"Pediatric Hydroxyurea Phase III Clinical Trial--Medical Coordinating Center"
| Request for Proposal No.: | NIH-NHLBI-HB-00-02 |
| Issue Date: | July 2, 1999 |
| Issued By: | Joanna Magginas Contracting Officer NIH/NHLBI Contracts Operations Branch II Rockledge Centre 6701 Rockledge Drive, MSC 7902 Bethesda, Maryland 20892-7902 |
| Purchase Authority: | Public Law 95-83, as amended |
| Small Business Set-Aside: | Yes; SIC Code 8731 |
| Offer Expiration Date: | 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." |
| Just in Time: | Yes |
| Proposal Intent Due Date: | July 30, 1999 |
| Proposal Due Date: | August 30, 1999, 4:30 PM (Eastern Standard Time) |
The National Heart, Lung, and Blood Institute (NHLBI) is soliciting proposals for the establishment of a Coordinating Center to participate in a multi-center clinical trial to determine if hydroxyurea therapy is effective in the prevention of chronic end organ damage in pediatric patients with sickle cell anemia.
The Sections included with this streamlined electronic RFP package are as follows:
Solicitation Form/Cover Letter
Statement of Work/Project Information/Study Design (Draft Protocol);
Deliverables/Reporting Requirements;
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.
Note: The Streamlined RFP References directory is located at URL:"http://www4.od.nih.gov/ocm/contracts/rfps/mainpage.htm".
The attachments/documents listed above represent all the necessary information required for the submission of a proposal for this acquisition. Following proposal submission and review, additional information will be requested by the Contracting Officer from all offerors which comprise the competitive range.
Although these documents contain sufficient information for you or your organization to submit a proposal, if you intend to submit a proposal in response to this RFP, IT IS ESSENTIAL THAT YOU IMMEDIATELY NOTIFY JOANNA MAGGINAS, CONTRACTING OFFICER, AT THE FOLLOWING INTERNET ADDRESS:
IF YOU DO NOT NOTIFY THE CONTRACTING OFFICER 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 RFP DIRECTORY WEB SITE.
The original and twenty (20) copies of your technical proposal and the original and six (6) copies of your business proposal must be received by the Contracting Officer 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 the Proposal". 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. 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, below.
You are reminded that the "Technical Proposal Cover Sheet" must be completed in full detail and used as the cover sheet for each copy of your technical proposal (a copy of this form is contained in the FORMS, FORMATS, AND ATTACHMENTS section of the STREAMLINED RFP REFERENCES.) This information will be used to ensure that there will be no conflict of interest when selecting review committee members.
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 PROPOSAL, 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, "FORMS, FORMATS, AND ATTACHMENTS" to download the forms listed in this specific RFP that you will need to submit a proposal, "REPRESENTATIONS AND CERTIFICATIONS" to download and complete the representations and certifications that must be submitted with your 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 Joanna Magginas at (301) 435-0360, fax (301) 480-3432. Collect calls will not be accepted.
Sincerely,
/s/
Joanna Magginas
Contracting Officer
STATEMENT OF WORK
Phase I - Planning, 12 months
Phase II - Active Clinical Trial, 48 months
Phase III - Trial Close-Out and Data Analysis, 12 months
The Contractor shall perform the following specific tasks:
For solicitation purposes, no subcontract costs should be proposed at this time. Upon finalization of the protocol, it is anticipated that additional funding will be negotiated.
PROJECT INFORMATION
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. The work to be performed involves clinical follow-up of pediatric patients recruited for the clinical trial. The 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.
The main objective of this study is to ascertain if hydroxyurea can prevent the onset of chronic end organ damage in young children with sickle cell anemia (Hb SS). 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 study arm) to receive either hydroxyurea or placebo. The children will be screened at study start-up for signs of abnormal brain, renal, pulmonary, 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 of hydroxyurea is thought to occur because it increases fetal hemoglobin levels. Therefore, if chronic end organ damage can be prevented in childhood, 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.
STUDY DESIGN (DRAFT PROTOCOL): This protocol is for contract purposes only. The final protocol will be developed during Phase I.
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.
The primary objectives of this clinical trial are:
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.
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.
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.
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.
Patients will be entered into this clinical trial during years 1 and 2 of Phase II.
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.
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
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
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.
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 hemoglobinStudies to be performed by the Blood and Chemistry Laboratory:
Complete Blood Count
Platelet Count
Fetal Hemoglobin
Serum creatinine, BUN
Liver enzymesStudies to be performed by the Cytogenetics Laboratory:
Cytogenetics Study
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)
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.
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.
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 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.
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.
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.
DELIVERABLES/REPORTING REQUIREMENTS
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) | Data Analysis Plan | 10 | Twelve months after contract start |
| (b) | Monthly Study Status Report | 3 | Monthly |
| (c) | Protocol and Manual of Operations | 23 | end of Phase I |
| (d) | Annual Progress Reports | 20 | Eleven months after contract start and annually thereafter |
| (e) | Minutes of Steering Committee & Executive Committee meetings |
13 | Within 30 days following each mtg. |
| (f) | Minutes of DSMB meetings | 10 | Within 30 days following each meeting |
| (g) | Reports requested by the DSMB on patients safety and health status |
11 | two weeks prior to DSMB meetings |
| (h) | Final Report | 4 | Expiration of Contract |
| (i) | Edited data tape and documentation |
to be determined | Six months prior to expiration |
| (j) | Public Use Data set | in accordance with NHLBI policy |
per Public Use Data Clause |
The items above shall be delivered to the following addressees:
| Addressee | Deliverable Item# | Quantity | |
|---|---|---|---|
| (1) | Contracting Officer BDR Contracts Section Contracts Operations Branch National Heart, Lung, and Blood Institute 6701 Rockledge Drive, MSC 7902 Bethesda, MD 20892-7902 |
F.1.(a) F.1.(b) F.1.(c) F.1.(d) F.1.(e) F.1.(f) F.1.(g) F.1.(h) |
1 1 1 1 1 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, MSC 7950 Bethesda, MD 20892-7950 |
F.1.(a) F.1.(b) F.1.(c) F.1.(d) F.1.(e) F.1.(f) F.1.(g) F.1.(h) F.1.(i) F.1.(j) |
2 1 2 2 2 2 3 3 to be determined in accordance with NHLBI policy |
| (3) | 7 DSMB Members (TBN) | F.1.(a) F.1.(b) F.1.(c) F.1.(d) F.1.(f) F.1.(g) |
7 1(chairperson) 7 7 7 7 |
| 4) | 10 Steering Committee Members (TBN) | F.1.(c) F.1.(d) F.1.(e) |
10 10 10 |
| (5) | Pharmacy Distribution Center (TBN) Blood and Chemistry Laboratory (TBN) Cytogenetics Laboratory (TBN) |
F.1.(c) F.1.(c) F.1.(c) |
1 1 1 |
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 period and will require information about planned activities for future reporting periods. The and specific content of these reports will be determined during prior to contract award.
For solicitation purposes only, it is estimated that reports will be required as follows:
The contractor shall submit a plan for the analysis of this randomized, double blind, placebo controlled trial.
The contractor shall submit a monthly study status report which will tabulate patient enrollment, vital status, and adverse events in the study population.
The contractor shall submit an annual progress report that documents and summarizes the results of that contract year, including recommendations and conclusions based on experience and results obtained.
The contractor shall submit complete and accurate minutes of all Steering Committee meetings, Executive Committee meetings, and DSMB meetings.
The contractor shall submit a final report that documents and summarizes the results obtained over the life of the contract due on or before the expiration date of the contract.
EVALUATION FACTORS FOR AWARD, INCLUDING TECHNICAL EVALUATION CRITERIA
Proposals submitted in response to this solicitation will be subjected to primary review by a group of scientists composed totally or predominantly of non-Federal workers convened by the Review Branch, Division of ExtrAmural Affairs, NHLBI. Secondary review will be conducted by NHLBI program staff. 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. The evaluation elements and weighing factors which will be used to evaluate the proposal are listed below.
GENERAL
The technical proposal will receive paramount consideration in the selection of the contractor for this acquisition. All evaluation factors, other than cost or price, when combined are significantly more important than cost or price. However, cost/price may become a critical factor in source selection in the event that two or more offerors are determined to be essentially equal following the evaluation of all factors other than cost or price. In any event, the Government reserves the right to make an award to that offeror whose proposal provides the best value to the Government.
The evaluation will be based on the demonstrated capabilities of the prospective contractors 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 proposals based on the detailed criteria listed below.
TECHNICAL EVALUATION CRITERIA
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.
| Weight | |
|---|---|
| 40% | Adequacy of technical approach to coordinate and manage a multicenter randomized clinical trial. The approach must include suitable plans for data management, data analysis, and for fulfilling medical coordinating center functions. Adequacy of plans for managing the data derived from this study, including plans for assessing the reliability and validity of the data collected.
Plans for fulfilling the Medical Coordinating Center functions, including methods for coordinating, monitoring, and managing all activities required for the collaborative development of the study protocol and for the conduct of activities as described in the study protocol. These activities include, but are not limited to, plans for the randomization of patients, intervention approaches, preparation and updating the manual of operations, oversight of standardization and quality control of data collection. |
| 30% | Qualifications and availability of personnel with experience relevant to the operation of a medical coordinating center for a complex multicenter randomized clinical trial. Personnel should have expertise in sickle cell disease, drug treatment distribution, adverse reactions to drug therapy, clinical laboratory expertise, as well as experience in data collection, monitoring, standardization, quality control, and preparation of scientific reports and manuscripts. |
| 20% | Adequacy of the organizational and administrative structure to participate in a complex multicenter randomized clinical trial. Experience in studies, both in the collection of data from multiple clinical and laboratory sites, as well as experience in monitoring the quality and timeliness of data. Institutional commitment to the program, and adequacy of proposed facilities, equipment, and space for accomplishing the Statement of Work. |
| 10% | Evidence in soliciting, awarding, and administering large, complex subcontracts. |
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 RFP:
RFP No. NHLBI-HB-00-02
TITLE OF RFP: Pediatric Hydroxyurea Phase III Clinical Trial--Medical Coordinating Center
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 NUMBER:
E-MAIL ADDRESS:
NAMES OF COLLABORATING INSTITUTIONS AND INVESTIGATORS (include Subcontractors and Consultants):
RETURN TO:
Review Branch or FAX TO: Dr. James Scheirer (301)480-3541
NIH, NHLBI
6701 Rockledge Drive MSC 7924
Bethesda MD 20892-7924
Attention: Dr. James Scheirer
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-00-02; TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY"
The number of copies required of each part of your proposal are:
TECHNICAL PROPOSAL: ORIGINAL* AND Twenty (20) COPIES
BUSINESS PROPOSAL: ORIGINAL* AND Six (6) COPIESDELIVER 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.
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."
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.
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 and Biological Research.
The small business size standard is 500 employees.
It is anticipated that one (1) award will be made from this solicitation and that award will be made on or about June 1, 2000.
It is anticipated that the award from this solicitation will be a multiple-year cost reimbursement, completion type contract with a period of performance of six years (seventy-two months), and that incremental funding will be used.
The following staffing patterns are broad guidelines which may be useful to the offeror. The staffing guidelines are based on the amount of work that will be required during the planning phase, the amount of data that will be generated during active patient follow-up in Phase II, and the amount of data analysis and manuscript writing that will occur during Phase III. All staffing levels should be accompanied by specific justifications as to the type and hours of work expected to be performed by all personnel. The categories and levels of effort presented are offered as information only and are not to be considered restrictive for proposal purposes. Levels of effort below include effort to administer the three subcontracts listed in the Statement of Work. If a consultant(s) is proposed, a letter of commitment must be provided.
| Position -Medical Coordinating Center | Level of Effort | ||
|---|---|---|---|
| Phase I | Phase II | Phase III | |
| Principal Investigator | 5% | 5% | 5% |
| Project Director | 90% | 90% | 90% |
| Statistician (Ph.D.) | 25% | 25% | 25% |
| Data Manager | 40% | 50% | 50% |
| Research Administrative Assistant | 50% | 50% | 50% |
| Data Entry Clerk | 25% | 50% | 50% |
| Programmer | 15% | 30% | 30% |
| Sickle Cell Consultant | 10% | 10% | 10% |
In accordance with FAR 52.233-2 SERVICE OF PROTEST (NOV 1988):
(a) Protests, as defined in Section 33.101 of the Federal Acquisition Regulation, that are filed directly with an agency, and copies of any protests that are filed with the General accounting Office (GAO) shall be served on the Contracting Officer (addressed as follows) by obtaining written and dated acknowledgment of receipt from:
Mr. Robert R. CarlsenHand-Carried Address:
National Institutes of Health
National Heart, Lung, and Blood Institute
Contracts Operations Branch
II Rockledge Center, Room 6122
6701 Rockledge Drive, MSC 7902
Bethesda, MD 20817U.S. Postal Service:
National Institutes of Health
National Heart, Lung, and Blood Institute
Contracts Operations Branch
II Rockledge Center
6701 Rockledge Drive, MSC 7902
Bethesda, MD 20892-7902
The copy of any protest shall be received in the office designated above within one day of filing a protest with GAO.
Compliance with the provisions of this clause by subcontractors will be the responsibility of the Contractor.
For solicitation purposes, assume the following travel requirements. Assume meetings will be held in Bethesda, Maryland: Phase I Travel
Planning meetings: 6 meetings X 3 travelers from MCC
Steering Committee Meeting: 1 meeting X 3 travelers from MCC
Data and Safety Monitoring Board Meeting: 1 meeting X 10 travelers (7 Data and Safety Monitoring Board members and 3 MCC staff members)
Phase II Travel
Steering Committee Meeting: 1 meeting/year X 5 travelers from MCC
Data and Safety Monitoring Board Meetings: 2 meetings/year X 10 travelers (7 Data and Safety Monitoring Board members and 3 MCC staff members)
Clinical Center Site Visits: 5 visits/year X 1 traveler from MCC
Mid-year executive meetings: 1 meeting/year X 2 travelers from MCC
Phase III Travel
Steering Committee Meeting: 1 meeting X 3 travelers from MCC
Data and Safety Monitoring Board Meetings: 2 meetings X 10 travelers (7 Data and Safety Monitoring Board members and 3 MCC staff members)
Mid-year executive meeting: 1 meeting X 2 travelers from MCC
Clinical Center Site Visits: 5 visits X 1 traveler from MCC
IMPORTANT: Technical proposals submitted in response to this RFP MUST NOT EXCEED 35 PAGES; however, this limitation does not include the cover sheet, table of contents, abstract or copies of biosketch or appendices. 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:
No Government furnished material, facilities, or equipment are envisioned for this acquisition.
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 cost 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; June 1, 2002 through May 31, 2003, 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 competitve range will be requested to submit a computer disk in Excel format.
Public use data will be released under this clinical trial. After publication of the primary clinical trial results, the coordinating center shall 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. If the contract expiration date does not allow the contractor to with the above time frame, the data shall be prepared and delivered at least thirty days prior to the contract expiration date.
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 shall not contain personal identifiers. The contractor shall coordinate preparation of the data with the NHLBI to assure patient confidentiality. The data shall be submitted on CD ROM, or other mutually agreed upon data medium that includes complete electronic documentation and data. Ancillary study data (not funded under this contract) are not required to be included in the public use data set, though the data may be included if agreed upon by the ancillary study investigator.
The contractor shall produce clear documentation for the public use data. The documentation must allow for use by investigators not familiar with the data set. The documentation must be written in WordPerfect or ASCII format, and must be included as a data set in the storage medium.
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.
This section identifies the items located in the Streamlined RFP References at URL "http://www4.od.nih.gov/ocm/contracts/rfps/mainpage.htm" that are applicable to this Request For Proposal (RFP).
TECHNICAL PROPOSAL FORMS (with original and every copy of technical proposal):
BUSINESS PROPOSAL FORMS:
OTHER--TO BE SUBMITTED LATER:
ANTICIPATED TO BE INCLUDED AS CONTRACT ATTACHMENTS:
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