Part A of the solicitation, to be awarded in FY 2000 in FY 1999, encompasses clinical trials and mechanistic studies in kidney and islet transplantation.

Parts B, C and D of the solicitation are Task Orders that may be issued by the Government based on scientific needs and opportunities and the availability of funds.

Overall scientific leadership and direction for the Collaborative Network will be carried out by an Executive Committee, composed of the Network Project Director, other scientific and clinical investigators, NIAID scientific staff, a representative of the Juvenile Diabetes Foundation International, and the Project Director for the Statistical and Clinical Coordinating Center. The Network Executive Committee will be responsible for: (1) the development and ongoing review and modification of the scientific agenda; (2) the establishment and implementation of procedures for the development, review and evaluation of concepts for clinical trials and mechanistic studies, including evaluation/selection criteria to be used; (3) setting priorities among proposed concepts; (4) monitoring and evaluating progress; (5) allocating resources; and (6) assessing the need for redirection in scientific focus and implementing necessary changes to redirect resources in order to accommodate new knowledge and changing opportunities.

Overall scientific leadership and direction for the Autoimmunity Centers of Excellence will be carried out by a Steering Committee, composed of Center basic and clinical investigators, NIAID scientific staff, and the Project Director for the Statistical and Clinical Coordinating Center. The Autoimmunity Center Steering Committee will be responsible for: (1) the development and ongoing review and modification of the scientific agenda; (2) the establishment and implementation of procedures for the development, review and evaluation of concepts for clinical trials and mechanistic studies, including evaluation/selection criteria to be used; (3) setting priorities among proposed concepts; (4) monitoring and evaluating progress; (5) allocating resources; and (6) assessing the need for redirection in scientific focus and implementing necessary changes to redirect resources in order to accommodate new knowledge and changing opportunities.

Both the Collaborative Network and the Autoimmunity Centers will design policies and procedures for the development and review of concepts for proposed clinical trials and mechanistic studies, and for the development and review of proposed clinical trials and mechanistic studies. All such policies and procedures shall be subject to review and approval by the Government. In addition, proposed concepts for clinical trials and mechanistic studies, as well as proposed clinical trials and detailed research plans for mechanistic studies, shall be subject to review and approval by NIAID staff and, when necessary, by external advisors selected by the NIAID to provide advice and assistance in the monitoring of these research programs.

Additional Information on the Scope and Requirements of This Solicitation

• The NIAID Autoimmunity Centers of Excellence will be supported through the Cooperative Agreement mechanism for a period of four (4) years, beginning in late FY 1999. The Statistical and Clinical Coordinating Center shall provide support for the NIAID Autoimmunity Centers of Excellence for a total period of five (5) years.

  The NIAID Collaborative Network for Clinical Research on Immune Tolerance will be supported through the contract mechanism for a period of seven (7) years, beginning in early FY 2000 late FY 1999. The Statistical and Clinical Coordinating Center shall provide support for the NIAID Collaborative Network for Clinical Research on Immune Tolerance for a total period of nine (9) years.

• For purposes of this solicitation, immune tolerance/immunomodulation is defined as a selective lack of an immune response to targeted antigens (e.g., alloantigens, autoantigens, or allergens) by any of a variety of approaches, including: deletion, induction of anergy, immune deviation, sequestration or suppression. Approaches may target antigen-specific receptors, molecules of the co-stimulation pathways, homing molecules, or other relevant molecules; and may use a variety of agents, including: antigens, peptides, altered peptides, monoclonal antibody blockade, cytokines, molecularly engineered cells or tissues, DNA vectors, or other relevant approaches.
• A broad range of statistical, technical, regulatory, clinical trial coordination and monitoring and administrative expertise will be necessary to carry out the requirements of this solicitation. The Government recognizes that a single institution or organization may not have the expertise and facilities necessary to perform all requirements and, therefore, that it may be necessary for the Prime Contractor to subcontract portions of the work to be performed. Offerors shall have flexibility in proposing a structure and organization capable of meeting the requirements of this work statement. However, the Prime Contractor should demonstrate proven expertise in: (1) providing statistical leadership for the design of clinical trials and the analysis of study results; (2) designing and administering data collection, management, quality assurance and reporting systems; (3) supporting regulatory and technical functions and requirements associated with Investigational New Drug (IND) Applications; (4) coordinating Data Safety and Monitoring Board activities, including the preparation of interim data and reports; and (5) supporting the technical and administrative functions of governing bodies of multi-site cooperative clinical research programs.
• Because the design and development path for the research to be carried out by the Collaborative Network and the Autoimmunity Centers of Excellence cannot be entirely anticipated, the Contractor shall be required to propose a plan for accommodating changes in the scientific direction of the clinical research to be conducted in order to capitalize on new scientific findings and therapeutic approaches relative to the functions of the Statistical and Clinical Coordinating Center. This plan shall include proposed methods to redirect personnel and fiscal resources, provide for the incorporation of additional statistical, clinical, technical, and administrative expertise, and curtail or discontinue personnel and fiscal resources when necessary to accommodate changing scientific priorities and opportunities.
• Agents, molecules and reagents for the clinical trials to be conducted by the Collaborative Network and the Autoimmunity Centers will be provided at no cost to the Contractor. Therefore, Business Proposals shall not include any costs associated with the purchase of investigational agents.
• The Contractor will be processing data from research activities sponsored by two different mechanisms. Data rights will be governed by the terms of the grant or contract. Data rights for the Autoimmunity Centers of Excellence are retained by the awardees of the cooperative agreements. Data rights for the Collaborative Network are retained by the Contractor(s) and data rights for the SACCC are retained by the Government in accordance with the "Rights in Data-General" clause, 52.227-14.

The Government contemplates awarding one (1) requirements cost-reimbursement type contract for accomplishing the tasks outlined in the Work Statement listed below.

Technical Proposals shall include individual plans for incorporating into the SACCC the requirements specified for Parts B, C, and D below. Each plan (for Part B, C, and D) shall address the following components of this expansion:

• A brief discussion of the overall approach for expanding the SACCC to incorporate support for Network studies including: (i) additional statistical, clinical, regulatory, technical and/or administrative expertise required; (ii) integration of data into the centralized database for Network clinical trials and mechanistic studies; and (iii) proposed changes in the administrative/organizational structure of the SACCC.
• A brief discussion of the statistical and clinical trial design features and considerations of importance in developing, implementing and monitoring studies, including considerations associated with: (i) the quantity and quality of pre-clinical and clinical data relative to existing experimental assays; (ii) key statistical parameters relative to the potential reliability, validity and specificity of new experimental assays, and (iii) key statistical issues relative to assessing the validity, reliability and specificity of experimental approaches versus standard measurements.

THE GOVERNMENT ANTICIPATES THAT DESCRIPTIONS OF APPROXIMATELY 7-10 PAGES EACH FOR PARTS B, C, AND D WILL BE ADEQUATE TO ADDRESS THIS REQUIREMENT.

Issuance of Task Orders for Parts B, C and D will be solely at the discretion of the Government and will be based on technical merit, need, and the availability of funds during the nine-year period of performance. If the Government decides to issue a Task Order, the Contractor will be provided with a detailed work statement. The Contractor shall submit a complete Technical Proposal addressing the requirements set forth in the Task Order work statement, as well as a Business Proposal, for review and evaluation by the Government (time allowed for proposal preparation in response to a task order request will vary depending on the task). The technical merit of all such proposals will be reviewed by NIAID and selected members of the NIAID Advisory Committee for Research on Immune Tolerance. The Government anticipates that the task orders under this contract will be awarded on a cost-reimbursement basis, however other pricing arrangements may be used if deemed appropriate.

V IV. STATEMENT OF WORK: PART A: KIDNEY AND ISLET TRANSPLANTATION

Part A of this solicitation encompasses the establishment of the Statistical and Clinical Coordinating Center and the provision of statistical, clinical coordination, technical, regulatory, and administrative support for clinical trials and mechanistic studies in kidney and islet transplantation undertaken by the NIAID Collaborative Network for Clinical Research on Immune Tolerance (hereafter referred to as the Network), and for pilot clinical trials and mechanistic studies in multiple autoimmune diseases undertaken by the NIAID Autoimmunity Centers of Excellence (hereafter referred to as the Centers).

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, and facilities, not otherwise provided by the Government under the terms of this contract, as needed to perform the work set forth below.

1. Establish and manage the Statistical and Clinical Coordinating Center (SACCC) for the Network and the Centers. The Contractor shall provide the statistical, clinical, technical, regulatory and administrative expertise necessary to carry out the tasks specified below, and other tasks as directed by the Project Officer:

1. Develop, implementation, refinement, and monitoring of all phases of clinical trials and studies of underlying mechanisms of tolerance induction and immune modulation for multiple immune-mediated diseases;
2. Design and conduct interim and final analyses of study data;
3. Conduct clinical site monitoring and training;
4. Establish and administer data collection, management, quality assurance and reporting systems;
5. Provide support for regulatory functions and requirements associated with Investigational New Drug (IND) applications;
6. Distribute and ensure quality control of study products;
7. Support the technical and administrative functions of the Network Executive Committee and the Center Steering Committee; and
8. Coordinate, provide administrative support, and prepare reports and statistical analyses for the activities of the independent Data and Safety Monitoring Board (DSMB).

2. Provide statistical leadership and clinical trial design expertise for the development of protocols at all phases to be conducted by the Network and the Centers, including the development of concepts for proposed clinical trials and the development of clinical protocols with respect to:
1. Delineation of the research questions to be addressed;
2. Selection of appropriate study populations and control or comparison groups;
3. Development of inclusion and exclusion criteria;
4. Calculation of sample size requirements for statistical significance for Phase I, II and III clinical trials;
5. Definition of clinical end-points and immune/surrogate markers;
6. Selection of randomization and stratification methods;
7. Definition of the number and type of patient samples and proposed methods for the collection;
8. Assessment of the feasibility of recruiting and retaining adequate numbers of study participants;
9. Design and development of study forms in collaboration with Network and Center investigators; and
10. Preparation and updating, as necessary, of a Manual of Operations for each clinical protocol delineating specific instructions, requirements and guidelines for the conduct of clinical trials by the clinical sites, including the clinical protocol, study forms, procedures for the collection, testing, storage and shipping of patient samples, and procedures for data collection, entry, verification and storage.
11. Participating extensively in the writing of proposed concepts and draft clinical protocols;
12. Arranging conference calls and meetings to review and modify, as necessary, proposed concepts and clinical protocols, including all costs associated with conference calls as well as travel expenses for SACCC staff, Network investigators and Center Investigators to attend concept development and protocol development meetings;
13. Distributing proposed concepts and clinical protocols to members of the Network Executive Committee and the Center Steering Committee for evaluation; and
14. Preparing and distributing final approved concepts and clinical protocols to the Network Executive Committee, the Center Steering Committee and all participating clinical sites.

5. As requested by the Project Officer, and in collaboration with Network and Center investigators, design and conduct interim and final statistical analyses of study data, prepare reports on the status of clinical trials and mechanistic studies, and participate in the preparation of scientific manuscripts and reports for publication and presentation at scientific meetings. This shall include, but not be limited to:
1. Preparing interim and final analyses of: the safety, toxicity and efficacy of tolerogenic and immunomodulatory treatments evaluated in Network and Center clinical trials; and the validity, reliability and specificity of techniques and methodologies used to assess underlying mechanisms;
2. Developing recommendations for modifications in the design of ongoing clinical trials and mechanistic studies with respect to statistical parameters such as sample size, control or comparison groups, clinical endpoints and immune/surrogate markers, etc.;
3. Preparing interim reports on accrual, retention, compliance, loss to follow-up and other statistical issues and problems relevant to the conduct of Network and Center clinical trials, and recommendations for improvements and modifications to resolve such issues and problems; and
4. Presenting all such reports, analyses and recommendations to the Network Executive Committee and the Center Steering Committee, and assisting in implementing necessary modifications approved by these governing bodies, including revised clinical protocols and research designs for mechanistic studies.

6. Establish and administer efficient, reliable and responsive systems for the collection, management, quality assurance and reporting of study data, as well as a system for electronic communication linkages among Network and Center clinical and mechanistic study sites, the NIAID, the Network Executive Committee and the Center Steering Committee. The Contractor shall develop and manage systems that provide for:
1. The collection, computer processing, storage, tracking and retrieval of all clinical and laboratory study data at a central data management facility;
2. Central computerized registration and randomization, where appropriate, of all patients on Network and Center protocols, or alternative non-computerized methods when appropriate;
3. Computerized study forms and systems for the remote entry and transmission of patient data from clinical sites to the central data management facility, or alternative non-computerized methods when appropriate;
4. Quality assurance and quality control procedures to evaluate and, when necessary, improve the accuracy, timeliness and completeness of data submitted by the clinical sites, including verification of the clinical and laboratory data used to determine that study participants have reached protocol-defined endpoints;
5. The development, implementation and maintenance of security requirements, including:
1. An Automated Information System (AIS) Security Profile, which at a minimum shall include: the System's Security Plan (SSP); the Risk Analysis (RA); the Continuity of Operations Plan (COOP; also known as the Contingency Plan);
2. A log or record of the results from testing the COOP, any existing plans and progress reports for implementing additional security safeguards and controls; and the system access authorization list. The profile shall be kept up-to-date for review and potential inspection upon demand by NIH/DHHS authorized agents. Upon request, copies of specified profile documents shall be presented to NIH/DHHS for its own system's security reporting purposes;
3. The preparation and submission, for Project Officer approval, of a RA following the guidance given in part 6, Chapter VI of the HHS IRM Manual. The RA is to be maintained and updated every three years, or in advance of implementing major system modifications or enhancements;
4. The preparation and submission of an annual SSP, following the instruction in OMB Bulletin 90-08, for review and approval by the Project Officer and the NIH SSO;
5. The development and maintenance of an up-to-date COOP following Part 6, Chapter V of the HHS IRM Manual. At a minimum, the COOP shall cover emergency operations, backup operations, and recovery plans to assure continuous operations of the system's facility. COOP testing shall be conducted and the results recorded at least every six months;
6. Plans, procedures, and a recommended schedule and budget for implementation of security safeguards required to satisfy the anticipated conditions of acquiring data from clinical and mechanistic study sites. This includes data integrity and security during electronic transmission, or during transit from the sites to the SACCC if non-electronic data transmission is used. All patient identifiable data is subject to the Privacy Act and DHHS regulations; and
7. Provision for the appropriate labeling, storage, handling, and disposal of sensitive or controlled data, media, and output.
6. Electronic communication linkages among Network and Center clinical and mechanistic study sites, the SACCC, the NIAID, the Network Executive Committee, and the Center Steering Committee.

8. Provide support for regulatory functions and requirements associated with Investigational New Drug (IND) Applications and the design, conduct, monitoring and analysis of clinical trials of experimental therapies. This shall include:
1. Establishing and maintaining a computerized tracking system for the receipt, follow-up, reporting, and disposition of adverse events for all Network and Center clinical trials to the Food and Drug Administration (FDA), the NIAID, appropriate Network and Center investigators, and the Network Executive Committee and the Center Steering Committee when appropriate. All procedures and systems must meet the guidelines and regulations of the FDA as related to processing of Adverse Event Reporting (AER) and safety information. This shall include:

1. Establishing and maintaining a system for SACCC central receipt of AER information 24 hours/day. This shall be accomplished by providing appropriately trained health care professionals during normal working hours and utilizing an answering machine/service after normal working hours and on weekends;
2. Establishing and maintaining a toll-free 800-telephone service for the receipt and triage of telephone calls from study participants concerning potentially serious problems that may require immediate attention by clinical site personnel. This service shall provide pre-recorded instructions and steps to be followed for direct patient reporting of potential problems, including identification of patient name, contact information, present location, protocol, clinical site, treating physician and nurse coordinator, etc. This service shall also provide for the notification of appropriate clinical site personnel or back-up on call site personnel within two (2) hours of the receipt of a patient telephone call.
3. Providing experienced clinical personnel as may be necessary to evaluate adverse event reports received from Network and Center clinical sites, and working with clinical site staff to clarify information, obtain follow-up information, and/or reconcile discrepancies between adverse event data reported versus adverse event data collected on study forms;
4. Within 24 hours of receipt, abstracting and entering adverse event data into the Network and Center central databases;
5. Preparing and distributing, by hard copy or electronic methods, Safety Reports or Information Reports on adverse events following the established FDA, NIAID, Network and Center guidelines and regulations;
6. Developing and distributing to participating clinical sites adverse event reporting forms, standard operating procedures for processing adverse event data, and appropriate instructions or manuals. The forms shall be developed in coordination with Network and Center investigators and shall conform to NIH, NIAID and FDA guidelines and regulations;
7. Developing, implementing and maintaining quality control/assurance procedures and ongoing training to ensure consistency, completeness and accuracy of adverse event reporting, coding and data entry; and
8. Generating and submitting reports to the Project Officer documenting site performance, as measured by accuracy and completeness of Adverse Event Reports, time required for response to queries, and SACCC performance, as measured by timely adverse event report disposition (i.e., time from receipt to entry into central databases, time from receipt to FDA reporting where applicable, and other tracking parameters identified by the Project Officer). These reports shall be prepared and submitted monthly or more frequently as may be necessary.
2. Develop and maintain a computerized clinical site registration system which includes, but is not limited to, the following tasks:
1. Filing and tracking registration documentation submitted by Network and Center clinical sites;
2. Preparing and submitting to the FDA, required registration documentation, including copies of the FDA 1572 forms, Curricula Vitae, Institutional Review Board (IRB) approval of each protocol, and IRB-approved consent forms for each protocol;
3. Responding to queries on the status of site registration from the clinical sites, NIAID, the Network Executive Committee and the Center Steering Committee; and
4. Confirming completion of all procedures necessary for study registration, and notifying clinical sites that registration has been completed for a particular protocol so that study products may be ordered and distributed.
3. Investigational New Drug Application (IND) sponsors for Network and Center clinical trials may include the NIAID, individual Network and Center investigators, and/or pharmaceutical companies. The Contractor shall be responsible for carrying out all regulatory requirements for NIAID- and investigator-sponsored INDs. In instances where the pharmaceutical company serves as the IND sponsor, the Contractor shall not be responsible for carrying out the regulatory functions outlined above. Approximately 70 percent of the clinical trials conducted by the Network and the Centers will involve IND sponsorship by the NIAID or by individual Network and Center investigators. The Contractor shall prepare, distribute and track Investigational New Drug Applications (INDs) sponsored by NIAID, Network and Center investigators, and, when appropriate, pharmaceutical companies. This shall include:

1. Providing technical and administrative assistance in the preparation and assembly of original and subsequent IND submissions;
2. Gathering information for use in the preparation of IND submissions, including pre-clinical screening, animal toxicity, chemistry, pharmacology, literature research and clinical research, contacting appropriate Federal and private organizations, including pharmaceutical companies; and editing, indexing, assembling and duplicating acquired data for subsequent submission to the FDA;
3. Obtaining letters from pharmaceutical company sponsors, NIAID and/or individual investigators authorizing the cross-filing of information from other sources for agents studied in clinical protocols under separate INDs;
4. Preparing statistical and technical information and other materials for meetings with officials of the FDA regarding the design, implementation and monitoring of Network and Center clinical trials and IND approval; responding to specific inquiries from FDA officials concerning clinical protocol design and IND submissions; and, when necessary, making presentations to FDA officials to explain protocol design and supporting safety, toxicity and efficacy data, clarify questions, and address concerns associated with IND approval;
5. Preparing, distributing and tracking of IND modifications as required to meet FDA requirements; and
6. Maintaining files on all IND correspondence and submissions to the FDA for Network and Center sponsored clinical trials.
4. Assist the Network and Centers in the preparation of FDA-required IND sponsor's interim and annual reports. These reports include narrative analysis and tabular summaries of all results of clinical trials. This includes retrieving and summarizing information to be included in FDA annual reports, drawn from, but not limited to: chronologies, pharmaceutical company information, the latest protocol versions, schema depicting the protocols, comparison charts of protocol requirements, statistical analyses, relevant abstracts, posters, papers and presentations, copies of adverse event summary reports, and lists of all submissions to the FDA. The Contractor shall provide copies of all interim and annual reports to the FDA, the Project Officer, the Network Executive Committee, the Center Steering Committee, and individual Network and Center investigators as may be necessary.

9. Establish and manage a system for the distribution and quality control of study products. For Network clinical trials, study products will be ordered by and dispensed to clinical site pharmacists. For Center clinical trials, study products will be dispensed directly to study participants by the SACCC drug distribution facility. The responsibilities of the Contractor with respect to the distribution and quality control of study products include:
1. Receipt and storage of study products, including:

1. Receiving shipments of study products from a variety of sources, including domestic contract manufacturers or packagers, commercial pharmaceutical companies, and foreign pharmaceutical companies and suppliers; reconciling shipping lists; noting conditions of receipt; and notifying Project Officer of any discrepancies or problems;
2. Receiving and processing through U.S. Customs any shipments from foreign suppliers;
3. Storing products as indicated on the manufacturer's label;
4. Monitoring storage conditions to guarantee and document continuous proper storage; and
5. Ensuring that all applicable FDA current Good Manufacturing Practice regulations are met.
2. Labeling and packaging of study products, including:
1. Labeling and packaging study products to provide supplies suitable for dispensing to individual patients at Network and Center clinical sites, using, where applicable, randomization schemes with patient numbers and corresponding treatment assignments;
2. Maintaining accurate records of all such labeled and packaged study products;
3. Providing the capability for patient specific, unit of use packaging, including blister packaging, when required;
4. Providing the capability to affix auxiliary labels for use on certain products and on outer shipping cartons; and
5. Providing facilities for the preparation of patient specific solid and liquid dosage forms.
3. Inventory control/quality assurance, including performing a physical inventory of supplies for each protocol at least monthly, notifying the Project Officer of any discrepancies that cannot be reconciled with the current inventory, and monitoring use rate and notifying the Project Officer of low inventories or unusual increases in product requests from Network and Center clinical sites.
4. Shipping and distribution of study products, including:
1. Processing Investigational Agent Request forms on a daily basis, confirming that the order is from an authorized Network or Center clinical site, filling the order and packaging the appropriate protocol-specific research product, dosage and quantity;
2. Supplying shipping cartons, cushioning materials, necessary labels (e.g., fragile), sealing tape, insulation materials, and all other supplies necessary to ensure safe and intact arrival of study products;
3. Supplying sufficient quantities of appropriate packaging (e.g., wet ice, dry ice, or cold packs) to ensure the safe and intact arrival of products requiring maintenance at low temperatures;
4. Shipping study agents to domestic and foreign Network and Center clinical sites so that shipments are received in a timely fashion. On a routine basis, most shipments should arrive within 24 hours.
5. Obtaining the appropriate licenses and permits required by local, state and Federal authorities for the safe import, storage and distribution of drugs, as well as the appropriate interstate, intrastate and foreign import/export shipping licenses and permits for transporting biologics and drugs;
6. On occasion, making shipments after hours or on weekends, as required. Except for emergency shipments or other extraordinary tasks, the Contractor/subcontractor shall be open and accessible during regular business hours; and
7. Providing storage for and performing the packaging and shipping of reports, documents, etc. related to study products distributed. All original Investigational Agent Request forms shall be retained for the duration of the contract and shall be accessible for audit.
5. Pharmaceutical services, including:
1. Reviewing Network and Center clinical protocols and providing the Project Officer with a written protocol evaluation, usually 1-2 pages in length, including estimates of the quantity of study products needed, comments regarding product handling concerns or packaging requirements;
2. Providing product information (e.g., special handling or shipping, study product preparation) to clinical site pharmacists or patients with every shipment;
3. Providing product ordering, transfer or return information to clinical site pharmacists or study participants;
4. Authorizing the transfer of products designated for one protocol to another, as permitted by FDA regulations and/or the pharmaceutical sponsor, and maintaining copies of Investigational Agent Transfer forms for the duration of the contract;
5. Providing evaluations of current study product usage and projections of anticipated requirements to manufacturers on a quarterly basis or as directed by the Project Officer. These evaluations will be reviewed and approved by the Project Officer before forwarding to manufacturers;
6. Preparing protocol-specific documents providing information regarding study product packaging, dosage strength and labeling for distribution to clinical site pharmacists; and
7. Establishing and maintaining a secured web site for clinical site pharmacists including but not limited to: protocol-specific information and requirements related to study products; procedures and forms for ordering study products; procedures and requirements for the return of study products; instructions to be provided to study participants; etc.
6. Provide security/safety measures and procedures, including: 24-hour security to prevent theft, misuse or damage; an automated 24-hour temperature monitoring system to ensure maintenance of appropriate temperature storage conditions; programs or systems for fire protection; and training on safety, security and appropriate handling of investigational agents to all personnel with access to the drug storage facility. The Contractor shall also be required to meet the requirements of the Drug Enforcement Agency for the storage of controlled substances.
7. Process and dispose of returned drugs, including: identifying and notifying affected investigators in the event that a lot of study product is recalled by the manufacturer or reaches the limit on its useful shelf life; receiving recalled, expired or unused study products returned from clinical sites and processing returns in conformance with local, state and Federal regulations; providing for the quarantine of returned products from other inventory; preparing computerized documentation of returns; and disposing of returned products in a manner prescribed by local, state and Federal regulations.
8. Maintain a dedicated computerized data processing system to keep inventories and distribution records. All documentation shall be available for annual audits as required by Federal regulations.

10. Coordinate and provide statistical, technical, administrative and logistical support for the activities of the Network Executive Committee and the Center Steering Committee responsible for the overall scientific direction, management and evaluation of these research programs. The Network Executive Committee will be composed of approximately 15 non-federal members. The Center Steering Committee will be composed of approximately 10 non-federal members. Meetings of the Network Executive Committee and the Center Steering Committee and their subcommittees will be held in the Bethesda, Maryland area. The SACCC Project Director and 1-3 additional SACCC staff will attend these meetings.
    • The Network Executive Committee will establish four (4) separate Subcommittees for: clinical trials; mechanistic studies; development of Standard Operating Procedures; and monitoring and evaluation of performance. The Network Subcommittees for clinical trials and mechanistic studies will be composed of approximately five members each, will meet twice annually for the seven year Network contract period, and will conduct bi-monthly conference calls. The Network Subcommittee for the development of Standard Operating Procedures will consist of approximately five members, will meet three (3) times during the first six (6) months of the contract, will meet at least annually thereafter, and will conduct quarterly conference calls for the seven year Network contract period.
    • The Center Steering Committee will establish two Subcommittees; one for clinical trials and the second for mechanistic studies, each composed of five members. These two Center Subcommittees will meet twice annually for the 4-year period of the Center awards, and will conduct quarterly conference calls. The Centers will establish up to five-protocol development Subcommittees that will meet three times per year via conference call.

Contractor support will include:

1. Membership on the Network Executive Committee and the Center Steering Committee by the SACCC Project Director, including participation in all meetings and conference calls convened by these governing bodies;
2. Scheduling, arranging lodging and meeting room facilities, and arranging appropriate teleconferencing services for: (i) three 2-day meetings of the Network Executive Committee per year for the seven (7) year Network contract period, and (ii) three 2-day meetings of the Center Steering Committee in the first year of the contract period, and semi-annual 2-day meetings thereafter; and (iii) monthly conference calls for both the Network Executive Committee and the Center Steering Committee. The Contractor shall provide for the transportation, meals and lodging expenses associated with participation in these meetings by the non-federal members of the Network Executive Committee and the Center Steering Committee;
3. Scheduling, arranging lodging and meeting room facilities, and arranging appropriate services for all meetings and conference calls of Subcommittees established by the Network Executive Committee and the Center Steering Committee. The SACCC Project Director, or his/her designated representative, shall participate in all Subcommittee meetings and conference calls.
4. Preparing, assisting in the preparation of, and distributing in advance of Network Executive Committee and Subcommittee and Center Steering Committee and Subcommittee meetings and conference calls a variety of materials, reports, analyses and recommendations for review. This shall include, but not be limited to:

1. Proposed concepts for clinical trials and mechanistic studies;
2. Proposed protocols for approved clinical trials and research designs for approved mechanistic studies;
3. Proposed modifications in the design of approved clinical trials and mechanistic studies;
4. Status of and issues surrounding FDA approval of INDs;
5. Status reports on the implementation of approved clinical trials and mechanistic studies, including accrual, retention, loss to follow-up, problems and issues with respect to data management and quality assurance, and recommendations for modifications/improvements where necessary;
6. Interim and final analyses of the results of clinical trials and mechanistic studies, including recommendations for protocol and mechanistic study modifications to ensure the validity, reliability and feasibility of completing approved studies; and
7. Preparing brief summaries of all decisions and recommendations of the Network Executive Committee and its Subcommittees and the Center Steering Committee and its Subcommittees.

5. Assisting the NIAID, the Network Executive Committee and the Center Steering Committee in the preparation of Standard Operations Procedures. This shall include, but not be limited to, policies and procedures governing:

1. The development, review, modification, and approval/disapproval of proposed concepts for clinical trials and mechanistic studies, proposed protocols for clinical trials and detailed research designs for mechanistic studies, including the development of criteria for the evaluation of the scientific rationale, feasibility and potential success of clinical trials and mechanistic studies;
2. The monitoring of progress with respect to the implementation of approved clinical trials and mechanistic studies, including appropriate reporting requirements for ongoing progress reviews and criteria for expanding, curtailing or discontinuing approved studies;
3. The development and implementation of criteria and procedures for the evaluation of clinical and mechanistic site performance, as well as policies for correcting site deficiencies and/or curtailing or eliminating approved sites;
4. Requests for interim and final analyses of clinical and laboratory study results;
5. The addition of clinical and mechanistic study sites to accommodate new knowledge and scientific opportunities; and
6. The preparation and review of scientific reports, manuscripts, abstracts and presentations on Network and Center study results;

11. Coordinate and provide statistical, technical and administrative support for the activities of the independent Data and Safety Monitoring Board (DSMB). The NIAID DSMB shall be composed of scientific and clinical experts, bioethicists, and other representatives as may be necessary. The DSMB, composed of approximately ten (10 members, will be appointed by the NIAID to oversee the clinical trials of both the Network and the Centers. The DSMB will meet semi-annually in the Bethesda, Maryland area to review clinical and laboratory data on Network and Center studies. Quarterly conference calls of the DSMB will be conducted. Transportation, meals and lodging costs associated with the participation of non-federal DSMB members shall be provided for by the contractor. Contractor services shall include:
1. As requested by the Project Officer, develop and revise, as necessary, Conflict of Interest (COI) and disclosure forms for all permanent and ad hoc DSMB members; coordinate the distribution and receipt of completed forms; assess conflict of interest; provide assessments and all forms to the Project Officer; and re-assess potential conflict of interest for permanent DSMB members on an annual basis or more frequently as may be appropriate; and
2. Schedule, arrange lodging and meeting room facilities, and arrange teleconference services for meetings and conference calls of the NIAID DSMB.
3. Distribute copies of all protocols for clinical trials and mechanistic studies to the NIAID DSMB members for review, including forms and procedures for obtaining informed consent; preparing summaries of all comments received from NIAID DSMB members; providing summaries of DSMB comments to the NIAID Project Officer, the Network Executive Committee and the Center Steering Committee; and participate in preparing responses to DSMB comments and designing modifications to Network and Center approved studies as necessary.
4. Prepare a variety of interim and final statistical analyses and reports for review by the NIAID DSMB, including:

1. Analyses of ongoing pilot and efficacy trials with respect to safety, toxicity and efficacy, including adverse event reports and assessments;
2. Study accrual and retention data, including issues and problems associated with the recruitment and retention of study participants; and
3. Recommendations for improvements and modifications in study protocols as may be necessary to enhance recruitment and retention, ensure the feasibility and scientific validity of inclusion and exclusion criteria and comparison and control groups, and assess the techniques and methodologies used to delineate underlying mechanisms.
5. Prepare summaries of the results of all NIAID DSMB meetings for review and approval by the Project Officer.

12. Coordinate and provide statistical, technical and administrative support for the activities of the NIAID Advisory Committee for Research on Immune Tolerance, to be appointed by the NIAID to oversee all research programs focused on the study of immune tolerance, and participate, as necessary, in annual meetings of this advisory committee to review the research conducted by the Network and the Centers. The NIAID Advisory Committee for Research on Immune Tolerance will be composed of approximately 12 non-federal members. Annual Advisory Committee meetings will be held in the Bethesda, Maryland area. Transportation, meals and lodging costs associated with the participation of Advisory Committee members in annual meetings will be provided by the contractor. Additionally, two conference calls of the NIAID Advisory Committee will be conducted each year for seven years. The contractor shall:

1. Schedule and arrange lodging and meeting room facilities for annual meetings of the NIAID Advisory Committee for Research on Immune Tolerance.
2. Schedule and arrange appropriate teleconference facilities for NIAID Advisory Committee conference calls;
3. Distribute existing analyses, reports and other information relative to the clinical trials and mechanistic studies conducted and proposed by the Network and Center research programs to NIAID Advisory Committee members;
4. Develop new analyses and reports as may be necessary for review by the NIAID Advisory Committee; and
5. Prepare summaries of all NIAID Advisory Committee meetings and distribute all such summaries to NIAID, the Network Executive Committee, and the Center Steering Committee as directed by the Project Officer.

Research leading to the development of improved treatments for autoimmune diseases, asthma and allergic diseases and transplant rejection is a major component of the mission of NIAID's Division of Allergy, Immunology and Transplantation. The Task Order activities specified below for Part B of this solicitation will expand the scope of the SACCC to include statistical, clinical, technical, coordination and administrative support for the Network with respect to the development of standardized assays and reliable markers of immune tolerance in kidney and islet transplantation, autoimmune diseases and/or asthma and allergic diseases.

The current lack of validated markers of immune tolerance has significant implications for the rational design of tolerogenic treatment protocols and the appropriate monitoring of study participants. The development of immune/surrogate markers of in vivo tolerance in humans is critical to advancing the application of tolerance induction therapeutic regimens. Sensitive indicators and/or predictors of early induction or loss of tolerance will facilitate clinical trials by expanding the universe of informed treatment options, including re-treatment to induce tolerance or standard therapy.

The development of useful immune/surrogate markers involves complex issues surrounding the selection, validation, quantitation, standardization, and population application of tolerance "biomarkers", and the design of clinical protocols to control the four major sources of variability which may confound clinical application: biological diversity, sampling diversity, variability of detection procedures, and validation against acknowledged disease endpoints. In addition, putative immune/surrogate endpoints should be biologically plausible, measurable by standardized and reliable assays, represent early events in the causal pathway, and exhibit dose-responses. Perhaps most importantly, immune/surrogate markers should be capable of measuring the effect of the intervention on clinical outcome. The identification and validation of a biomarker as a valid immune/surrogate marker for tolerance is a stepwise process involving smaller "transitional" studies and larger second-generation trials in which both primary outcome and putative surrogates are measured. Transitional studies are used to move new markers from the laboratory into evaluation in humans, and are designed to address specific questions of assay validity, treatment/marker associations, marker/disease associations, and inter- and intra-individual variability. Promising markers need to be further developed and then tested in current and future clinical trials in transplantation, autoimmune disease and asthma and allergic disease to definitively address the issues of optimal representation, and to test the adequacy of markers to capture the effect of treatment on clinical outcome. Unfortunately, clinical studies frequently lack the statistical power to allow definitive conclusions about the value of potential immune/surrogate markers or are terminated before sufficient evidence can be accumulated. The choice of surrogate markers will differ by disease and by tolerogenic approach and additional research is needed to identify the most useful markers for monitoring the course of specific types of immune modulation and tolerance induction.

Independently, and not as an agent of the Government, the Contractor shall furnish all necessary services, qualified personnel, materials, equipment and facilities, not otherwise provided by the Government under the terms of this contract, as needed to:

Expand the SACCC to Provide statistical, clinical, regulatory, technical and administrative expertise to the Network for the development and validation of tolerance assays for kidney and islet transplantation, asthma and allergic diseases, and autoimmune diseases. Network requirements in this area include: (i) further development of existing experimental immune system surrogate markers for the induction, maintenance and loss of tolerance; (ii) identification and testing of new immune system surrogate markers; and (iii) refinement of existing assays and the development and validation of new assays to establish broadly applicable, standardized measures of immune tolerance. The Contractor shall provide expertise and assistance to the Network in the following areas:

1. Design, implementation, refinement and monitoring of research studies to develop and validate assays to measure the induction, maintenance and loss of immune tolerance, including assistance in the preparation of proposed concepts and detailed research designs, and NIAID and Network Executive Committee review of proposed concepts and detailed research designs;
2. Design and conduct of interim and final analyses of research results, and in the preparation of manuscripts, abstracts, and reports on study findings for publication and presentation;
3. Establishment and administration of efficient, reliable and responsive systems for the collection, management, quality assurance and reporting of study data;
4. Development of training materials and the provision of training for clinical site staff, as necessary, with respect to the use of experimental assays for study participants enrolled in Network clinical trials;
5. Clinical site monitoring to ensure adherence to clinical protocols involving the use of experimental assays, timely and accurate collection, storage and shipping of patient samples, and completeness, timeliness and accuracy of data collection and entry;
6. Assistance in carrying out regulatory functions and adhering to Federal regulatory requirements associated with the use of experimental assays in Network clinical trials; and
7. Coordination, administrative and logistical support for the activities of the Network Subcommittee on Tolerance Assay Development and Validation.

Research leading to the development of improved treatments for autoimmune diseases is a major component of the mission of NIAID's Division of Allergy, Immunology and Transplantation. The activities specified in the Task Order for Part D of this solicitation will expand the scope of the SACCC to include statistical, clinical, regulatory, technical, coordination and administrative support for Network clinical trials and mechanistic studies in autoimmune diseases.

Efforts to induce tolerance in autoimmunity have focused primarily on the oral administration of antigens. Oral administration of both high and low dose antigen results in a phenomenon termed "oral tolerance" in which the immune response to subsequent systemic administration of antigen is blocked. Oral tolerance can be induced in animal models and is now being evaluated in human diseases. However, the encouraging responses in animal studies have not been duplicated in recent clinical trials of rheumatoid arthritis and multiple sclerosis. There are a number of promising tolerogenic approaches other than oral tolerance that can be pursued in immune-mediated diabetes and other autoimmune diseases. These include: costimulatory blockade; anti-cytokine monoclonal antibodies; hematopoietic stem cell and bone marrow transplantation; and gene transfer-based therapies for cytokine modulation. The rationale for pursuing clinical trials in autoimmunity is supported by promising pre-clinical studies as well as the availability of tolerogenic reagents and molecules.

Independently, and not as an agent of the Government, the Contractor shall furnish all necessary services, qualified personnel, materials, equipment and facilities, not otherwise provided by the Government under the terms of this contract, as needed to:

Expand the SACCC to Provide statistical, clinical, regulatory, technical and administrative expertise to the Network for clinical trials and mechanistic studies of tolerogenic approaches for the treatment of autoimmune diseases. The Contractor shall provide expertise and assistance to the Network in the following areas:

1. Design, implementation, refinement and monitoring of clinical trials and mechanistic studies in autoimmune diseases, including assistance in the preparation of proposed concepts for clinical trials and mechanistic studies, proposed clinical protocols, and detailed research designs for mechanistic studies, and the review of all proposed concepts, clinical protocols and research designs by the NIAID and the Network Executive Committee;
2. Design and conduct of interim and final analyses of study data, and in the preparation of manuscripts, abstracts, and reports on study findings for publication and presentation;
3. Establishment and administration of efficient, reliable and responsive systems for the collection, management, quality assurance and reporting of data from Network clinical trials and mechanistic studies in autoimmune diseases, as well as expansion of the Network's electronic communication linkages to include additional investigators in autoimmune diseases;
4. Conduct of clinical site monitoring and training for all Network clinical sites participating in clinical trials in autoimmune diseases;
5. Support for the regulatory functions and requirements associated with Investigational New Drug Applications (INDs) and the design, conduct, monitoring and analysis of clinical trials of experimental therapies for autoimmune diseases;
6. Coordination, administrative and logistical support for the expanded activities of the Network Executive Committee with regard to the scientific direction, management, monitoring and evaluation of clinical trials and mechanistic studies in autoimmune diseases;
7. Expansion of the SACCC system for the distribution and quality control of study products to include experimental agents for the treatment of autoimmune diseases;
8. Coordinate and provide statistical, technical and administrative support for the activities of the NIAID DSMB relative to Network studies in autoimmune diseases; and
9. Coordinate and provide statistical, technical and administrative support for the activities of the NIAID Advisory Committee for Research on Immune Tolerance with regard to Network studies of autoimmune diseases.

Research leading to the development of improved treatments for asthma and allergic diseases is a major component of the mission of NIAID's Division of Allergy, Immunology and Transplantation. The activities specified in the Task Order for Part C of this solicitation will expand the scope of the SACCC to include statistical, clinical, regulatory, technical, coordination and administrative support for Network clinical trials and mechanistic studies of tolerogenic approaches for the treatment of asthma and allergic diseases.

Asthma and allergic diseases are attractive models for the development of new approaches to alter the human immune response. These diseases are increasing in prevalence and account for high medical and social costs. Despite the availability of proven therapies and many new agents in development, even the most effective pharmacotherapies have serious limitations. Some data suggest that either reduced allergen exposure, or conventional allergen immunotherapy, can block the development and/or exacerbations of asthma. However, there are obstacles to translating these findings into clinical practice, perhaps because present approaches to environmental control do not sufficiently reduce allergen levels, and because conventional immunotherapy causes only weak modulation of the human immune response. The most promising approach is to develop new methods of inhibiting allergic immune responses and/or inducing tolerance to allergens.

The development of new approaches would be enhanced by the many widely available, well standardized and clinically validated tests, including blood studies, skin tests, and pulmonary function tests, that can be used to characterize allergic responses from the immunological and physiological perspectives. Moreover, it may soon be possible to enhance the identification and stratification of at-risk individuals based on the discovery of genes that predispose to asthma and atopy.

Allergen immunotherapy was developed empirically ~80 years ago, and relatively little effort has been made to develop more robust and long-lasting allergen immunotherapies, based on fundamental principles of immunology. However, concerns about the efficacy of conventional immunotherapy have stimulated research into new approaches to tolerize to allergen. A variety of avenues are being explored and build on the fact that many clinically important allergens have been identified, purified, cloned, epitope-mapped, produced as biologically active recombinant proteins, and administered safely by mucosal and cutaneous routes. With these reagents, the timing, dose, route, and molecular form for the allergen can be tightly controlled. Approaches that combine non-antigen-specific methods (e.g., second signal blockade and cytokine modulation) and antigen-specific tolerance induction regimens appear very promising in animal models and are close to entering Phase I and/or Phase II clinical studies in humans. Among these are: (1) "DNA vaccines" comprised of plasmid DNA encoding recombinant allergens, which induce long-lasting allergen-specific tolerance in mice; (2) immunostimulatory oligonucleotides, small sequences of bacterial DNA that drive the Th1 immune responses when co-administered with protein allergens; (3) T cell costimulatory blockade in conjunction with allergen challenge; (4) peptide vaccines representing T cell epitopes of allergen (5) immunization with Mycobacterium vaccae, which non-specifically drives Th1 immune responses; (6) monoclonal antibodies to IgE, which deplete plasma IgE and down-regulate mast cells and basophil receptors for IgE; and (7) co-administration of allergen and cytokines.

Independently, and not as an agent of the Government, the Contractor shall furnish all necessary services, qualified personnel, materials, equipment and facilities, not otherwise provided by the Government under the terms of this contract, as needed to:

Expand the SACCC to provide statistical, clinical, regulatory, technical and administrative expertise to the Network for clinical trials and mechanistic studies of tolerogenic approaches for the treatment of asthma and allergic diseases. The Contractor shall provide expertise and assistance to the Network in the following areas:

1. Design, implementation, refinement and monitoring of clinical trials and mechanistic studies in asthma and allergic diseases, including assistance in the preparation of proposed concepts for clinical trials and mechanistic studies, proposed clinical protocols, and detailed research designs for mechanistic studies, and the review of all proposed concepts, clinical protocols and research designs by the NIAID and the Network Executive Committee;
2. Design and conduct of interim and final analyses of study data, and in the preparation of manuscripts, abstracts, and reports on study findings for publication and presentation;
3. Establishment and administration of efficient, reliable and responsive systems for the collection, management, quality assurance and reporting of data from Network clinical trials and mechanistic studies in asthma and allergic diseases, as well as expansion of the Network's electronic communication linkages to include additional investigators in asthma and allergic diseases;
4. Conduct of clinical site monitoring and training for all Network clinical sites participating in clinical trials in asthma and allergic diseases;
5. Support for the regulatory functions and requirements associated with Investigational New Drug Applications (INDs) and the design, conduct, monitoring and analysis of clinical trials of experimental therapies for asthma and allergic diseases;
6. Coordination, administrative and logistical support for the expanded activities of the Network Executive Committee with regard to the scientific direction, management, monitoring and evaluation of clinical trials and mechanistic studies in asthma and allergic diseases;
7. Expansion of the SACCC system for the distribution and quality control of study products to include experimental agents for the treatment of asthma and allergic diseases;
8. Coordinate and provide statistical, technical and administrative support for the activities of the NIAID DSMB relative to Network studies in asthma and allergic diseases; and
9. Coordinate and provide statistical, technical and administrative support for the activities of the NIAID Advisory Committee for Research on Immune Tolerance with regard to Network studies of asthma and allergic diseases.

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 shall be brief and factual and prepared in accordance with the format specified below.

1. BIMONTHLY ACCRUAL AND SITE REGISTRATION REPORT

1. For each clinical site enrolling study participants in open clinical protocols: projected overall accrual at each site; date of first enrollment; actual accrual to date; summary of all eligible patients per month and to date; and reasons for non-entry of eligible patients;
2. For each clinical site in the process of registering and obtaining approval to participate in open clinical protocols: outstanding requirements for approval; anticipated date of approval; projected accrual; and any anticipated problems with protocol approval/implementation;
3. Summary of the projected versus actual accrual to date for all approved clinical sites, and reasons for non-entry of eligible patients;
4. For each approved mechanistic study associated with an open clinical protocol: status of implementation; status of collection, shipping and receipt of patient samples; problems and/or issues associated with the collection, shipping or receipt of patient samples; and recommendations for resolving any such issues or problems; and
5. Recommendations for modifications in study design, clinical site monitoring, or clinical site training appropriate to improve overall or site-specific accrual, including recommendations for increasing the number of participating clinical sites.

2. MONTHLY ADVERSE EVENT REPORT

The Contractor shall submit a report on all adverse experiences for each Network-sponsored open clinical protocol and each Center-sponsored open clinical protocol, including copies of adverse experience report forms. Three copies shall be provided to the NIAID Project Officer.

3. QUARTERLY STATUS REPORT ON CONCEPT, PROTOCOL, AND MECHANISTIC STUDY DEVELOPMENT

Every three months, the Contractor shall submit a report summarizing the status of the following, with a separate report prepared for Network activities and a separate report prepared for Center activities:

1. Pending concepts for proposed clinical trials and mechanistic studies, including: lead investigator(s); stage of development; step within the NIAID and the Network/Center review process; actions required for final approval, modification or disapproval, including unresolved issues, questions or problems; and time frame for completion of review, approval, modification or disapproval;
2. Approved concepts for clinical protocols and mechanistic studies under development, including: lead investigator(s); stage of development; step within the NIAID and Network/Center review process; actions required for final approval, modification or disapproval, including unresolved issues, questions or problems; and time frame for completion of NIAID and Network/Center review, approval or disapproval;
3. Copies of all pending and approved concepts; and
4. A summary of issues or problems encountered with respect to the NIAID and/or the Network/Center review and decision-making process, including recommendations for modifications and improvements to enhance the timeliness, efficiency or thoroughness of the review processes.

Three (3) copies of both reports shall be provided to the NIAID Project Officer; additionally, one copy of the Network report shall be provided to the Chair of the Network Executive Committee, and one copy of the Center report shall be provided to the Chair of the Center Steering Committee.

4. QUARTERLY STATISTICAL REPORTS

On a quarterly basis, the Contractor shall submit separate reports summarizing the status of proposed, interim and final analyses of the results of clinical trials and mechanistic studies sponsored by the Network and the Centers. This shall include:

1. Title, author(s), brief description, status of review/approval of proposed analyses, including any pending issues, problems or modifications;
2. Title, author(s), brief description and status of approved analyses, including any pending issues, problems or modifications; and
3. Recommendations for additional interim and final analyses for clinical trials and mechanistic studies.

Three (3) copies of the Quarterly Statistical Reports shall be provided to the NIAID Contracting Officer.

5. QUARTERLY CENTER STUDY REPORT

Quarterly and at the completion of each Center study, the Contractor shall submit a summation of the work performed and the results obtained. This report shall be in sufficient detail to explain comprehensively the tasks accomplished and the results achieved, and shall summarize data analyses performed in text, tabular and graphical form. This report shall include but not be limited to a summary of all relevant descriptive information for all clinical sites combined, as well as for each site individually (e.g., accrual data, attrition, number of forms received, number of data edits, clinical site monitoring reports, adverse events, safety information, etc.

6. ANNUAL REPORT

On an annual basis, the Contractor shall submit a report summarizing the results of the entire contract work for the period covered, with separate reports prepared for the requirements of this contract with respect to the activities of the Network and the Centers as specified below. These Annual Reports shall be in sufficient detail to explain comprehensively the results achieved. Annual Reports shall be submitted thirty (30) days prior the anniversary date. Three (3) copies of these reports shall be provided to the NIAID Project Officer.

1. STATISTICAL DESIGN CONSIDERATIONS
1. The advantages and disadvantages of the various approaches to the statistical design of ongoing and completed Network and Center clinical trials and mechanistic studies relevant for the assessment of the safety, toxicity and efficacy of tolerogenic and immunomodulatory treatments for immune-mediated diseases, including: control and comparison groups, inclusion and exclusion criteria, sample size; research ; research questions addressed; clinical end-points and immune/surrogate markers, number and type of patient samples, etc., and
2. Recommendations for improved statistical approaches and methods to enhance the ability to assess disease stage and activity, therapeutic effect and underlying mechanisms.
2. STANDARD OPERATING PROCEDURES, including:
1. Development and review proposed concepts for clinical trials and mechanistic studies, including for evaluation and prioritization;
2. Development, review and implementation of approved protocols and mechanistic studies, including criteria for evaluation and prioritization;
3. Clinical site monitoring and training with respect to adherence to protocol requirements, data collection and quality assurance, adherence to regulatory requirements, etc.;
4. Preparation, review and approval of requests for statistical analyses;
5. Review and approval of publications, abstracts, reports and presentations;
6. Monitoring and evaluating the performance of clinical and mechanistic study sites and procedures for addressing performance problems; and
7. The Network Executive Committee or the Center Steering Committee may develop other policies and procedures as.
3. CLINICAL SITE MONITORING AND TRAINING, including:
1. Clinical site training activities conducted, including written materials on Network- and Center-specific standard operating procedures and protocol-specific requirements;
2. Issues and problems encountered in the training and monitoring of Network and Center clinical sites; and
3. Recommendations for modifications/improvements in training materials and/or standard operating procedures to ensure adherence to protocol requirements, standard operating procedures and regulatory requirements.
4. THE DISTRIBUTION AND QUALITY CONTROL OF STUDY PRODUCTS, including: receipt, labeling, storage, distribution, security, inventory quality assurance, shipping, evaluations of usage, and disposition of returned investigational agents.
5. REGULATORY FUNCTIONS AND REQUIREMENTS, including the status of INDs, issues and problems in the development, FDA review and approval of INDs, and recommendations for improvements/modifications in SACCC and Network and Center regulatory procedures.
6. DSMB RESPONSIBILITIES AND PROCEDURES, including: procedures for the review of interim and final analyses of study data and recommendations for improvements in the analyses prepared for DSMB review and the nature and type of study data generated by Network and Center sites; etc.
7. MONITORING PROGRESS AND EVALUATING PERFORMANCE, including an assessment of policies and procedures used by the Network and the Centers, and recommendations for improvements.
8. FINAL DELIVERABLE: At the completion of the contract, the Contractor shall deliver to the Contracting Officer a cleaned and edited public use data set, on media to be determined at the time of delivery, as specified by the Project Officer, and copies of all data management tools, including, but not limited to, data documentation and data dictionaries, data entry software and editing programs to allow reading and analysis of the data. The Contractor shall provide to the Government appropriate computer programs capable of: (1) reading and manipulating all data, and (2) creating SAS compatible databases. Additionally, at the completion of the contractor, the Contractor shall deliver to the Project Officer an audit trail of all raw data corrections, hard copies of the original data collected from study participants from all studies supported by this contract, and all logs and other records related to data collection, entry, editing, analysis and transfer.

2. Understanding of the scope and objectives of the contract, recognition of potential difficulties that may arise in performing the work required, and understanding of the close coordination necessary between the NIAID, the Network Executive Committee, the Center Steering Committee, the clinical sites and other site personnel.
3. Adequacy of the administrative and organizational framework, with lines of authority and responsibility clearly demonstrated, and adequacy of the work plan, with proposed time schedule for achieving contract objectives and maintaining quality control over the implementation and operation of the project.

2. QUALIFICATIONS AND AVAILABILITY OF PROPOSED PERSONNEL = Points: 35

Demonstrated expertise, appropriate training, experience and availability of the statistical, clinical, regulatory, technical and administrative staff required to plan and implement the requirements of this project as described in the work statement.

1. Leadership and Management Structure

Proposed scientific, clinical, regulatory, technical and administrative leadership of the SACCC. This shall include the documented training, expertise, experience, leadership/management skills and availability of the Project Director and the surrounding leadership of the SACCC to successfully plan and manage the project.

2. Scientific, Clinical, Technical and Administrative Staff

Documented training, expertise, experience and availability of the proposed other professional, technical and administrative staff, documented ability to perform their roles in carrying out the requirements of this project, expertise and experience in similar projects, and their time commitment.

3. Subcontractors

   Documented training, expertise, experience and availability of proposed subcontractor(s), their documented capability to perform the requirements of this project, experience in similar projects, and their time commitment.

3. FACILITIES AND RESOURCES = Points: 15

   Documented availability and adequacy of facilities, equipment and resources necessary to carry out all phases of this project.

1. NUMBER AND TYPE OF AWARD(S)

It is anticipated that one (1) award will be made from this solicitation and that the award will be made on/about September 30, 1999.

It is contemplated that the award from this solicitation will be a Requirements cost-reimbursement type contract with a period of performance of nine (9) years.

2. DEFINITIONS

Requirements Contract - FAR 16.503 defines a requirements contract as a contract that provides for filling all actual purchase requirements of designated Government activities for supplies and services during a specified contract period, with deliveries or performance to be scheduled by placing orders with the contractor.

Task Order Contract - FAR 16.501-1 defines a task order contract as a contract for services that does not procure or specify a firm quantity of services (other than a minimum or maximum quantity) and that provides for the issuance of orders for the performance of tasks during the period of the contract.

3. ESTIMATE OF EFFORT AND VALUE

5. SMALL BUSINESS SUBCONTRACTING PLAN

For those concerns other than small business concerns, subcontracting plans will be required when the cumulative dollar amount for tasks issued against the contract exceed $500,000 in accordance with P.L. 95-507. The small, small disadvantaged, and women owned business subcontracting plans will have to reflect goals that allow the maximum practicable subcontracting opportunities retroactive to day one of the effective date of the contract. As subsequent tasks may be issued against the contract once small, small disadvantaged, and women-owned small business subcontracting goals have been established, the subcontracting goals will be subject to modification with each subsequent task.

6. LIMITATION ON SUBCONTRACTING

The restrictions set forth in FAR Clause 52.219-14, Limitation on Subcontracting, will apply to each individual order issued under a task or delivery order contract. The section applicable to this solicitation is FAR Clause 52.219-14(a)(1) and states "Services (except construction). At least 50 percent of the cost of contract performance incurred for personnel shall be expended for employees of the concern.

7. LIMITATION ON PERIOD OF PERFORMANCE OF ORDERS

The clause at FAR 52.216-21, Requirements, permits orders issued during the effective period of the contract, and not completed within that period, to be completed within the time specified in the order. The time specified in such orders, however, will not extend unreasonably beyond the contract expiration date.

8. SIC CODE AND SIZE STANDARD

Note: The following information is to be used by the offeror in preparing its Representations and Certifications, specifically in completing the provision entitled, SMALL BUSINESS PROGRAM REPRESENTATIONS, FAR 52.219-1:

1. The standard industrial classification (SIC) code for this acquisition is 8999.

(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.

2. 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.

9. TASK ORDER CONTRACT AND DELIVERY ORDER CONTRACT OMBUDSMEN
1. FAR 16.505(b)(4) requires that each agency designate a task order contract and delivery order contract ombudsman who will be responsible for reviewing complaints from contractors and ensuring that all contractors are afforded a fair opportunity to be considered for orders.
2. The Ombudsmen for R&D task and delivery order contracts is Dr. James F. O'Donnell. Correspondence from awardees on multiple award R&D task and delivery order contracts may be forwarded to the following address:

12. 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 that 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, Item F.6., of the STANDARD RFP INSTRUCTIONS AND PROVISIONS, General Instructions.)

13. SAFETY AND HEALTH DEVIATION - PHS 352.223-70 (AUG 1997)

(a) To help ensure the protection of the life and health of all persons, and to help prevent damage to property, the Contractor shall comply with all Federal, State, and local laws and regulations applicable to the work being performed under the contract. These laws are implemented and/or enforced by the Environmental Protection Agency, Occupational Safety and Health Administration, and other agencies at the Federal, State, and local levels (Federal, State and local regulatory/enforcement agencies.)

(b) Further, the Contractor shall take or cause to be taken such additional safety measures as the Contracting Officer, in conjunction with the project or other appropriate officers, determines to be reasonably necessary. If compliance with such additional safety measures results in an increase or decrease in the cost or time required of performance of any part of work under the contract, an equitable adjustment will be made in accordance with the applicable "Changes" Clause as set forth in the contract.

(c) The Contractor shall maintain an accurate record of, and promptly report to the Contracting Officer, all accidents or incidents resulting in the exposure of persons to toxic substances, hazardous materials or hazardous operations; the injury or death of any person; and/or damage to property incidental to work performed under the contact and all violations for which the Contractor has been cited by any Federal, State, or local regulatory/enforcement agency. The report shall include a copy of the notice of violation and the findings of any inquiry or inspection, and an analysis addressing the impact these violations may have on the work remaining to be performed. The report shall also state the required action(s), if any, to be taken to correct any violation(s) noted by the Federal, State, or local regulatory/enforcement agency and the time frame allowed by the agency to accomplish the necessary corrective action.

(d) If the Contractor fails or refuses to comply promptly with the Federal, State, or local regulatory/enforcement agency's directive(s) regarding any violation(s) and prescribed corrective action(s), the Contracting Officer may issue an order stopping all or part of the work until satisfactory corrective action (as approved by the Federal, State, or local regulatory/enforcement agencies) has been taken and documented to the Contracting Officer. No part of the time lost due to any such stop work order shall be subject to a claim for extension of time or costs or damages by the Contractor.

(e) The Contractor shall insert the substance of this clause in each subcontract involving toxic substances, hazardous materials, or hazardous operations. Compliance with the provisions of this clause by subcontractors will be the responsibility of the Contractor.

14. PRIVACY ACT SYSTEM OF RECORDS

    This procurement action requires the Contractor to do one or more of the following: design, develop or operate a system of records on individuals to accomplish an agency function in accordance with the Privacy Act of 1974, Public Law 93-579, December 31, 1974 (5 USC 552a) and applicable agency regulations. Violation of the Act may involve the imposition of criminal penalties.

    The Privacy Act System of Records Notice that applies to this RFP was published in the Federal Register dated April 7, 1997, Vol. 62 No. 66, Pages 16596-16602. This notice will be incorporated into any contract resulting from this RFP. If you would like a copy, please contract the Contracting Officer identified in the cover letter to this RFP.

15. PROPOSAL INTENT RESPONSE SHEET

1. TECHNICAL PROPOSAL COVER SHEET .............................. Page 1
2. TECHNICAL PROPOSAL TABLE OF CONTENTS ................ Page 2
3. SUMMARY OF OBJECTIVES AND METHODS (Abstract)*... Page 3
4. TECHNICAL PLAN (Refer to Technical Proposal Instructions located in the Standard RFP Instructions and Provisions.)

5. OTHER SUPPORT (A "Summary of Current and Proposed Activities" for all Key Personnel must be provided; this form is located in FORMS, FORMATS, ATTACHMENTS) -- Page ____  
6. HUMAN SUBJECTS, PARTICIPATION OF CHILDREN AND MINORITY AND GENDER ISSUES NOT OTHERWISE ADDRESSED (If applicable)
7. VERTEBRATE ANIMALS (IF APPLICABLE) -- Page ____
8. "Technical Proposal Cost Information" summary spreadsheet -- Page ____
9. LITERATURE CITED -- Page ____   
10. APPENDICES (Protocols, policy manuals, etc. for above Technical Plan; list each Appendix; Appendices must be clear and legible, and easily located.)  

APPLICABLE RFP REFERENCES