RFP No. NIH-NIAID-DMID-97-07 Title: "SEXUALLY TRANSMITTED DISEASES CLINICAL TRIALS UNIT (STD CTU)" Issued by: Carl R. Henn Contracting Officer NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 DATE ISSUED: AUGUST 27, 1996 PROPOSAL DATE DUE: JANUARY 15, 1997, 4:30 P.M. (EST) Ladies and Gentlemen: You are invited to submit a proposal in accordance with the requirements of this RFP (NIH-NIAID-DMID-97-07) for a "SEXUALLY TRANSMITTED DISEASES CLINICAL TRIALS UNIT (STD CTU)." The Government contemplates the award of one (1), five (5) year, cost- reimbursement, completion type contract as a result of this RFP. The documents included with this electronic RFP package are as follows: I. Streamlined RFP a. Introduction, Background, Work Statement and Work Statement Attachments, dated August 27, 1996 (Attachment 1) b. Deliverables and Reporting Requirements, dated August 27, 1996 (Attachment 2) c. Evaluation Factors for Award, dated August 27, 1996 (Attachment 3) II. Specific RFP Instructions and Provisions, dated August 27, 1996 (Attachment 4) III. Applicable RFP References, dated August 27, 1996 (Attachment 5) In addition to this directory which provides access to this streamlined RFP, there are five 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 identity of these additional documents are detailed in Attachment 5 (Applicable RFP References) of this RFP. If you are unable to download any of these documents, please contact Sara M. Southard, Contract Specialist, by phone/fax/internet at the numbers/addresses listed below. The attachments 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 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 Contract Specialist no later than January 15, 1997, at 4:30 p.m. local time at the address listed in Attachment 4, Item 4. Due to the National Institute of Allergy and Infectious Diseases' current budget restrictions, it is recommended that any proposed annual increase in costs for inflation be limited to no more than 4% of total costs per year which is also the maximum currently allowed by the NIH for research projects. Final inflation increases will be subject to negotiation, taking into consideration the most current consumer price index (CPI). BE ADVISED THAT PORTIONS OF YOUR TECHNICAL PROPOSAL ARE SUBJECT TO PAGE LIMITATIONS. The format and content of your TECHNICAL PROPOSAL along with page limitation information is detailed in the "Technical Proposal Table of Contents/Format", Attachment 4, Item 9. In addition, 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 the NIH Gopher under the FORMS, FORMATS, AND ATTACHMENTS subdirectory found in C. RFP REFERENCES.) New policies require submission of more detailed information than what 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, 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 conflicts of interest when selecting review committee members. Your attention is further directed to the "Proposal Intent" form contained in Attachment 4, Item 10. Please complete this form and return it to this office on or before December 20, 1996. This will allow us to expedite preparations for the peer review of proposals. 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 intend to submit a proposal in response to this RFP, IT IS ESSENTIAL THAT YOU IMMEDIATELY NOTIFY MS. SARA SOUTHARD, CONTRACT SPECIALIST, OF THE NIAID CONTRACTING OFFICE AT THE FOLLOWING INTERNET ADDRESS: ss63e@nih.gov IF YOU FAIL TO NOTIFY THE CONTRACTING OFFICE OF YOUR INTEREST, YOU WILL NOT RECEIVE NOTIFICATION OF AMENDMENTS ISSUED TO THE RFP. HOWEVER, ALL AMENDMENTS WILL BE POSTED ON THE NIH GOPHER AND/OR NIH HOME PAGE. Questions concerning any areas of uncertainty which in your opinion require clarification or correction, must be furnished in writing to Sara Southard. Your questions should be received no later than October 18, 1996, at the address indicated in Attachment 4, Item 4 (Fax or E-mail is also acceptable.) and marked "Offeror's Questions, RFP-NIH-NIAID-DMID-97-07." If you have any additional questions regarding this RFP, please contact Sara Southard at the internet electronic mail address ss63e@nih.gov , by phone at 301/402-6289, or by fax at 301/480-5253. Collect calls will NOT be accepted. Sincerely, /s/ Rosemary McCabe Hamill Chief, IAD Contract Section Contract Management Branch National Institute of Allergy and Infectious Diseases Attachments: 1 - 5 ***************************************************************** ***************************************************************** RFP-NIH-NIAID-DMID-97-07 I. STREAMLINED RFP ATTACHMENT 1 8/27/96 INTRODUCTION ------------ The objective of the acquisition is to support clinical trials to test safety and efficacy of biomedical and behavioral interventions aimed at prevention and control of sexually transmitted diseases (STDs). Diseases or pathogens of interest include, but are not limited to: chlamydial infection; gonorrhea; syphilis; chancroid; human papillomavirus (HPV) infection; genital herpes (herpes simplex virus 1 & 2 infections), human herpes virus 8 (Kaposi's sarcoma virus) and human immunodeficiency virus (HIV) infection as it is associated with other STDs (both in terms of increased transmission rates of HIV and alteration of the natural history of STDs). The syndromes of interest include, but are not limited to: pelvic inflammatory disease (and sequelae - infertility, ectopic pregnancy and chronic pelvic pain); adverse outcomes of pregnancy; and cervical cancer as well as other genital cancers associated with HPV infection. Viral hepatitis and cytomegalovirus infection are addressed in other programs of the National Institute of Allergy and Infectious Diseases (NIAID) and are not of interest in this solicitation. These prevention and control strategies encompass primary, secondary and tertiary prevention. The interventions of interest include, but are not limited to: topical microbicides, vaccines, diagnostics tests, screening tests, therapeutics and behavior change. Although the scope of interventions is broad, the number of microbicides, vaccines, diagnostic tests, behavioral interventions, that are appropriate for clinical trials is finite. That said, a prioritization process with respect to category of intervention and specific intervention will be implemented and those interventions of highest priority will be selected for study in the STD CTU. It is anticipated that one completion type contract will be awarded. BACKGROUND ---------- The mission of the NIAID's STD program is to foster, develop, and administer a research program that will contribute to the reproductive health of people and specifically lead to prevention and control of STDs. The broad, public health goals of the research program are: - prevention of STDs; - prevention of infertility; - prevention of adverse outcomes of pregnancy; - prevention of reproductive tract neoplasia; - prevention of human immunodeficiency virus (HIV) infection; and - prevention of other chronic STD sequelae. In order to accomplish our mission, strategies for primary, secondary and tertiary prevention of STDs must be evaluated. Strategies for primary prevention (prevent infection) would include, but are not limited to, topical microbicides, vaccines or behavior change, e.g. increased use of male condoms; secondary prevention strategies (prevent transmission of the infection to others) might include diagnostic screening and treatment; diagnosis and use of single-dose therapies; or behavior change, e.g. self-screening based on mild symptoms or risk behaviors; tertiary prevention strategies (interventions to prevent disease progression and chronic sequelae) might focus on pelvic inflammatory disease and infertility; adverse outcomes of pregnancy; HPV and cervical cancer; or HIV infection. WORK STATEMENT -------------- The Contractor, independently and not as an agent of the government, shall furnish all services, qualified professional and technical personnel, volunteer populations, materials, equipment and facilities not otherwise provided by the government under the terms of this contract, as needed to evaluate biomedical and behavioral interventions to prevent and control sexually transmitted diseases (STDs). Specifically the contractor shall: I. Conduct clinical trials to evaluate interventions to prevent and control STDs, including human challenge studies as appropriate. Contract efforts may include, but are not limited to, clinical trials to evaluate topical microbicides, vaccines, diagnostic tests, therapeutics and behavioral interventions. {NOTES TO OFFEROR: 1. The offeror should describe how an existing clinical and laboratory facility can support the various studies, or describe the establishment of such facilities or collaborations to support the various studies. 2. A well-trained, experienced, and balanced staff to conduct clinical trials is required. The primary investigator (PI) should have an M.D. and/or Ph.D. degree and should have demonstrated expertise in clinical trials related to STDs involving appropriate populations. The team of experts in the diseases of interest should include a nursing staff, experts in adolescent medicine; behavioral science; infectious diseases including STDs, pelvic inflammatory disease and adverse outcomes of pregnancy; obstetrics/gynecology, including colposcopy; clinical trials evaluating vaccines, diagnostic tests, therapeutics, behavioral interventions; epidemiology and biometry. Effective nursing staff are critical to the success of intervention trials and a Research Nurse Coordinator should be identified. Technical personnel, trained and experienced in collecting specimens, and performing assays and laboratory procedures should be included. The offeror should describe coverage of administrative responsibilities. 3. A two page biosketch of each proposed professional should be included in the proposal.} II. Provide and retain patients as required for all clinical trials to ensure timely completion of protocols. {NOTES TO OFFEROR: 4. The availability of appropriate populations is critical to the effective testing of candidate interventions. Offeror's technical proposal should include a detailed description of the types of populations available; consideration should be given to incidence and prevalence of STDs. Estimates of the target populations for the clinical trials efforts are as follows: adolescents, 14-17 years old, (50%); young adults, 18-24 years (30%); adults 25 years and older (20%). Studies may require testing in healthy volunteers at low risk for STDs as well as populations at high risk for STDs. Depending upon the study, monogamous, contracepting women may be required. In other studies sero- positive and/or sero-negative volunteers may be required. 5. For contracts dealing with clinical research, it is NIH policy that women and members of minority groups and their sub-populations 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. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research". A copy of this publication is contained in this RFP Gopher under the RFP REFERENCES - FORMS, FORMATS and INSTRUCTIONS directory.} III. Conduct rigorously designed clinical trials to evaluate safety and effectiveness of topical microbicides, diagnostic tests, therapeutics and behavioral interventions for the prevention of STDs. ALL STUDIES ARE SUBJECT TO PROJECT OFFICER APPROVAL. {NOTES TO OFFEROR: 6. Two sample, detailed, protocols and consent forms should be submitted with the proposal and should demonstrate a thorough understanding of clinical evaluation of the interventions described. i. One Phase I protocol should focus on an approach to the diagnosis of subclinical pelvic inflammatory disease; the offeror should first describe the characteristics of the diagnostic approach followed by an appropriate protocol. The protocol need not describe the use of a currently available product. If a theoretical product or approach is described, the offeror should include sufficient detail to permit determination of the appropriateness of the protocol. The Offeror should consider the Meeting Summary of the NIAID Workshop on Pelvic Inflammatory Disease, December 1994, Attachment 1.A. ii. One Phase II protocol should address the safety/ efficacy of a vaginal topical microbicide to prevent chlamydial infection in an adolescent population. The microbicide protocol need not involve the use of a currently available product. The offeror should describe the "theoretical product" in sufficient detail so as to enable determination of the protocol's appropriateness. The Offeror should consider the International Working Group on Vaginal Microbicides' Recommendations for the Development of Vaginal Microbicides (a copy of this document is available from the NIAID Contracting Officer upon request) and the World Health Organization's (WHO) Manual for Colposcopy, copies of which are available through the WHO, Geneva, Switzerland. iii. The protocols should neither be underway presently nor have been sponsored or reviewed by the NIAID previously. The protocols should document how the Offeror can best address the intent of this RFP. 7. It is anticipated that a representative Phase I study might involve 12-20 patients for a two week time period or a 2-4 month time period depending upon the nature of the intervention being tested; a representative Phase II study would involve 100 patients for a 2-6 month time period. However, the Offeror should justify the number of participants and the study duration proposed in the sample protocols.} IV. Conduct rigorously designed clinical trials to determine vaccine safety, immunogenicity, reactogenicity, optimal dose and schedule; where appropriate, conduct challenge studies in human volunteers immunized with candidate vaccines for gonorrhea or chancroid. Both vaccines and controls shall be challenged with virulent pathogens to assess protection. ALL STUDIES ARE SUBJECT TO PROJECT OFFICER APPROVAL. {NOTES TO OFFEROR: 8. Two sample, detailed, protocols and consent forms should be submitted with the proposal and should demonstrate a thorough understanding of clinical evaluation of the interventions described. i. One Phase I protocol should address the safety of a vaccine for human papillomavirus infection designed to ameliorate disease by inducing regression of genital warts. This protocol need not involve the use of a currently available or "under-development" vaccine. The offeror should describe the "theoretical vaccine" in sufficient detail so as to enable determination of the protocol's appropriateness. If the protocol submitted has been conducted previously it must be so identified. The protocol should document how the Offeror can best address the intent of this RFP. ii. One Phase II protocol should describe a study to assess the safety/effectiveness of a prophylactic vaccine for gonorrhea or chancroid, using the human challenge model of experimental urethritis or skin infection, respectively. This protocol need not involve the use of a currently available or "under-development" vaccine. The offeror should describe the "theoretical vaccine" in sufficient detail so as to enable determination of the protocol's appropriateness. If the protocol submitted has been conducted previously it must be so identified. The protocol should document how the Offeror can best address the intent of this RFP. 9. It is anticipated that a representative Phase I study would involve 12-20 patients for a two week time period or a 2-4 month time period depending upon the nature of the intervention being tested; a representative Phase II study would involve 100 patients for a 2-6 month time period. A representative human challenge experiment would involve 25- 50 people for a two week period. However, the Offeror should justify the number of participants and the study duration proposed in the sample protocols.} V. Collect, appropriately store and conduct assays on sera and other clinical specimens to determine volunteer eligibility and from study participants, as required in the protocol. {NOTE TO OFFEROR: 10. The Offerer should include a complete description of the clinical and laboratory facilities and capabilities required to run assays, in order to document the 1) appropriateness of the population; 2) the safety of the intervention; and 3) the effect of the intervention. A plan for long term follow-up (up to, but not to exceed, monthly evaluations for one year) should be included. Should non- routine or "special" assays be necessary, testing may be arranged by the government, and the offeror will be asked to ship specimens to the appropriate site for assay.} VI. Organize and administer the clinical and associated laboratory research activities of the contract: a. Receive and process concepts for proposed studies. b. Develop and implement a protocol review process that ensures scientific needs are met and that individual protocols are prioritized across the spectrum of existing protocols. c. Write protocols and case report forms and submit to the NIAID Project Officer for review and approval. d. Track the current status of concepts, protocols, active trials, abstracts and publications. e. Prepare clinical trials agreement which includes a delineation of responsibilities of industry, the STD clinical trials unit and the NIAID in the implementation of each trial. The list of responsibilities should be submitted for review to the Project Officer prior to the initiation of each trial. {NOTE TO OFFEROR: 11. With respect to VI.e., the list of responsibilities is to be included, regardless of who has primary responsibility. A sample list is given in Attachment 1.B.} VII. Coordinate submission of protocols, consent forms (including parental assent forms, where applicable), site registration information, local Institutional Review Board (IRB) approval documents, and other Investigative New Drug (IND) or New Drug Application (NDA) information to the Clinical and Regulatory Affairs Branch, Division of Microbiology and Infectious Diseases, NIAID, for those protocols in which the NIAID holds the IND. Ensure that documents are revised and finalized as necessary after review by the Project Officer, the NIAID Clinical and Regulatory Affairs Branch, the local IRB and the regulatory authorities. a. Serve as coordinator for the conduct of clinical trials in the case of multi-site trials. b. Receive and ship reagents and samples, code patients, reagents, and samples, and coordinate all of the subcontractors' activities (if applicable). c. Develop and follow a detailed plan for on-site monitoring; offeror shall monitor according to the plan to ensure completeness and accuracy of study data and adherence with established research standards and protocol requirements and regulatory guidelines. VIII. Develop policies and standard operating procedures for the conduct of the clinical trails, site evaluation criteria, publication criteria, and manuals of operation. All policies and standard operating procedures are subject to approval by the Project Officer. IX. The Principal Investigator shall attend and participate in the semi-annual meetings of the Directors of the STD Cooperative Research Centers (STD CRCs) held in Bethesda, MD, to discuss on- going protocols and future clinical trials agenda with the STD CRC Directors. {NOTES TO OFFEROR: 12. Offerors should include travel costs for the Principal Investigator to attend these 1-day semi-annual meetings in their cost proposal. 13. The STD CRC Directors will act as consultants to the Project Officer and the Principal Investigator of the STD CTU. Additional consultants and advisory activities may be sought and arranged on an as needed basis, by the Project Officer.} X. Organize and conduct an annual, 1-2 day investigators' meeting involving STD CTU and NIH staff. This meeting shall include presentation and review of data, progress updates on all studies, discussion of proposed protocols and establishment of the group's standard operating procedures and research priorities to update the proposed scientific agenda for subsequent submission to the Project Officer. {NOTE TO OFFEROR: 14. The location of these annual meetings will rotate between the Contractor's site and the NIH, Bethesda, MD. The Offeror should assume that there will be approximately ten (10) meeting participants. The Offeror's cost proposal should include travel expenses for the STD CTU Principal Investigator, two STD CTU Investigators, and the Nurse Coordinator to attend the meetings held at the NIH. For meetings held at the Contractor's site, all STD CTU doctoral level staff and the Nurse Coordinator should attend.} XI. Collect, store, manage and analyze data from the conduct of the clinical trials. Prepare and publish all manuscripts and presentations involving data from the clinical trials, including those sponsored by pharmaceutical trials. The Project Officer shall have access to all data generated with the support of this contract and shall review and approve all resulting manuscripts and abstracts before publication. {NOTE TO OFFEROR: 15. The current guidelines for publications resulting from work sponsored by this contract are provided in Attachment 1.C.} {GENERAL NOTES TO THE OFFEROR: 16. Award of the contract does not commit the government to approve the studies outlined or the proposed protocols. The Project Officer will determine which studies are actually undertaken. 17. In general, direct patient costs will not be reimbursed as allowable costs under this contract, except for the cost to house participants in the human challenge studies. Exception for other direct patient costs, on a case by case basis, may be made by the Project Officer. The Offeror should present a plan to indicate how the patient costs associated with the submitted protocols can be covered. Typically this has involved industrial support or co-sponsorship by a General Clinical Research Center. 18. For the purposes of planning and budgeting, assume that fourteen (14) clinical trials will be initiated over the life of the contract with approximately 50% being Phase I and 50% being Phase II. 19. A detailed organizational chart should be provided that shows the administrative structure, reporting structure, supervisory roles, the interactions between the groups and projects, etc. 20. The technical proposals submitted in response to this RFP are subject to page limitations. Please see the RFP Attachment 4, Item 9, "Technical Proposal - Table of Contents", for additional details.} ******************************************************************** Attachment 1.A SUMMARY OF A WORKSHOP ON PELVIC INFLAMMATORY DISEASE ____________________________________________________ March 31, 1995 DRAFT Prepared by: P. Hitchcock & J. Gomez OBJECTIVES AND STRUCTURE OF THE MEETING --------------------------------------- On December 16, 1994, the STD Branch of the National Institutes of Allergy and Infectious Diseases convened a Workshop on Pelvic Inflammatory Disease to discuss and recommend appropriate research strategies for the Institute to pursue that would lead to a reduction of PID and associated sequelae. Based on the Institute's long standing interest in conducting clinical trials to test interventions that would prevent PID associated sequelae - one question that we specifically wanted to address was, "Are we in a position to do such a trial and if not what issues need to be resolved before such a trial could be undertaken?". Other critical questions included: Do we know enough to do a clinical study on diagnosis of PID? What is the current working hypothesis with respect to the development of PID? What are the possible determinants of PID? The meeting was divided into two parts; the first part consisted of four brief background presentations, the second part consisted of informal discussion. The first presentation, by Dr. Jorma Paavonen, focused on the PID prevention and control efforts in Northern Europe. The purpose was to demonstrate and discuss a successful PID prevention model that has been implemented using existing technology. The second presentation, by Dr. Roberta Ness, summarized the clinical challenges facing PID researchers. The purpose was to focus on the opportunities for and impediments to doing treatment trials for PID. The third and fourth presentations, by Dr. Peter Rice and Dr. Walter Stamm, were summaries of research efforts in the PID Program Projects at Boston University and University of Washington, respectively. The purpose was to assess the progress of our current PID research efforts as a prelude to deliberating on appropriate future directions. HIGHLIGHTS OF PRESENTATIONS --------------------------- The Northern European Model: Dr. Paavonen presented data from Norway and Finland that indicated the declining trends of gonorrhea. In 1991 there were 92 cases of gonorrhea in Norway and 600 in Finland. (A similar trend has occurred in Sweden as well.) The decline of chlamydial infections is similar but not as dramatic. He speculated that this may be due to the asymptomatic nature of the infection (25% of men and 75% of women are asymptomatic); specifically the criteria for screening may be differentially affected. In both countries, declines in rates of PID have followed, as has ectopic pregnancy rates in Finland. Concurrently, there has been a change in the epidemiology and clinical manifestations of PID. When detected, the disease seems to be milder; he speculated that this may be due to decreased IUD use and increased use of hormonal contraceptives. Given the trend towards milder disease, diagnostic problems have been exacerbated and the apparent number of cases may be lower than the actual number. Clinical Challenges: Dr. Ness began by identifying the current clinical perceptions about PID and focused remarks on her assessment of the current clinical realities. The perceptions are: 1) we have made little diagnostic progress on PID; 2) we cannot do treatment trials because we cannot diagnose the disease; 3) we cannot do treatment trials because we cannot follow the patients; and 4) we do not need to do treatment trials because once the disease is diagnosed, the damage is done. The realities are: 1) laparoscopy is the most specific test; the positive predictive value increases if used in combination with other signs/symptoms; 2) treatment trials do depend upon the diagnostic capabilities but laparoscopy will identify damaged tubes in women who have no recollection of PID episodes; 3) studies are being done with PID patients, follow up issues are challenging but the patients' mothers have proven to be a good way to track them; 4) the treatment trials that have showed no impact on infertility did not employ optimal therapies. In the discussion period that followed, most of the participants felt that there were a number of caveats associated with the current realities, these are reflected in the recommendations. Dr. Holmes added that the use of ligase chain reaction (LCR) to diagnose chlamydial infection in cervical and tubal samples is clearly going to increase the sensitivity of laparoscopy for the diagnosis of PID. In the monkey model, rates of positive results using culture compared to LCR were as follows: cervical 82%, tubal 47% and cervical 100%, tubal 87% respectively. Boston University PID Program Project: Dr. Rice presented an overview of their ongoing research which is based on combining clinical and laboratory investigations. They are conducting a clinical study which is focused on identifying and characterizing factors that influence transmission from males to females and then determining whether the women have evidence of PID. The index cases are male STD clinic patients, with culture proven gonorrhea or chlamydial infection, that have had two or more contacts in 30 days; the clinic population is 80% African American, and 90% of individuals are of low socioeconomic status. The female partners are enrolled and evaluated; virtually all of them are asymptomatic. Analysis of the number of exposures and the infection status revealed a surprising finding: there is no increase in infection with multiple exposures; about 25% of the women appear to be immune to gonorrhea. Cultures and molecular analysis of the strains from partners revealed 98% concordance. Analysis of the immunological features of the susceptible and resistant contacts revealed that antibodies to Protein I and LPS were protective and antibodies to Protein III were associated with susceptibility. Studies of chlamydial infection revealed similar pattern of resistance with only 50-60% of the women being susceptible. Interestingly there were multiple serovars found in both the men and the women; most, but not all, were concordant. In terms of evidence for PID in the contacts of infected men, 25% of women had a positive endometrial culture and biopsy (plasma cell endometritis). University of Washington PID Program Project: Because of the region X chlamydial control program, the population in the Seattle area has a low prevalence of chlamydial infection (4%). In this study, women who were members of a group health cooperative were surveyed for demographic, behavioral and clinical characteristics that have been proven, by the Seattle group, to identify women at risk for chlamydial infection. High risk women were randomized to an intervention or a control group. The intervention group was screened and treated for chlamydial infections whereas symptom driven diagnosis and treatment was provided in the control group. The incidence of PID was 8% in the intervention group compared to 18% in the controls. The conclusion is that selective screening and treatment of chlamydial cervicitis can contribute to PID control efforts even in a low risk populations. It is estimated that treatment of 44 cases of chlamydial infection would prevent 15 cases of PID. A cost effective analysis is now in progress. When urine-based diagnostic tests for chlamydial infection become available, different kinds of screening programs can be considered. SUMMARY OF CRITICAL RESEARCH ISSUES ----------------------------------- Based on a series of discussions, prior to and during the workshop, a number of critical research issues were identified. Behavioral Research ------------------- Important behavioral research issues focused on two broad categories: host and provider. HOST (includes both patient and partner) ----------------------------------------- - sexual behavior - contraceptive practices - douching - organism-specific risks - risks associated with type/stage of PID - male partner characteristics and behaviors - screening and treatment - symptom recognition - treatment compliance - partner notification - awareness of link between PID and infertility - other behaviors to prevent PID and sequelae PROVIDER -------- - bias in perception of at-risk women - screening/prevention - diagnosis - treatment recommendations - health care setting - physician training Clinical/Epidemiological Research --------------------------------- Important clinical/epidemiological research issues fell into four broad categories: diagnostics, treatment, natural history, and management. DIAGNOSTICS - methods for diagnosis of acute PID, silent PID, and long term sequelae - significance of cervicitis and endometritis - development of serological diagnostic capabilities - role of LCR and PCR in detecting organisms in upper tract - significance of non-STD microbiological findings - role of screening and case-finding in PID prevention TREATMENT - broad spectrum therapy for chlamydial infection, gonorrhea, anaerobes, ureaplasma, and mycoplasmas - role of anti-inflammatory therapy - role of single dose therapies - long term outcome measures associated with current treatment regimens NATURAL HISTORY - persistence versus recurrent infection - immunology - PID in HIV-infected women male partner - risk factors for PID, acute PID, silent PID, tubal scarring MANAGEMENT - in-patient versus out-patient management - development of more effective algorithms using new diagnostic methods as adjuncts - development of prototypes for PID case management - cost effectiveness analyses of current practices - development of follow-up strategies for at-risk women Basic Research -------------- Basic research issues were categorized as either pathogen or host related. PATHOGEN - virulence factors for gonococcal and chlamydial PID: factors which influence invasion, ascension, scarring, persistence, immunopathogenesis, and symptomatic versus asymptomatic infections - non-STD organisms: virulence factors (as above) and requisite conditions for pathogenesis - pathogenesis: interplay with host factors, including elicitation of "auto antibodies", deleterious cytokines or steroid hormones, and complement-mediated damage - PID vaccine development correlates of protection, avoiding vaccine induced damage to the reproductive tract; significance of antigenic variation/MOMP polymorphism HUMAN HOST - genetics: immuno-genetics, cyto-genetics - normal defenses: flora, pH, mucin, defensins, etc. - reproductive hormones: role in protection, pathogenesis; relevance in puberty, during menses, contraceptives - immunity: role in protection, pathogenesis; characterization of mucosal and systemic immunity in infection; role of cellular and antibody constituents; - study of chlamydial heat shock protein 60 ANIMAL MODELS - development - characterization - relevance (strengths and weaknesses) - study of chlamydial heat shock protein 60 GROUP CONSENSUS --------------- The group considered whether or not it was appropriate, at this time, to conduct a clinical trial testing interventions to prevent the acquisition of PID and the long term sequelae of PID, specifically tubal scarring, ectopic pregnancy and infertility. The consensus was that a clinical trial is not feasible at this point in time. There was uniform agreement that the major obstacle to a trial is the absence of diagnostic capabilities for asymptomatic or silent PID. Furthermore, there was remarkable agreement about the critical gaps in our knowledge of PID, including the ideas that vaginitis/cervicitis is necessary but perhaps not sufficient to cause PID and that the microbes, the host (the patient and the partner) and the provider all play key roles in the development of PID. Two cross cutting themes were apparent in the deliberations and final recommendations: the application of medical advances to the problem and the consideration of the ethical-issues in PID clinical research. ADDITIONAL DISCUSSION ISSUES ---------------------------- During the informal discussion period a number of new issues as well as confirmation of issues generated in the pre-meeting activities were addressed. Behavior: - Patient/Partner Behaviors: Perception of normal will influence symptom recognition (e.g, is a vaginal discharge normal, how much how often, what kind?) . In the absence of a gold standard for diagnosing PID, surrogate measures such as cervicitis or infertility, might be used. The outcome measures will influence identification of risk associated behaviors. - Provider Behaviors: Clinical research is needed to determine if practitioners are using CDC treatment guidelines for PID. The variations in health care settings and provider specialty should be evaluated. The role (and type) of medical education in enhancing the ability of the provider to recognize and treat PID needs to be studied. Clinical: - Endometrial Biopsy: Clinical research (including application of modern technology for evaluation) is needed to better characterize the chronology, prevalence and significance of endometritis as a part of PID and as an indicator of tubal infection. - Laparoscopy: Doing a second procedure (second look) after treatment may be an effective way to measure tubal damage as opposed to longer term clinical manifestations of tubal damage. - Magnetic Resonance Imaging (MRI): Clinical research is needed on the capabilities of MRI to detect uterine or endometrial changes. The goal would be to use this as a gold standard in order to identify reliable and reproducible markers of PID that would be inexpensive and more appropriate for resource limited settings. - Treatment: Research is needed on the chronology of events in PID to determine when/if cervical infection should be treated as if there were concurrent upper tract infection. Basic Research: - Immunology: Basic research is needed to delineate the cell mediated immune response including the epitope specificity of that response, the immuno-histopathology (e.g., the role of cytotoxic T-cells in delayed hypersensitivity) and the immunogenetics of the host (e.g., HLA type). - Microbiology: Research is needed on the role of other agents in the etiology of PID. This aspect of PID microbiology is poorly characterized and not understood. - Serology: Research is needed on serologic markers of tubal damage, including antibodies and cytokines. - Reproductive Endocrinology: Research on the influence of natural or exogenous reproductive hormones on susceptibility, resolution, progression or symptoms of PID is needed. RECOMMENDATIONS: ---------------- Based on the deliberations of the group the following recommendations were made vis a vis research needs and opportunities for the immediate future: - Clinical research on the diagnosis of PID, especially asymptomatic PID, should be given the highest priority, with special emphasis on the positive predictive value of the test. - Further clinical research on screening and treating asymptomatic cervical infections as an effective approach to PID prevention is needed. - Support for basic research into the pathogenesis of PID will provide important information leading to more effective behavioral, therapeutic and immunological interventions. - High priority should be given to development and characterization of an animal model of PID, especially one that includes tubal scarring. - Research into patient/partner and provider behaviors is likely to provide important information needed to develop effective interventions for PID prevention and control. ******************************************************************** Attachment 1.B Sample List of Responsibilities _______________________________ The Contractor shall prepare for approval by the Project Officer a list of responsibilities to indicate who will: Generate consent forms Approve consent forms Distribute consent forms to sites* Conduct site assessment/orientation/start-up visits* Collect pre-study regulatory documents Sponsor IND Submit protocol and regulatory documents to FDA Ship study medication to repository or sites* Generate randomization codes Hold randomization codes Perform CRF/drug supply/regulatory site monitoring* Perform QA monitoring Report serious adverse events to FDA - 3 & 10 day reports - annual safety reports Monthly update of enrollment, ADE's, and waivers Harvest completed CRFs Conduct secondary review of CRFs Log in CRFs, generate queries to investigators Perform data entry and logic checks Resolve all queries and ensure audit trail Submit annual IND report to FDA Submit any protocol revisions, updated 1572s to FDA Obtain copies of annual IRB renewals from the sites Design CRF Print CRF Distribute CRFs to sites* Maintain lab samples (serum/isolate) in a repository Serve as central lab facility for drug levels/susceptibilities Analyze data Present data to DSMB * Note: Intended for multi-center studies. ******************************************************************** Attachment 1.C GUIDELINES FOR MANUSCRIPT WRITING _________________________________ 1. For publication of the primary results from each official study, a Writing Committee will e appointed. This Committee will typically consist of: a. the study principal investigator (P.I.). b. the responsible biostatistician. C. any other individuals, e.g., investigators, Operations Office staff, who have contributed substantially to the study as determined by the study P.I. 2. The Chair of the Writing Committee will be the study P.I. 3. For a joint studies with the ACTG or other collaborative groups the Writing Committee will be merged with a similarly constituted Writing Committee from the appropriate collaborative group. 4. The Writing Committee will prepare drafts of a manuscript. Before submission of the final draft to a peer-reviewed journal, the draft should be circulated to all participating investigators. the Operations Office. the Principal Investigator and representatives of industry (where appropriate) for comments and suggestions and to the NIAID for approval by the Project Officer. 5. If additional manuscripts result from any official study, additional Writing Committees can be constituted. The same general guidelines will apply. 6. Authorship and its order for a given manuscript should reflect workload, intellectual contribution, and patient contribution. The composition of authorship will differ depending on the number of institutions involved, the number of patients, and the nature of any special assessments, such as laboratory studies. 7. The first author of the manuscript will usually be the Study P.I. (Writing Committee Chair). The masthead for authorship of a manuscript will be determined by journal guidelines. For example, the number of authors may vary from a few (3-5) to many (15-25). The ultimate order of names on the masthead will be determined by the Writing Committee Chair. If there is any appeal about the order of authors, the final decision will be made by the Principal Investigator. 8. The NIAID Contract number must be provided in the Acknowledgement section. 9. In addition to authorship, a manuscript should acknowledge all participating institutions (sites) enrolling evaluable patients. The listing of institutions should be in order of evaluable patients. The listing may include up to 4 persons per participating institution, the participating Central Staff, and the appropriate industry participants. 10. The selection of the journal will be at the discretion of the Chair of the Writing Committee. 11. Copies of the final draft submitted for publication should be sent to each of the authors the administrator, Operations Office, and the Project Officer. 12. After journal review of a manuscript has been completed. the dialogue between Editors, Reviewers, and the Writing Committee should be handled at the Writing Committee level. Correspondence from the Editors including the reviews.should be distributed to each of the authors listed in the masthead. and to the Administrator, Operations-Office. 13. A copy of the final revised manuscript should be sent to each of the authors and the Administrator. Operations Office. GUIDELINES FOR ABSTRACTS ________________________ 1. These guidelines (listed above) would apply, where appropriate, to abstracts. 2. No presentation of primary results from any study may be made without the approval of the P.I., biostatistics unit, and the Project Officer. 3. A copy of all abstracts, based on official studies, must be submitted to the Administrator, Operations Office, and the Project Officer, simultaneously with submission for presentation. ******************************************************************** ******************************************************************** RFP-NIH-NIAID-DMID-97-07 ATTACHMENT 2 8/27/96 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; in addition to the number of hard copies requested in each case, an electronic copy shall be submitted on diskette or by electronic mail (Email). These reports are subject to 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) QUARTERLY TECHNICAL PROGRESS REPORTS - by the fifteenth working day of the month following the end of each three month period, the Contractor shall submit four (4) copies of the quarterly Technical Progress Report, comprising three (3) 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 name 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. 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 next three months; and f. Pre-prints and reprints shall be submitted along with the report. Quarterly 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 and shall include information regarding numbers of women and minority subjects enrolled in trials. 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. An annual report will not be required for the period when the final report is due. Pre-prints and reprints not submitted in the quarterly report shall be submitted. The annual report will also append all relevant manufacturing documents available for the Project Officer's confidential review, these include, but are not limited to: quality control (QC) documentation; formal accelerated and real-time stability protocols; component specifications; manufacturing procedures. (3) FINAL REPORT - By the expiration date of the contract, the Contractor shall submit ten (10) copies of a comprehensive Final Report, as above, comprising nine (9) copies to the Project Officer and one (1) copy to the Contracting Officer. These final reports shall detail, document and summarize the results of the entire contract period of performance. These reports shall be in sufficient detail to explain comprehensively the results achieved. Pre-prints and reprints not included previously shall be submitted. (4) SUMMARY OF SALIENT RESULTS - With the annual and final reports the Contractor shall submit a summary (not to exceed 200 words) of salient results achieved during performance of the contract. (5) OTHER REPORTS - To facilitate compliance with regulatory requirements, the Contractor shall submit to the Project Officer (10) copies of a brief summary of each ongoing and completed protocol one year and thirty days after FDA approvals go into effect. 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 any anticipated delays with reasons. ******************************************************************** ******************************************************************** RFP-NIH-NIAID-DMID-97-07 ATTACHMENT 3 8/27/96 EVALUATION FACTORS FOR AWARD ____________________________ 1. COMPARATIVE IMPORTANCE OF THE 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 will become paramount. In any event the Government reserves the right to make an award to the best advantage of the Government, cost and other factors considered. 2. GENERAL The technical proposal will receive paramount consideration in the selection of the Contractor for this acquisition. The evaluation will be based on the demonstrated capabilities of the prospective contractor 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. 3. MANDATORY QUALIFICATION FOR FACILITIES Prior to award the offeror must document the adequacy and suitability of the facilities for performing all of the requirements of the Work Statement. 4. 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 60 Documented technical adequacy and feasibility of the proposed plans to conduct Phase I and Phase II clinical trials of biomedical and behavioral interventions on topical microbicides, vaccines, diagnostics tests, screening tests, therapeutics and behavior change to prevent and control STDs. Adequacy, suitability and availability of necessary populations, including women and minorities as documented in the proposal. Documented technical adequacy and feasibility to collect store and analyze specimens. (20 points each) a) PHASE I AND II TRIALS OF TOPICAL MICROBICIDES, DIAGNOSTIC TESTS, THERAPEUTICS AND BEHAVIORAL INTERVENTIONS -- This includes the comprehensive approach, suitability and originality of the sample clinical protocols cited in the Work Statement, appropriateness of consent forms and data collection forms, demonstrated ability to recruit, retain, monitor and follow-up appropriate and relevant populations. b) PHASE I AND II TRIALS OF THERAPEUTIC AND PREVENTIVE VACCINES -- This includes the comprehensive approach, suitability and originality of the sample clinical protocols cited in the Work Statement, appropriateness of consent forms and data collection forms, demonstrated ability to recruit, retain, monitor and follow-up appropriate and relevant populations and the approach to investigating gonorrhea or chancroid utilizing the established human challenge models. c) COLLECTION, APPROPRIATE STORAGE AND ANALYSIS OF CLINICAL SPECIMENS -- This includes the comprehensive approach and technical adequacy of clinical and laboratory capabilities to perform all assays. 2. Management of Work 20 Adequacy of plans for organizing, and administering the clinical and laboratory research activities of the contract. (10 points each) a) PREPARATIONS FOR CLINICAL TRIALS -- This includes the suitability of proposed processes to review and prioritize concepts, write and review protocols, and all attending documentation. b) ADMINISTRATION AND MONITORING OF CLINICAL TRIALS -- This includes the suitability of the plan to develop and administer policies and standard operating procedures. 3. Personnel 20 Documented adequacy and relevance of expertise, experience, education/skill, and availability of personnel for performing all the requirements. (10 points each) a) CLINICAL TRIALS STAFF -- The primary investigator (PI) should have an M.D. and/or Ph.D. degree with expertise in clinical trials related to STDs involving appropriate populations. The team of professional personnel including the nursing staff, with documented clinical trials expertise, should have composite experience in: 1) adolescent medicine; 2) infectious diseases including STDs, pelvic inflammatory disease and adverse outcomes of pregnancy; 3) obstetrics/gynecology, including colposcopy; 4) clinical trials evaluating vaccines, diagnostic tests, therapeutics, behavioral interventions; 5) epidemiology and biometry. The capabilities and expertise of the designated Research Coordinator should be documented. The support staff should possess the requisite experience to perform their clerical and administrative duties. b) LABORATORY PERSONNEL -- The technical personnel and their supervisor(s) should be trained and experienced in performing assay and laboratory procedures. TOTAL POSSIBLE POINTS.................................... 100 5. 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-97-07 ATTACHMENT 4 8/27/96 II. 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 5, "Applicable RFP References." 1. SIC CODE AND SMALL BUSINESS SIZE STANDARD (NIH 3150) (JUN 1988) Note: The following information is to be used by the offeror in preparing its Representations and Certifications (See Attachment 5, Item 4. of this RFP.), specifically in completing the provision entitled, SMALL BUSINESS PROGRAM REPRESENTATIONS (OCT 1995), FAR 52.219-1: (a) The standard industrial classification (SIC) code for this acquisition is 8733. (b) (1) The small business size standard is $5,000,000. (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 $5,000,000. (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. 2. NUMBER AND TYPE OF AWARD(S) (NIH 2980) (APR 1984) It is anticipated that one (1) award will be made from this solicitation and that award will be made on or about September 30, 1997. It is anticipated that the award from this solicitation will be multiple-year cost reimbursement, completion type contract with a period of performance of 5 years, 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]. 3. 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 total direct labor effort to be approximately 4,500% (900%/year). 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 Effort* 5 YR Category Yr 1 Yr 2 Yr 3 Yr 4 Yr 5 TOTAL -------- ---- ---- ---- ---- ---- ----- P.I. 30% 30% 30% 30% 30% 150% Investigators 220% 220% 220% 220% 220% 1,100% RNs 350% 350% 350% 350% 350% 1,750% Biostat. Support 50% 50% 50% 50% 50% 250% Technicians 200% 200% 200% 200% 200% 1,000% Admin. Support 50% 50% 50% 50% 50% 250% ==== ==== ==== ==== ==== ====== TOTAL 900% 900% 900% 900% 900% 4,500% * Effort in the above chart was based on 100% effort = 2,080 hours per year, which includes holidays and other paid absences. If you are using a different base, please state the work year used in your proposal. The above level of effort is the Government's estimate of the effort that will be necessary to satisfactorily accomplish the objective of these studies, and it will be used as a basis for negotiations. However, you can propose deviations from this estimated level of effort, with justification. 4. PACKAGING AND DELIVERY OF THE PROPOSAL (NIH 2995) (JUL 1994) 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-97-07" "TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY" Number of Copies: ----------------- Technical Proposal: ORIGINAL AND 20 COPIES Business Proposal: ORIGINAL AND 5 COPIES If hand delivered or delivery service: -------------------------------------- Contract Specialist Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard Rockville, Maryland 20852 If using U.S. Postal Service: ----------------------------- Contract Specialist Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 * 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" and handled in accordance with PHSAR 352.215-10 LATE PROPOSALS, MODIFICATIONS OF PROPOSALS AND WITHDRAWALS OF PROPOSALS (NOV 1986). 5. 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 S. 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. 6. PRIVACY ACT SYSTEM OF RECORDS The Privacy Act System of Records Notice that applies to this RFP was published in the Federal Register dated January 13, 1993, Vol. 58, No. 8, Pages 4226-4228. This notice will be incorporated into any contract resulting from this RFP. If you would like a copy, please contact the Contracting Officer identified in the cover letter to this RFP. 7. PHS 352.223-70 SAFETY AND HEALTH (APRIL 1984) (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 will consult, comply with, and include in all applicable subcontracts, the following standards, as appropriate: (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) Recommendations for Prevention of HIV Transmission in Health- Care Settings, Morbidity and Mortality Report, August 21, 1987, Vol. 35, No. 2S. (3) Update: Universal Precautions for Prevention of Transmission of Human Immunodeficiency Virus, Hepatitis B Virus, and Other Bloodborne Pathogens in Health-Care Settings. Morbidity and Mortality Weekly Report, June 24, 1988, Vol. 37, No. 24. (4) Agent Summary Statement for Human Immunodeficiency Viruses (HIV); Included are GTLV-III, LAV, HIV-1, and HIV-2. Morbidity and Mortality Weekly Report, April 1, 1988, Vol. 37, No. S4. (5) Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs, NIH Publication No. 83-2621. (6) NIH Guidelines for the Laboratory Use of Chemical Carcinogens, NIH Publication No. 81-2385. The above, (1) - (6), may be obtained from: Division of Safety Office of Research Services National Institutes of Health Building 31, Room 1CO2 31 Center Drive, MSC 2260 Bethesda, Maryland 20892-2260 (7) Guidelines for Research Involving Recombinant DNA Molecules (49 FR 46266 or latest revision) and Administrative Practices Supplement. These may be obtained from: Office of Recombinant DNA Activities Office of Science Policy and Legislation National Institutes of Health Building 31, Room B1C34 31 Center Drive, MSC 2250 Bethesda, Maryland 20892-2250 (8) Procedures for the Domestic handling and Transport of Diagnostic Specimens and Etiologic Agents, National Committee for Clinical Laboratory Standards, July 17, 1985, Vol. 5. This may be obtained from: National Committee for Clinical Laboratory Standards 771 East Lancaster Avenue Villanova, Pennsylvania 19085 Further, the Contractor shall take or cause to be taken such additional safety measures as the Contracting Officer may determine to be reasonably necessary; Provided, that if compliance with such additional safety measures results in a material increase in the cost or time of performance of the contract, an equitable adjustment will be made in accordance with the clause of this contract entitled "Changes." (b) Prior to commencement of work, the Contractor will submit in writing its plan for complying with the safety and health provisions of this contract, and will meet with the Contracting Officer or his/her designated representative to discuss and develop a mutual understanding relative to administration of the overall safety program. (c) During the performance of work under this contract, the Contractor shall comply with all procedures prescribed by the Contracting Officer for the control and safety of persons visiting the job site and will comply with such requirements to prevent accidents as may be prescribed by the Contracting Officer. (d) The Contractor will maintain an accurate record of, and report to the Contracting Officer in such manner as the Contracting Officer may prescribe, all accidents and incidents resulting in death, traumatic injury, occupational disease, and/or damage to all property incident to work performed under the contract. (e) The Contracting Officer shall notify (if otherwise, confirm in writing) the Contractor of any noncompliance with the provisions of this clause and corrective action to be taken. After receipt of such notice, the Contractor shall immediately take such corrective action. (Such notice, when delivered to the Contractor or its representative at the site of the work, shall be deemed sufficient for the purpose.) If the Contractor fails or refuses to comply promptly, the Contracting Officer may issue an order stopping all or part of the work until satisfactory corrective action has been taken. No part of the time lost due to any such stop order shall be the subject of claim for extension of time or for costs or damages by the Contractor. (f) The Contractor shall insert the substance of this clause in each subcontract involving the use of hazardous materials or operations. Compliance with the provisions of this clause by subcontractors will be the responsibility of the Contractor. 8. 52.227-6 ROYALTY INFORMATION (APR 1984) (a) Cost or charges for royalties. When the response to this solicitation contains costs or charges for royalties totaling more than $250, the following information shall be included in the response relating to each separate item of royalty or license fee: (1) Name and address of licensor. (2) Date of license agreement. (3) Patent numbers, patent application serial numbers, or other basis on which the royalty is payable. (4) Brief description, including any part or model numbers of each contract item or component on which the royalty is payable. (5) Percentage or dollar rate of royalty per unit. (6) Unit price of contract item. (7) Number of units. (8) Total dollar amount of royalties. (b) Copies of current licenses. In addition, if specifically requested by the Contracting Officer before execution of the contract, the offeror shall furnish a copy of the current license agreement and an identification of applicable claims of specific patents. 9. TECHNICAL PROPOSAL TABLE OF CONTENTS/FORMAT (NOTE: INSTRUCTIONS TO OFFERORS ARE INDICATED IN PARENTHESES OR AS FOOTNOTES.) SECTION # PAGE # 1. TECHNICAL PROPOSAL COVER SHEET (Format in Section C of Gopher RFP: FORMS, FORMATS, ATTACHMENTS) .............. 1 2. TECHNICAL PROPOSAL TABLE OF CONTENTS ....................... 2 3. SUMMARY OF OBJECTIVES AND METHODS* ......................... 3 4. TECHNICAL PLAN ** (Refer to Technical Proposal Instructions, Section C.1., Standard RFP Instructions and Provisions, Gopher RFP for more detail) a. WORK STATEMENT 1. Objectives .................................. 4 2. Approach .................................... ____ 3. Methods ..................................... ____ 4. Schedule .................................... ____ b. 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 floor plan in Section 6, below) ........................ ____ c. 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 (technical support/ subcontractors/consultants) ................. ____ [Note: For personnel, include 2 page biosketch and the form entitled "Summary of Current and Proposed Activities" under Sections 5 and 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 Directory found in Section C, Gopher RFP)......... ____ b. "Technical Proposal Cost Information" form (located in Section C, Gopher RFP, FORMS, FORMATS, & ATTACHMENTS)...................................... ____ c. Laboratory Design and Floor Plan (clearly indicate the space available for this Project)............. ____ * State the proposal's broad, long-term objectives and specific aims. Briefly and concisely describe the research design and methods for achieving these goals (limit to one page). ** Sections 4.a. through 4.d. above MUST NOT EXCEED 200 PAGES (this does not include copies of resumes/biosketches and any required forms or protocols, but only the NARRATIVE description of the Technical Plan). 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. ********************************************************** 10. PROPOSAL INTENT RESPONSE SHEET PROPOSAL INTENT --------------- RFP No.: NIH-NIAID-DMID-97-07 PLEASE REVIEW THE ATTACHED REQUEST FOR PROPOSAL. FURNISH THE INFORMATION REQUESTED BELOW AND RETURN THIS PAGE BY THE EARLIEST PRACTICABLE DATE. 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: __________________________________________________________ __________________________________________________________ [ ] DO NOT INTEND TO SUBMIT A PROPOSAL FOR THE FOLLOWING REASONS: __________________________________________________________ __________________________________________________________ TYPED NAME AND TITLE: _______________________________ INSTITUTION: ________________________________________ SIGNATURE: __________________________________________ TELEPHONE NO.: ______________________________________ DATE: _______________________________________________ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - COLLABORATORS/CONSULTANTS - Provide name(s) and institution(s): (Continue list on reverse if necessary) ________________________________________________________________ ________________________________________________________________ RETURN TO: CMB, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 Attn: Sara M. Southard RFP NIH-NIAID-DMID-97-07 Fax # 301/480-5253 PLEASE RETURN BY DECEMBER 20, 1996 ************************************************************ ******************************************************************** RFP-NIH-NIAID-DMID-97-07 ATTACHMENT 5 8/27/96 III. APPLICABLE RFP REFERENCES ------------------------------ This section identifies the items located in the Gopher directory "C. 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" (below). 2. The following items are applicable from the file entitled" OPTIONAL RFP INSTRUCTIONS AND PROVISIONS": (1) LATE PROPOSALS, MODIFICATIONS OF PROPOSAL, AND WITHDRAWALS OF PROPOSALS, PHS 352.215-10 (2) HUMAN SUBJECTS (3) CARE OF LIVE VERTEBRATE ANIMALS - NOTICE TO OFFERORS OF REQUIREMENT FOR ADEQUATE ASSURANCE OF PROTECTION OF VERTEBRATE ANIMAL SUBJECTS (SEP 1985), PHSAR 352.280-2(a) (4) SMALL, SMALL DISADVANTAGED AND WOMEN-OWNED SMALL BUSINESS SUBCONTRACTING PLAN, FAR 52.219-9 [NOTE: A Subcontracting Plan is not due with the initial proposal. The Contracting Officer will notify offerors if a plan becomes due.] (5) INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS 3. The following items are applicable from the subdirectory entitled "FORMS, FORMATS, AND ATTACHMENTS": Applicable to Technical Proposal -------------------------------- (1) Technical Proposal Cover Sheet (2) Technical Proposal Cost Information, Dec 1988 (3) Summary of Current and Proposed Activities, July 1995 Applicable to Business Proposal ------------------------------- (4) Contract Pricing Proposal, SF-1411, (Rev. 10/95) (5) Proposal Summary and Data record, NIH-2043 (Rev. 6/82) (6) Business Proposal Cost Information (7) Disclosure of Lobbying Activities, OMB SF-LLL To Become Contract Attachments ------------------------------ (8) Invoice/Financing Requests Instructions for NIH Cost- Reimbursement Type Contracts, NIH(RC)-1, JUN 1992 (9) Instructions for Completing Form NIH 2706 (Financial Report (10) Procurement of Certain Equipment, NIH(RC)-7 (11) Research Patient Care Costs, NIH(RC)-11 (12) NIH Women and Minority Policy (13) Protection of Human Subjects - Assurance Identification/ Certification/Declaration, OF 310 Other - to be submitted as directed by Contracting Officer ---------------------------------------------------------- (11) Certificate of Current Cost or Pricing Data, NIH-1397 (12) Subcontracting Plan 4. The Representations and Certifications are applicable and a completed copy must be submitted with offeror's business proposal. 5. The "Sample Contract Format-General" is applicable. ******************************************************************** End of document