DEFENSE HEALTH AGENCY 19.2 Small Business Innovation Research (SBIR) Program

Proposal Submission Instructions

The Defense Health Agency (DHA) SBIR Program seeks small businesses with strong research and development capabilities to pursue and commercialize medical technologies.

Broad Agency Announcement (BAA), topic, and general questions regarding the SBIR Program should be addressed according to the DOD SBIR Program BAA. For technical questions about a topic during the pre-release period, contact the Topic Author(s) 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 DHA SBIR Program should be submitted to the DHA SBIR Program Management Office (PMO) at:

E-mail - usarmy.detrick.medcom-usamrmc.mbx.dhpsbir@mail.milPhone - (301) 619-5146

PHASE I PROPOSAL SUBMISSION

Follow the instructions in the DOD SBIR Program BAA for program requirements and online proposal submission instructions.

DHA SBIR Phase I Proposals have four Volumes: Proposal Cover Sheets, Technical Volume, Cost Volume and Company Commercialization Report. Please note that the DHA SBIR will not be accepting a Volume Five (Supporting Documents) as noted at the DOD SBIR website. The Technical Volume has a 20-page limit including: table of contents, pages intentionally left blank, references, letters of support, appendices, technical portions of subcontract documents (e.g., statements of work and resumes) and any other attachments. Do not 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 $250,000 over a period of up to six months.

The DHA SBIR Program will evaluate and select Phase I proposals using the evaluation criteria in Section 6.0 of the DOD SBIR Program BAA. Due to limited funding, the DHA SBIR Program reserves the right to limit awards under any topic and only proposals considered to be of superior quality will be funded.

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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.

RESEARCH INVOLVING ANIMAL OR HUMAN SUBJECTS

The DHA SBIR 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.

PHASE II PROPOSAL SUBMISSION

Phase II is the demonstration of the technology found feasible in Phase I. All DHA SBIR 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 DHA SBIR PMO. Submission instructions are typically sent toward the end of month five of the phase I contract. The awardees will receive a Phase II window notification via email with details on when, how and where to submit their Phase II proposal.

Small businesses submitting a Phase II Proposal must use the DOD SBIR 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 sbirhelpdesk@u.group (9:00 am to 6:00 pm ET).

The DHA SBIR Program will evaluate and select Phase II proposals using the evaluation criteria in Section 8.0 of the DOD SBIR Program BAA. Due to limited funding, the DHA SBIR Program reserves

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the right to limit awards under any topic and only proposals considered to be of superior quality will be funded.

Small businesses submitting a proposal are 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. DHA SBIR Phase II Cost Volumes must contain a budget for the entire 24-month Phase II period not to exceed the maximum dollar amount of $1,100,000. 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. DHA SBIR Phase II Proposals have four Volumes: Proposal Cover Sheets, Technical Volume, Cost Volume and Company Commercialization Report. The Technical Volume has a 40-page limit including: table of contents, pages intentionally left blank, references, letters of support, appendices, technical portions of subcontract documents (e.g., statements of work and resumes) and any 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 40-page limit.

Technical Volumes that exceed the 40-page limit will be reviewed only to the last word on the 40 th 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.

PHASE II ENHANCEMENTS

The DHA SBIR Program has a Phase II Enhancement Program which provides matching SBIR funds to expand an existing Phase II contract that attracts investment funds from a DOD Acquisition Program, a non-SBIR government program or eligible private sector investments. Phase II Enhancements allow for an existing DHA SBIR Phase II contract to be extended for up to one year per Phase II Enhancement application, and perform additional research and development. Phase II Enhancement matching funds will be provided on a dollar-for-dollar basis up to a maximum $550,000 of SBIR 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.

TECHNICAL AND BUSINESS ASSISTANCE (TABA)

The DHA SBIR Program does not participate in the Technical and Business Assistance (formally the Discretionary Technical Assistance Program). Contractors should not submit proposals that include Technical and Business Assistance.

The DHA SBIR Program has a Technical Assistance Advocate (TAA) who provides technical and commercialization assistance to small businesses that have Phase I and Phase II projects.

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DHA SBIR 19.2 Topic Index

DHA192-001 Development of a Clinical Decision Support Tool for Early-Detection of Directed Energy-Induced Injury to the Retina

DHA192-002 Treatment of Vestibular Impairment of Service Members after Traumatic Brain Injury through Use of an Individualized, Portable Neuromodulation Device

DHA192-003 Forward Deployable Full Spectrum Oculomotor Assessment (OMA) and TBI Diagnostic Device

DHA192-004 Solutions for Self-Control of Urinary Function and ControlDHA192-005 Real Time Measurements of Tympanic Membrane and Middle Ear MechanicsDHA192-006 Tympanic Membrane Repair Material

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DHA SBIR 19.2 Topic Descriptions

DHA192-001 TITLE: Development of a Clinical Decision Support Tool for Early-Detection of Directed Energy-Induced Injury to the Retina

TECHNOLOGY AREA(S): Biomedical

ACQUISITION PROGRAM: Office of the Principal Assistant for Acquisition- USAMRMC

OBJECTIVE: To develop a clinical decision support tool that can be utilized by medics/physicians at Role 3/4 to automatically identify retinal damage after laser exposure.

DESCRIPTION: Laser injury to the retina does not cause immediate pain therefore it may be undetected until long-term damage to the retina causes vision loss. Currently Role 3 and Role 4 medics and physicians do not have the ability to quickly detect retinal damage after laser exposure. This deficiency reduces quality of care and increases the time to return to duty. A clinical decision support tool to detect laser-induced retinal injury will enable decisions to be made at the Role 3 level and allow physicians to determine the best treatment plan. Lasers are extensively used by the military in designators, rangefinders and guidance systems. Many of these devices operate at wavelengths that are absorbed by the human eye which can produce harmful effects. In addition, high energy laser directed energy weapons have been progressively evolving and there is the possibility that anti-eye laser weapons are being developed. Their use would cause new types of combat casualty which have not yet been extensively experienced, but which will require accurate diagnosis to ensure effective medical solutions. The development of accurate and smart ocular diagnostic technology will expand the capability of clinicians to diagnose and treat ocular injuries induced by laser exposure at the point-of-injury as well as point-of-care. The proposed technology will provide improved field-care capabilities, reduce recovery time of injured warfighters, and help minimize complications of wound healing after trauma or surgery. This test if developed would be a valuable tool in the hands of eye care providers worldwide to assist in the evaluation of laser induced retinal injuries.

Payoff: Soldiers will receive appropriate care and will return to duty more quickly. Quality of care will be improved for soldiers who suffer laser-induced retinal injury that may not be detected immediately after exposure without a rapid portable diagnostic tool.

PHASE I: Develop clinical decision support tool algorithms for rapid analysis of fundus images of the retina before and after laser injury. The retinal images will first go through a rigorous image enhancement phase, image data augmentation, and pixel normalization. Following the enhancement and augmentation processes, algorithms will be developed to identify retinal abnormalities associated with laser damage. Optimize and validate the laser –induced injury detection technology in human fundus images. The end product must achieve high sensitivity and accuracy > 95%. Create protection plan for intellectual property.

PHASE II: Transition algorithms developed in Phase I. Develop a fully functional prototype. Define the parameters including ease of use, sensitivity and specificity. Develop strategy to acquire FDA approval as a clinical decision support tool. Identify commercial and clinical partners for Phase III. Develop a detailed business plan outlining monetary return on investment within two years of completion of Phase II (sales, licensing agreements, venture capital, non-SBIR grants).

PHASE III DUAL USE APPLICATIONS: Perform experiments as necessary to prepare for FDA review of an IND application. Conduct market analysis. Initiate a Phase I clinical trial to validate utility of a clinical decision support tool to detect laser-induced retinal injury. The diagnostic methodology once developed will be commercialized and made available to the military including forward deployed medics, FSTs and Combat Support Hospitals (CSH). Demand for this device in emergency rooms, ophthalmology and optometry practices worldwide is expected to be high. The portable rapid retinal damage detection tool will also be highly useful to non-military health care providers due to increased use of lasers in the civilian sector, ie fiberoptics and industry. Coordinate with Vision

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Center of Excellence to facilitate FDA approval and dissemination of the product to military clinicians.

REFERENCES:1. Mainster MA, Stuck BE and Brown JJr. 2004. Assessment of alleged retinal laser injuries. Arch Ophthalmol. 122:1210-1217.

2. Harris MD1, Lincoln AE, Amoroso PJ, Stuck B, Sliney D. 2003. Laser eye injuries in military occupations. Aviat Space Environ Med. Sep;74(9):947-52.

3. Marrugo, A. G., & Millan, M. S. (2011). Retinal image analysis: preprocessing and feature extraction. In Journal of Physics: Conference Series (Vol. 274, No. 1, p. 012039). IOP Publishing.

4. Grewal, P. S., Oloumi, F., Rubin, U., & Tennant, M. T. (2018). Deep learning in ophthalmology: a review. Canadian Journal of Ophthalmology.

5. Razzak, M. I., Naz, S., & Zaib, A. (2018). Deep Learning for Medical Image Processing: Overview, Challenges and the Future. In Classification in BioApps (pp. 323-350). Springer, Cham.

KEYWORDS: Laser, Retina, Machine-learning, Deep Learning Architecture

DHA192-002 TITLE: Treatment of Vestibular Impairment of Service Members after Traumatic Brain Injury through Use of an Individualized, Portable Neuromodulation Device

TECHNOLOGY AREA(S): Biomedical

ACQUISITION PROGRAM: Office of the Principal Assistant for Acquisition- USAMRMC

OBJECTIVE: To develop a wearable portable stimulator to stimulate the vestibular system and produce immediate improvements in dizziness, balance, gait and overall vestibular function. To enable Service Members to return to duty after suffering injuries that result in vestibular dysfunction.

DESCRIPTION: Mild traumatic brain injury (mTBI) has been called the “signature injury” of the recent conflicts in Iraq and Afghanistan.1-2 Documentation of vestibular symptoms following these injuries is common, with over 50% of soldiers reporting dizziness post injury and an additional 5-6% complaining of dizziness post-deployment.3 Vestibular damage is not only related to symptoms of dizziness and vertigo but also visual disturbance and imbalance contributing to increased fall risk. Veterans from a wide variety of backgrounds and multiple eras are faced with vestibular impairment and its associated consequences. A recent study of 13,746 OEF/OIF veterans found a 22.4% incidence of vestibular impairment and vestibular dysfunction has been demonstrated in 25% of veterans from the first Gulf War, with commonly reported symptoms including nausea (52%) and dizziness (17%). Correction of dizziness and balance issues remains largely unsolvable from the pharmacy counter. Vestibular rehabilitation, a specialized form of therapy, is the primary treatment strategy to improve symptoms of dizziness related to mTBI/concussion and other pathologies of the inner ear. Limitations with access to skilled rehabilitation providers - both on and off the battlefield - delays treatment, prolongs symptoms and negatively affects an individual’s readiness for duty.

Recent research has demonstrated a minimal amount of electrical vestibular stimulation with stochastic resonance can improve stability in patients with vestibular hypofunction.4 Researchers have also shown that a weak electric “noise” can improve balance and motor skills in patients with Parkinson’s disease.5 Building on these research advances, a portable device which can be worn to stimulate the vestibular system using stochastic resonance could significantly enhance the capability to effectively and expeditiously provide relief from vestibular decrements and therefore represents a significant deployment related health solution. Such a solution would directly address a current force capability gap in the ability to proficiently treat and rehabilitate vestibular injury and balance

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dysfunction. The objective of this topic is to support development of a portable stimulator, about the size of a hearing aid, which can be worn by the end user to deliver a type of vestibular stimulation resulting in relief. A portable stimulator to enhance vestibular function would improve physical function and enable individuals to seamlessly continue duty tasks. If proven effective over a longer term, this device could be made available to veterans or civilians with chronic balance problems, an area where there are currently limited treatments.

PHASE I: Phase I projects for this topic will conceptualize the technology and identify design specifications. The proposed device should be portable and non-invasive, similar to a hearing aid, and be able to deliver subsensory electrical noise. Studies have shown stability improvements from stochastic resonance using vestibular electrical stimulation when the frequency of stimulation is restricted to a narrow band, less than 5 Hz, while amplitudes of stimulation have ranged from the microampere range to the 1.5-mA range4. Therefore, levels of electrical noise should be low (<2 Hz noise signal), well below a consciously detectable perception, and should be capable of delivering a constant bipolar stimulus in the mA range with minimal user interaction. By the end of Phase I, technical parameters should be solidified, and operational functionality established. Clinical experts with insight into relevant patient populations should be consulted during the initial design phase for future clinical studies.

PHASE II: Based on Phase I design parameters, Phase II work will demonstrate, optimize and validate what constitutes a functional prototype. Phase II projects will demonstrate the ability of the non-invasive, portable device to improve functional capacity (e.g., balance, relieve dizziness) in a population shown to have vestibular impairment. Data obtained in Phase II will provide proof-of-concept that the device will provide abatement of vestibular impairment and improve physical function. Confirmation of no awareness of stimulus should be demonstrated during clinical testing to ensure input noise is at a sub-perceptual threshold. Parameters including device class, general controls, substantial equivalence, and premarket approval will be defined. Clinical experts with insight into relevant patient populations should be consulted as the system is being fully optimized. Potential commercial and clinical partners for Phase III and beyond should be identified. Phase II technical proposals should include a plan for commercial production of the prototype, including potential manufacturing partnerships and funding strategy. The FDA regulatory plan and an outline for approval are deliverables from Phase II.

PHASE III DUAL USE APPLICATIONS: Phase III will focus on work that derives from, extends, or logically concludes efforts performed under SBIR agreements. A description of how the technology and device will transition from research to operational capacity should be provided. A proposed DOD customer, such as health care providers at RoC 2 and 3 responding to mTBI in active duty Service Members, and regulatory requirements for these end users should be provided. During Phase III, additional experiments funded by sources other than the SBIR Program will be performed as necessary to ensure FDA IDE approval. A protocol of stimulation parameters that aligns to the Phase II requirements and demonstrates the medical efficacy and feasibility, should be finalized and made commercially viable. A plan for protection of intellectual property should be created and executed. A detailed market analysis will be conducted, an initial application will be submitted for the technology chosen, and a Phase I clinical trial will be initiated. Military application: The effort is relevant to military research efforts in mTBI/concussion. Commercial application: There are currently limited treatments for patients suffering with vestibular loss. This stimulator could easily be translated into a wearable device for other patient populations suffering with vestibular loss and balance impairments.

REFERENCES:1. Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA. Mild traumatic brain injury in U.S. Soldiers returning from Iraq. N Engl J Med. 2008;358:453‐463.

2. Schwab KA, Ivins B, Cramer G, Johnson W, Sluss‐Tiller M, Kiley K, et al. Screening for traumatic brain injury in troops returning from deployment in afghanistan and iraq: Initial investigation of the usefulness of a short screening tool for traumatic brain injury. The Journal of head trauma rehabilitation. 2007;22:377‐389.

3. Terrio H, Brenner LA, Ivins BJ, Cho JM, Helmick K, Schwab K, Scally K, Bretthauer R, Warden D. Traumatic brain injury screening: preliminary findings in a US Army Brigade Combat Team. J Head Trauma Rehabil. 2009

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Jan-Feb; 24(1):14-23.

4. Mulavara AP, Fiedler MJ, Kofman IS, Wood SJ, Serrador JM, Peters B, Cohen HS, Reschke MF, Bloomberg JJ. Improving balance function using vestibular stochastic resonance: optimizing stimulus characteristics. Exp Brain Res. 2011 Apr;210(2):303-12.

5. Khoshnam M, Häner DMC, Kuatsjah E, Zhang X, Menon C. Effects of Galvanic Vestibular Stimulation on Upper and Lower Extremities Motor Symptoms in Parkinson's Disease. Front Neurosci. 2018 Sep 11;12:633. doi: 10.3389/fnins.2018.00633. PMID:30254564.

KEYWORDS: mTBI, Concussion, Vestibular Function, Inner Ear, Portable Stimulator, Balance.

DHA192-003 TITLE: Forward Deployable Full Spectrum Oculomotor Assessment (OMA) and TBI Diagnostic Device

TECHNOLOGY AREA(S): Biomedical

ACQUISITION PROGRAM: Office of the Principal Assistant for Acquisition- USAMRMC

OBJECTIVE: Current oculomotor assessment practices in clinical bed-side and field environments utilize non-instrumented measures that rely on subjective (Kontos 2018) or observational measures to identify deficits. While these solutions have some limited clinical utility, they lack the capability to appreciate sub-clinical but pathological oculomotor signatures or to localize neuropathology necessary for appropriate diagnosis, management, and disposition of an injured Warfighter. An operationally feasible oculomotor measurement solution which measures physiologic eye movement characteristics would minimize or obviate reliance on subjective measures to diagnose and characterize concussion related oculomotor dysfunction.

DESCRIPTION: The development of sensitive TBI assessment practices are particularly important in cases where subtle deficits may go underappreciated potentially resulting in premature or inappropriate return to duty decisions which could impact the well-being of the SM, the unit, and potentially adversely impact overall mission success. The use of an instrumented assessment tool capable of characterizing performance in specific oculomotor sub-systems could provide better diagnosis, injury localization, and injury characterization data to guide management, rehabilitation, and disposition decisions in operational environments. Comprehensive oculomotor assessment requires measurement across a broad spectrum of physiologic sub-systems with distinct and integrated neuroanatomy to drive the full range of functional eye movements including rapid re-fixation, smooth pursuit, and gaze stability during head movements (Cheever et al 2018). The assessment of saccades- rapid re-foviating eye movements which direct gaze to specific targets of interest or provide compensatory refoviation to augment gaze stability; smooth pursuit eye movements which allow smooth following of a moving visual target; optokinetic (OKN) eye movements facilitating rapid visual motion processing; and the ability to stabilize gaze during rapid head motion (vestibulo-ocular reflex (VOR): are typically impaired following TBI. At present, comprehensive vestibular and oculomotor testing is limited by the fact that the gold standard video-oculography (VOG) systems are not only unsuitable for field use, they do not control the position of a visual target in space, a feature which is critical to ensure diagnostic accuracy in the measurement of saccadic and smooth pursuit eye movements.

PHASE I: Develop and provide a prototype of a portable oculomotor assessment (OMA) system consisting of a lightweight goggle head module (< 200 grams) that incorporates binocular tracking cameras, a minimum 9 degree-of-freedom Inertial Measurement Unit, and a laser projection and position control unit. The head module should communicate via wired connection to a lightweight (< 1500 grams) laptop computer or comparable data processing, storage, and display unit (DPU) housed in an impact resistant case suitable for transport in a small rucksack or utility bag. The system’s DPU should support > 3 hours continuous use, data storage, processing, and clinical data display. The laptop/ clinician interface should be loaded with a user-intuitive software interface supporting the execution of proof of concept oculomotor assessment algorithms with demonstrated adherence to the aforementioned technical

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and output specifications.

Required Phase I deliverables include: 1) a research design for engineering a portable oculomotor assessment (OMA) device; 2) A preliminary partially ruggedized prototype system with proof of concept testing and data sufficient to demonstrate the ability to capture, transmit, process, store, analyze, and report functional scores for saccadic (i.e. stationary head and stationary target that instantaneously jumps to a new position and vestibular catch up/ compensatory eye movements), smooth pursuit (i.e. stationary head and moving target), OKN (i.e. stationary head and moving vertical target lines), combined eye/head coordination (moving head and moving target) and VOR (moving head and stationary target) function; 3) demonstrate capability to deliver aforementioned clinical output from the oculomotor assessment system in a clinically useful format to inform clinical decision making relative to normative human performance data.

PHASE II: Validate the prototype of a compact, modular, ruggedized OMA system that can be used in an operational (field) setting to collect and analyze eye, head and target position motion data and display clinically relevant results of assessment on the laptop unit. The Phase II system should consist of the head module sensors that communicate via wire to the laptop serving as the data storage, processing and display unit.

Required Phase II deliverables will include:1. Validated ruggedization standards should include system’s ability to perform in rainy conditions, vibration tolerant to support transport without damage on military aircraft and vehicles, and impact resistance sufficient to withstand a drop of up to 5 feet.2. Battery life should be sufficient to support at least 3 hours of continuous use.3. Mass of head unit and laptop should not exceed 200 grams and 1500 grams, respectively.4. Recharging should be compatible with existing military power source availability and require no longer than 60 minutes to achieve 80% of full charge.5. Sampling rate and resolution should be sufficient to reliably characterize the bandwidth of oculomotor, OKN and VOR physiological systems.6. Algorithms supporting computation of clinical outcome measures should allow for periodic updates by the manufacturer as the state of the science advances to allow integration of emerging assessment conditions using specific measurements.7. Algorithms to process oculomotor, OKN and VOR data should compute stable, repeatable performance data (saccade size and timing, smooth pursuit gain, OKN gain and time constant, VOR gain during sinusoidal and transient head rotations).8. Relevant clinical outputs from OMA should include evidence-based characterization of oculomotor, OKN and VOR function. A functional score for each physiological system ranging from 0 (complete loss) to 1 (completely normal) will be generated and a single TBI likelihood score will be generated with suggestions to likely cortical region of injury.9. Outputs should be exportable to a stand-alone monitor, a printable output chart, and in a format that may be saved within a patient’s electronic medical record.10. Propose Sensitivity and Specificity values using an index score of oculomotor findings that predict presence or absence of central nervous system pathology associated with mild or moderate traumatic brain injury.11. Deliver a plan for the FDA clearance process and deliver a manufacturing plan.

PHASE III DUAL USE APPLICATIONS: Develop and deliver a user’s manual and provisional instructions for use which can support reasonable clinical adoption and sustainment within 10 hours of instruction. Conduct preliminary validation testing to characterize human performance under field conditions in a sample of Active Duty Service Members or a like age, gender and ability matched cohort. Validation of the prototype system should additionally include ability to discriminate healthy control personnel from a cohort with known TBI associated deficits. Based on results of system validation studies, system output should provide an aggregate estimate of duty readiness in the form of a “Green”, “Yellow” or “Red” signal on the clinician interface to indicate how closely patient performance approximates that of the patient’s baseline function and healthy control and duty ready personnel in each oculomotor sub-system.

Plans on the commercialization/technology transition and regulatory pathway should lead to eventual FDA clearance/approval. The small business should also consider a strategy to secure additional funding from non-SBIR

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government sources and /or the private sector to support these efforts. In addition to the stated DOD purpose of assessing injured Service Members with suspected TBI in the training or operational environments, potential civilian customers for this technology may include clinicians or organizations who assess persons with suspected concussion, oculomotor, OKN or vestibular deficits in rural, remote, and underserved regions. Additionally, clinicians assessing pre- and post-injury performance in athletes at risk for acquired head injury in pediatric, collegiate, or professional populations also likely constitute a significant commercial target population.

REFERENCES:1. Kontos AP, Collins MW, Holland CL, Reeves VL, Edelman K, Benso S, Schneider W, Okonkwo D. Preliminary Evidence for Improvement in Symptoms, Cognitive, Vestibular, and Oculomotor Outcomes Following Targeted Intervention with Chronic mTBI Patients. Mil Med. 2018 Mar 1;183(suppl_1):333-338. PMID: 29635578.

2. Cheever KM, McDevitt J, Tierney R, Wright WG. Concussion Recovery Phase Affects Vestibular and Oculomotor Symptom Provocation. Int J Sports Med. 2018 Feb;39(2):141-147. PMID: 29190849.

KEYWORDS: Oculomotor measurement, Concussion Assessment, Vestibular Assessment, Saccadic Assessment

DHA192-004 TITLE: Solutions for Self-Control of Urinary Function and Control

TECHNOLOGY AREA(S): Biomedical

ACQUISITION PROGRAM: Office of the Principal Assistant for Acquisition- USAMRMC

OBJECTIVE: To develop, design, and demonstrate new technology or therapies for injured Service Members that will allow patient or caregiver control over urination.

DESCRIPTION: The Department of Defense has an urgent need for clinical genitourinary technologies that will allow for patients to control their own urine flow. While proposed solutions may be suitable for those who have lost tissue as the result of injury, the primary user will likely be those suffering from neurogenic dysfunction.

Urinary dysfunction may be the result of traumatic injury to the lower body or may be neurogenic in nature, resulting from damage or disease of the central nervous system [1]. Traumatic injuries may involve damage or complete loss of tissues necessary for urinary function. Neurogenic damage may not affect specific genitourinary tissues but can still prevent control over urinary function. Approximately 70-84% of spinal cord injury (SCI) patients will have neurogenic bladder dysfunction (NBD), translating to ~32,000 SCI veterans with NBD [2].

The current clinical standard for treatment of bladder and urinary tract defects is catheterization, which can range from intermittent catheterization, requiring no surgery or permanent implants, to creation of a stoma, bypassing the urethra to empty the bladder directly. Intermittent catheterization is the use, several times a day, of a straight catheter that can be done independently by some patients, or a Foley catheter that allows continuous drainage into a drainage bag worn by the patient. The alternative is creation of a stoma that allows insertion of a catheter. The drawbacks for these procedures are the need for repeated catheter insertion and the need for external collection bags.

For Service Members sustaining these injuries, the use of a catheter may be required for decades. There is an inherent risk of infection and catheters may become blocked. Some evidence indicates certain bacteria encourage the development of encrustations that may block the catheter within 24 hours [3]. Catheter related urinary tract infections contribute to more than 40% of nosocomial hospital infections [4]. In addition to these risks, the ongoing costs for lifelong catheterization can be high. The average life span post SCI is over 40 years [5]. With catheters, pads and other supplies costing ~$600/month, this translates to almost $350,000 in a lifetime. For the VA alone, this adds up to over $23 million per year.

The ultimate goal of this project is to develop new technologies or therapies that can replace standard catheterization to allow a user to control their own urinary function. The ability to restore urinary function to injured Service

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Members would improve quality of life, enhance the ability to engage in the activities of daily living, and reduce the need for hospital visits for catheter care. This would be used at Role of Care 4 and with VA populations.

PHASE I: In the Phase I effort, innovative efforts for restoring urinary function will be conceptualized and designed. Such solutions should be devices, and should not include cellular, tissue or biological components. Phase I efforts can support early concept work (i.e., in vitro studies), or efforts necessary to support a regulatory submission, which do not include animal or human studies, such as stability studies, shipping studies, etc. Proposed technologies should be formulated, and the fabrication or production procedures should be developed for a representative device. The Phase I effort should also include fabrication experiments and benchmarking that demonstrate an adequate capability for meeting the expected challenges in fabricating the proposed technology. It is expected that physical attributes of devices such as patency, user control, urine retention and incontinence, and infection control will be predicted as a function of the material and device structure. Specific milestones for devices include the ability for the user to control urination, to control potential bacterial colonization or infection, and to maintain patency.

Proposed solutions should: 1) be gender neutral, 2) be suitable for both urinary tract trauma and neurogenic bladder dysfunction; 3) be both anatomical and functional; 4) replace chronic catheter usage; and 5) be operable by either a patient or a caregiver without specialized training.

Proposed solutions should not: 1) rely on nerve stimulation or nerve conductivity to enable function; 2) require diversion of urine to external containers; 3) require specialized clothing that would prevent normal socialization; 4) require frequent readjustments or maintenance by health care personnel; 5) contain components that open within the urine stream; 6) require metals to be in contact with urine; 7) increase the risk of kidney stones; or 8) be solely focused on urine volume sensing.

PHASE II: In the Phase II effort, a prototype technology or therapy should be fabricated and demonstrated. The performance of the technology should be fully evaluated in terms of patency, user control, urine retention and incontinence, and ability to resist bacterial colonization or infection. The last requirement is especially critical for implanted devices as unresolved bacterial contamination could be life threatening and require removal of an implant. Phase II results should demonstrate understanding of requirements to successfully enter Phase III, including how Phase II testing and validation will support a regulatory submission. Phase II studies may include animal or human studies, portions of effort associated with the same, or work necessary to support a regulatory submission which does not involve animal or human use, to include, but not limited to manufacturing development, qualification, packaging, stability, or sterility studies, etc. The researcher shall also describe in detail the transition plan for the Phase III effort.

The Food and Drug Administration regulatory requirements vary depending on the device classification. As part of the phase II effort, the performer is expected to develop a regulatory strategy to achieve FDA clearance for the new technology. Interactions with the FDA regarding the device classification and an Investigational Device Exemption (IDE), as appropriate, should be initiated. Essential design and development documentation to support FDA clearance, as described in the Quality System Regulation (21 CFR 820.30), should be captured including but not limited to design planning, input, output, review, verification, validation, transfer, changes, and a design history file. The project needs to deliver theoretical/experimental results that provide evidence of efficacy in animal models. The studies should be designed to support an application for FDA clearance.

PHASE III DUAL USE APPLICATIONS: During phase III, it is envisioned that requirements to support an application for device clearance from the FDA should be completed. As part of that, scalability, repeatability and reliability of the proposed technology should be demonstrated. Devices should be fabricated using standard fabrication technologies and reliability. The proposal should include a commercialization or technology transition plan for the product that demonstrates how these requirements will be addressed. They include: 1) identifying a relevant patient population for clinical testing to evaluate safety and efficacy and 2) GMP manufacturing sufficient materials for evaluation. The small business should also provide a strategy to secure additional funding from non-SBIR government sources and /or the private sector to support these efforts. Potential DOD funding mechanisms include research programs managed by the Congressionally Directed Medical Research program (CDMRP), which can be found at www.cdmrp.army.mil. Relevant research programs may include the Spinal Cord Injury Research Program (SCIRP) or the Joint Warfighter Medical Research Program (JWMRP).

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This technology/therapy is envisioned for use in surgical intervention to repair urinary dysfunction in fixed medical treatment facilities. As such, the technology should have both military and civilian applications. Procurement of such technology would be at the discretion of the medical treatment facility.

REFERENCES:1. Panicker JN, et al. Lower urinary tract dysfunction in the neurological patient: clinical assessment and management. Lancet Neurol. 2015 Jul;14(7):720-32.

2. Dorsher PT, McIntosh PM. Neurogenic Bladder. Adv Urol. 2012;2012:816274. doi: 10.1155/2012/816274.

3. Lowthian P. The dangers of long-term catheter drainage. Br J Nurs. 1998 Apr 9-22;7(7):366-8, 370, 372 passim.

4. Bronsema, D. A., Adams, J. R., Pallares, R., & Wenzel, R. P. (1993). Secular trends in rates and etiology of nosocomial urinary tract infections at a university hospital. Journal of Urology, 150, 414-416.

5. Middleton JW, Dayton A, Walsh J, Rutkowski SB, Leong G, Duong S. Life expectancy after spinal cord injury: a 50-year study. Spinal Cord. 2012 Nov;50(11):803-11. doi: 10.1038/sc.2012.55.

KEYWORDS: Catheter, Urinary Dysfunction, Neurogenic Dysfunction, Genitourinary, Intermittent Catheterization.

DHA192-005 TITLE: Real Time Measurements of Tympanic Membrane and Middle Ear Mechanics

TECHNOLOGY AREA(S): Biomedical

ACQUISITION PROGRAM: Office of the Principal Assistant for Acquisition- USAMRMC

OBJECTIVE: The intent of this SBIR is to develop a medical device that can provide real time analysis of middle ear mechanics, measure the defect to bridge the ossicular reconstruction and measure the tension on the repaired tympanic membrane intraoperatively

DESCRIPTION: The ongoing conflicts in Asia as result in numerous service members sustaining blast injury to the tympanic membrane. The morbity results in hearing loss and in many patients require surgical repair. The post-operative hearing result remains less than ideal for our services members. The modern era of tympanoplasty was ushered in by Wullstein and Zollner. Tympanomastoid surgery is quite successful in controlling infection and preventing recurrent disease, with reported success rates in excess of 80–90%. However, it is well recognized that post-operative hearing results are often unsatisfactory, especially in cases with advanced lesions of the ossicular chain or those with nonaeration of the middle ear. As when, the ossicular chain has to be reconstructed, long-term closure of the air-bone gap to < 20 dB occurs in 40–70% of cases when the stapes is intact, and in only 20–55% when the stapes superstructure is missing. Otologic surgeons have a good general appreciation of various anatomical and pathological reasons for failure of tympanoplasty, such as nonaeration of the middle ear, abnormalities of the reconstructed TM and inefficient sound transmission via the reconstructed ossicular chain. However, a quantitative understanding of the acoustical consequences of structural variations of a reconstructed ear is generally lacking. Liston et al., used intra-operative auditory evoked responses during ossiculoplasty and found that minor changes in prosthesis positioning on the order of 0.5–1.0 mm had relatively large effects on hearing (varying up to 20 dB). A clinical observation that postsurgical ears that seem almost identical in structure may demonstrate markedly differing degrees of conductive hearing loss. Small changes in structure have the capacity to have large effects on function. This is also important because small changes in graft and prosthesis position can occur as part of the healing process, which is beyond control of the otologic surgeon. There are major deficiencies in the quest to improve post-tympanoplasty hearing results. There is lack of quantitative understanding of middle ear mechanics, acoustics in the reconstructed middle ear and tension on the repaired tympanic membrane with real time acoustic

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knowledge.

PHASE I: Phase I will focus on designing a prototype and determining the technical feasibility of creating a medical device that has the potential to acquire tympanic membrane and middle ear biomechanics perioperatively. The device will include tension measurement on the tympanic membrane intraoperatively, determine ossicular mobility and as well as appropriate length of ossicular prosthesis. Implement the current knowledge of biomechanics of the ear into the device. Perform modeling on per and post-operative surgical outcomes using available technology. Demonstrate product design features and establish performance goals. Provide detailed information on data variables on tympanic membrane and middle ear biomechanics. Estimate the cost of such a device and its usability within the current operative environment within roles 3 and 4 care in the Military Health system. Define the potential risk of using such a device intraoperatively due to technology during development (laser, optical, heat transfer).

PHASE II: Based on the product from Phase 1 design is to produce a prototype that can then be validated using animal models or cadaveric model. Demonstrate accurate and real-time measures of the tympanic membrane per operatively and post operatively. Validate hearing outcome measures using middle ear biomechanics measurements. The device may integrate with current surgical equipment. There should be consultation with otologic surgeon during design validation. Phase II should outline an FDA regulatory plan. The organization will engage potential partners or consultants for clinical testing.

PHASE III DUAL USE APPLICATIONS: During Phase III, additional experiments will be performed as necessary to prepare for FDA approval. It is required that this device to commercialized and made available to the military health system which may include combat trauma acute rehabilitation with levels 3 and 4 of care. A detailed market analysis will be conducted and acquire potential private funding for commercialization. The device will be utilizing peri-operatively for surgical planning and intra operatively to improve ossiculoplasty outcomes.

REFERENCES:1. Dornhoffer JL, Gardner E. Prognostic factors in ossiculoplasty: a statistical staging system. Otology and Neurotology. 2001;22:299–304

2. Mishiro Y, Sakagami M, Adachi O, Kakutani C. Prognostic factors for short- term outcomes after ossiculoplasty using multivariate analysis with logistic regression. Arch Otolaryngol Head Neck Surg. 2009;135:738–41

3. Liston SL, Levine S.C., Margolis RH, et al. Use of introperative auditory brainstem responses to guide prosthesis positioning. Laryngoscope 1991;101:1009-12

4. Aarnisalo, A.A., Cheng, J.T., Ravicz, M.E., Furlong, C., Merchant, S.N., Rosows‘ki, J.J., 2009. Motion of the tympanic membrane after cartilage tympanoplasty determined by stroboscopic holography. Hearing Research 263 (1–2), 78–8

5. Rosowski, J.J., Mehta, R.P., Merchant, S.N., 2004. Diagnostic utility of laser-Doppler vibrometry in conductive hearing loss with normal tympanic membrane. Otology & Neurotology 25 (3), 323–332

KEYWORDS: Ossiculoplasty, Middle Ear Mechanics, Biomechanics, Tympanic membrane.

DHA192-006 TITLE: Tympanic Membrane Repair Material

TECHNOLOGY AREA(S): Biomedical

ACQUISITION PROGRAM: Office of the Principal Assistant for Acquisition- USAMRMC

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OBJECTIVE: The development of an innovated material/device that can be used to repair tympanic member perforations with limited or no anesthesia. The material can be in the form of a gel, 3d printed material, and other bio material and be used with endoscopes or minimal operative equipment. The material will be employed at level III battlefield of care after injury.

DESCRIPTION: The last 20 years of armed conflict has resulted in exposure of service members to high intensity sound or blast overpressure waves. The direct consequences of high-intensity noise and blast injuries to the auditory system are hearing loss and tympanic membrane rupture in some cases. Rupture of the eardrum or tympanic membrane (TM) was reported in over 10,000 service members during evaluation at field level III of care. The resultant injury may not receive definitive care for several months post injury until care is accomplished at level IV of care. The result is loss of return to duty status. The injury is a burden to the individual due to hearing loss. Many otologic surgeons contributed to the development and refinement of tympanoplasty techniques. Tympanoplasty surgery is quite successful in the modern area in the operative theater. The plethora of surgical techniques currently employed, the wide variety of autograft, homograft and synthetic materials are available and the continued innovation in biosynthetic materials for otologic use all attest to the fact that reconstructing the tympanic membrane continues to evolve. However, the current cost of performing tympanoplasty in the hospital operating room can be very expensive. The cost of health care continues to increase, the need for performing surgery in the office is now more a common place. We propose to develop a minimally invasive surgical material to repair tympanic membrane perforation that can occur far forward in the battlefield which has the potential to quickly return service members to duty.

PHASE I: During Phase one, determine and define the material composition that will be tolerated within the middle ear and close/repair a tympanic membrane perforation. The product has no ototoxic potential to both the auditory or vestibular system. Design requirements may include ease of use, minimal equipment or activation process and be delivered minimally invasive. It must be stable, have ease of storage (heat and cold tolerance) and be applied with ease. Demonstration of a prototype is desirable with some early in vitro data. The product should have function and closure rates of tympanic membrane repair that meets the industry standard. The product should be easily removed from the graft site during early healing stages, if necessary, otherwise it should dissolve or incorporate into the healed tympanic membrane. Model key elements of tympanoplasty repair biomechanics, which may include detailed analysis of auditory performance. Design/develop an innovative concept along with limited testing of potential materials. The product will be used by Otolaryngologist at level 3-4 of care.

PHASE II: Detail analysis of the selected material/device that will include optimal biological properties that are safe and perform equal or better outcomes than standard tympanoplasty. The material should be delivered with minimal surgical tools with no need for an operative suite. The in vivo efficacy will be established. Parameters include ease of use and overall stability across a wide range of conditions. Validation of efficacy will be determined through animal models, histology, and/or other appropriate measures. Clinical experts with insight into tympanic membrane trauma and relevant patient populations should be consulted during optimization and animal validation. Early clinical trials should be considered. Potential commercial and clinical partners for Phase III and beyond should be identified, and a detailed explanation should be provided for how the small business will obtain a monetary return on investment. Phase II should outline an FDA regulatory plan as well consult subject matter experts with military experience.

PHASE III DUAL USE APPLICATIONS: During Phase III, additional in vivo experiments will be performed as necessary to prepare for FDA review. It is required that this device to commercialized and made available to the military and as well to the private sector. Clinical trials should be underway. Close communication with military surgeons on the development on the product should be considered. Small business should have a strategy in place to secure funding from the private sector. Device a plan that will bridge the gap between laboratory-scale innovation and entry into a recognized Food and Drug Administration (FDA) regulatory pathway leading to commercialization of the product that will be made available for purchase by the military health system and private sector.

REFERENCES:

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1. S. N. Merchant · M. J. McKenna · J. J. Rosowski Current status and future challenges of tympanoplasty Eur Arch Otorhinolaryngol (1998) 255: 221–228

2. R.T. Chavan, S.M. Ingole and S.N. Birajdar Overview of Tympanoplasty techniques and results Int. J. of Oto and Head and Neck Surg

3. Carlos R Esquivel, Mark Parker, Kwame Curtis, Andy Merkley, Phil Littlefield, George Conley, Sean Wise, Brent Feldt, Lynn Henselman, Zsolt Stockinger; Aural Blast Injury/Acoustic Trauma and Hearing Loss, Military Medicine, Volume 183, Issue suppl_2, 1 September 2018, Pages 78–82,

4. Helling ER: Otologic blast injuries due to the Kenya Embassy Bombing. Mil Med 2004; 169(11): 872–76.14.

KEYWORDS: Tympanoplasty, Endoscopes, Technique, Hearing, Ototoxicity.

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