RFP # C REQUEST FOR PROPOSAL. Voriconazole Pharmacokinetics Studies

Transcription

1 RFP # C REQUEST FOR PROPOSAL Voriconazole Pharmacokinetics Studies BMT CTN Protocol 0101 A Randomized Double-blind Trial of Fluconazole vs. Voriconazole for the Prevention of Invasive Fungal Infections in Allogeneic Blood and Marrow Transplant Patients ISSUED BY: National Marrow Donor Program 3001 Broadway St. N.E. Broadway Ridge, Suite 100 Minneapolis, MN November 29, 2010 Proposal Must Be Returned By January 5, :00 p.m. Central Time Page 1 of 14 Blood and Marrow Transplant Clinical Trials Network Request for Proposal RFP C

2 National Marrow Donor Program RFP # C Table of Contents Section I General Information Page 3 A. National Marrow Donor Program Contact B. Milestone Schedule Section II Background Page 4 A. Program Establishment B. Project Objectives Section III Scope of Work Page 6 A. Project Deliverables/Requirements Section IV Budget Page 10 A. Pricing and Reimbursement B. Best Value C. Office of Management and Budget Circulars D. Travel Section V Submission Procedure Page 11 A. Preparation of Formal Response B. Terms Section VI Evaluation for Award Page 14 A. Response Evaluation B. Award Attachments Attachment 1 Attachment 2 Attachment 3 Attachment 4 Attachment 5 Business Information Sheet Substitute W-9 and Business Classification Form Certifications Regarding Debarment & Lobbying Price per Sample/Modeling Consultation Form Budget Sheet Page 2 of 14

3 SECTION I GENERAL INFORMATION A. National Marrow Donor Program (NMDP) Contact Questions concerning this solicitation should be submitted December 1 December 16, 2010 via to: Renẻe Carby Contracts Representative National Marrow Donor Program Coordinating Center 3001 Broadway Street N.E. Broadway Ridge, Suite 100 Minneapolis, MN Telephone: Fax: rcarby@nmdp.org B. Milestone Schedule Please note that a formal proposal, comprised of the Technical Response & Business Response, for the purpose of this RFP is due no later than January 5, 2:00 p.m. Central Time. Formal proposals must be delivered to the NMDP representative named in Section I A. Release of RFP November 29, 2010 Submission of Written Questions December 1 16, 2010 Responses to Questions December 2 17, 2010 Formal Proposals Due by 2:00 p.m. Central Time January 5, 2011 Contractual Award TBD Responses to any questions shall be considered as part of the Statement of Work. Page 3 of 14

4 SECTION II BACKGROUND A. Program Establishment In October 2001, the National Institutes of Health (NIH), through the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) established the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The purpose of the BMT CTN is to conduct large multi-institutional clinical trials. These trials address important issues in hematopoietic stem cell transplantation (HSCT), thereby furthering understanding of the best possible treatment approaches and promoting the efficient comparison of novel treatment methods and management strategies of potential benefit to children and adults undergoing blood or marrow transplants. Participating BMT CTN investigators collaborate through an organization designed to maintain continuity of operations, to facilitate effective communication and cooperation among participating transplant centers and with collaborators at the National Institutes of Health, and to offer trials participation to patients in all regions of the U.S. The BMT CTN is committed to including widespread transplant community participation in these trials. This commitment extends also to the many research investigators that currently support the numerous clinical protocols, pharmacokinetics and biomarker research studies associated with HSCT trials. The NIH awarded a grant to the Medical College of Wisconsin (MCW) for the operation of the BMT CTN Data and Coordinating Center (DCC) to oversee clinical trial operations for the BMT CTN. The DCC is comprised of the Statistical Office of the Center for International Blood and Marrow Transplant Research (CIBMTR ) at MCW, the National Marrow Donor Program (NMDP) and the EMMES Corporation. National Heart, Lung, and Blood Institute (NHLBI) provided funding to the BMT CTN to conduct a Phase III, randomized, double-blind, multicenter, prospective, comparative study of fluconazole versus voriconazole in the prevention of fungal infections in allogeneic transplant recipients. The primary objective of the study was to compare the fungal-free survival rates between the two study arms through Day 180. The NMDP is committed to its global mission to extend and improve life through innovative stem cell therapies. The NMDP also provides resources for patients and physicians, and conducts research to improve the outcomes of stem cell transplantation. Among other activities, the NMDP is responsible to contract with laboratories, hospitals, suppliers and other organizations participating in BMT CTN projects. The NMDP, on behalf of the BMT CTN, NCI, NHLBI, and the protocol team led by Study Chairpersons, John Wingard, M.D. of the University of Florida College of Medicine, and Thomas Walsh, M.D. of the Weill Cornell Medical College of Cornell University, are collectively referred to as the Network for purpose of this RFP. The Network is requesting a firm proposal to fulfill the Scope of Work for this study. Page 4 of 14

5 B. Project Objectives 1. Background and Rationale: This trial was designed to compare the efficacy of fluconazole 400 mg/day PO (or IV at the same dose if the patient is unable to tolerate it PO) with voriconazole 200 mg PO BID (or IV at the same dose if the patient is unable to tolerate it PO) in prevention of fungal infections in allogeneic hematopoietic transplant recipients during the first 180 days after transplant. Children aged < 12 years received age-appropriate dosing. The primary objective was to compare the fungal-free survival rates between the two study arms during the first 180 days. Secondary objectives were to compare invasive fungal infection rates, overall mortality due to fungal infection, engraftment rates, acute and chronic GVHD rates, reasons for failure (e.g., plasma concentrations, tolerance, fungal sensitivity, etc.), and to perform exploratory analyses of quantitative aspects of the galactomannan assay. The relative safety of the two antifungals was also assessed through the collection of post-transplant toxicities, serious adverse event reports and routine laboratory monitoring. The protocol in its entirety can be viewed on the BMT CTN public website: It was reasoned that given the high mortality rate associated with documented fungal infections in BMT patients despite aggressive therapy with amphotericin B, strategies to prevent infections are warranted and may be more effective than trying to treat a documented established infection. Allogeneic BMT patients are at special risk for infection due to aggressive or prolonged immunosuppressive therapy and are subject to a high case fatality rate. Antifungal agents such as fluconazole and voriconazole can be administered orally, have good activity against several fungal pathogens and are less toxic than amphotericin B. The availability of intravenous formulations of both agents permit continued compliance with the regimen in the event that the patient cannot tolerate oral medications. Although voriconazole has a wider antifungal spectrum than fluconazole, there are more drug interactions requiring greater vigilance over the immunoprophylaxis regimen, and there is the potential for greater toxicity. Whether or not, on balance, the potential benefit outweighs these potential risks can only be determined in a prospective, randomized trial. The main results of the trial were as follows: Despite trends to fewer IFIs (7.3% vs. 11.2%, p = 0.12), Aspergillus infections (9 vs. 17, p = 0.09), and less frequent empiric antifungal therapy (24.1% vs. 30.2%, p = 0.11) with voriconazole, FFS rates (75% vs. 78%, p = 0.49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and overall survival (OS) and the incidence of severe adverse events were also similar. The report in its entirety can be read in pubmed (Wingard JR et al Randomized double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection (IFI) after allo hematopoietic cell transplantation (HCT). Blood Sep 8. [Epub ahead of print]. Page 5 of 14

6 2. Pharmacokinetics Study Design and Objectives: Peripheral blood samples for the analysis of plasma voriconazole concentrations was obtained on Day 14 and 28 of therapy, and at onset of serious suspected study drug toxicities and at onset of possible, presumptive, probable or proven infection (prior to start of antifungal therapy). Blood samples were collected in relationship to administration of the study drug in one of three windows of time after the start of the infusion or administration of the oral dose: Window 1 is 1-5 hours after start of the infusion; Window 2 is 5-8 hours after start of infusion; Window 3 is 8-12 hours after start of the infusion. Qualified laboratories and Principal Investigator considering participation in this study will be required to provide the following expertise and analytical services: Determine voriconazole concentrations in frozen plasma samples. For each pharmacokinetics (PK) sampling period, steady-state PK parameters of voriconazole are to be calculated from plasma concentration-versus-time data. PK parameters calculated should include at a minimum: (1) the estimated area under the plasma concentration-time curve, (2) the maximum observed concentration of drug in plasma at steady state and (3) the time to maximum observed concentration of drug in plasma. Provide expertise and collaboration with study Protocol Team members to model the descriptive data above against a known patient population provided by the laboratory principal investigator and to compare blood PK parameters against development of invasive fungal infection and drug toxicity, among other important transplant outcomes. SECTION III SCOPE OF WORK A. Project Deliverables/Requirements: 1. Experience, Accreditation and Participation in Proficiency Testing Programs Laboratory must be able to document expertise, relevant recent experience and contributions of the Principal Investigator and supporting laboratory staff in performing validated sample extraction and analysis procedures on patient samples. Laboratory is asked to list any relevant laboratory certifications, accreditations and any federal, state or local licenses, and will provide evidence of participation in any laboratory proficiency programs related to the scope of work of this study. 2. Facilities and Resources The Laboratory shall have an established facility and the resources necessary to receive, process and store incoming samples, and, then to accommodate the testing of samples. The purchase of equipment will not be reimbursed as a separate element under this Agreement. Page 6 of 14

7 3. Records and Audit The Laboratory shall maintain such records, and establish and adhere to such procedures as may reasonably be required to document its performance under this project. The Laboratory shall maintain all records associated with performance of its obligations under this project for the term of this project and for no less than five years thereafter. For the duration of the period during which those records are maintained, the NMDP and its duly authorized agents, agents of the state or federal government, shall have access to all information, records and copies of records regarding the Laboratory s performance during the Laboratory s regular business hours upon reasonable notice and demand. During the period of performance of Services, the DCC will have the right, at reasonable times, and upon reasonable written notice, to perform at the DCC s expense: (i) on-site quality assurance audits of the Services performed by the Laboratory and (ii) on-site inspections of the documentation, record keeping and Standard Operating Procedures, records and facilities of the Laboratory which are specific to the Services being provided by the Laboratory. The purpose of an audit or inspections is to ensure the adequacy of the performance records, and that the activities are being performed are in accordance with the Laboratory s responsibilities. 4. Sample Shipments and Sample Accessioning Laboratory will receive a single shipment of frozen patient plasma samples from the BMT CTN Sample Repository via priority overnight Fed Ex service. Laboratory must be available to accept sample shipment, on an agreed upon day, during normal business hours Tuesday through Friday of the designated week. The Laboratory shall ensure prompt accessioning of the received samples into inventory using an electronic inventory database. Samples shall be processed within time frames required for sample integrity and quality for all testing procedures. The Laboratory shall accurately identify and track all samples through the stages of receipt, storage, and reporting of results. The Network will provide necessary supplies for the collection, identification, packaging and shipping of all patient samples to the Laboratory. Each plasma sample aliquot will be labeled with a unique alpha/numeric bar-coded label. Laboratory will also receive both electronic ( ) and hard-copy manifests, which includes pertinent sample collection information. The electronic sample manifests, including Fed Ex tracking information, will be sent via to the project laboratory on the day the sample is shipped. A printed manifest will be included with the samples shipped to a project laboratory. Page 7 of 14

8 5. Sample Type and Projected Sample Estimates A single 5 ml (2.5 ml for patients less than 12 years old) peripheral blood sample was collected at each time point in a sodium heparin containing Vacutainer tube. Within the recommended minutes of collection (some extended center processing time frames most likely exist, but were not able to be documented in this study), blood samples were centrifuged for 20 minutes at 450 x g or 1500 rpm. The plasma was removed and placed into a single cryovial and cryopreserved at -70ºC. Clinical sites then periodically shipped frozen samples to the BMT CTN Sample Repository for long-term storage at -80ºC. Patient peripheral blood samples were collected, processed and plasma frozen during the 2004 to 2006 time frame. Projected currently available sample estimates used in this RFP are as follows (approximately 800 total analyses): Complete Day 14 & Day 28 sample sets: 200 Day 14 only samples: 200 Day 28 only samples: 200 Event-driven samples: 9 However, there will be no guarantees or minimum commitments to the total number of samples to be tested. Retesting, loss, or replacement of samples due to Laboratory s failure in its responsibilities or failure to follow laboratory procedures will be at the expense of the Laboratory. 6. Laboratory Testing/Analysis Requirements Qualified laboratory Principal Investigators considering participation in this study will be required to provide the following expertise and analytical services: Determine voriconazole concentrations in frozen plasma samples. For each pharmacokinetics (PK) sampling period, steady-state PK parameters of voriconazole are to be calculated from plasma concentration-versus-time data. PK parameters calculated should include at a minimum: (1) the estimated area under the plasma concentration-time curve, (2) the maximum observed concentration of drug in plasma at steady state and (3) the time to maximum observed concentration of drug in plasma. Provide expertise and collaboration with study Protocol Team members to model the descriptive data above against a known patient population provided by the laboratory principal investigator and to compare blood PK parameters against development of invasive fungal infection and drug toxicity, among other important transplant outcomes. 7. Laboratory Quality Control Program Laboratory will archive the results of all general instrument controls and quality control samples included in the same run as samples being tested in this project. Laboratory will have existing Standard Operating Procedures (SOPs) and use appropriate quality control materials for all analytic procedures to be used for this study. Procedures must include the Laboratory s quality control program for the Page 8 of 14

9 validation/qualification of all reagents and instrumentation proposed for this study. Supporting staff must have validated training and experience with all instrumentation, QC and all analytical procedures. 8. Database Requirements Laboratory must have the capability to manage sample and the analysis result data using a computer database. The Laboratory shall ensure that the database is secure with user identification and password protection. The database shall be routinely (at least weekly) backed up on disk or tape, and a copy must be stored off-site in a protected environment. The Laboratory must ensure that the back up procedures result in successful restoration of the database. The Laboratory agrees to provide to the NMDP upon request, a Disaster Recovery Plan to protect the database in the event of computer failure or corruption of files. The Laboratory shall protect against: a. Physical and electronic intruders from the outside. b. Unauthorized use of computers, data and other resources. c. Improper use of systems by authorized individuals. d. Computer viruses and willful destructive applications. e. Natural and man-made disasters. 9. Timelines for Plasma Sample Testing and Reporting Pharmacokinetics Results Laboratory will be asked to complete all voriconazole sample testing and have Principal Investigator approved sample concentration results within 60 days from the time the Laboratory receives the sample shipment from the BMT CTN Repository. The calculation of steady-state pharmacokinetics parameters of voriconazole from plasma concentration-versus-time data should be completed within approximately the next 30 days. The Protocol Team and laboratory Principal Investigator will then develop and implement a plan for modeling the descriptive data against a known patient population provided by the laboratory principal investigator. Laboratory will electronically submit completed results to BMT CTN in a report format that will be subject to approval by BMT CTN DCC and Protocol Team. Laboratory shall also provide all other reports as reasonably requested by BMT CTN out of its database of study-specific information. 10. Performance Criteria Laboratory performance for this project will be evaluated on the following: a. Receive and test samples according to SOW. b. Report verified final test results as instructed by the DCC. c. Met quality control standards as defined in Laboratory SOPs. 11. Sample Storage and Disposal Laboratory acknowledges that its employees and representatives who will be working with the samples submitted for analysis could be exposed to HIV, hepatitis or other Page 9 of 14

10 diseases. Laboratory will take all required and reasonable precautions to reduce the risk of exposure to such diseases. a. Laboratory will dispose of biohazardous waste according to local, state and federal regulations. b. Samples may only be utilized for the purposes of this project only, unless express written permission is granted by the BMT CTN DCC. SECTION IV BUDGET A. Pricing and Reimbursement The Laboratory should submit pricing that will be sufficient to fulfill the requirements of Section IV of this RFP. Refer to Attachment 4, Price Schedule, and Attachment 5, Budget Sheet, for the format required for submitting pricing and budgeting in response to this solicitation. NMDP reserves the right to release pricing and budgetary details in Attachment 4 and Attachment 5 to funding source(s) for this project if applicable. Payment will be made for testing and data analysis upon satisfactory completion and receipt of Principal Investigator verified results and review by the DCC and Protocol Team. The NMDP reserves the right to question, reject, or accept materials which might indicate the reasonableness of the offer. B. Best Value The NMDP standard for award is "Best Value (refer to Section VI Evaluation for Award ). Best value decisions are a combination of factors such as: technical excellence, price, quality, past performance, and other indicators. C. Office of Management and Budget (OMB) Circulars If applicable, the pricing supplied must comply with the appropriate OMB cost principles set forth in the following documents and are incorporated by reference in 45 CFR and 92.22: OMB Circular A-21 Cost Principles for Educational Institutions OMB Circular A-122 Cost Principles for Non-Profit Institutions 45 CFR Part 74, Appendix E Principles for Determining Costs Applicable to Research and Development under Grants and Contracts with Hospitals. D. Travel When necessary, the BMT CTN will provide for and schedule all travel arrangements. Travel costs should not be included in your bid. Page 10 of 14

11 SECTION V SUBMISSION PROCEDURE A. Preparation of Formal Response Please review requirements in this solicitation carefully. Instructions for preparing each section are provided below to assist in submitting a response. You must follow the instructions or delay may occur in the consideration of the proposal. Your response package must be received by the NMDP by the required date and time and to the attention of the individual cited in Section I. The Formal Response must contain the following information in writing: 1. Preparation of the Technical Response The Technical Response must contain the following information and shall not be more than 12 pages in length (any additional supporting information that is deemed by the Bidder as necessary may be included as an attachment). Should it be determined that further clarification and/or information is needed the Bidder will receive written notification of such request: a. Brief overview of your Laboratory s current overall capabilities and the specific experience and capabilities to perform the technical requirements of this proposal. This should include a description of any unique capabilities, expertise or experiences that can be offered to the BMT CTN, including a list of any recent comparative contracts or grants. i. Provide up to three (3) letters of support documenting relevant and recent research study collaborations and/or clinical voriconazole PK testing services. ii. Provide a brief description and listing of any relevant publications from your laboratory that are related to the scope of work detailed in this RFP. b. Description of how your Laboratory will complete the Statement of Work, including: i. Name and title of the Principal Investigator to be listed on the potential subsequent agreement. Only one Principal Investigator may be named. Provide the percentage of time the Principal Investigator will dedicate to this project and provides to existing or other proposed efforts. Submit a brief NIH Biographical Sketch as well as a description of the Principal Investigator s qualifications and direct experience with the assays and procedures related to the objectives of this project. The Principal Investigator named on the Business Information Sheet, Attachment 1, must be the same as identified in the Technical Response. Page 11 of 14 Blood and Marrow Transplant Clinical Trials Network Request for Proposal RFP C

12 ii. Names, qualifications, and direct experience with the assays and procedures related to the objectives of this project, for the key laboratory personnel who will be involved with the project. Please indicate the percentage of time each key person will dedicate to this project and how much of their time is dedicated to existing or proposed efforts. iii. Describe the methodologies, validated testing procedures, reagents and instrumentation and data analysis methodology that will be used in this project to satisfy or exceed the study objectives and reporting requirements of this study. Describe procedures to monitor, qualify and validate the quality of the reagents and instrumentation used. In addition to the elements above, this section of the Technical Response should also include the following: Indicate the minimum and desired volume of plasma that is required for successful completion of testing. If the laboratory has also validated procedures for serum, please indicate whether plasma and serum derived test data could be normalized in some way and used together for descriptive comparisons, modeling efforts and analysis of primary/secondary study outcomes. Provide a list of all sample/patient-related information that is required to accurately perform all technical/analytical aspects of this study. Provide a proposed example of how you envision communicating study results for these research patient samples. Highlight and describe any potential innovative approaches proposed in the context of this scope of work, which might add additional technical/analytical value and/or provide cost-effective solutions. iv. Provide a brief description concerning the availability of data from a suitable patient population(s) for the modeling of the descriptive data generated in this study. v. Describe sampling handling and data analysis workflow. Describe your Laboratory s current use of quality control materials and quality assurance measures related to the specific assays detailed in the scope of work for this study. vi. While not a definitive requirement for this study, please provide copies of any laboratory certifications, accreditations, and any federal, state or local licenses related to this scope of work. If available, provide evidence for participation in any laboratory proficiency programs related to the scope of work of this study. 2. Preparation of the Business Response. The Business Response must contain the following information: a. Completed Business Information Sheet (Attachment 1): Page 12 of 14

13 i. Only one Principal Investigator can be named. The Principal Investigator named will be the person cited in any resulting agreement. This person will have responsibility to fulfill the scope of work of the agreement. ii. The business contact is the person authorized to conduct negotiations and legally obligate the Laboratory, or to enter into discussions with the NMDP, pending authorization of the business officer, on behalf of the Laboratory. This person will be the NMDP s primary contact for any contractual or business matters regarding this RFP and any resultant agreement. iii. Indicate the authorized business officer who will sign any resultant agreement. This is the person authorized to obligate the Laboratory, usually someone in the Business, Finance, or Contracts office. b. Completed Price Sheet. The response must be in the format provided in Attachment 4. c. Completed Budget Sheet. The response must be in the format provided in Attachment 5. If additional information is requested, the NMDP will specify the nature and the form of the supporting documentation. d. Business documentation including: i. Completed and signed Substitute W-9 form and Business Classification form (Attachment 2) ii. Signed Certifications Regarding Debarment & Lobbying (Attachment 3) 3. Required Copies a. One (1) original of the entire proposal comprised of the Technical Response and Business Response, containing the forms indicated in IV.A.2.b. and d. above. (marked ORIGINAL) b. Two (2) complete copies of the Business Response, containing the forms indicated in IV.A.2.b. and d. above (marked COPY). c. Four (4) complete copies of the Technical Response (marked COPY). 4. Procurement Notices a. Any resultant award will be subject to the availability of funds within the Network. The final decision to fund this effort, in whole or in part, is solely that of the NMDP in conjunction with the Network. Any such decision is not subject to dispute. Page 13 of 14

14 B. Terms b. The term of the award shall commence approximately mid-2011 and may continue and remain in effect for approximately 1 year, or upon notice of termination, whichever would be first. c. All responses must remain valid for at least one hundred eighty (180) days. This effort is part of a multi-center clinical trial consortium funded by the National Institutes of Health. Additional terms provided with the award reflect requirements of a multi-center clinical trial. By submitting this proposal the Laboratory agrees it will comply with the Publication language of the BMT CTN ( BMT CTN Administrative MOP, Chapter 8 ). Refer to for further information. SECTION VI EVALUATION FOR AWARD A. Response Evaluation The NMDP will evaluate the Laboratory s ability to meet the specifications in described in Section III (Scope of Work). The NMDP, in collaboration with the Network, will: 1. Review the Formal Response to assess value to the Network, and determine the potential Laboratory s overall reliability and ability to perform the contemplated contract. 2. Seek clarifications or reject all or a portion of the proposal. 3. Issue an award to a Laboratory based on the criteria outlined in Sections III and IV. B. Award The NMDP may issue a contractual agreement without discussion to a Laboratory whose offer provides the best value to the Network technical, price and other factors considered. The NMDP may or may not provide you with an opportunity to revise or improve your offer or to provide a best and final offer prior to award of any Agreement. As such, your original proposal should present your best response to this request. As a condition of submission of a proposal, you agree to participate in such negotiations in good faith with the goal of entering into an agreement under terms and conditions conducive for the completion of the objectives, deliverables and requirements in this RFP as outlined herein. Page 14 of 14