You are here

Wearable medical device to diagnose in-theater opioid intoxication of the warfighter

Description:

TECHNOLOGY AREA(S): Bio Medical 

OBJECTIVE: To provide passive, on-warfighter diagnostic capability for intoxication subsequent to exposure to opioid threat agents. Capabilities sought are intended for use in far-forward deployed settings and must be effective and suitable to diagnose intoxication (disease) with high clinical sensitivity within a timeframe from exposure up to presentation of outward symptoms (i.e. the detectable pre-clinical phase) 

DESCRIPTION: The U.S. Department of Defense (DoD) seeks to develop and field diagnostic capabilities for detection of exposure to the ever-growing opioid class of chemical threat agents. Opioids are a drug class that includes heroin, synthetic opioids such as fentanyl (and analogues), and pain relievers such as oxycodone, hydrocodone, codeine, morphine, and others. Side effects of opioids include sedation, nausea, respiratory depression, and euphoria. Fentanyl and its analogues have rapid onset of symptoms and vary in duration of action (1). They are 50-10,000 times more potent than morphine (2, 3), which suggests quantities leading to accidental life-threatening exposure may occur on the level of an individual even within groups in confined spaces. Because of the risks associated with the low dose required for rapid onset of impairment, there is interest in pairing a wearable medical device with use of an automated on-body medical countermeasure delivery system. Detecting exposure and diagnosing intoxication at the point-of-need prior to outward, observable clinical symptoms could enable warfighter performance preservation by triggering opioid antagonist administration and supporting battlefield decisions. This topic seeks to identify robust, diagnostic markers of opioid intoxication that can be measured and interpreted by a wearable device. Wearable environmental sensors that identify this class of pharmaceutical-based agent, and have the potential for clinical-decision support by elevating suspicion, are also of interest. This topic seeks feasibility demonstration, initial performance baseline, and potential for Food and Drug Administration (FDA) clearance of innovative, wearable solutions. Ability of the wearable to trigger a confirmatory test (trigger-to-test), support subsequent treatment decisions (trigger-to-treat), or, ultimately, directly initiate automated drug delivery via an on-body delivery system of an opioid antagonist should be presented. 

PHASE I: Conduct proof-of-concept experiments to demonstrate wearable technologies that collect, process, and interpret markers of opioid intoxication or sense warfighter exposure to opioids. Feasibility regarding use of an existing platform to produce a medically-relevant prognosis or diagnosis should be discussed with clear identification of developmental hurdles and supported with preliminary data. Proposed Phase I efforts should be designed to collect data to directly address identified hurdles. This phase should also determine and document modifications, including in both hardware and software, needed in subsequent efforts to achieve the primary goal of providing data to support medical decision-making. Phase I should also result in experimental designs including candidate diagnostic targets as well as a demonstration of relevant animal models to define human intoxication with chemical threats as appropriate. Preliminary design inputs and performance specifications and potential user needs assessment are also of interest in this phase. Outputs/deliverables from Phase I will support decisions to continue development into Phase II. The proposed approach should address the following key factors: • Diagnostic markers – the proposed approach should identify intoxicant or host-derived diagnostic markers, including physiological metrics that are highly specific to the causative class of agent(s) or are prognostic with algorithmic analysis as a system. Markers should be detectable within an easily accessible sample, or within the personal environment of the wearer, and within the time window of symptomology specified earlier. • Sample matrix – the proposed approach should define the matrix or matrices where the diagnostic markers reproducibly accumulate to detectable levels during disease. Sample matrices targeted should be compatible with self-aid or buddy-aid (i.e. Army Medical Role 1). A passive sampling and analysis method, free of user interventions, is most desirable. • Diagnostic window – a proposed timeframe critical to interpretation of markers should be defined and supported with at least preliminary data prior to conclusion of Phase I. Markers should preferably be detectable within 5 minutes of exposure and prior to symptom onset. At a minimum, detection should be consistent with the rapidly-acting nature of opioids or other relevant chemical threats so as to support subsequent treatment decisions. 

PHASE II: This development phase may begin with a draft design of final system configuration, but should result in an assemblage of all system components into an approximate configuration of the final operational form factor, i.e. a brassboard test model. This brassboard should demonstrate functionality of the system with all software components (operational and analytical). An optimization plan and finalized critical design requirements should be established and documented in this phase. Animal studies, following good laboratory practices, should be proposed and conducted as appropriate to validate diagnostic targets. An estimate of each system component (critical and non-critical) cost, development cost, and projected timelines should be prepared. A business case for the proposed product, including final system price, should be developed. Prototype detection systems should be developed for the purpose of validation studies, testing candidate diagnostic targets identified in Phase I. Prototype systems during Phase II, if necessary, can be moderately complex, laboratory-based methods that are suitable for answering key questions relevant to each marker. However, the final form-factor of the diagnostic device should be a low-cost, light-weight wearable that is easy to operate by a warfighter in a far-forward, combat setting. Phase II efforts must subsequently inform selection of the most promising targets prior to Phase III. Marker validation studies will define: • Sample matrix selection • Marker signal strength • Diagnostic window • Inclusivity • Sensitivity and Specificity • Organophosphate vs opioid differentiation • Alignment with human performance degradation (prognostic and diagnostic power) 

PHASE III: During Phase III, perform in vitro diagnostic (IVD instrument and/or assay development efforts, as well as analytical and clinical studies needed for submission to the U.S. Food and Drug Administration (FDA). A detailed regulatory strategy document should be prepared to include at least a draft Intended Use statement, specimen requirements, clinical trial approach, product sponsorship, and manufacturing plan. The preliminary validation data from the down-selected diagnostic targets of Phase II should inform the final design specifications required for the development of IVD assays, hardware, and software with additional considerations for a Clinical Laboratory Improvement Amendment (CLIA)-waived complexity rating (5). Additionally, modifications informed by end-user or stakeholder feedback should be incorporated into the design for the selected prototype to be supplied to the DoD. Considerations include, but are not limited to, operational temperature ranges, assay and reagent stability, data export capabilities with and without the use of network connectivity, interface usability, test result storage, and the degree to which the system could be expanded to accommodate additional tests. A single, reusable, expandable platform is the desired system architecture; however, single-use tests may be considered if they provide a significant life-cycle cost advantage to the Government. All development efforts will adhere to industry practices (e.g. cGMP and ISO13485:2016) required or expected for the end-state goal of FDA clearance through the 510(k) or de novo regulatory pathways. Teaming with, or licensing of, system components resulting from any phase of this SBIR project to a third-party IVD device developer/manufacturer is acceptable, subject to the rules governing small business participation in SBIR Phase III. Opioid diagnostics could additionally be useful to the public first-responders, Civil Support Teams (CST) on public mission, and law enforcement agents in the United States. The public health concern centers on drugs of abuse or patients with addiction, which is a different population. However, use of a wearable, early-warning, medical device could improve the experience and risk of the public first-responder, or law enforcement agent, who may face accidental exposure to threat agents when providing on-scene aid. 

REFERENCES: 

1: "WCPI Focus on Pain Series: The Three Faces of Fentanyl" Aspi.wisc.edu. Archived on 2010-06-10

2:  "DrugFacts: Fentanyl" National Institute on Drug Abuse, US National Institutes of Health. June 2016.

3:  "Commission on Narcotic Drugs takes decisive step to help prevent deadly fentanyl overdoses" Commission on Narcotic Drugs, United Nations Office on Drugs and Crime. 16 March 2017.

4:  CLIA Categorizations (n.d.), retrieved December 2nd, 2014 from http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/IVDRegulatoryAssistance/ucm393229.htm

KEYWORDS: Opioids, Fentanyl, In Vitro Diagnostic, Naloxone, On-body, CBRN 

CONTACT(S): 

Jason Opdyke 

(301) 619-2881 

jason.a.opdyke.civ@mail.mil 

Leanne Chacon 

(301) 619-8434 

US Flag An Official Website of the United States Government