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Digital Markers for Marijuana Intoxication

Description:

Number of Anticipated Awards: 3-4.
Phase I and Fast-Track proposals will be accepted. Fast-Track proposals include Phase I and Phase II activities.
Budget (total costs):
Phase I: $225,000 for 6 months
Phase II: $1,500,000 for 2 years
Fast-Track budget may not exceed $1,725,000 and Fast-Track duration may not exceed 2 years 6 months.
It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded.
Objective
This RFP solicits the research and development of digital markers for detection of acute marijuana intoxication. In the content of this solicitation the digital markers are described as smart phone-based diagnostic test data or real time, data-driven signals. The proposed digital markers must be created on Apple Inc.’s ResearchKit or/and Android ResearchStack frameworks. Both frameworks are open-source software platform which make it easy for researchers and developers to create mobile applications (apps) for specific biomedical research questions by circumventing the development of custom code. Mobile app development on custom platforms will not be funded. Then, the offerors are expected to test the apps clinically and validate the embedded digital markers. It is envisioned that the developed and validated digital markers will be consolidated into novel digital health tools for use in clinical research and law enforcement procedures.
Background
As marijuana is being medically and recreationally legalized in many states, there is a growing concern over marijuana intoxication. A major public health concern is the increased risk of marijuana-impaired driving, because the number of individuals testing positive for marijuana constituents and the proportion who was involved in traffic fatalities doubled in the three years. According to the 2017 report issued by the Governors Highway Safety Association (GHSA) and the Foundation for Advancing Alcohol Responsibility, drugs are now involved in more fatal U.S. crashes than alcohol alone, and marijuana-impaired driving significantly contributes to this trend. However, currently there is no quantitative biologic test that can accurately determine whether an individual is acutely impaired following marijuana consumption.
When marijuana is absorbed, the concentration of tetrahydrocannabinol (THC), one of the psychoactive marijuana constituents, decreases rapidly in the blood stream due to the distribution through the hepatic metabolism and absorption into fat cells. Over time, THC is slowly released back into the bloodstream and subsequently excreted in the urine. The rapid and variable absorption and release of THC into the blood stream makes it difficult to correlate the level of THC with impairment in chronic marijuana users. In addition, due to the multiple marijuana species, there are over 100 marijuana metabolites. These metabolites can be detected in the blood, however, they have been not associated with the psychoactive effects of marijuana use. This translates into unreliable blood tests for marijuana detection which have high rate of false positive results. One alternative is a saliva-based screening tool. The oral fluid is easy to collect, non-invasive, and is associated with recent cannabis intake. Unfortunately, recent studies have shown that the saliva-based tests have a two-to five-fold greater

variability than the blood tests, and the level of marijuana detection is also not precise. In the absence of a quantitative, biospecimen-based test for marijuana intoxication and psychomotor impairment, the Diagnostic and Statistical Manual IV (DSM
V) test remains the only diagnostic gold standard used by drug recognition experts and mental health professionals.
Using digital parameters of person's psychomotor impartment in the response to the marijuana consumption may represent more reliable and correlative approach for diagnostics. To test this hypothesis, the National Institute on Drug Abuse (NIDA) plans to support the identification, development, testing and validation of digital markers for detection of psychomotor impairment due to marijuana intoxication. To increase the project efficiency and to increase interoperability and sustainability of the research tools produced as the result of this solicitation, NIDA requests that the proposed markers be developed and clinically validated using mobile applications created on Apple Inc.’s ResearchKit or Android ResearchStack frameworks. Both frameworks are open-source and allow researchers and developers to easily create biomedical apps by circumventing the development of custom code. Due to the availability of these pre-coded platforms, NIDA will limit the costs directly associated with the app design to no more than $50,000 per project (with the maximum of $30,000 for the Phase I and $20,000 for the Phase II). Mobile app development on custom platforms will not be funded. The majority of proposed work should be focused on testing objective digital variables in response to marijuana intoxication-associated impairment and correlate those digital variables with one of more existing or (novel) biomarkers, imaging technologies and DSM V test results. Offerors are expected to have in-house capabilities or the established practice or experience to detect THC in biological specimens and quantify the level of the cognitive/psychomotor impairments in human subjects.
The app features may leverage and integrate with the internal sensors, compatible add-apters and external hardware to monitor the measurable markers of marijuana intoxication. Examples of the app features may include, but not limited to, accelerometer, microphone, gyroscope, facial or eye pupil’s changes recognition software, glucometers, inhalers, skin voltage sensor, heart rate sensor, other existing and newly developed sensors.
In the future, the clinical studies using the validated apps may be more cost-efficient than the analogous ones using physiological biomarkers. The Fast Track projects may include consolidation of the validated markers into novel digital health technologies/tools to be used in the future outside of the research purposes. It is envisioned that the final app/tool will meet the FDA device class II designation.
The developed products could have enormous impact meeting a critical, unmet need for clinical research and law enforcement procedures.
Phase I Activities and Expected Deliverables
Develop a mobile application prototype and test its feasibility to measure psychomotor impairment following marijuana consumption. Conduct research on selection of the digital markers of marijuana intoxication.
Technical Requirements
1.
Identify and describe selected digital markers. Customize the variables to be highly specific to the detection of marijuana-dependent dysfunction. Present the conceptual framework of the selected digital markers.
2.
Develop a prototype of mobile application software using ResearchKit or/and Android ResearchStack frameworks with integration of digital markers. Create a video of the app prototype to clearly demonstrate the app functionality. Develop the white paper describing the app built upon the proposed markers and the design of the “proof-ofconcept” study.
3.
Conduct the “proof-of-concept” study testing feasibility and usability of digital biomarkers to detect marijuana intoxication
a.
Obtain IRB approval for clinical studies.
b.
Enroll healthy volunteers for the pilot clinical study and screen them for eligibility.
c.
Demonstrate the capability of the app in the pilot clinical study. NIDA requests that the offerors should use NIDA Drug Supply Program to obtain marijuana or TCH for this clinical research.
https://www.drugabuse.gov/researchers/research-resources/nida-drug-supply-program
d.
Determine the feasibility by achieving reproducible, highly sensitive measurements of the cognitive/psychomotor impairment.
e.
Compare the digital data with clinical standards (biological specimens or imaging technologies) and DSM V tests.

Phase II Activities and Expected Deliverables
Test and validate the mobile application to measure cognitive and psychomotor impairment at marijuana intoxication.
Technical Requirements
1.
Revise and improve software in response to the needs identified in the Phase I. Optimize the digital variables as needed. Complete the enhanced software design based on the final system requirement document.
2.
Determine efficiency and sensitivity of the digital markers to quantitatively measure the cognitive/psychomotor impairment at a known doses of THC.
3.
Determine the app performance by demonstrating of the linear range, detection limits, and specificity.
4.
Validate the digital biomarkers with a large cohort of marijuana users using clinical standards (biological specimens or imaging technologies) and DSM V test. Determine the residual effects of recent marijuana intake vs cumulative effects of chronic use vs poly-substance abuse (including alcohol and stimulants). Expand the statistical data and determine sensor accuracy and precision levels. Verify the diagnostic specificity, sensitivity and reproducibility.
5.
Test the digital biomarkers for confounding effects of a) pre-existing cognitive and educational deficits; b) co-mobility with other psychiatric disorders, and c) medications for drug abuse or other neurologic disorders. Validate objectivity and reliability.
6.
Conduct the efficiency survey with professionals representing the target end-users. Collect survey’s feedback and analyze the data.
7.
Prepare the plan to address FDA-regulations if a Health IT Tool is to be used in the future outside of the research purposes.
8.
Prepare strategy for implementation and dissemination.

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