Innovation Crossover Research Life Sciences/Biomedical Health Informatics. Distribution Statement A: Approved for Public Release

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Innovation Crossover Research Life Sciences/Biomedical Health Informatics 1

Innovation Crossover Preliminary Research Report Life Sciences/Biomedical Health Informatics Context/Scope This paper represents research conducted by OVO Innovation for the NSWC Crane Innovation Crossover event October 12-13, 2016. This research is intended to provide more insight into key challenges that were identified within the four technology clusters (Advanced Manufacturing, Cyber/IT, Life Sciences and DoD Technologies) first documented in the Battelle report. OVO consultants interviewed subject matter experts (SMEs) from the private sector, academia and the government identified by NSWC Crane to gather insights into key challenges in each cluster. This report is meant to inform the participants of the Innovation Crossover event and identify new research and new technologies that might address the key challenges. This research was collected during August and September, 2016. The reports were submitted by OVO to NSWC Crane in late September 2016. Introductory Narrative The Innovation Crossover event, scheduled for 12-13 October 2016 in Bloomington is the culmination of months of planning and hard work. Some of this preparatory work involved the initial Battelle study which identified key technology clusters (Advanced Manufacturing, Life Sciences, Cyber/IT and DoD Technologies) in southern Indiana. From these clusters NSWC Crane and its contractor OVO Innovation conducted further, more detailed research, to examine detailed challenges and opportunities in each technology cluster. The reports attached document the research OVO conducted with subject matter experts identified by NSWC Crane in academia, industry and in the government. The reports are meant to document specific challenges within each technology cluster that could become areas of joint research and cooperation across the three constituents in southern Indiana. The reports are provided to you to help you prepare for your participation in the upcoming Innovation Crossover event and to frame both the challenges and active research underway to address these challenges. 2

Problem Context Problem or Challenge: Health Informatics Enable patient-centered health care through development of point-of-care, wireless, and personal health informatics technologies. Develop informatics technologies to provide information and feedback on people serving to allow instant access to their vital signs and the ability to direct medicine, hydration or other needs remotely, as well as provide remote diagnosis. 3

Problem Context Problem or Challenge: Mechanisms Transform advances in knowledge of cellular and molecular disease mechanisms into precise medical diagnostics and therapeutics. 4

Overview: Mechanisms Early stages of research into mechanisms at the cellular/molecular level Biomarkers for disease states Research exists for decades, but opening up new frontiers Challenge is translating knowledge into therapeutic action Extraordinary complexity of human biology/physiology Systems don t operate independently; difficult to design effective experiments Models needed to guide decisions on what to measure/monitor and what to do with the data 5

Technologies: Informatics Informatics is "the interdisciplinary study of the design, development, adoption and application of IT-based innovations in healthcare services delivery, management and planning. 1 More simply, the collection, management, and analysis of medical data. 1 Procter, R. Dr. (Editor, Health Informatics Journal, Edinburgh, United Kingdom). Definition of health informatics [Internet]. Message to: Virginia Van Horne (Content Manager, HSR Information Central, Bethesda, MD). 2009 Aug 16 [cited 2009 Sept 21], found on https://www.nlm.nih.gov/hsrinfo/informatics.html 6

Problem Relevance Benefits to adoption of medical informatics technology Improved patient compliance with treatment Improved monitoring by patients and medical professionals more granular data for diagnosis and treatment Improved access to care through remote diagnosis and treatment More data available for analysis through medical research community Future: ability to create custom treatments for patients (personalized medicine) 7

Scope For the purposes of this research, we ve defined the scope of the challenge to be the complete set of technologies that can be used to remotely monitor, measure, or detect changes in physiological, neurological, or cognitive function. This includes the sensors themselves, as well as the related technologies such as analytics, platforms, packaging, and user experience. 8

Research Sensors Wired and wireless Variety of modalities Wearable (external device, or on skin) Implantable (subcutaneous) Ingestible Injectable 9

Examples Implantable force sensor from RPI 1 Glucose monitoring tattoo from UCSD 2 Smart contact lens/glucose monitor from Google 3 Injectable computer from University of Michigan 4 1 https://www.asme.org/engineering-topics/articles/bioengineering/implantable-sensors-make-medical-implants-smarter 2 http://pubs.acs.org/doi/abs/10.1021/ac504300n 3 http://www.healthline.com/diabetesmine/newsflash-google-is-developing-glucose-sensing-contact-lenses 4 http://medcitynews.com/2016/06/injectable-computer-tumor-pressure/ 10

Research Data generated by informatics natural for advanced analytics Find correlations between variables Detect weak signals in noisy data sets Develop better models to identify causality (if it exists) Use with medical device manufacturing data to track performance of individual products Data can be for an individual or a population (23andme.com, e.g.) Indiana University School of Informatics and Computing Computer Science + Informatics + Library Science 11

Research IBM has been spending billions acquiring health-related data and using artificial intelligence (AI) expertise to mine it through IBM Watson Health and partnerships with universities and clinics. Source: https://www.ibm.com/watson/health/ 12

Research Most popular informatic devices are health/biometric trackers, like FitBit Is 10,000 steps per day the right target? How do we know? Other devices can measure blood glucose, heart rate, oximetry many others Based on understanding mechanisms, we can decide what particular quantity to measure for each individual and condition. New devices can be designed for these functions. 13

Research Personalized medicine is the Holy Grail but we need to know exactly what is appropriate for each patient Normal for the population normal for individual What is the control level for a given patient? Need models of physiological/neurological function to identify what to measure University of Toledo cognitive-related biomarker research Duke suicide-related biomarker research 14

Research Scenario provided by IU: Gut biome Is it healthy or not? How do we monitor it? What models do we have of its function? How, when, and why would we modify it? (We do it all the time with antibiotics.) 15

Research Scenario provided by Cook Medical: Stent to protect aneurismal wall Put a sensor on the stent bypass MRI for monitoring What information would we want? What would we do with it when we got it? Additional scenario: implant sensor into blood vessel, monitor 30 days, design 3D-printed custom stent 16

Research Sensors/Devices Current devices have error rates as high as 25% Unacceptable Devices must be dummy proof and ultra reliable Remove people from the equation altogether 17

Summary Future of healthcare is to reduce trips to hospitals and offices for care leading to increased demand for remote reporting. Significant activity developing devices to monitor wide range of variables Future devices may be designed based on understanding of underlying mechanisms and set appropriate targets Biocompatibility of materials remains a challenge Advanced analytics look for signals in structured and unstructured data 18

Summary Significant challenges surround the data: How do you manage this data and analyze it? Who has access to the data? How to integrate with Electronic Health Records? How do we visualize or report the data? What do you do with the data? Is it actionable? The last question raises another challenge: what are the underlying disease mechanisms to guide what data should be collected and how should it be analyzed? 19

Sources Subject Matter Experts consulted / interviewed Rajesh Naik, PhD (Air Force Research Laboratory) David Puleo, PhD (University of Kentucky) David Daleke, PhD (Indiana University) Sean Chambers, PhD (Cook Medical, Inc.) Additional sources noted in footnotes throughout report. 20

Inter-related challenges Life Sciences/Biomedical Three inter-related areas of focus 1. Non-radiation based imaging 2. Informatics technology 3. Cellular and molecular disease mechanisms 21

Inter-related purposes Imaging: Observation Informatics: Measure and monitor Mechanisms: Prevention and healing Overall goal: Personalized or precision medicine 22

Mechanisms support all Imaging: What to observe? Informatics: What to measure? Mechanisms: How does it work? 23