SOURCES SOUGHT
A -- Combination Drug Therapy for Penetrating Brain Injury
- Notice Date
- 4/15/2016
- Notice Type
- Sources Sought
- NAICS
- 541712
— Research and Development in the Physical, Engineering, and Life Sciences (except Biotechnology)
- Contracting Office
- Department of the Army, U.S. Army Medical Research Acquisition Activity, U.S. Army Medical Research Acquisition Activity, Attn: MCMR-AAA, 820 Chandler Street, Frederick, MD 21702-5014, Maryland, 21702-5014, United States
- ZIP Code
- 21702-5014
- Solicitation Number
- W81XWH-16-R-0032
- Point of Contact
- Flodean Billings, Phone: 3016192648
- E-Mail Address
-
flodean.p.billings.civ@mail.mil
(flodean.p.billings.civ@mail.mil)
- Small Business Set-Aside
- N/A
- Description
- Title: Combination Drug Therapy for Penetrating Brain Injury Solicitation: W81XWH-16-R-0032 Notice Type: Sources Sought Response Date: 21 April 2016 Classification Code: A- Research and Development NAICS: 541- Professional, Scientific, and Technical Services 541712-R&D in biotechnology Synopsis: The Government requires non-personal technical support to successfully perform the projects, tasks, and subtasks outlined below designed to support the Walter Reed Army Institute of Research (WRAIR) in their Evaluation of improved therapeutic effects of neuroprotection combination therapies in the PBBI model. PERFORMANCE WORK STATEMENT (PWS) Brain Trauma, Neuroprotection and Neurorestoration Branch (BTNN) Center for Military Psychiatry and Neuroscience Walter Reed Army Institute of Research Title: Combination Drug Therapy for Penetrating Brain Injury 1.0 Background: In the past 20 years, numerous Phase II/Phase III clinical trials for moderate/severe TBI have failed to show clinically significant neuroprotective efficacy, despite a plethora of promising pre-clinical evidence from TBI animal models. One major reason cited for these disappointing outcomes is that single-drug or monotherapy approaches that target single or limited mechanisms are simply not adequate to address the complex and dynamic milieu of the injured brain. In recognition of the limitations of the monotherapy approach to treating TBI, increased attention is now being directed toward developing combination therapeutic strategies. Recently, a panel of TBI experts came to the consensus that the heterogeneity of TBI provides a strong rationale for the hypothesis that combination therapies will improve clinical outcomes compared to current single-agent interventions. The key criteria for a successful pre-clinical combination therapy is to (1) improve the therapeutic effects achieved via monotherapy through the synergistic interaction of the drug constituents in their combination and (2) to effectively lower the risk of adverse effects by using sub-threshold doses of the individual constituents in their combination. Walter Reed Army Institute of Research (WRAIR) will conduct comprehensive preclinical studies aimed at combination therapies for both neuroprotection and seizure protection using the military relevant PBBI model and an isobolographic experimental design in order to develop improved neuroprotective treatment of TBI through combination therapies. The isobolographic method, which is derived from the principle of dose equivalence, represents the "gold standard" pharmacological approach for detecting drug interactions. 2.0 Scope: This Performance Work Statement (PWS) defines the requirements of procurement of technical expertise and support services necessary to perform experimental design and data analysis of drug combination studies with the penetrating ballistic-like brain injury (PBBI) traumatic brain injury (TBI) model in support of the Brain Trauma, Neuroprotection and Neurorestoration (BTNN) Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research (WRAIR). The Contractor representative shall secure the provisions necessary to meet the government (BTNN, WRAIR) objectives and perform the tasks described in this PWS. 3.0 Objectives: The objective of this requirement is to facilitate the timely and efficient execution of the research by providing the provisions necessary to meet the BTNN objectives and perform the tasks described in this PWS. The primary objective of this Task will focus on evaluating improved therapeutic effects of neuroprotection combination therapies in the PBBI model. For these tasks, a combination therapy is defined as the treatment consisting of a pair of two (or more) neuroprotective agents administered at predetermined dose ratios which are calculated based on their ED50 (median effective dose) generated from their monotherapy D-R curve. While monotherapy evaluation of additional drugs is ongoing, the first 3 drugs to be included in combination studies will be determined by the Principal Investigator based on mechanisms of action and an established dose-response (D-R) profile when tested individually as a monotherapy in the PBBI model. To meet the objectives the contractor: • Shall evaluate two categories of drugs: neuroprotective agents (NA) and anti-epileptic drugs (AEDs) in a rat model of severe TBI. • Shall define the pharmacological nature of the combination therapy as synergism, additivity, or potentiation, the isobolographic analysis of drug-drug interactions will be used, which requires an experimental design in two phases: Phase I (monotherapy) will establish the dose-response (D-R) curve of each individual drug within the respective drug category and Phase II (combination therapy) will evaluate the combined effects of a pair of drugs selected from Phase I within each drug category. • Shall choose compounds that had previously demonstrated therapeutic efficacy in preclinical TBI models and were FDA-approved (in some formulation) for other clinical indications. • Shall provide technical expertise to conduct and analyze the data collected from the Phase I and Phase II studies. • Shall provide scientific and technical support for the research, development, and efficacy evaluation of singular and combination therapies. • Shall provide support to design research experiments to meet the goals of the tasks, process research data files, analyze research data, prepare manuscripts, author and present scientific protocols. 4.0 General Information: 4.1 Period Of Performance: The period of performance for this tasking is 1 base year and 4 option years for a total of five years. Base year: 1 June 2016 - 30 May 2017 Option year 1: 1 June 2017 - 30 May 2018 Option year 2: 1 June 2018 - 30 May 2019 Option year 3: 1 June 2019 - 30 May 2020 Option year 4: 1 June 2020 - 30 May 2021 4.2 Contracting Officer's Representative (COR): The COR or CORs will be identified by separate letter. The COR monitors all technical aspects of the contract and assists in contract administration The COR is authorized to perform the following functions: • Assure that the Contractor performs the technical requirements of the contract • Perform inspections necessary in accordance with PWS • Maintain written and oral communications with the Contractor concerning technical aspects of the contract • Issue written interpretations of technical requirements, including Government drawings, designs, specifications • Monitor Contractor's performance and notify both the Contracting Officer and Contractor of any deficiencies • Coordinate availability of government furnished property, and • Provide site entry of Contractor personnel A letter of designation issued to the COR, a copy of which is sent to the Contractor, states the responsibilities and limitations of the COR, especially with regard to changes in cost or price, estimates or changes in delivery dates. The COR is not authorized to change any of the terms and conditions of the resulting order. 5.0 Required Tasks: The tasks outlined in this document will support two funded Core proposals and one extramural proposal for isobolographic combination drug development studies for FY16-21 period of performance. 5.1 Monotherapy D-R Profiles for Established Neuroprotective Drugs /Combination Drug Therapy Studies. The Contractor shall, with the level of independence that would be expected of a Subject Matter Expert, support this task to: 5.1.1 Assist in the design of each monotherapy dose response experiment (at least 8 different drugs). 5.1.2 Perform analysis of data from monotherapy dose response experiments. 5.1.3 Contribute to the development of criteria for ranking individual drugs based on their overall effects related to the dose response efficacy. 5.1.4 Guide the design of each combination therapy experiment, to include evaluation and selection of the appropriate ratio of drug dose. 5.1.5 Establish proof-of-principle therapeutic efficacy for a novel CRADA-sponsored drug in the PBBI model and evaluate the full dose-response monotherapy profile. 5.1.6 Assume responsibility for the data analysis of the combination therapy experiments to include the statistical analysis and isobolar and other graphical representation of the observed interactions. 5.1.7 Provide input into the mechanistic interpretation that arises from analysis of determined isoboles. 5.1.8 Advise on the use of appropriate statistical and other analyses on collected data. 5.2 The Contractor shall, with the level of independence that would be expected of a Subject Matter Expert, support this task to: 5.2.1 Instruct designated individuals in the laboratory on the principals of drug synergism and dose-effect data analysis. 5.2.2 Using probit and logit analysis provide detailed instruction on calculation methods for the statistical analysis of the data for drug combination studies. 5.2.3 Train, mentor, and lead civilian/contractor scientists under this task order. The expected results of this research effort is to develop improved neuroprotective treatment of TBI through combination therapies, the overarching focus of this proposal is to conduct comprehensive preclinical studies aimed at combination therapies for neuroprotection using the PBBI model evaluating neuroprotective drugs that are already approved by the FDA for other clinical indications. 6. DELIVERABLES: 6.1 Prior to separating from the WRAIR, voluntarily or involuntarily, the Contractor shall deliver the following items to the Contracting Officer's Representative at 503 Robert Grant Avenue, Silver Spring, MD 20910-7500. This information can be provided by hard copy or electronic format. • Laboratory notebooks • Research data 6.2 When requested by the COR, the Contractor shall deliver a monthly progress report describing all work done in support of this PWS by the 10th day of each month for the preceding month, to the COR. (For example, the 10th August report would cover work performed during July.) 6.3 When applicable, the Contractor shall deliver summary reports from conferences and meetings within 10 business days of the conclusion of the conference or meeting. 6.4 The contractor shall provide either written reports or presentations covering: drafts of research protocols and statistical data analysis. 6.5 A final typewritten report (2 copies) summarizing the work performed and the results and conclusions derived shall be submitted to the COR. 8. TRAVEL: The contractor is not required or authorized to travel at Government expense as part of this contract. 9. SUGGESTED SUPPORT: Personnel qualifications: 9.1 Must be considered a Subject Matter Expert in conducting comprehensive preclinical studies aimed at combination therapies for neuroprotection and seizure protection using the military relevant PBBI model and an isobolographic experimental design. 9.2 Experimental design should include isobolographic analysis of drug-drug interactions. Expertise in complex drug combination analysis and isobolic design. 9.3 Experience in conducting research in the area of Pharmacology with specific experience in isobologic analysis of drug-drug interactions. 9.4 Extensive publication record in complex combination analysis and isobolic design 9.5 The minimun level of education is Ph.D. in Pharmacology. 10. GOVERNMENT (BTNN, WRAIR) FURNISHED ITEMS: 11. WORK SCHEDULE AND LOCATION: Work under this contract is to be performed at the contractor's facility. On-site work is to be done at WRAIR, 503 Robert Grant Avenue, Silver Spring, MD. RFI INSTRUCTIONS: Interested parties are asked to respond to this RFI and submit a capabilities statement that supports the focus of this RFI. Please review the place of performance requirements. Please submit written responses via email in Microsoft Office 2000 or 2007 format. All responses should be complete: in 12-point font; and not to exceed 5 pages total, including graphics, tables, and appendices. No hardcopies shall be accepted. No written solicitation document is available at this time. Telephone requests will not be honored, and no bidders list shall be maintained. No inquiries regarding any potential future acquisition activities shall be entertained. There is proprietary information involved in this requirement which may preclude some established clinical trial centers from competing on this requirement, although no decisions have been finalized at this time. Potential offerors are requested to direct all questions via email to the Point of Contact listed below. Responses are due to the Point of Contact, Ms. Flodean Billings at email: flodean.p.billings.civ@mail.mil no later than 9:00AM EST, Thursday, April 21 2016 CAUTION: This is an active requirement. Contractors are strictly prohibited from discussing this requirement with any member of the program office. All discussion shall be with the point of contact listed above. DISCLAIMER: This RFI is issued solely for information and planning purposes and does not constitute a solicitation. Neither unsolicited proposals nor any kinds of offers will be considered in response to this RFI. Responses to this notice are not offers and will not be accepted by the Government to form a binding contract. Responders are solely responsible for all expenses associated with responding to this RFI. All information received in response to this RFI that is marked proprietary will be handled accordingly. Responses to the RFI will not be returned.
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FBO.gov Permalink
(https://www.fbo.gov/spg/USA/USAMRAA/DAMD17/W81XWH-16-R-0032/listing.html)
- Place of Performance
- Address: Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland, 20910, United States
- Zip Code: 20910
- Zip Code: 20910
- Record
- SN04085641-W 20160417/160415234340-1dc3c4c3f61a0379e901e8d5cfe1d39b (fbodaily.com)
- Source
-
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