RFP No. NIH-NHLBI-HB-00-01

"Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG)--Clinical Center"

Request for Proposal No.: NIH-NHLBI-HB-00-01
Issue Date: July 2, 1999
Issued By: Joann A. Ciufolo, Contracting Officer
NIH, National Heart, Lung, and Blood Institute
BDR Contracts Section, Contracts Operations Branch
6701 Rockledge Drive, MSC 7902
Bethesda, Maryland 20892-7902
Purchase Authority: Public Law 95-83, as amended
Small Business Set-Aside: No; SIC Code: 8731
Just in Time: Yes
Proposal Intent Due Date: July 30, 1999
Proposal Due Date: August 30,1999, 4:30 PM (EST)


Ladies and Gentlemen:

The National Heart, Lung, and Blood Institute (NHLBI) is soliciting proposals for Clinical Centers to participate in the "Pediatric Hydroxyurea Phase III Clinical Trial". The major objective of this double-blind, placebo-controlled, multi-center clinical trial is to study the efficacy of hydroxyurea therapy in the prevention of chronic end organ damage in pediatric patients with sickle cell anemia (HbSS). The Government anticipates that approximately 10 contracts will be awarded for a period of six years as a result of this RFP.

This Streamlined Technical Request For Proposal (RFP) consists of this combined solicitation form and cover letter (PART A), and three components, as follows:

  1. Work Statement/Background and History/Statement of Work;
  2. Deliverables/Reporting Requirements; and
  3. Evaluation Factors for Award, including Technical Evaluation Criteria.

These components contain the technical information required for the submission of a proposal for this acquisition. In addition, there are two other sections in this specific RFP. The section entitled "Specific RFP Instructions and Provisions" contains, for example, the address for delivery of your proposal and the new NHLBI Public Use Data clause. The section entitled "Applicable RFP References" lists those items in the STREAMLINED RFP REFERENCES directory that apply to this RFP, including forms for submission of the proposal. The Streamlined RFP References directory is located at URL: "http://www4.od.nih.gov/ocm/contracts/rfps/mainpage.htm." The documents listed above represent all of the necessary information required for submission of a proposal. If you intend to submit a proposal in response to this RFP, IT IS ESSENTIAL THAT YOU IMMEDIATELY NOTIFY JOANN A. CIUFOLO, CONTRACTING OFFICER, AT THE FOLLOWING INTERNET ADDRESS:

jc84g@nih.gov

IF YOU DO NOT NOTIFY THE CONTRACTING OFFICE OF YOUR INTENT TO SUBMIT A PROPOSAL, YOU WILL NOT RECEIVE AN INDIVIDUAL NOTICE OF ANY AMENDMENTS TO THE RFP, IF ANY ARE ISSUED. HOWEVER, ALL AMENDMENTS WILL BE POSTED ON THE NIH WEB SITE.

The original and twenty-five (25) copies of your technical proposal and the original and six (6) copies of your business proposal must be received by the Contracting Office no later than August 30, 1999, at 4:30 p.m. local time at the address listed in the item entitled "Packaging and Delivery of Proposals". Also, please complete the form entitled "Proposal Intent Response Sheet" and send it to the address indicated therein on or before July 30, 1999. This will allow us to expedite preparations for the peer review of proposals (Please note the special instructions for completing this form written on the form itself.). Finally, your proposal must be organized and submitted in accordance with the "Technical Proposal Table of Contents." All three of these items are found under the "Specific RFP Instructions and Provisions" portion of this RFP, which follows the technical evaluation criteria section.

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. (This form is contained in this NIH WEB site under the FORMS, FORMATS, AND ATTACHMENTS file found in STREAMLINED RFP REFERENCES.) This information will be used to ensure that there will be no conflict of interest when selecting review committee members.

Offers will be valid for 120 days unless a different period is specified by the offeror on the form entitled, "Proposal Summary and Data Record, NIH 2043" also located at the site for FORMS, FORMATS, AND ATTACHMENTS.

NOTE: If your proposal is not received by the contracting officer or designee at the place and time specified, then it will be considered late and handled in accordance with the phs clause 352.215-10 entitled, "late proposals, modifications of proposals, and withdrawals of proposals". The full text is in the optional rfp instructions and provisions file of the Streamlined RFP References Directory.

SUBMISSION OF PROPOSALS USING FACSIMILE OR E-MAIL IS NOT AUTHORIZED.

NOTE: DIRECTIONS FOR ACCESSING THE "STREAMLINED RFP REFERENCES" REFERRED TO THROUGHOUT THIS RFP ARE AS FOLLOWS:

After reviewing this Request For Proposal, type in URL: "http://www4.od.nih.gov/ocm/contracts/rfps/mainpage.htm". In this directory, entitled "NIH Request For Proposals Directory", following the list of NIH Institutes by name, is the section entitled "STREAMLINED RFP REFERENCES". Select (click on) each section you wish to review:

"STANDARD RFP INSTRUCTIONS AND PROVISIONS" for proposal preparation instructions and other standard provisions,

"OPTIONAL RFP INSTRUCTIONS AND PROVISIONS" for the special provisions identified in this specific RFP,

"FORM, FORMATS, AND ATTACHMENTS" to download the forms listed in this specific RFP that you will need to submit a proposal, and

"SAMPLE CONTRACT FORMAT-GENERAL" to view some of the clauses that are typical for inclusion in a Research and Development type contract issued by NIH.

If you have any additional questions regarding this RFP, please contact Ms. Ciufolo at (301) 435-0359, fax (301) 480-3432. Collect calls will not be accepted.

Sincerely,

/s/ Joann A. Ciufolo

Contracting Officer


WORK STATEMENT

Project Description

The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) will be a randomized, double blind placebo controlled trial to determine if hydroxyurea can prevent the onset of chronic end organ damage in young children with sickle cell anemia (HbSS). The work to be performed involves clinical follow-up of pediatric patients recruited for the clinical trial. The BABY HUG Clinical Centers will perform the actual patient follow-up examinations. The Medical Coordinating Center will be responsible for endpoint adjudication, drug treatment distribution, and performance of clinical laboratory studies outlined in the protocol.

Background and History

The main objective of this trial is to ascertain if hydroxyurea can prevent the onset of chronic end organ damage in young children with sickle cell anemia. Sickle cell anemia is a complex syndrome with multiple organ system disturbances brought about by the interplay of genetic, humoral, vascular and environmental factors. The clinical course can be one of abrupt and insidious exacerbations and remissions, often migratory and repetitive. These events may result in impairment of function, permanently damaged organs, and ultimately death (Platt, O., et al., Pain in sickle cell disease, rates and risk factors, New England Journal of Medicine, 325: 11-16, 1991). Although there is wide variability in the clinical expression of sickle cell disease, this complex set of clinical manifestations is experienced by most patients. In addition, there is no evidence that the primary disease process is different in children when compared with adults with regard to painful episodes. However, children have a higher incidence of respiratory viral infections, and are susceptible to pneumococcal septicemia. With the successful completion of the MSH Trial in adults, attention has now been focused on the use of this agent in children (Charache, S., et al., Effects of hydroxyurea on the frequency of painful crises in sickle cell anemia, New England Journal of Medicine, 332:1317-1333, 1995).

This trial will involve the recruitment of 200 children aged 6 months to 24 months with Hb SS (100 into each trial arm) to receive either hydroxyurea or placebo. The children will be screened at trial start-up for signs of abnormal brain, renal, pulmonary, and splenic function, and for developmental milestones. They will then be randomly assigned to receive either hydroxyurea or placebo. They will be followed with yearly studies of chronic end organ damage of the major organ systems listed above.

The CSSCD has demonstrated that sickle cell anemia patients with increased painful episode rates die at a younger age (Platt, O., Thorington, B.D., Brambilla, D.J., Milner, P.F., Rosse, W., Vichinsky, E., Kinney, T.R., Pain in sickle cell disease: rates and risk factors, New England Journal of Medicine, 325:1476-1481, 1991). In addition, increased levels of fetal hemoglobin are associated with improved survival, and is probably a reliable childhood forecaster of adult life expectancy (Platt, O.S., Brambilla, D.J., Rosse, W.F., Milner, P.F., Castro, O., Steinberg, M., Klug, P.P., Mortality in sickle cell disease: life expectancy and risk factors for early death, New England Journal of Medicine, 330:1639-1644, 1994). The beneficial effect produced by hydroxyurea is thought to occur because it increases fetal hemoglobin levels. Therefore, if chronic end organ damage can be prevented in early childhood by hydroxyurea administration, and if the crisis rate can be decreased by hydroxyurea use early in life, sickle cell anemia patients may experience increased longevity and an improved quality of life.


THE STUDY DESIGN (DRAFT PROTOCOL)
This protocol is for contract purposes only.
The final protocol will be developed during Phase I.

August 1999

PEDIATRIC HYDROXYUREA PHASE III CLINICAL TRIAL
DRAFT PROTOCOL

INTRODUCTION

The objective of this clinical trial is to determine if hydroxyurea therapy is effective in the prevention of the onset of chronic end organ damage as determined by surrogate markers in pediatric patients with sickle cell anemia. This clinical trial will involve the cooperation of pediatric clinical centers with expertise in treating sickle cell anemia, and a coordinating center which will oversee drug distribution, central laboratory functions, and data collection.

In 1995, the Multicenter Study of Hydroxyurea (MSH Trial) demonstrated that hydroxyurea is effective in decreasing the frequency of painful crises, hospitalizations for crises, acute chest syndrome, and blood transfusions. The recently completed phase II study of hydroxyurea in children (PED HUG) demonstrated that children have a response to hydroxyurea similar to that seen in adults in terms of increasing fetal hemoglobin levels and total hemoglobin, and decreasing complications associated with sickle cell anemia. In addition, this study demonstrated that the drug does not adversely affect growth and development between the ages of 5 and 15. A recently completed pilot study of hydroxyurea given to children between the ages of 6 months and 24 months demonstrated that the drug is tolerated well by small infants, and provided evidence that the fetal hemoglobin switch can be forced to remain in the "on position" by hydroxyurea administration.

A Special Emphasis Panel (SEP) met on April 12, 1996 to review the results of the MSH Trial and the progress to date of the PED HUG study. The SEP recommended to the National Heart, Lung, and Blood Institute that a randomized double blind placebo controlled trial be undertaken in young children to test the hypothesis that hydroxyurea can prevent the onset of chronic end organ damage in children recruited before two years of age. Surrogate markers of end organ damage were suggested to be used to evaluate pulmonary, renal, splenic, and brain function as well as developmental mile stones.

OBJECTIVES OF THE TRIAL

The primary objectives of this clinical trial are:

  1. To determine whether or not treatment with hydroxyurea will reduce by at least 50% the rate of chronic end organ damage as determined by surrogate markers in young pediatric patients with sickle cell anemia.

  2. To determine the relationship of fetal hemoglobin to the pathophysiology of end organ damage in sickle cell anemia.

  3. To determine the relationship of the frequency of acute chest syndrome and changes in pulmonary function studies to changes in fetal hemoglobin levels.

  4. To determine the relationship of changes in splenic function to changes in fetal hemoglobin levels.

  5. To determine the relationship of changes in hepatic function to changes in fetal hemoglobin levels.

  6. To determine the relationship of changes in renal function to changes in fetal hemoglobin levels.

  7. To determine the relationship of changes in magnetic resonance imaging of the brain and neuropsychologic functioning to fetal hemoglobin levels.

  8. To determine the effects of hydroxyurea on cytogenetics of blood cells.

PHASING

It is expected that this clinical trial will be performed in 3 phases.

PHASE I - PLANNING PHASE - 12 Months

The final protocol will be developed, forms will be designed, and the Manual of Operations will be prepared. Each peripheral clinic site will obtain IRB approval of the protocol and consent form.

PHASE II - ACTIVE CLINICAL TRIAL - 48 Months

During this phase, patient recruitment, follow-up, and exit from the study will occur.

PHASE III: STUDY CLOSE OUT AND DATA ANALYSIS - 12 Months

During this phase, data analysis and manuscript preparation will occur.

DESIGN FEATURES

  1. Protocol Overview

    The Pediatric Hydroxyurea Phase III Clinical Trial is a multicenter, randomized, double-blind, placebo controlled trial. The projected length of patient enrollment is two years. Eligible patients will be children with sickle cell anemia (Hb SS) between the ages of 6 months and 24 months who will be randomized to receive either hydroxyurea or placebo. Each subject will be followed through the end of Phase II and will be followed with surrogate markers for end organ damage to the lung, liver, kidney, spleen, and brain.

  2. Patient Eligibility

    Male and female infants with hemoglobin SS between the ages of 6 and 24 months will be eligible for entry into this clinical trial. Subjects must not have any contraindications to the administration of hydroxyurea.

  3. Sample Size

    A total of 200 children will be recruited for this trial, to be randomized as follows: 100 to receive hydroxyurea and 100 to receive placebo.

  4. Patient Entry

    Patients will be entered into this clinical trial during years 1 and 2 of Phase II.

    1. Consent form:

      Appropriate consent for patient entry into the trial will be carried out at each center. The parent/legal guardian of each patient will be given a consent form to read and sign prior to the patient's entry. This form will contain a description of the goals of the trial, a description of the examinations and tests which will be given to the patient as part of the trial, as well as expectations of the patient as a trial participant. This consent form will be given to the patient's parent/legal guardian by a member of the clinical center staff who will act as a witness and sign the form below the signature of the parent or legal guardian.

    2. The entry evaluation will include:

      Studies to be performed at the peripheral clinic site:

      Medical History
      Complete physical including neurologic evaluation
      Urinalysis for protein and hemoglobin

      Studies to be performed at the Blood and Chemistry Laboratory:

      Complete Blood Count
      Platelet Count
      Fetal Hemoglobin
      Blood drawn for haplotype determination if not obtained previously
      Serum creatinine

      Studies to be performed at the Cytogenetics Laboratory:

      Cytogenetics study

    3. Special studies will include:

      Studies to be read centrally by the Endpoint Adjudication Panel:

      MRI, MRA
      Pulmonary Function tests with arterial blood gases
      Developmental milestones
      Urinary osmolarity, creatinine clearance
      Liver and spleen scan

  5. Drug Therapy

    All patients enrolled in this trial will receive either hydroxyurea or placebo. The patients will be seen every 2 weeks at which time blood specimens will be obtained and shipped to the Blood and Chemistry Laboratory. Blood counts and other blood studies performed at the Blood and Chemistry Laboratory will be used to monitor for hydroxyurea toxicity (bone marrow depression). The Medical Coordinating Center will obtain blood study results from the Blood and Chemistry Laboratory daily and will review the studies with the Pharmacy Distribution Center to determine the dose recommendation for hydroxyurea or placebo. Dosage adjustments or temporary treatment stops will be performed for placebo subjects so that patients and peripheral clinic staff will be blind to treatment assignments. The Pharmacy Distribution Center will ship hydroxyurea and placebo supplies to the clinic for each patient on a regular basis. No patient can receive a new drug prescription until a blood specimen has been shipped to the Blood and Chemistry Laboratory and evaluated for toxicity. Blood specimen containers and mailers will be provided by the Blood and Chemistry Laboratory.

  6. Interim Monitoring

    It is expected that the following studies will be required every two weeks, and will be performed by the Blood and Chemistry Laboratory:

    Complete Blood Count
    Platelet Count

    The following studies will be required every four weeks, and will be performed by the Blood and Chemistry Laboratory:

    Fetal Hemoglobin
    Serum creatinine, BUN
    Liver enzymes

    The following will be done every 6 months:

    Studies to be performed at the clinic site:

    Medical History
    Complete physical including neurologic evaluation
    Urinalysis for protein and hemoglobin

    Studies to be performed by the Blood and Chemistry Laboratory:

    Complete Blood Count
    Platelet Count
    Fetal Hemoglobin
    Serum creatinine, BUN
    Liver enzymes

    Studies to be performed by the Cytogenetics Laboratory:

    Cytogenetics Study

  7. Studies at Exit

    The following studies will be obtained at study exit:

    Studies to be done at the clinic site:

    Medical History
    Complete physical including neurologic evaluation
    Urinalysis for protein and hemoglobin

    Studies to be performed/interpreted by the Central Laboratory/Endpoint Adjudication Panel:

    Complete Blood Count
    Platelet Count
    Fetal Hemoglobin
    Cytogenetics study
    Serum creatinine
    MRI, MRA
    Pulmonary Function tests with arterial blood gases
    Developmental milestones
    Urinary osmolarity, creatinine clearance
    Liver and spleen scan
    Pre-school primary intelligence, revised (WPPSI-R)
    Woodcock-Johnson for 4 year olds
    NEPSY
    Family Environmental Scale
    Achenbach Child Behavior Checklist
    Beery Test of Visual Motor Integration (VMI)

  8. Trial Endpoints

    The primary endpoints will be a 50% reduction in rates of damage to the major organs (liver, lung, spleen, kidneys, brain) with surrogate markers of organ function to be used during follow-up in Phase II of the trial. Interim analyses and stopping rules to assure subject safety will be established during the planning phase.

  9. Clinical & Laboratory Follow-up Evaluations

    Study subjects will be evaluated in accordance with good patient care. It is expected that the subjects will be seen every 2 weeks to receive complete blood counts and prescriptions for study medications. Study subjects will have routine laboratory studies done to ascertain hydroxyurea effectiveness and toxicity, as well as studies done to ascertain the onset of major end organ function. In addition, all acute and chronic complications will require reporting on an "event" form. All blood studies will be performed centrally to maintain the study blind of treatment assignment at the participating clinical centers.

  10. Study Organization

    1. Project Office - The Program Office is located in the Sickle Cell Disease Scientific Research Group of the Division of Blood Diseases and Resources, NHLBI. It is responsible for NHLBI oversight of this clinical trial, including scientific conduct and administration of this trial. A member of the Contracts Operations Branch, Division of Extramural Affairs, NHLBI, and staff of the Office of Biostatistics Research, Division of Epidemiology and Clinical Applications will work closely with the Sickle Cell Disease Scientific Research Group Staff.

      1. Data and Safety Monitoring Board (DSMB) - appointed by NHLBI to provide oversight of this clinical trial; will review the final protocol before patient recruitment begins. The DSMB will recommend to the NHLBI whether accumulated data warrant protocol changes or early trial termination because of efficacy, futility, or adverse events. The DSMB will meet periodically to review recruitment, interim analyses, and make recommendations concerning patient safety, data integrity, and operation of the trial. The board will include individuals with expertise in hematology, statistics, bioethics, and will have no direct relationship to any of the entities responsible for the conduct of the trial. Data will be privileged and shared only with the DSMB during Phases I and II. The chairperson of the Steering Committee, Coordinating Center staff, and NHLBI staff will attend all meetings of the DSMB. The chair of the Steering Committee will remain blinded to all outcome variables during Phases I and II.

    2. Medical Coordinating Center - The Medical Coordinating Center will be responsible for the statistical design of the trial, the development of operational and analytical methodology, data coordination, study treatment distribution, and all laboratory functions. In addition, the Medical Coordinating Center will be primary liaison to the following entities: Endpoint Adjudication Panel, Blood and Chemistry Laboratory, Pharmacy Distribution Center, and Cytogenetics Laboratory.

      1. Endpoint Adjudication Panel - a group of consultants not involved in the clinical trial will review all clinical events and major end organ studies to adjudicate endpoints; these individuals will be blinded to study treatment assignments.

      2. Blood and Chemistry Laboratory - will be responsible for performance of all blood studies including complete blood counts, serum chemistries, and hydroxyurea blood levels. These functions will be done centrally to prevent the investigators at the clinical centers from knowing study treatment assignments (i.e., to maintain the trial blind).

      3. Pharmacy Distribution Center - will be responsible for filling and distributing all trial medication prescriptions (hydroxyurea and placebo). Distribution of study medication will occur after review of the subject's blood count every two weeks. No study medication will be dispensed unless a blood count is received and reviewed by the Blood and Chemistry Laboratory and Pharmacy Distribution staff.

      4. Cytogenetics Laboratory - will be responsible for the performance of cytogenetics studies on all trial participants.

        During Phase I: The Medical Coordinating Center will develop the protocol, manual of operations, develop data collection forms; and coordinate the management of the trial with the NHLBI and the participating centers by arranging for such meetings and conference calls as are needed to accomplish the foregoing and continue the management of the trial; take minutes of meetings of the Steering Committee, Executive Committee, and the Data and Safety Monitoring Board; arrange for and be the repository for minutes of meetings of other committees and subcommittees; assist NHLBI in obtaining and maintaining IND for hydroxyurea usage in young children; establish protocol for shipment of blood and serum samples to the Blood and Chemistry laboratory; establish protocol for prescription and shipment of study treatments from the Pharmacy Distribution Center to the clinical sites.

        During Phase II: During the active phase of the clinical trial, the Medical Coordinating Center will be responsible for distribution of drug treatments based on blood and chemistry counts of the study subjects. This will involve active coordination between the Pharmacy Distribution Center, the Blood and Chemistry Laboratory, and the Medical Coordinating Center to monitor for drug treatment toxicity as well as planned treatment stops for the placebo arm subjects. The Medical Coordinating Center will be responsible for tracking and editing of all study data forms, and site visits to clinical sites to monitor study performance. In addition, the coordinating center will be responsible for routing of some blood samples to the NHLBI Blood Specimen Repository for storage and future studies. The Medical Coordinating Center will be responsible for providing a monthly study status report which will summarize recruitment, adverse events, and treatment stops and starts. The Medical Coordinating Center will be responsible for preparing and distributing reports to the NHLBI appointed Data and Safety Monitoring Board outlining study progress and statistical analyses of primary and secondary endpoint variables.

        During Phase III: The Medical Coordinating Center will be responsible for finalization of data after completing study form edits, and will be responsible for performing primary and secondary analyses. In addition, the Medical Coordinating Center will take the lead in preparation of reports for the Data and Safety Monitoring Board and publications subcommittees as manuscripts are prepared for publication in the scientific literature.

    3. Clinical Centers: During the active phase of the clinical trial, the clinical centers will be responsible for following the study subjects to monitor clinical responsiveness to study treatments, to assess growth and development, and to monitor for toxicity to study treatments. The clinical centers will be responsible for providing comprehensive care for sickle cell anemia to the study subjects. The clinical centers will participate in annual steering committee meetings, and periodic conference calls and subcommittee meetings as needed. The clinical centers will provide data in a timely fashion to assure patient safety and adherence to protocol as developed by the Steering Committee, and will cooperate with site visit teams from the coordinating center and NHLBI who will monitor clinical trial performance.

      The clinical centers will identify and recruit 200 children with sickle cell anemia between the ages of 6 and 24 months to participate in this clinical trial. The clinical centers will participate in the finalization of the protocol and identification of consultants at their sites for obtaining clinical studies of lung, brain, hepatic, splenic, and kidney function in the study subjects.

      The clinical centers will participate in preparation of publications for scientific literature. The clinical centers will organize the orderly close-out of patients and their study files.

    4. Committees:

      Steering Committee - will be composed of all participating clinical center principal investigators, principal investigators of the coordinating center, blood and chemistry laboratory, pharmacy distribution center, and cytogenetics laboratory. The Steering Committee will be responsible for organizing and planning the trial, and monitoring trial progress. Principal investigators are expected to participate in special writing committees as needed. The Steering Committee will meet annually in Bethesda, Maryland. The Chair and Vice-chair will be elected by the members of the Steering Committee. There will be only one designated voting member per Clinical Center. This member must be present to vote.

      1. Executive Committee - subcommittee of Steering Committee to act on all items as needed that require action between annual Steering Committee meetings, including protocol revisions after the planning phase, manual of operations revisions, and revisions of special studies. Members will be chairpersons of the subcommittees, principal investigator of the Medical Coordinating Center, a representative from the nurse coordinators, and the Sickle Cell Disease Scientific Research Group staff. The Chair of the Steering Committee will serve as chair of the Executive Committee. Membership on the Executive Committee will rotate annually with a total of 4 representatives from the Clinical Centers being elected each year. The Executive Committee will meet via conference call monthly, with additional meetings called by the Chair as necessary.

      2. Publications Committee - subcommittee of Steering Committee which will evaluate all manuscript and ancillary study proposals. Approval of the Publications Committee is required prior to publication.

      3. Writing Committees - these committees will prepare for publication data pertinent to the trial and submit manuscripts for approval to the Publications Committee. Members of the Writing Committees will be able to review data for manuscript preparation directly with the Medical Coordinating Center staff.


STATEMENT OF WORK

Specifically, the Contractor shall serve as a clinical center for the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG). This project will include approximately 10 clinical centers, a medical coordinating center, and three subcontracts under the medical coordinating center for a drug distribution pharmacy, blood and chemistry laboratory, and cytogenetics laboratory. The Contractor shall perform the following specific tasks:

Phase I:

During this phase, prior to patient entry, the Clinical Center shall:

  1. Participate in the development and finalization of the protocol as a member of the Steering Committee. The final protocol must be approved by the NHLBI.

    The draft protocol "Pediatric Hydroxyurea Phase III Clinical Trial" (see above) is hereby made a part of the contract. It is mutually agreed that future revisions of this protocol are considered to be incorporated by reference into this contract without further contract modification. The manual of operations, upon its completion, is made part of the contract by reference.

  2. Obtain Institutional Review Board (IRB) approval of study protocol and informed consent forms.

  3. Submit annual and other reports as indicated. Deliverables (a), (b), (c), (f)

Phase II - Patient Entry and Follow-up:

  1. Enroll at least 20 infants in the United States with sickle cell anemia (Hb SS) between the ages of 6 months and 2 years of age whose parents or legal guardians would consent to have their children participate in this clinical trial of hydroxyurea to prevent chronic end organ damage. The minimum number of patients for enrollment per center is 20. Obtain informed consent for patient enrollment.

  2. Forward eligibility blood samples to the Blood and Chemistry Laboratory as described in the protocol. Costs associated with shipping blood samples shall be borne by the Blood and Chemistry Laboratory. Deliverable (e)

  3. Enter patients into trial, and perform entry tests as indicated by the trial protocol.

  4. Enter and edit forms as requested by the Medical Coordinating Center as indicated by the trial protocol. Deliverable (d)

  5. Follow and monitor patients as outlined in the protocol.

  6. Provide administrative oversight of the Clinical Center and transmit complete and accurate patient clinical data to the Medical Coordinating Center in accordance with the procedures set forth in the protocol.

  7. Follow the guidelines set forth in the Planning Phase not only in the execution of the protocol, but also in conscientiously participating in all committee and subcommittee meetings of which the Principal Investigator and the center staff are members.

  8. Participate in the analysis of data and the writing of trial papers.

  9. Oversee exit of the trial subjects from the clinical trial.

Phase III - Data Analysis, Documentation, and Manuscript Production:

  1. Participate in the analysis and writing of all trial manuscripts and reports.

  2. All publications of data from this trial shall be overseen and coordinated by the Publications Committee, a subcommittee of the Steering Committee which is advisory to the NHLBI.


REPORTING REQUIREMENTS/DELIVERABLES

  1. Technical Progress Reports

    In addition to the required reports set forth elsewhere in this Schedule, the preparation and submission of regularly recurring Technical Progress Reports will be required in any contract resulting from this solicitation. These reports will require descriptive information about the activities undertaken during the reporting periods.

    1. Annual Reports

      The contractor shall submit an annual report that documents and summarizes the results of that contract year, including recommendations and conclusions based on experience and results obtained. Five (5) reproducible copies are due at the end of eleven months of contract performance and annually thereafter. An annual report is not required in the last year of the contract.

    2. Final Report

      The contractor shall submit a final report that documents and summarizes the results obtained over the life of the contract, on or before the expiration date of the contract. Five (5) reproducible copies are due on or before the last day of the contract performance period.

    3. Progress Reports for Clinical Research Study Populations

      The contractor shall submit, on an annual basis, a report detailing the gender and ethnic classifications of all clinical trial subjects. This report shall be submitted in accordance with ARTICLE F.1. DELIVERIES of this contract.


PROGRESS REPORT FOR CLINICAL RESEARCH STUDY POPULATIONS FORMAT
Study Title: Pediatric Hydroxyurea Phase III Clinical Trial
Date:

Provide the number of subject enrolled in the study to date according to the following categories:

  American
Indian or
Alaskan
Native
Asian or
Pacific
Islander
Black,
not of
Hispanic
Origin
Hispanic White,
not of
Hispanic
Origin
Other
or
Unknown
Total
Female              
Male              
Unknown              
TOTAL              

Subpopulations of the minority groups should also be reported, using a similar format.

DELIVERIES

Satisfactory performance of this contract shall be deemed to occur upon delivery and acceptance by the Contracting Officer, or the duly authorized representative, of the following items in accordance with the stated delivery schedule.

The items specified below as described in SECTION C, ARTICLE C.2 shall be delivered F.O.B. destination as set forth in FAR 52.247-35, F.O.B. DESTINATION WITHIN CONSIGNEE'S PREMISES (APRIL 84) and in accordance with and by the dates specified below, and any specifications stated in SECTION D, PACKAGING, MARKING, AND SHIPPING of this contract:

Item Description Quantity Delivery Schedule
(a) Annual Report 5 Eleven months after contract start
and annually thereafter
(b) Final Report 5 Completion of contract
(c) Progress Report for Clinical
Research Study Populations
2 Eleven months after contract start
and annually thereafter
(d) Clinical Data In accordance with protocol In accordance with protocol
(e) Blood & serum samples In accordance with protocol In accordance with protocol
(f) Public use data set In accordance with NHLBI
policy
Within one year after primary
publication

The items above shall be delivered to the following addressees:

Addressee Deliverable Item# Quantity
(1) Contracting Officer
BDR Contracts
Contracts Operations Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 6140, MSC 7902
Bethesda, MD 20892-7902
F.2.(a)
F.2.(b)
F.2.(c)
1
1
1
(2) Project Officer
Sickle Cell Disease Scientific Research Group
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 10148, MSC 7950
Bethesda, MD 20892-7950
F.2.(a)
F.2.(b)
F.2.(c)
F.2.(f)
4
4
1
According to NHLBI policy
(3) Pediatric Hydroxyurea Medical Coordinating Center
(to be determined):
F.2.(d)
F.2.(f)
As directed by Study Protocol
(4) Blood and Chemistry Laboratory
(to be determined)
F.2.(e) As directed in Study Protocol


EVALUATION FACTORS FOR AWARD WITH TECHNICAL EVALUATION CRITERIA

GENERAL

The technical proposal will receive paramount consideration in the selection of the Contractors for this acquisition. All technical evaluation factors, when combined are significantly more important than cost/price and small disadvantaged business (SDB) participation. However, cost/price and (SDB) participation may become critical factors in source selection in the event that two or more offerors are determined to be essentially equal following the evaluation of all technical factors. Cost/Price is significantly more important than SDB participation. In any event, the Government reserves the right to make an award to the best value to the Government, cost and other factors considered.

The evaluation will be based on the demonstrated capabilities of the prospective contractor in relation to the needs of the project as forth in the RFP. The merits of each proposal will be evaluated carefully. Each proposal must document the feasibility of successful implementation of the requirements of the RFP. Offerors must submit information sufficient to evaluate their proposal based on the detailed criteria listed below.

This research project involves human subjects. NIH Policy requires that women, members of minority groups and their subpopulations, and children 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.

Past performance is not an evaluation criterion but it will be considered when determining contractor responsibility using the information required by the "Qualifications of the Offeror" portion of the "Standard RFP Instructions and Provisions" of the RFP References Directory.

Award of this RFP will be made only to offerors located in the United States.

TECHNICAL EVALUATION CRITERIA - Pediatric Hydroxyurea Phase III Clinical Trial

The evaluation criteria are used by the technical evaluation committee when reviewing the technical proposals. The criteria below are listed in the order of relative importance with weights assigned for evaluation purposes. Offerors must provide detailed plans and/or strategies for handling the workload and tasks defined in the Statement of Work.

Weight
30% Documented ability to identify and recruit at least 20 children between the ages of 6 months and 24 months with hemoglobin SS who are not currently on hydroxyurea. Documentation should include a table that lists the number of patients followed at the clinical site in this age group with Hb SS during the preceding 5 years.
25% Scientific merit of offeror's clinical trial design to test the efficacy of hydroxyurea in the prevention of chronic end organ damage in children between the ages of 6 months and 24 months with sickle cell disease. The proposed trial should include concrete plans for the retention of trial subjects, plans to assess and follow-up subjects, methods of endpoint ascertainment, and other relevant details. This section is to be limited to 10 pages of text. The final trial design will be selected later, and this exercise is for the purpose of evaluation.
20% Experience, expertise, and availability of proposed personnel to implement and conduct the trial. Experience in the treatment of children with sickle cell anemia and direct involvement with patients must be documented.
15% Adequacy of proposed organization and administrative structure.
10% Availability of all facilities and equipment to be used specifically for the proposed effort. Assurance that the facilities are available to permit completion of the patient evaluations.


II. SPECIFIC RFP INSTRUCTIONS AND PROVISIONS

Notice to Offerors: This section 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 under Section III. Applicable RFP References.

The following specific RFP instructions and provisions apply to this Request For Proposal:

  1. Proposal Intent Response Sheet (Please submit on or before July 30, 1999)
  2. Packaging and Delivery of Proposal
  3. Government Notice for handling of proposals
  4. Privacy Act System of Records
  5. SIC Code and Small Business Size Standard
  6. Notice of Price Evaluation Adjustment for Small Disadvantaged Business Concerns
  7. Number and Type of Awards
  8. Estimate of Effort
  9. Service of Protest
  10. Safety and Health
  11. Travel requirements for proposal preparation purposes
  12. Special Requirements
  13. Other Provisions
  14. Technical Proposal Table of Contents


  1. PROPOSAL INTENT RESPONSE SHEET

    RFP No.: NHLBI-HB-00-01

    TITLE OF RFP: Pediatric Hydroxyurea Phase III Clinical Trial - Clinical Centers

    Furnish the information requested below and return this page by July 30, 1999. Your expression of intent is not binding but will assist us in planning for proposal evaluation.

    *Please include in your response a listing of all intended collaborators (Investigators) to your proposal by name and institution or organization.


    I INTEND TO SUBMIT A PROPOSAL

    COMPANY/INSTITUTION NAME:

    ADDRESS:

    PROJECT DIRECTOR'S NAME:

    TITLE:

    TELEPHONE & FAX NUMBER:

    E-MAIL ADDRESS:

    * NAMES OF COLLABORATING INSTITUTIONS AND INVESTIGATORS
    (include Subcontractors and Consultants):





    RETURN TO:

    Review Branch
    NIH, NHLBI
    6701 Rockledge Drive MSC 7924
    Bethesda MD 20892-7924
    Attention: Dr. James Scheirer

    or FAX TO: Dr. James Scheirer at
    (301) 480-3541


  1. PACKAGING AND DELIVERY OF THE PROPOSAL

    Your proposal shall be organized as specified in the "Standard RFP Instructions and Provisions." Shipment and marking shall be as follows:

    EXTERNAL PACKAGE MARKING

    In addition to the address cited below, mark each package as follows:

    "RFP NO. NHLBI-HB-00-01  TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY"

    NUMBER OF COPIES

    The number of copies required of each part of your proposal are:

    TECHNICAL PROPOSAL: Original* and Twenty-five (25) Copies

    BUSINESS PROPOSAL: Original* and Six (6) Copies

    DELIVER PROPOSAL TO:

    If hand delivered or delivery service:

    Review Branch
    Division of Extramural Affairs
    National Heart, Lung, and Blood Institute
    Rockledge Building, Room 7091
    6701 Rockledge Drive MSC 7924
    Bethesda, MD 20817-7924

    If using U.S. Postal Service:

    Review Branch, Division of Extramural Affairs
    National Institutes of Health
    National Heart, Lung, and Blood Institute
    6701 Rockledge Drive MSC 7924
    Bethesda, MD 20892-7924

    * THE ORIGINAL PROPOSAL MUST BE READILY ACCESSIBLE FOR DATE STAMPING.


  1. GOVERNMENT NOTICE FOR HANDLING OF PROPOSALS

    An offeror shall place this notice on top of each copy of its technical proposal:

    "This proposal shall be used and disclosed for evaluation purposes only, and a copy of this Government notice shall be applied to any reproduction or abstract thereof. Any authorized restrictive notices which the submitter places on this proposal shall also be strictly complied with. Disclosure of this proposal outside the Government for evaluation purposes shall be made only to the extent authorized by, and in accordance with, the procedures in HHSAR paragraph 315.608-72."

    (For information regarding authorized restrictive notices, offerors should refer to the "Confidentiality of Proposals" section of the STANDARD RFP INSTRUCTIONS AND PROVISIONS.)


  1. 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. This most recent 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.


  1. SIC CODE AND SMALL BUSINESS SIZE STANDARD

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

    The standard industrial classification (SIC) code for this acquisition is 8731, Commercial Physical Research. The small business size standard is 500 employees.

    THIS REQUIREMENT IS NOT SET-ASIDE FOR SMALL BUSINESS. However, the FAR requires in every solicitation (except for foreign acquisitions) the inclusion of the SIC code and corresponding size standard which best describes the nature of the requirement in the solicitation.


  1. NOTICE OF PRICE EVALUATION ADJUSTMENT FOR SMALL DISADVANTAGED BUSINESS CONCERNS

    In accordance with FAR Clause 52.219-23, Notice of Price Evaluation Adjustment for Small Disadvantaged Business Concerns, incorporated in Section I.3., offerors will be evaluated by adding a factor of 10 percent to the price of all offers, except offers from small disadvantaged business (SDB) concerns that have not waived the price evaluation adjustment. In addition, offerors that satisfy the exception requirements under subparagraph (b) of FAR Clause 52.219-23 will not have the price evaluation adjustment factor added to their offers.

    A SDB concern may elect to waive the price evaluation adjustment, in which case the factor will be added to its offer for evaluation purposes. (The agreements in paragraph (d) of FAR Clause 52.219-23 do not apply to offerors that waive the price evaluation adjustment.) If the SDB concern elects to waive the price evaluation adjustment, it will be evaluated under the Small Disadvantaged Business Participation Factor cited in Section M, and participation in performance of the resultant contract shall include the work expected to be performed by SDB 7concerns at the prime contract level. Small businesses, other than SDB concerns, will also be evaluated under the Small Disadvantaged Business Participation Factor cited in Section M. Any targets will be incorporated into and become part of the resulting contract.

    CREDIT UNDER THE SMALL DISADVANTAGED BUSINESS PARTICIPATION FACTOR IS NOT AVAILABLE TO SMALL DISADVANTAGED BUSINESS CONCERNS THAT RECEIVE A PRICE EVALUATION ADJUSTMENT.


  1. NUMBER AND TYPE OF AWARDS

    It is anticipated that ten (10) awards will be made from this solicitation and that award will be made on or before June 1, 2000. It is anticipated that the award from this solicitation will be a multiple-year cost completion type contract with a period of performance of six years (seventy-two months), and that incremental funding will be used.


  1. ESTIMATE OF EFFORT

    It is estimated that percent effort to be provided per Phase is as indicated below. It is expected that a completion, cost-reimbursement type contract will be awarded as a result of this RFP. To assist you in the preparation of your proposal, the Government considers the effort below to be approximate. This information is furnished for the offeror's information only and is not to be considered restrictive for proposal purposes. The levels of effort shown below are based on recruitment and follow-up of 20 patients, and includes levels of effort anticipated for one clinical center.

    Labor Category Phase 1 Phase 2 Phase 3
    Principal Investigator 10.0% 10.0% 10.0%
    Clinic Nurse Coordinator 50.0% 100.0% 100.0%
    Total: 60.0% 110.0% 110.0%

    The level of effort (time) devoted to the project must be compatible with the scientific and technical approach proposed. The principal investigator must have training and actual experience in pediatric hematology and the care of children with sickle cell anemia. The clinical center team must have demonstrated experience in the performance of randomized phase 3 clinical trials and multicenter epidemiologic studies.

    The categories and levels of effort presented are offered as guidelines for preparation of a proposal. They represent the approximate types and FTE amounts required.


  1. SERVICE OF PROTEST (AUG 1996) - FAR 52.233-2

    1. Protests, as defined in section 33.101 of the Federal Acquisition Regulation, that are filed directly with an agency, and copies of any protests that are filed with the General accounting Office (GAO) shall be served on the Contracting Officer (addressed as follows) by obtaining written and dated acknowledgment of receipt from:

      U.S. Postal Address: Ms. Joann A. Ciufolo, Contracting Officer
      National Institutes of Health
      National Heart, Lung, and Blood Institute
      Contracts Operations Branch
      Rockledge 2, Room 6140
      6701 ROCKLEDGE DR MSC 7902
      BETHESDA MD 20892-7902
      Hand Delivery: Ms. Joann A. Ciufolo, Contracting Officer
      National Institutes of Health
      National Heart, Lung, and Blood Institute
      Contracts Operations Branch
      Rockledge 2, Room 6140
      6701 ROCKLEDGE DR MSC 7902
      BETHESDA MD 20817

    The copy of any protest shall be received in the office designated above within one day of filing a protest with GAO.


  1. SAFETY AND HEALTH DEVIATION PHS 352.223-70 (AUGUST 1997)

    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 this 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).

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

    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 contract 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.

    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 stop work order shall be subject to a claim for extension of time or costs or damages by the Contractor. The Contractor shall insert the substance of this clause in each subcontract involving toxic substances, hazardous materials, or operations. Compliance with the provisions of this clause by subcontractors will be the responsibility of the Contractor.


  1. TRAVEL REQUIREMENTS FOR PROPOSAL PREPARATION PURPOSES

    Plans should be made for the following travel.

    Year 1: Planning Meetings 6 meetings for 1 traveler
    (P.I.) held in Bethesda, Maryland
    Annual Steering Committee Meeting 1 meeting for 2 travelers
    (P.I. and nurse coordinator) held in Bethesda, Maryland
    Years 2
    thru 6:
    Annual Steering Committee Meeting 1 meeting for 2 travelers
    (P.I. and nurse coordinator) held in Bethesda, Maryland


  1. SPECIAL REQUIREMENTS

    Patient Population - At least twenty (20) children between the ages of 6 months and 24 months with sickle cell disease (Hb SS) to be recruited per clinical center.

    Clinical Trial Design - Offerors are expected to include as a part of their proposal a clinical trial design to test the efficacy of hydroxyurea in the prevention of chronic end organ damage in children between the ages of 6 months and 24 months with HbSS. The proposed trial should include concrete plans for the retention of trial subjects, plans to assess and follow-up subjects, methods of endpoint ascertainment, and other relevant details. This section is to be limited to 10 pages of text. The final trial design will be later, and this exercise is for the purpose of evaluation.

    Special Studies - The Clinical Centers are expected to arrange for the performance of the following studies at their sites: urinalysis, urinary osmolarity, creatinine clearance, pulmonary function studies with arterial blood gases, liver and spleen scan, MRI, MRA, neuropsychological studies (pre-school primary intelligence, Woodcock Johnson for 4 year olds, NEPSY, Family Environmental Scale, Achenbach Child Behavior Checklist, Beery Test of Visual Motor Integration).

    Shipping of Specimens to Blood and Chemistry Laboratory - Kits for packing and shipment of specimens will be provided to BABY HUG Clinical Centers by the Blood and Chemistry Laboratory contractor (to be named). Costs for supplies and prepaid airbills shall be borne by the Blood and Chemistry Laboratory contractor.

    OMB Clearance - It is expected that a clinical exemption from OMB review will be obtained by the NHLBI for this trial because data forms are considered part of the patient's record.


  1. OTHER PROVISIONS

    Government Furnished Facilities and Equipment

    No Government furnished material, facilities, or equipment are envisioned for this acquisition.

    Cost/Pricing Information

    The offeror's business proposal shall include the basic cost/pricing information specified in the Standard RFP Instructions and Provisions, under the Streamlined RFP References Directory referenced in this RFP. In addition, the Government may require offerors included in the competitive range to submit additional information substantiating their proposed costs or prices. This additional cost/pricing information will be requested after establishment of the competitive range, and potentially includes payroll documentation, vendor quotes, invoice prices, and/or any other information deemed necessary by the Contracting Officer to evaluate the reasonableness of the price or to determine cost realism. The information may also include submission and certification of or pricing data.

    Note that the cost proposal you will prepare in response to this RFP will cover the period June 1, 2000 through May 31, 2006. Costs should be proposed for each year of the contract as follows: June 1, 2000 through May 31, 2001; June 1, 2001 through May 31, 2002; and so on through May 31, 2006.

    For your convenience, a standard cost proposal spreadsheet in Excel format is available under the Standard RFP References directory in the FORMS, FORMATS, AND ATTACHMENTS file: "http://www4.od.nih.gov/ocm/contracts/rfps/buscost.htm". Offerors determined to be in the competitive range will be requested to submit a computer disk in Excel format.

    NHLBI Public Use Data Clause - Clinical Center
    (This clause will be made a part of the contract.)

    Public use data will be released under this clinical trial. After publication of the primary clinical trial results, the coordinating center will prepare the data and deliver it to the NHLBI. The data shall be prepared in a format suitable for use by the public. Such release is expected to occur no later than three years after the primary publication. The coordinating center shall provide the data to the NHLBI within two years of the primary publication so that the NHLBI can check the data before release. This will provide time for NHLBI review, discussion of the data, and opportunity for any changes needed in content or presentation prior to release.

    The public use data set will include the baseline visit, interim visit(s), and outcome data, including laboratory measurements. Inclusion of raw data that has been processed into summary information shall be discussed with the Project Officer prior to submission. Data prepared for release will not contain personal identifiers. Preparation of the data will be coordinated with the NHLBI to assure patient confidentiality.

    The study investigators will be expected to answer basic questions regarding data set characteristics, format and content, during the study. Documentation is expected to be of the highest quality so that such questions will be minimized.

    Data will not be prepared for public use if the investigators and NHLBI believe that they are unreliable or invalid. These exceptions must be justified in writing through the coordinating center to the NHLBI, and will be reviewed and, if the NHLBI concurs, approved in writing by the Director of the Division that sponsored the study.


  1. TECHNICAL PROPOSAL TABLE OF CONTENTS

    Please number each page of text. Type density and size must be 10-12 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.

    The technical proposal should be organized as follows:

    SECTION

    1. Technical Proposal Cover Sheet in "FORMS, FORMATS, ATTACHMENTS" --Page 1
    2. Technical Proposal Table of Contents--Page 2
    3. Summary of Objective and Methods (Abstract)*--Page 3
      State the proposal's objectives. Briefly and concisely describe the research design and methods for achieving these goals. DO NOT EXCEED one page in providing the abstract. Identify the RFP Number, Institution and Principal Investigator on the abstract.
    4. Technical Plan--Page 4
      (Refer to Technical Proposal Instructions , found in Standard RFP Instructions and Provisions.)
      1. Personnel
        1. List of all Personnel in the project including Subcontractors, Consultants/Collaborators, by name, title, department and organization--Page#
          Provide two-page biosketches for investigators and narratives, including role in program, expertise, and related experiences, for:
        2. Principal Investigator/Project Director--Page#
        3. Other Investigators--Page#
        4. Additional Personnel--Page#
      2. Statement of Work (4b. no more than 35 PAGES single-spaced)
        1. Objectives--Page#
        2. Approach--Page#
        3. Methods--Page#
        4. Schedule--Page#
      3. Facilities, Equipment and Other Resources--Page#
        List/describe all facilities, equipment and other resources available for this project.
      4. Other Considerations/documentation--Page#
        1. Documentation of submission to IRB of draft protocol and consents
    5. Other Support--Page#
      Complete the Form "Summary of Current and Proposed Activities." All key personnel must be listed on this form. The form is located in the Streamlined RFP References under "FORMS, FORMATS, ATTACHMENTS"
    6. Human Subjects and Minority and Gender Issues Not Otherwise Addressed--Page#
    7. Technical Proposal Cost Information--Page#
      (Format in "FORMS, FORMATS, ATTACHMENTS")
    8. Literature Cited--Page#
    9. Appendices--Page#
      Appendices, Literature citations, and 4b. through 7 above are not to exceed 100 pages single-spaced. List each Appendix and identify the number of pages for each one. Appendices must be clear and legible, and easily located.


III. APPLICABLE RFP REFERENCES

This section identifies the items found in the subdirectory entitled RFP REFERENCES that are applicable to this Request For Proposal (RFP). The files identified below must be retrieved, in whole or in part, in order to submit a proposal in response to this RFP.

  1. The entire file entitled "STANDARD RFP INSTRUCTIONS AND PROVISIONS" is applicable to this RFP, except as modified by the inclusion of items from the "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS" below.

  2. The following items are applicable from the file entitled "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS." The full text of the provisions is available in the file. List of provisions which apply to this specific RFP:
    1. Late Proposals, Modifications of Proposal, and Withdrawals of Proposals
    2. Human Subjects
    3. Small, Small Disadvantaged, and Women-Owned Small Business Subcontracting Plan
    4. Inclusion of Women and Minorities in Research Involving Human Subjects
    5. "JUST IN TIME"

  3. The following items are applicable to this specific RFP and are located in the file entitled "FORMS, FORMATS, ATTACHMENTS":

    Technical Proposal Forms (with original and every copy of technical proposal)

    Technical Proposal Cover Sheet
    Summary of Current and Proposed Activities
    Technical Proposal Cost Information
    Technical Proposal Table of Contents
    Protection of Human Subjects Assurance/Identification/Certification/Declaration, OF310

    Business Proposal Forms

    Business Proposal Cost Information
    Proposal Summary and Data Record, NIH-2043, with every copy of business proposal.
    Disclosure of Lobbying Activities, OMB SF-LLL, only one completed and signed original. This form is not required if there are no lobbying activities to disclose.

    Contract Negotiation Forms/Attachments

    DHHS Small, Small Disadvantaged, HUBZone and Woman-owned small Business Subcontracting Plan
    Certificate of Current Cost or Pricing Data, NIH-1397
    Representations and Certifications are applicable
    Sample Contract Format-General - R&D Cost Reimbursement

    Contract Forms and Attachments

    Invoice/Financing for Cost Reimbursement Type Contracts, NIH(RC)-1
    Procurement of Certain Equipment, NIH(RC)-7
    NIH 2706, Financial Report for Individual Project/Contract Instructions
    NIH 2706, Financial Report for Individual Project/Contract Form
    Research Patient Care Costs, NIH(RC)-11
    Annual Technical Progress Report Format for Each Study


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