SOURCES SOUGHT
B -- Warfarin Pharmacogenetics Study
- Notice Date
- 2/1/2005
- Notice Type
- Sources Sought
- NAICS
- 541990
— All Other Professional, Scientific, and Technical Services
- Contracting Office
- Department of Health and Human Services, Food and Drug Administration, Office of Acquisitions and Grants Services, 5630 Fishers Lane, Room 2129, Rockville, MD, 20857-0001
- ZIP Code
- 20857-0001
- Solicitation Number
- HHSF223200510011C
- Response Due
- 2/16/2005
- Archive Date
- 3/3/2005
- Description
- This announcement is a Sources Sought Synopsis. Its purpose is to generate responses from qualified 8(a), HUBZONE, veteran owned, disabled veteran owned, or small business companies, which have the interest and ability to test the hypothesis that knowing the genotype of the metabolizing enzyme, CYP2C9, and using this knowledge to guide dosing will improve the time within the therapeutic range and reduce over-anticoagulation and the initial risk of bleeding complications of the anticoagulant medication, warfarin. In order to prospectively determine if knowledge of CYP2C9 alleles improves the safety and efficacy of warfarin therapy and warrants genotyping of CYP2C9 when initiating anticoagulant therapy, this study will prospectively compare standard-of-care versus pharmacogenetics-guided warfarin treatment. Companies responding to this synopsis must indicate whether they are interested in this project as a prime contractor or as a possible subcontractor. Companies interested in this requirement as a subcontractor must indicate their areas of expertise that would support a prime contractor in the performance of the work described below. The NAICS code for this procurement is 541990. Contractors must submit a capability statement describing their company's experience and ability to conduct as the prime contractor or support as a subcontractor research to investigate the prospective predictive value of pharmacogenetics in determining the proper dose and safety of prescription drugs and sex differences in women and men. A two and one half year contract is intended. The evaluation process of Offerors submitting capability statements as a prime contractor will determine whether Offerors are able to meet the following research requirements: (1) Study Subjects - Four hundred Caucasian male and female patients over 18 years who are undergoing the initiation of warfarin therapy and requiring a target INR value between 2 and 3 will be enrolled. Written informed consent will be obtained prior to any study procedures. History and physical examination will be conducted at screening to assure appropriate inclusion and exclusion criteria are met. Patients will be genotyped for CYP2C9 prior to being enrolled in the study. Given the frequency of the CYP2C9 variant enzymes is ~33% (individuals with at least one variant allele), to recruit 400 subjects (with at least one variant alleles), approximately 1200 subjects may need to be screened. Patients with at least one CYP2C9 variant alleles (*2 or *3) will be recruited and randomly allocated to the control (standard-of-care, n=200) or pharmacogenetics-guided groups (n=200). An additional blood sample will be collected to determine the vitamin K epoxide reductase complex subunit 1 (VKORC1) genotype in post hoc analysis. Patients' demographic characteristics will be recorded: sex, age, weight, height, and indication for warfarin therapy, additional medical problems, and concurrent medications. If a subject is removed from the study for any reason(s), this shall be noted and the reason reported on a case report form. Subjects shall be free to withdraw from the study at any time. (2) Study Design - A randomized, prospective, double-blind, parallel study will be conducted in patients with indication for the initiation of warfarin therapy. Multiple clinical centers may participate provided each clinical center uses the same approach for dosing and frequency monitoring. (3) Outcome Measures - The primary efficacy end point of this study will be the time within therapeutic range INR of 2-3 (TTR) and the primary safety end point will be the time to first above-range INR. The above-range INRs are defined as measurements of 4.0 or greater. The secondary end points are as follows: time to first INR in therapeutic range; time to stable warfarin dosing; number and timing of serious or life-threatening bleeding events; number of venous thromboembolism or pulmonary embolism events; mean warfarin daily doses during the induction and the maintenance periods; number of INR monitoring; number of warfarin dose adjustments; frequency of hemorrhage; bleeding events when INR is within therapeutic INR range; concentration of S-warfarin at steady state; and number and % of INR values above 3 or below 2. Post hoc analysis of VKORC1 will be conducted to determine the effect of VKORC1 genotype on the primary and secondary outcome measures. (4) Human Subjects Study Requirements - All research conducted, supported, or regulated by any US Government Agency is subject to certain uniform requirements of the Federal Policy for the Protection of Human Subjects including IRB membership, IRB review and approval criteria, IRB operations and record keeping, and informed consent. Research involving human subjects and funded by the Food and Drug Administration must receive approval from FDA's Research Involving Human Subjects Committee (RIHSC) prior to enrolling human subjects. The criteria for the selection and screening of subjects including the inclusion and exclusion criteria shall be discussed in the proposal. The Contractor shall understand and comply with ethical principles and regulatory requirements involving human subjects research as specified in the Federal regulations for the Protection of Human Subjects, 45 CFR 46. The Contractor shall remain in compliance with the Health and Human Services (HHS) policies and procedures that concern the conduct of human subjects research. The contractor shall work with the FDA Project Officer throughout the process of IRB approval to coordinate activities of both Human Subjects Protection Committees. (5) Analytical Methods - Analytical methods shall accurately determine all relevant variables needed to conduct the study including geneotype of 2C19, warfarin and metabolite(s) concentrations in the blood, INR and plasma levels of vitamin K and VKORC1. Validation information to adequately address the (a) accuracy, (b) precision, (c) selectivity, (d) sensitivity, (e) reproducibility and (f) stability of the method shall be referenced. See Guidance for Industry - Bioanalytical Method Validation at http://www.fda.gov/cder/guidance/index.htm for method validation specifics. (6) Data Analysis and Interpretation - Statistical methods to test the hypothesis that genotyping improves TTR by 20% or reduces the hazard ratio to 1/2 in time to first above INR (INR greater or equal 4) in patients with at least one CYP2C9 variant allele shall be described. Statistical methods for analyzing all relevant variables including age, sex, ethnic factors, diet (Vitamin K intake), drug and herbal interactions, co-morbid disease, social influences (smoking, alcohol), changes in vitamin K or warfarin absorption (e.g., GI factors or drug effects), changes in warfarin metabolism (e.g., liver disease or drug effects), changes in Vitamin K-dependent coagulation factor synthesis or metabolism (e.g., liver disease, drug effects, or other medical conditions), other effects of undisclosed concomitant drug use, or patient compliance issue shall be described. (7) Safety Assessments - All adverse events shall be recorded and reported according to the applicable regulations (see 21 CFR 310.305, 21 CFR 312.32, 21 CFR 314.50, 21CFR 314.80, 21 CFR 314.81, 21 CFR 314.98, 21CFR 600.80, 21 CFR 600.81, 21 CFR 601.28). Descriptions of adverse events shall provide information that will allow for interpretation of the event, including, but not limited to: dose and duration of therapy, outcome of the event, including treatment if any, whether blood concentrations of the drug were within sub-therapeutic, therapeutic, or toxic ranges, physiological characteristics of the subject (stage of pregnancy, age, underlying medical condition, etc.), and presence of possible confounders (polytherapy, other drugs, etc.) The evaluation process of Offerors submitting capability statements as a subcontractor will consist of a subjective assessment of the Offeror's expertise and experience in supporting any portion of the work described above. Interested Offerors shall provide (1) a summary list of similar work previously performed or being performed; (2) the professional qualifications and specific experience of staff who may be assigned to the requirement; resumes for proposed key personnel should be included; (3) any other specific and pertinent information as pertains to this Sources Sought Notice that would enhance FDA's consideration and evaluation of the information submitted. Responses must reference Request for Information (RFI) number HHSF223200510011C and include the following: (1) name and address of firm, (2) type of business (i.e.: small business, small disadvantaged 8(a) certified, HUBZONE, woman-owned small business, small disadvantaged business (not 8(a) certified), veteran-owned small business, disabled veteran owned business, etc.) (3) two points of contact: name, title, phone, fax and e-mail, (4) DUNS number, (5) NAICS codes, (6) contractor's capabilities statement which provides the information stated above, (7) list of customers covering the past 5 years including a summary of similar work performed, contract number, contract type, dollar value for each customer, reference and customer point of contact with phone number, and identify your role as either the Prime or Subcontractor. THIS SYNOPSIS IS FOR INFORMATION AND PLANNING PURPOSES AND IS NOT TO BE CONSTRUED AS A COMMITMENT BY THE GOVERNMENT. THIS IS NOT A SOLICITATION ANNOUNCEMENT FOR PROPOSALS AND NO CONTRACT WILL BE AWARDED FROM THIS ANNOUNCEMENT. NO REIMBURSEMENT WILL BE MADE FOR ANY COSTS ASSOCIATED WITH PROVIDING INFORMATION IN RESPONSE TO THIS ANNOUNCEMENT AND ANY FOLLOW-UP INFORMATION REQUESTS. RESPONDENTS WILL NOT BE NOTIFIED OF THE RESULTS OF THE EVALUATION. ALL INFORMATION SUBMITTED IN RESPONSE TO THIS ANNOUNCEMENT MUST ARRIVE ON OR BEFORE THE CLOSING DATE.
- Place of Performance
- Address: Contractor site
- Record
- SN00743355-W 20050203/050201211739 (fbodaily.com)
- Source
-
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