SBIR-STTR Award

Principal Investigator/Program Director (Last, First, Middle): Abstract We propose to design and deploy a handheld breath-based "personal" medication adherence monitoring system (MAMS) which will meet the criteria of the solicitation from the National Institute of Mental Health (NIMH) for "Development of information, instruments or methodologies to improve and/or track adherence to complex HIV/AIDS drug therapies for Hispanic and African American populations". MAMS will consistent of a modified miniature battery powered gas chromatograph (mGC) capable of detecting the presence of a "taggant" or a metabolite of the taggant on the breath of an individual shortly after ingestion of a medication containing it. MAMS will include hardware and software capable of recording the detection of the "taggant", storing the information for later analysis, and notifying, in real-time by wireless or other communications, a healthcare provider if medication is not taken as prescribed. We will explore FDA approved "generally recognized as safe" (GRAS) compounds as taggants. The "taggants" can be applied as a coating to the medication, be added along with the medication to a special capsule or be added as an excipient. We have considerable expertise in the detection of drugs in exhaled breath and are knowledgeable about the properties of candidate "taggants" and their metabolites. Our Specific Aims are: Specific Aim 1: Identify 6-8 chemically diverse taggant candidates from GRAS compound databases that will likely generate appropriate EDIM(s) at doses currently permitted by the FDA in exhaled breath after oral ingestion. Either the taggant or taggant metabolite(s) could qualify as an EDIM. Specific Aim 2: Test whether the GRAS taggant candidates identified in Specific Aim 1 are suitable for MAMS in humans by sequentially analyzing the concentrations of taggant(s) and taggant metabolite(s) in breath after oral ingestion of the taggant using the "gold standard" analytical technique, GC-MS. Specific Aim 3: Design and build a mGC device to reliably measure in real-time the gas phase concentration of two suitable EDIMs identified in Specific Aim 2. Nonadherence to prescribed medication regimens is a major health issue in the US which costs our healthcare system over $100 billion annually. Nonadherence is a major cause of morbidity and mortality. It can result in a public health threat if, for instance, a patient fails to adhere to an antibiotic or antiviral medication. This can lead to the emergence of resistant organisms. We propose to develop a small portable device that a patient can blow into shortly after taking their medication which will detect and document that the appropriate medication was taken at the proper time. This technology should improve adherence rates, especially in high-risk populations.

Thesaurus Terms:
AIDS therapy, biosensor device, breath composition, reagent /indicator, technology /technique development, therapy compliance biomedical equipment development, computer assisted patient care, drug screening /evaluation, miniature biomedical equipment, oral administration, patient monitoring device, portable biomedical equipment behavioral /social science research tag, bioengineering /biomedical engineering, clinical research, gas chromatography mass spectrometry, human subject

Building on our Phase I achievements, we will design and deploy a handheld, breath-based medication adherence monitoring system (adherence system) to identify adherence for clinical trials. The system consists of a miniature, battery powered gas chromatograph (the device) capable of measuring volatile metabolites (e.g., butanone) on an individual's breath after ingestion of a medication containing taggants (e.g., 2-butanol). This data can be sent to and evaluated by health care personnel via HIPAA-compliant information technology to allow opportunity to improve medication adherence. In Phase II activities, we propose a plan to optimize the design of the adherence system. The proposal consists of 7 aims. Specific Aim 1: Chemistry - characterize "generally recognized as safe" taggants for definitive adherence in humans. a) Determine breath pharmacokinetic parameters of two definitive taggants and their key volatile metabolites in fasting humans (months 1-6), and b) create a chemistry backup program to develop new definitive taggants (months 1-24). [Specific Aim 2: Food Interference - further validate that food does not interfere with this adherence system (months 6-12)]. Note: new aims are bracketed and in Georgia font. Specific Aim 3: Pharmacy - optimize the means whereby taggants are interfaced to pharmaceutical products for definitive adherence (months 1-24). Specific Aim 4: Portable Gas Sensor - finalize design of the mGC-MOS, a) optimize mGC and MOS components of mGC-MOS unit, b) design, implement and optimize a breath collection device, and c) identify a contract manufacturer (months 1-12). [Specific Aim 5: Information Technology and Data Processing - develop methods and techniques to locally store, transmit, remotely archive, and distribute adherence data in a HIPAA-compliant manner. Develop signal processing algorithms to improve taggant detection accuracy of device. (months 1-12) Specific Aim 6: Adherence System Accuracy - Conduct a pilot study in humans to test system performance (months 12-18). Specific Aim 7: Behavioral (Usability) Adherence System Evaluation - Conduct a pilot study in high risk, HIV/AIDS patients to test acceptance of the system (months 18-24).] The ability to stratify medication adherence rates to safety and efficacy parameters and linking adverse events to medication ingestion will lead to optimal decisions regarding clinical trial drugs safety and efficacy.

Public Health Relevance:
Nonadherence to prescribed medication regimens is a major health issue in the US which costs our healthcare system over $100 billion annually. Nonadherence is a major cause of morbidity and mortality. It can result in a public health threat if, for instance, a patient fails to adhere to an antibiotic or antiviral medication. This can lead to the emergence of resistant organisms. We propose to develop a small portable device that a patient can blow into shortly after taking their medication which will detect and document that the appropriate medication was taken at the proper time. This technology should improve adherence rates, especially in high-risk populations, and provide pharmaceutical companies and the FDA with an improved data set for evaluating drugs in clinical trials.

Public Health Relevance Statement:
Program Director/Principal Investigator (Last, First, Middle): Project Narrative Nonadherence to prescribed medication regimens is a major health issue in the US which costs our healthcare system over $100 billion annually. Nonadherence is a major cause of morbidity and mortality. It can result in a public health threat if, for instance, a patient fails to adhere to an antibiotic or antiviral medication. This can lead to the emergence of resistant organisms. We propose to develop a small portable device that a patient can blow into shortly after taking their medication which will detect and document that the appropriate medication was taken at the proper time. This technology should improve adherence rates, especially in high-risk populations, and provide pharmaceutical companies and the FDA with an improved data set for evaluating drugs in clinical trials. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page

NIH Spending Category:
Bioengineering; Clinical Research; Clinical Trials; Mental Health

Project Terms:
2-butanol; AIDS therapy; AIDS/HIV; AIDS/HIV problem; Academia; Achievement; Achievement Attainment; Adherence; Adherence (attribute); Adverse Experience; Adverse event; Algorithms; Antibiotic Agents; Antibiotic Drugs; Antibiotics; Antiretroviral Therapy, Highly Active; Antiviral Agents; Antiviral Drugs; Antivirals; Archives; Area; Behavioral; Biological; Blood; Butanones; Chemicals; Chemistry; Clinical Trials; Clinical Trials, Unspecified; Collection; Contracting Opportunities; Contracts; Data; Data Set; Dataset; Deglutition; Detection; Development; Device Designs; Devices; Drug Kinetics; Drugs; Electronics; Evaluation; Exhalation; Exhaling; Expiration, Respiratory; Fasting; Food; Future Generations; Gas Chromatography; Gases; Generations, Future; Grant; Guidelines; HAART; HIV/AIDS; HIV/AIDS problem; Health; Health Care Costs; Health Care Providers; Health Costs; Health Personnel; Healthcare Costs; Healthcare Providers; Healthcare Systems; Healthcare worker; Highly Active Antiretroviral Therapy; Human; Human, General; Individual; Industry; Information Technology; Ingestion; Intermediary Metabolism; International; Lead; Link; METBL; Man (Taxonomy); Man, Modern; Manufacturer; Manufacturer Name; Mass Spectrum; Mass Spectrum Analysis; Measures; Medication; Metabolic Processes; Metabolism; Method LOINC Axis 6; Methodology; Methods; Methods and Techniques; Methods, Other; Miscellaneous Antibiotic; Monitor; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; NIH; National Institutes of Health; National Institutes of Health (U.S.); Oral; Organism; Pathway interactions; Patients; Pb element; Performance; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Preparations; Pharmaceuticals; Pharmacies; Pharmacokinetics; Pharmacologic Substance; Pharmacological Substance; Pharmacy facility; Phase; Photometry/Spectrum Analysis, Mass; Pilot Projects; Population; Principal Investigator; Programs (PT); Programs [Publication Type]; Protocols, Treatment; Public Health; RGM; Regimen; Reporting; Research; Resistance; Reticuloendothelial System, Blood; Safety; Science of Chemistry; Site; Spectrometry, Mass; Spectroscopy, Mass; Spectrum Analyses, Mass; Spectrum Analysis, Mass; Swallowing; System; System, LOINC Axis 4; Systems, Health Care; Techniques; Technology; Testing; Therapeutic; Time; Treatment Protocols; Treatment Regimen; Treatment Schedule; United States National Institutes of Health; anti-retroviral therapy, highly active; antiretroviral therapy; base; clinical investigation; computerized data processing; conference; cost; data processing; design; designing; drug discovery; drug/agent; fasted; fasts; fight against; health care personnel; health care worker; health provider; healthcare personnel; heavy metal Pb; heavy metal lead; high risk; improved; living system; medical personnel; medication adherence; medication compliance; metal oxide; new technology; pathway; pilot study; prevent; preventing; programs; prototype; public health medicine (field); public health relevance; resistant; resistant strain; sec-butyl alcohol; sensor; signal processing; symposium; treatment provider; usability; vapor phase chromatography