Defense health program (dhp) 16. C small Business Technology Transfer (sttr) Program Proposal Submission Instructions



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DEFENSE HEALTH PROGRAM (DHP)

16.C Small Business Technology Transfer (STTR) Program

Proposal Submission Instructions

The DHP STTR Program seeks small businesses with strong research and development capabilities to pursue and commercialize medical technologies.


The DHP STTR Program harnesses the collective knowledge and experience of scientists and engineers, to identify and put forward research and development (R&D) topics to stimulate a partnership of ideas and technologies between innovative Small Business Concerns (SBCs) and Research Institutions (RIs) through Federally-funded R&D to address DHP needs.
Broad Agency Announcement (BAA), topic, and general questions regarding the STTR Program should be addressed according to the DoD STTR Program BAA. For technical questions about the topic during the pre-release period, contact the Topic Authors listed for each topic in the BAA. To obtain answers to technical questions during the formal BAA period, visit https://sbir.defensebusiness.org/sitis.
Specific questions pertaining to the DHP STTR Program should be submitted to the DHP STTR Program Management Office (PMO) at:

E-mail - usarmy.detrick.medcom-usamrmc.mbx.dhpsbir@mail.mil

Phone - (301) 619-5047
The DHP Program participates in two DoD STTR BAAs each year. Proposals not conforming to the terms of this BAA will not be considered. Only Government personnel will evaluate proposals with the exception of technical personnel from Laulima Government Solutions, LLC will provide Advisory and Assistance Services to DHP, providing technical analysis in the evaluation of proposals submitted against DHP topic number:


  • DHP16C-004 Integrated System for Field, Clinic and Laboratory Preparation of Biological Specimens for Microscopy


PHASE I PROPOSAL SUBMISSION
Follow the instructions in the DoD Program BAA for program requirements and proposal submission instructions at http://www.acq.osd.mil/osbp/sbir/solicitations/index.shtml.
STTR Phase I Proposals have four Volumes: Proposal Cover Sheets, Technical Volume, Cost Volume and Company Commercialization Report. The Technical Volume has a 20-page limit including: table of contents, references, letters of support, appendices, technical portions of subcontract documents (e.g., statements of work and resumes) and any other attachments. Do not include blank pages, duplicate the electronically generated Cover Sheets or put information normally associated with the Technical Volume in other sections of the proposal as these will count toward the 20-page limit.
Only the electronically generated Cover Sheets, Cost Volume and Company Commercialization Report (CCR) are excluded from the 20-page limit. The CCR is generated by the proposal submission website, based on information provided by small businesses through the Company Commercialization Report tool.

Technical Volumes that exceed the 20-page limit will be reviewed only to the last word on the 20th page. Information beyond the 20th page will not be reviewed or considered in evaluating the offeror’s proposal. To the extent that mandatory technical content is not contained in the first 20 pages of the proposal, the evaluator may deem the proposal as non-responsive and score it accordingly.


Companies submitting a Phase I proposal under this BAA must complete the Cost Volume using the on-line form, within a total cost not to exceed $150,000 over a period of up to six months.
The DHP STTR Program will evaluate and select Phase I proposals using the evaluation criteria in Section 6.0 of the DoD STTR Program BAA. Due to limited funding, the DHP STTR Program reserves the right to limit awards under any topic and only proposals considered to be of superior quality will be funded.
Proposals not conforming to the terms of this BAA, and unsolicited proposals, will not be considered. Awards are subject to the availability of funding and successful completion of contract negotiations.
If a small business concern is selected for a STTR award they must negotiate a written agreement between the small business and their selected Research Institution that allocates intellectual property rights and rights to carry out follow-on research, development, or commercialization.

PHASE II PROPOSAL SUBMISSION
Phase II is the demonstration of the technology found feasible in Phase I. All DHP STTR Phase I awardees from this BAA will be allowed to submit a Phase II proposal for evaluation and possible selection. The details on the due date, content, and submission requirements of the Phase II proposal will be provided by the DHP STTR Program Office either in the Phase I award or by subsequent notification.
Small businesses submitting a Phase II Proposal must use the DoD electronic proposal submission system (https://sbir.defensebusiness.org/). This site contains step-by-step instructions for the preparation and submission of the Proposal Cover Sheets, the Company Commercialization Report, the Cost Volume, and how to upload the Technical Volume. For general inquiries or problems with proposal electronic submission, contact the DoD SBIR/STTR Help Desk at (1-800-348-0787) or Help Desk email at sbirhelp@bytecubed.com (9:00 am to 6:00 pm ET).
Phase II proposals will be reviewed for overall merit based upon the criteria in section 8.0 of this BAA.  STTR Phase II proposals have four Volumes:  Proposal Cover Sheet, Technical Volume, Cost Volume and Company Commercialization Report.  The Technical Volume has a 40-page limit including: table of contents, pages intentionally left blank, technical references, letters of support, appendices, technical portions of subcontract documents (e.g., statements of work and resumes) and any attachments.  However, offerors are instructed to NOT leave blank pages, duplicate the electronically generated cover pages or put information normally associated with the Technical Volume in others sections of the proposal submission as these will count toward the 40-page limit.  ONLY the electronically generated Cover Sheets, Cost Volume and CCR are excluded from the 40-page limit. The CCR is generated by the submission website based on information provided by small businesses through the “Company Commercialization Report” tool.
Technical Volumes that exceed the 40-page limit will be reviewed only to the last word on the 40th page. Information beyond the 40th page will not be reviewed or considered in evaluating the offeror’s proposal. To the extent that mandatory technical content is not contained in the first 40 pages of the proposal, the evaluator may deem the proposal as non-responsive and score it accordingly.
Small businesses submitting a proposal are also required to develop and submit a technology transition and commercialization plan describing feasible approaches for transitioning and/or commercializing the developed technology in their Phase II proposal.
DHP Phase II Cost Volumes must contain a budget for the entire 24-month Phase II period not to exceed the maximum dollar amount of $1,000,000. These costs must be submitted using the Cost Volume format (accessible electronically on the DoD submission site), and may be presented side-by-side on a single Cost Volume Sheet.  The total proposed amount should be indicated on the Proposal Cover Sheet as the proposed cost. Phase II proposals should be structured as follows: the first 10-12 months (base effort) should be approximately $500,000; the second 10-12 months of funding should also be approximately $500,000. The entire Phase II effort should not exceed $1,000,000.
PHASE II ENHANCEMENTS
The DHP STTR Program has a Phase II Enhancement Program which provides matching STTR funds to expand an existing Phase II contract that attracts investment funds from a DoD Acquisition Program, a non-SBIR/non-STTR government program or private sector investments. Phase II Enhancements allow for an existing DHP STTR Phase II contract to be extended for up to one year per Phase II Enhancement application, to perform additional research and development. Phase II Enhancement matching funds will be provided on a dollar-for-dollar basis up to a maximum $500,000 of STTR funds. All Phase II Enhancement awards are subject to acceptance, review, and selection of candidate projects, are subject to availability of funding, and successful negotiation and award of a Phase II Enhancement contract modification.
DISCRETIONARY TECHNICAL ASSISTANCE (DTA)

The DHP STTR Program does not participate in the Discretionary Technical Assistance Program. Contractors should not submit proposals that include Discretionary Technical Assistance.


The DHP STTR Program has a Technical Assistance Advocate (TAA) who provides technical and commercialization assistance to small businesses that have Phase I and Phase II projects.
RESEARCH INVOLVING HUMAN OR ANIMAL SUBJECTS
The DHP STTR Program discourages offerors from proposing to conduct human subject or animal research during Phase I due to the significant lead time required to prepare regulatory documentation and secure approval, which will significantly delay the performance of the Phase I award.
The offeror is expressly forbidden to use or subcontract for the use of laboratory animals in any manner without the express written approval of the US Army Medical Research and Material Command's (USAMRMC), Animal Care and Use Review Office (ACURO). Written authorization to begin research under the applicable protocol(s) proposed for this award will be issued in the form of an approval letter from the USAMRMC ACURO to the recipient. Furthermore, modifications to already approved protocols require approval by ACURO prior to implementation.
Research under this award involving the use of human subjects, to include the use of human anatomical substances or human data, shall not begin until the USAMRMC’s Office of Research Protections (ORP) provides authorization that the research protocol may proceed. Written approval to begin research protocol will be issued from the USAMRMC ORP, under separate notification to the recipient. Written approval from the USAMRMC ORP is also required for any sub-recipient that will use funds from this award to conduct research involving human subjects.
Research involving human subjects shall be conducted in accordance with the protocol submitted to and approved by the USAMRMC ORP. Non-compliance with any provision may result in withholding of funds and or termination of the award.

DHP STTR 16.C Topic Index



DHP16C-001

Developing Software for Pharmacodynamics and Bioassay Studies

DHP16C-002

Mask integrated Volatile Organic Compound (VOC) sensor for real-time warfighter physiological status monitoring in extreme and toxic environments

DHP16C-003

Automated Scoring Program for Rodent Ultrasonic Vocalizations (USVs)

DHP16C-004

Integrated system for field, clinic and laboratory preparation of biological specimens for microscopy

DHP16C-005

Portable, Non-Contact, Quantitative, Physiology and Health Assessment Imaging System

DHP16C-006

Real-time Multimodal Imaging and Diagnostic Device for Determining Extent of Airway Injury and Compliance

DHP16C-007

No Power Bionic Lower Extremity Prostheses


DHP STTR 16.C Topic Descriptions



DHP16C-001

TITLE: Developing Software for Pharmacodynamics and Bioassay Studies

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Traditional dose-response models depend on monotonic data and often fail when applied to non-monotonic data. Assessment of dose response should be an integral part of establishing the safety and efficacy of any drug. The objective of this topic is to develop a novel approach applicable to general pharmacologic, toxicological, or other biomedical data, that exhibit a non-monotonic dose-response relationship for which traditional parametric models fail. Software will be developed to analyze dose-response relationships using both monotonic and non-monotonic data.

DESCRIPTION: Identifying dose response, and developing dose-response models, is essential in determining safe and hazardous levels and dosages for drugs, potential pollutants, and other substances to which humans or other organisms are exposed. Drug efficiency is primarily determined by the drug-target binding affinity. In pharmacodynamics projects, the drug-target affinity is usually assessed by comparing dose-response curves; the stronger the drug binds to the target, the steeper the curve. One of the critical indices of the dose-response curve, the half-maximal inhibitory concentration (IC50), is commonly used to compare the binding affinities of drugs to the same target. The IC50 represents the concentration of a drug that is required for 50% of maximal inhibition in vitro. To estimate the IC50 value, parametric logistic models (PLMs) are well accepted. The advantages of a parametric logistic model are that (a) it is symmetrical about the IC50; (b) it is monotonic; and (c) parameters such as IC50 can be easily estimated under certain conditions. But these advantages become restrictive when some conditions fail. Recent researches on human immunodeficiency virus mutants developing resistance to antiviral drugs show that the dose-response curve may not always be monotonic (Zhang et al. 2013). If a PLM is used to fit data when the dose-response pattern is non-monotonic, the fit is poor, and the estimated IC50 and other parameters are not reliable, and may even be misleading. Finding appropriate estimation of IC50 and other parameters for this type of dose-response relationship poses statistical challenges, and several parametric and nonparametric methods have been proposed in the statistical literature. For example, Ramsay [1988] studied the use of monotone splines to model a dose-response function. Hall and Heckman [2000] proposed an alternative approach that focuses on “running gradient” estimation over very short intervals. To appropriately estimate the pattern of observations and then estimate IC50, Zhang et al. (2013) developed a robust modeling strategy to test whether (a) the model fitting is comparable to a PLM when the observed data are monotonic, and (b) the model fitting yields reasonable estimates when the data pattern is non-monotonic and a PLM would not work. Military agencies, government agencies and private sponsors would all benefit from new and improved approaches to reasoned exploratory data analysis in analyzing and describing dose-response data.

PHASE I: Since the real dose-response relationship is often non-monotonic and traditional monotonic model fitting leads to results that either do not converge or are biased, a new and novel approach is needed. Zhang et al. (2013) used robust modeling with local linear regression to fit a large survey dataset and showed the nonparametric model is better suited than traditional monotonic models to fit this J-shaped curve; this model might be extended to other shape curves. A potential limitation of the proposed method is its performance with a moderate sample size.

In Phase I, the following tests should be completed:


1. Perform and summarize the current dose-response model by monotonic and non-monotonic approach and perform and symmetrize monotonicity testing.
2. Verify and modify the Zhang et al. approach and other non-linear approaches.
3. Perform a simulation study to compare the selected model and monotonic modeling for a variety of sample sizes.
4. Select the best approaches including classic dose-response models and the proposed model, and design an algorithm which answers at a minimum, the following questions:
a. Is there any drug effect?
b. What is the maximum tolerated dose?
c. What is the nature of the dose-response relationship?
d. Is IC50 optimal to measure the relationship?
e. Does a nonlinear dose-response model work?
f. If so, does its IC50 concur with that obtained using the Zhang et al. method?
5. Develop the work plan for Phase II

PHASE II: In Phase II, the selected contractor should use both actual data and simulation data to verify and modify the following:


1. When the dose-response relationship and associated parameters such as IC50 are studied, the proposed approach is robust and efficient, verified and modified by the following conditions: if the monotonicity assumption is satisfied, the results based on the proposed method closes to those based on traditional sigmoidal model fitting; if monotonicity is not satisfied, the approach can realistically estimate the parameters, such as IC50.
2. Using this newly developed approach, important dose-response features will not be omitted.
3. The proposed method can also be used for other dose-response modeling scenarios, such as hormesis dose-response curves used in toxicology.
4. The approach can also be used to estimate the half-maximal effective concentration, which is commonly used when the drug enhances its target's activity, and the lethal dose 50%, or the lethal concentration or time of a toxic substance or radiation representing the dose needed to kill half the tested population.
Then the selected contractor will develop computer software for implementing the proposed statistical methods and make it available for public use. The software should have the following features:
5. A variety of model-based approaches to dose-response assuming a functional relationship between the response and the dose following a pre-specified parametric model.
6. A variety of fitted models used to test if a dose-response relationship is present, and estimate other parameters of interest.
7. Modeling the dose-response relationship generally requires additional assumptions as opposed to using multiple comparison procedures, but can provide additional information - the software can examine these assumptions and handle missing data.
8. A variety of models may be used to characterize a dose-response relationship: linear, quadratic, orthogonal polynomials, exponential, linear in log-dose, and non-parametric.
9. The software can help users select the suitable model according the data, and will be made available to the scientific community.

During this phase, the performance of the software will be evaluated in a variety of studies to conclusively demonstrate that it meets the requirements of this topic. By the conclusion of Phase II, the selected contractor will have completed the development of the software. The contractor will provide a report that summarizes the performance of the software to the Walter Reed Army Institute of Research.

PHASE III DUAL USE APPLICATIONS: In Phase III, the STTR performer's software will be available for military and civilian use. We envision that the team that develops the software will market it for Government laboratory use, and negotiate commercial licensing with commercial and academic markets. As an alternative, any or all of these artifacts might be released into the open source community through organizations such as the Open Source Electronic Health Record Alliance (OSEHRA) or Open Health IT Tools or similar organizations for open sources licensing. Based on negotiations with the types of government and commercial organizations cited, it is possible that hybrid commercial and open source licensing could occur. In the case where these artifacts are released into the open source community, the STTR awardee would need to develop and provide a plan to state how it would sell additional consulting, software implementation and/or training services around their workflow model, technical implementation guidelines, and/or software controls.

REFERENCES:

1. Ramsay J (1988) Monotone regression splines in action. Statistical Science 3: 425–441

2. Bowman A, Jones M, Gijbels I (1998) Testing monotonicity of regression. Journal of Computational and Graphical Statistics 7: 489–500

3. Hall, P. and Heckman, N. E. (2000). Testing for monotonicity of a regression mean by calibrating for linear functions, Annals of Statistics 28: 20-39.

4. Zhang, H., Holden-Wiltse, J., Wang, J. and Liang, H. (2013). A strategy to model nonmonotonic dose-response curve and estimate IC50, PLOS ONE 8: 1-7 (e69301).

KEYWORDS: Dose-Response, Maximal Inhibitory, Non-Monotonic, Parametric Logistic Model,

Robust Parametric Logistic Model, Safety Dosage,



DHP16C-002

TITLE: Mask integrated Volatile Organic Compound (VOC) sensor for real-time warfighter physiological status monitoring in extreme and toxic environments

TECHNOLOGY AREA(S): Biomedical

OBJECTIVE: Develop a miniaturized, orthogonal (i.e. multi-modal) sensor system to detect and quantify exhaled volatile organic compounds (VOCs) in austere operational environments. This system will be used to establish and monitor the frequency, magnitude, and chemical make-up of exhaled VOCs to detect the generation of specific VOC profiles associated with maladaptive physiological responses, alert the operator and supervisor(s) to injury prior to performance decrement, and correlate exposure parameters to injury onset for potential mitigation prior to warfighter compromise. The developed system must be real-time, able to be integrated into all current flight masks and regulators, conform to industry standard safety guidelines with respect to use in enriched oxygen atmospheres in hypobaric and hyperbaric conditions, include ability for volatile library expansion, uploading and display of disease specific VOC algorithms, maintain a log of acquired data, and be capable of logistically maintainable use between missions.

DESCRIPTION: High concentrations of supplemental oxygen are used routinely by pilots and divers prior to and during missions to prevent and treat decompression sickness, avoid detection during covert operations, and to support oxygenation following pulmonary injury. Oxygen use is limited however, by the onset of pulmonary oxygen toxicity (PO2T) which can significantly damage pulmonary tissues leading to decreased performance among other adverse effects. PO2T is traditionally diagnosed after the fact by symptomatology and chest X-ray. Current policy focuses on preventing PO2T in an operational environment by adhering to exposure limits that were developed based on empirical evidence of PO2T. Multi day diving with a ppO2 of 1.3 ATA is limited to 4 h per day for 16 h per week (1). However, the effectiveness of these limits can vary greatly among individuals; without an individualized test for PO2T, these exposure limits can unduly restrict operational duration, delay return to duty, and significantly impact mission readiness. A VOC based breath test for PO2T would provide a novel, sensitive, objective, and direct measure of PO2T for pilots, divers, and patients, improving oxygen exposure limits in all populations.

Breath analysis of VOCs is a non-invasive technique that has a high probability of predicting and monitoring the onset of pulmonary injury due to a wide variety of environmental and infectious exposures (2). Currently breath samples are absorbed into a tube containing a binding matrix and transported to the lab to be desorbed and analyzed. Gas chromatography-mass spectrometry (GC-MS) and absorption spectrometry are used to measure VOCs from these samples to create a VOC profile. To date, more than 3,000 VOCs have been detected in exhaled breath, 1% of which are likely to contain disease-specific VOCs, such as alkanes, isoprenes, benzenes and methyl alkanes. VOCs have successfully detected disease states including lung cancer (3) and pulmonary tuberculosis, and are actively researched for monitoring pulmonary oxygen toxicity, acute hypoxia, radiation exposure, heart transplant rejection, viral influenza, and breast cancer. This VOC based technology may also support other operational scenarios that are associated with pulmonary injury to include: high altitude operations, noxious substance inhalation, exposures to natural or weaponized biologic agents, and exposure to radioactive substances.




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