by the contractor, antigen or antibody reagents will be made available by the Government. Wherever relevant or appropriate, assays shall be conducted in a standardized manner, and in cooperation and collaboration with other Government-supported laboratories as directed by the Project Officer.) (NOTE 3 TO THE OFFEROR: In order to demonstrate that the Offeror understands the approach to, and has the capacity to undertake clinical evaluation of a malaria vaccine, the Offeror must submit a sample protocol for safety and immunogenicity testing of a vaccine based on the MSP-1 antigen from blood-stage P. falciparum parasites in an alum formulation, involving a minimum of 50 subjects, followed by efficacy evaluation in a minimum of 500 subjects. This shall include a "Vaccine Evaluation Plan" describing detailed strategies, with appropriate justification, for: 1) Development of the clinical trial design, including but not limited to, determination of the required sample size for efficacy testing based on current knowledge of re-infection rates in the population, choice of clinical endpoints, and compliance with regulations for protection of human subjects; 2) Recruitment, enrollment and randomization of subjects, including exclusion criteria; 3) Drug treatment prior to immunization; 4) Assessment of safety and immunogenicity, assuming an immunization protocol involving three intramuscular injections given at times 0, 1 and 4 months, including plans for data management and reporting of any adverse reactions to NIAID, as well as protocols for immunologic assays to be performed; 5) Follow-up for assessment of safety and efficacy upon natural re- exposure to the parasite; 6) Analysis of the resulting efficacy data (i.e. an analytic plan). This "Vaccine Evaluation Plan" is required for evaluation of the offeror's technical approach, and a budget for this Plan should be included in the cost proposal. Any clinical trials ultimately carried out under Part B will be planned and executed as directed by the Project Officer.) 4. Prepare detailed protocols, consent forms, etc. for submission to the Project Officer and Institutional Review Boards at relevant U.S. and foreign institutions for approval and for NIAID to submit to the FDA as part of an Investigational New Drug (IND) package. Amend as necessary after comments by the Project Officer, local IRB, and regulatory authorities. Final protocols shall, at a minimum, include the following sections: an introduction, including background and rationale; a statement of the study objectives; criteria for selection of subjects, and enrollment procedures; clinical and laboratory evaluations to be performed; plans for data management, collection, and monitoring, and for reporting of adverse events; a complete description of the study treatment; and statistical considerations, including general design issues, endpoints, sample size, accrual and power, monitoring and analysis, stopping rules. 5. Manage the information generated, including transmission, storage, maintenance of confidentiality, retrieval, validation, and analysis. Report all adverse reactions to the DMID Clinical and Regulatory Affairs Branch, the NIAID Medical Officer, and the Project Officer. 6. Attend and support regularly scheduled meetings of a Data and Safety Monitoring Board (DSMB), as well as investigator meetings to be held for purposes of protocol and study development and/or evaluation. (NOTE 4 TO OFFEROR: For planning purposes, assume semi-annual meetings of the DSMB, which will involve 10 persons and will take place in the Bethesda, MD, area. In addition, assume an average of two investigator meetings/year to rotate between the field site and the Bethesda, MD area. Travel costs for the Principal Investigator, essential co-investigators and appropriate external advisors should be included in the business proposal.) 7. Coordinate the preparation of all manuscripts and presentations involving data from the project, for publication in a timely manner. All publications shall acknowledge NIAID support and be submitted to the Project Officer for review and clearance, prior to publication. The Project Officer shall have access to all data generated with the support of this contract. (GENERAL NOTES TO OFFEROR: Only when the need arises will the Government invoke the Optional Activities in Part B. Because the actual protocol design or number of subjects to be enrolled in the Optional contract Activities of Part B is not known at this time, the "Vaccine Evaluation Plan" is presented for evaluation of the offeror's technical approach. The business proposal for Part B should comprise costs for the administration, conduct and reporting of the "Vaccine Evaluation Plan", including meetings described in (6). As negotiations progress for Part B, alternative and additional Options may be presented to the offeror for response, e.g. the costs required to enroll a different number of subjects or to test a different type of prophylactic or therapeutic method. The business proposal should present TOTAL COSTS including: 1) FIXED COSTS to include effort in trial design, meeting costs, data analysis costs, technical and financial reporting costs; 2) VARIABLE COSTS to include costs related to the actual conduct of the clinical trial. These costs should include related effort, patient treatment costs, materials and supplies, and assays.) _-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_- ATTACHMENT A.2 SAFETY CONTROLS AND STANDARDS A. In order to provide safety controls for protection to the life and health of employees and other persons; for prevention of damage to all property; and for avoidance of work interruptions in the performance of the contract; the Contractor and any subcontractors shall comply with the following standards or subsequent issues, and any supplements. In addition, the Contractor shall comply with all applicable Federal, state and local laws, codes, ordinances and regulations, including obtaining of all required licenses and permits in connection with biological and hazardous materials. (1) Biosafety in Microbiological and Biomedical Laboratories, U.S. Department of Health and Human Services, Centers for Disease Control (CDC) and the NIH, HHS Pub. No. (CDC) 93-8395. (2) NIH Guidelines for the Laboratory Use of Chemical Carcinogens, NIH Publication No. 81-2385. (3) Occupational Safety and Health Administration (OSHA) Publications: (I) 29 CFR Part 1910.1030, Occupational Exposure to Blood Borne Pathogens; Final Rule; and (ii) 29 CFR Part 1910, Occupational Exposure in Laboratories; Final Rule. The above, 1 and 2, may be obtained from: Division of Safety Office of Research Services National Institutes of Health Building 31 - Room 1C02 Bethesda, Maryland 20892 OSHA Publications listed above (item 3) may be obtained by contacting US Government Publication Office at (202) 783-3238. B. The contractor, or subcontractor, shall identify any particular safety standards that are not referenced above as applicable to a particular reagent, and after approval by the Project Officer, communicate that information to the recipient of the reagent. _-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_- ******************************************************************** RFP-NIH-NIAID-DMID-98-19 ATTACHMENT B (10/23/97) DELIVERABLES AND 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 - Part A 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 (3) copies of a semi-annual Technical Progress Report, comprising two (2) 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. A table reporting the numbers of women and minority subjects enrolled in each clinical trial. American Asian or Black, Hispanic White, Other Total Indian Pacific not of not of or or Islander Hispanic Hispanic Unknown Alaskan origin origin Native Female Male TOTAL g. 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 four (4) copies of an Annual Technical Progress Report, as above, comprising three (3) 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 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 four (4) copies of a comprehensive Final Report, as above, comprising three (3) 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. 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 seven (7) 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. Technical Reports - Part B When the Government exercises the Optional Contract Activities in Part B, Technical Progress reports shall be due on a quarterly basis. In addition to the schedule described above, the Contractor shall submit two (2) copies of the quarterly progress report to the Project Officer and one (1) copy to the Contracting Officer. C. 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. D. Technical Report Distribution Copies of the technical reports shall be submitted as follows: Type of No. Addressee Due Dates report Copies Semi-Annual 3 Project Officer Semi- Progress Annually (Specific dates will be listed in the contract document) Semi-Annual 1 Contracting Officer Same as Progress CMB/NIAID/NIH above Solar Building, Room 3C07 6003 Executive Blvd. MSC 7610 Bethesda, MD 20892-7610 Annual 3 Same as P.O. above Annually (Specific dates will be listed in the contract document) Annual 1 Same as C.O. above Same as above Final 3 Same as P.O. above Expiration date Final 1 Same as C.O. above Same as above E. Other Deliverables. The Contractor, subject to approval of the Contracting Officer, shall deliver to the Government, or its designee, research reagents as specified under Article 7 of the Work Statement. ******************************************************************** RFP-NIH-NIAID-DMID-98-19 ATTACHMENT C (10/23/97) PROPOSAL EVALUATION CRITERIA ---------------------------- 1. GENERAL Proposals submitted in response to this solicitation will be subjected to review by an ad hoc technical review committee. 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 proposal 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. While high competency is sought, capabilities that exceed those needed for successful performance of the contract work statement are not required. 2. COMPARATIVE IMPORTANCE OF PROPOSALS Selection of an offeror for contract award will be based on an evaluation of proposals against two factors. The factors in order of importance are technical merit and cost. Although technical factors are of paramount consideration in the award of the contract, cost is also important to the overall contract award decision. Technical merit is significantly more important than cost. Costs for Part A will be more important than Part B costs to the selection decision. Offerors are advised that award will be made to that offeror whose proposal provides the best overall value to the Government. Site diversity is also a factor in the decision. Program staff intends to establish a geographically balanced program using this RFP. This is a multiple award RFP, and the government will consider possible overlap and under- representation in making the award decision. 3. PROPOSAL 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. Part A and Part B will be evaluated separately. In order to be eligible for a contract award, both Part A and Part B must be determined to be acceptable. Following evaluation of both Part A and Part B, a final score for each proposal will be calculated by weighting as follows: 75% Part A and 25% Part B. TECHNICAL EVALUATION CRITERIA - PART A 1. Technical Approach (80 Points) The technical adequacy and feasibility of the proposed plans for establishment of multidisciplinary field sites for clinical and field-based research on malaria, including: a) Documented adequacy and feasibility of the proposed methods and approaches for epidemiologic studies, development and validation of case definitions and diagnostics, training, and collection of reagents for the NIAID repository. (40 Points) b) Documented adequacy and suitability of the field sites with regard to establishment of appropriate collaborative arrangements with local government and scientists, access to appropriate human populations in areas of substantial malaria morbidity and predictable parasite transmission, access to requisite academic, laboratory and clinical facilities; plans for communications linkage between collaborators and other network members. (20 points) c) Documented adequacy and suitability of the methods and approaches proposed for the integrated research component on malaria pathogenesis and immunity. (20 Points) 2. Personnel and Experience Documented adequacy and relevance of the expertise, experience, education, and availability of the Principal Investigator, co- investigators and staff for conducting all aspects of the Work Statement, including expertise in conducting clinical research on malaria. (20 Points) TOTAL 100 Points TECHNICAL EVALUATION CRITERIA - PART B 1. Technical Approach (80 Points) The technical adequacy and feasibility of the proposed plans for conducting safety, immunogenicity and efficacy trials of vaccines or drugs against malaria, including: a) Documented technical adequacy and feasibility of the methods and approaches proposed in the "Vaccine Evaluation Plan", appropriateness of the consent forms and plans for fulfilling regulatory requirements, appropriateness and feasibility of proposed methods and approaches for determining vaccine immunogenicity, adequacy and feasibility of plans for handling and interpreting data, and appropriateness of the overall plan for managment of this clinical research effort. (50 Points) b) Adequacy, suitability and availability of the necessary populations, including demonstrated ability to recruit, retain and follow-up patients. (30 Points) 2. Personnel and Experience Documented adequacy and relevance of the expertise, experience, education, and availability of the Principal Investigator, co- investigators and staff for conducting all aspects of the Work Statement, including expertise in infectious diseases, pediatrics, and clinical trials. (20 Points) TOTAL 100 Points ******************************************************************** RFP-NIH-NIAID-DMID-98-19 ATTACHMENT D (10/23/97) SPECIFIC RFP INSTRUCTIONS AND PROVISIONS ---------------------------------------- NOTICE TO OFFERORS: This attachment contains proposal instructions and information which are 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. References to additional, more general information, and forms regarding proposal preparation are contained in Attachment E, "Applicable RFP References." ------------------------------------------------------- 1. NUMBER AND TYPE OF AWARD(S) (NIH 2980) (APR 1984) It is anticipated that three (3)to five (5) awards will be made from this solicitation and that the awards will be made on/about September 25, 1998. It is anticipated that the award from this solicitation will be a cost reimbursement completion type contract with a 5 year performance period, and that incremental funding will be used [see paragraph (6) of Business Proposal Instructions, in the "Standard RFP Instructions and Provisions" of the Gopher RFP] 2. ESTIMATE OF EFFORT It is expected that a completion type contract will be awarded as a result of this RFP. To assist you in the preparation of your proposal, the Government considers the effort to be approximately 11,750%. This estimate is furnished for the offeror's 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 Labor Category Annual Effort Total Principal Investigator 50% 250% Research Associates 1000% 5000% Field Workers & Nurses 1300% 6500% Total 2350% 11750% These percentages are based on a 12 month calendar year. 3. SERVICE OF PROTEST (AUG 1996) - FAR 52.233-2 (1) 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), shall be served on the Contracting Officer (addressed as follows) by obtaining written and dated acknowledgment of receipt from: Hand-Carried Address: Carl R. Henn Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard Rockville, MD 20852 Mailing address (U.S.) Postal Service Carl R. Henn Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard (MSC 7610) Bethesda, MD 20892-7610 NOTE: All material sent to this office by Federal Express should be sent to the Hand Carried Address. (2) The copy of any protest shall be received in the office designated above within one day of filing a protest with the GAO. 4. PACKAGING AND DELIVERY OF THE PROPOSAL (NIH 2995) (JUL 1994) Your proposal shall be organized as specified in Section C.1., "Standard RFP Instructions and Provisions". 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-98-19 TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY" -------------------------------------------------------------------- NUMBER OF COPIES The number of copies required of each part of your proposal are as specified below. TECHNICAL PROPOSAL: ORIGINAL AND 19 COPIES BUSINESS PROPOSAL: ORIGINAL AND 5 COPIES NOTE: THE ORIGINAL PROPOSAL MUST BE READILY ACCESSIBLE FOR DATE STAMPING. -------------------------------------------------------------------- -------------------------------------------------------------------- COPIES TO: If hand-delivered or delivery service Carl R. Henn Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard Rockville, MD 20852 If using U.S. Postal Service Carl R. Henn Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard (MSC 7610) Bethesda, MD 20892-7610 NOTE: All material sent to this office by Federal Express should be sent to the Hand Carried Address. 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," in accordance with PHSAR 352.215-10, Late Proposals, Modifications of Proposals and Withdrawals of Proposals (NOV 1986). 5. TECHNICAL PROPOSAL TABLE OF CONTENTS/FORMAT-ORGANIZATION OF THE TECHNICAL PROPOSAL PLEASE USE THE FOLLOWING FORMAT TO ORGANIZE AND PRESENT YOUR TECHNICAL PROPOSAL. THIS WILL AID IN THE REVIEW OF THE PROPOSALS RECEIVED. TECHNICAL PROPOSAL TABLE OF CONTENTS/FORMAT (NOTE: INSTRUCTIONS TO OFFERORS ARE INDICATED IN PARENTHESES OR AS FOOTNOTES.) PAGE NUMBERS 1. TECHNICAL PROPOSAL COVER SHEET (Format in Section C of Gopher RFP: FORMS, FORMAT & ATTACHMENTS)...............1 2. TECHNICAL PROPOSAL TABLE OF CONTENTS ..................... 2 3. SUMMARY OF OBJECTIVES AND METHODS (Abstract)* ............ 3 4. TECHNICAL PLAN** (Refer to Technical Proposal Instructions, located in the Gopher RFP, STANDARD RFP INSTRUCTIONS AND PROVISIONS, for more details) a. STATEMENT OF WORK 1. Objectives ........................................ 4- 2. Approach .......................................... ___ 3. Methods ........................................... ___ 4. Schedule .......................................... ___ b. PERSONNEL (List by name, title, department and organization, and detail each person's qualifications and role in the Project; provide narrative for: 1. Principal Investigator/Project Director ........... ___ 2. Other Investigators ............................... ___ 3. Additional Personnel e.g. technical support/ subcontractors/consultants) ....................... ___ [Note: For personnel, include 2 page biosketch/resume and the form entitled "Summary of Current and Proposed Activities" under Items 5. and 6. below.] c. FACILITIES/RESOURCES AND DIRECT COSTS (list/describe all equipment, facilities and other resources available for this project; attach "Technical Proposal Cost Information" form, and marked laboratory/clinical space floor plan in Item 6. below)........................................ ___ d. OTHER CONSIDERATIONS (provide brief narrative of any unique arrangements, safety procedures in place, animal welfare issues, human subject and minority and gender issues, etc.) ........................................ ___ 5. APPENDICES (protocols, literature citations, resumes/biosketches, policy manuals, etc. for above Technical Plan); list each Appendix; Appendices must be clear and legible, and easily located ............................... ___ 6. OTHER ATTACHMENTS: a. "Summary of Current and Proposed Activities" (All Key Personnel must be listed on this form; it is located in the FORMS, FORMATS, ATTACHMENTS subdirectory found in the Gopher RFP)......................................... ___ b. "Technical Proposal Cost Information" form (located in the Gopher RFP, FORMS, FORMATS, & ATTACHMENTS).......... ___ c. Laboratory and Clinical Facility Design and Floor Plan (clearly indicate the space available for this Project).. ___ 7. * State the proposal's broad, long-term objectives and specific aims. Describe concisely the research design and methods for achieving these goals. ** Section 4 should be presented once for Part A and a second time for Part B. This will provide a clear distinction between the two parts and will facilitate the review process. Sections 4.a. through 4.d. above MUST NOT EXCEED 100 PAGES (This does not include copies of resumes and any required forms, but only the NARRATIVE description of the Technical Plan). This limit applies to the combined page count for Section 4 narrative for both Part A and Part B. The front side of a page equals one page (front and back of a page equals two pages). Type density and size must be 10 to 12 points. If constant spacing is used, there should be no more than 15 cpi, whereas proportional spacing should provide an average of no more than 15 cpi. There must be no more than six lines of text within a vertical inch. -_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_- 6. PROPOSAL INTENT RESPONSE SHEET RFP No. NIH-NIAID-DMID-98-19 MALARIA: Clinical Research and Trial Preparation Sites in Endemic Areas Please review the attached Request for Proposals. Furnish the information requested below and return this page by December 22, 1997. Your expression of intent is not binding but will greatly assist us in planning for proposal evaluation. =============================================== [ ] DO INTEND TO SUBMIT A PROPOSAL FOR THE FOLLOWING: RFP No. NIH-NIAID-DMID-98-19 MALARIA: Clinical Research and Trial Preparation Sites in Endemic Areas [ ] DO NOT INTEND TO SUBMIT A PROPOSAL FOR THE FOLLOWING REASONS: ____________________________________________________________________ COMPANY/INSTITUTION NAME: _________________________________________ ADDRESS: _________________________________________ _________________________________________ _________________________________________ _________________________________________ PROJECT DIRECTOR'S NAME: _________________________________________ TITLE: _________________________________________ SIGNATURE: _________________________________________ (Date) TELEPHONE NUMBER AND E-MAIL ADDRESS: _________________________________________ NAMES OF COLLABORATING INSTITUTIONS AND INVESTIGATORS (include Subcontractors and Consultants): ____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________ ____________________________________________________________________ (Continue list on reverse if necessary) =============================================== RETURN TO: CMB, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard (MSC 7610) Bethesda, MD 20892-7610 Attn: Carl Henn RFP-NIH-NIAID-DMID-98-19 _-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_- 7. SIC CODE AND SIZE STANDARD Note: The following information is to be used by the offeror in preparing its Representations and Certifications (see Section C.4 of the Gopher RFP), specifically in completing the provision entitled, SMALL BUSINESS PROGRAM REPRESENTATIONS (JAN 1997), FAR 52.219-1: The standard industrial classification (SIC) code for this acquisition is 8733. The small business size standard is $5.0 million. 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. 8. GOVERNMENT NOTICE FOR HANDLING PROPOSALS AN OFFEROR SHALL PLACE THIS NOTICE ON TOP OF EACH COPY OF ITS TECHNICAL PROPOSAL. This proposal shall be used and disclosed for evaluation purposes only, and a copy of this Government notice shall be applied to any reproduction or abstract thereof. Any authorized restrictive notices which the submitter places on this proposal shall also be strictly complied with. Disclosure of this proposal outside the Government for evaluation purposes shall be made only to the extent authorized by, and in accordance with, the procedures in HHSAR paragraph 315.608-72. (For information regarding authorized restrictive notices, offerors should refer to the "Confidentiality of Proposals" section of the STANDARD RFP INSTRUCTIONS AND PROVISIONS subdirectory of the RFP REFERENCES directory of the Gopher RFP.). RFP-NIH-NIAID-DMID-98-19 ATTACHMENT E APPLICABLE RFP REFERENCES ------------------------- This section identifies the items found in the Gopher directory entitled RFP REFERENCES that are applicable to this RFP. 1. The entire file entitled "STANDARD RFP INSTRUCTIONS AND PROVISIONS" is applicable to this RFP, except as otherwise may be modified by the inclusion of an item from the "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS". 2. The following items are applicable from the file entitled "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS": a. LATE PROPOSALS, MODIFICATIONS OF PROPOSAL, AND WITHDRAWALS OF PROPOSALS, PHS 352.215-10 b. HUMAN SUBJECTS NOTICE TO OFFERORS OF REQUIREMENTS OF 45 CFR PART 46, Protection of Human Subjects (SEPTEMBER 1985) c . CARE OF LIVE VERTEBRATE ANIMALS d. SMALL BUSINESS AND SMALL DISADVANTAGED BUSINESS SUBCONTRACTING PLAN (does not apply to small business or to work performed in foreign countries) Note: A Subcontracting Plan is not due with the initial proposal. The Contracting Officer will notify offerors if a plan becomes due. e. PAST PERFORMANCE INFORMATION f. FACILITIES CAPITAL COST OF MONEY (for commercial organizations) 3. The following items/files are applicable from the subdirectory entitled "FORMS, FORMATS, AND ATTACHMENTS": Applicable to Technical Proposal a. Technical Proposal Cover Sheet b. Technical Proposal Cost Information, Dec. 1988 c. Summary of Current and Proposed Activities, July 1995 d. Technical Proposal Table of Contents, July 1995 Applicable to Business Proposal e. Contract Pricing Proposal, SF 1411, (Rev. 10/95) f. Proposal Summary and Data Record, NIH-2043 (Rev. 9/96) g. Business Proposal Cost Information h. Disclosure of Lobbying Activities, OMB Form SF-LLL, Dec. 1989 To Become Contract Attachments i. Invoice/Financing Requests Instructions for NIH Cost-Reimbursement Type Contracts, NIH(RC)-1, May1997. j. Procurement of Certain Equipment, NIH(RC)-7 (OMB Bulletin 81-16), Apr. 1984. k. Form NIH 2706 (Financial Report) and Instructions for Completing Form NIH 2706 Note: Financial reports are not always required. This will be discussed during negotiations. l. Protection of Human Subjects Assurance Identification/Certification/Declaration, Optional Form 310, (Rev. 1/95). Other-to be submitted as directed by Contracting Officer m. Certificate of Current Cost or Pricing Data, NIH-1397. n. Subcontracting Plan Format 4. The Representations And Certifications are applicable. 5. The "Sample Contract Format-General" is applicable.