Innovation: A Vital Ingredient for the

Advancement of Medicine, Society Medical Devices and mHealth

mHEALTH Israel 2014

Marvin J. Slepian, M.D.Professor of Medicine and Biomedical Engineering

McGuire Scholar, Eller College of Management

Director, Arizona Center for Accelerated Biomedical Innovation

Director, Interventional Cardiology

Sarver Heart Center

University of Arizona

Tucson, Arizona

If we look back over time we see that Medicine has continued to evolve at a progressively accelerating pace

Anatomy

Physiology

Pathology

Pharmacy/

Pharmacognosy

ECG

Endoscopy

Antibiotics

Chemistries

Imaging

Biomarkers

Mechanistic/Designer Biomolecules

Telemetry

Robotics

> 100 > 50

University of Chicago 2012Norman Rockwell 1945

Fildes

“The Doctor”

1891

Lisinopril

To advance, Medicine has relied on Innovation

Innovation is all around us

Innovation is an opportunity

Operative Hypotheses

To remain as an effective leading force in the US, world-wide and

society in general, Medicine has to actively adopt Innovation in its

teaching and culture, rather than letting it occur passively.

Innovation Thinking and Science is a valuable skill set.

Innovation is needed to overcome the many stresses that exist

on Medicine today - increased prevention, better Dxics and Txics

cost-effectiveness, increased access to care

Medicine is a tremendous arena, laboratory or workshop in which

to be Innovative, i.e. alternative career = biomedical innovator.

Medical Innovations, new diagnostic, Pharma or devices

remains an important economic engine for the US and Israel.

Arizona Center for AcceleratedBioMedical Innovation (ACABI)

Center specifically dedicated to:

1. Addressing unmet needs – broadly in the BioMedicalScience arena

2. Maximizing the therapeutic and commercial value of University discoveries and technology, often unrealized

ACABI as a center is “creativity engine” - a mechanism,

to facilitate the rapid transformation of novel scientific

discoveries and new technologies into therapeutic

solutions (products), that may be rapidly brought forth

as clinical therapeutic realities.

NY Times June 3, 2013

Now

$>6 TT

WSJ 1/8/14

Infant Mortality

United States 78.2 83.1 42nd!

World Population Growth

Every second4 babies born, 2 people die = growth by 2

200,000 people/d75MM people/yr1.2% annual growth rateWorld population doubles every 60 yrs

9 BB World population in 2050

Improvement Dx/Tx < Population Growth

VBWG

*

Center for Medicare & Medicaid Services (CMS)

Focused on Readmissions (any admission to the same

hospital occurring within 30d of discharge)

Marker of poor quality care, wasted revenue and

inefficient use of resources

17.6% of all admissions = readmission < 30d (MedPAC report 2007)

$15BB additional spending due to readmissions

Pneumonia 18%

AMI 20%

Heart Failure 24% 2010 Readmission Rates CMS

Reimbursement withholding - Readmissions FFY 2013

Hospital acquired conditions 2015

Joint replacement, stenting, CABG

Unmet Needs/ Emerging Trends

Enhanced/Efficient Dx, Improved Therapeutics

Precision Health/ Personalized health

Reduction of cost, Doing more with less

Outcomes Research & Comparative Effectiveness

Address of Health Care Disparities

Well Care vs. Sick Care

Digitized Self/ Quantified self

Shift of Focus of Care Site

and Responsibility

Patient Clinic

HospitalPatient

ClinicHospita

l

Present Model Future Model

*

Innovation

Latin

In and novare

To make something new

To change

Idea - Innovation Continuum

Idea

Innovation

Invention

Translation

Implementation

Innovation: Drivers

Innate curiosity

Reinterpretation

Interpretation

CreativitySpontaneousInduced

UnmetNeeds

Financialopportunity

Corporatedirectives

GovernmentAgency directives

Competition

Entrepreneurship

Crises

Challenges

Fear

Innovation: Foci

Anywhere in the value chain (driven innovation)

InventionTechnologyPrototypingTestingManufacturingScaling

Regulatory approvalSalesMarketingDistributionQuality controlCustomer relationsBusiness ModelDelivery of care

Premise: Innovation Can be Taught

Mind trainingPrepared mindOpen mind

Key is to dissect the steps to:Idea generationInvention

Execution

Innovation

Innovation Methodology: Generic

Describe – need, problem, item – verbal, written

Analyze – what it does, how it works, each step, action, effect

What is good, what is bad, what is missing

“Go somewhere”

Take each step – improve, change, evolve, add, subtract

Cutting Edge Science/TechnologyBuilding Blocks for Innovation

“Omics” – Genomics, Proteomics, Metabolomics

Biomaterials

Drug Delivery

Robotics

Microelectronics

Nanotechnology

Telemetrics, Remote monitoring

Microfluidics

Connectivity/Web innovation

The Innovation Space

TraditionalAcademic

Focus, Focus, Focus

Innovationspace

Flight of ideas

Two competing world viewsDynamic tension between both

Schoenmakers and Duyster Research Policy 39:1051, 2010

Reviewed 300,000 patents

157 selected as Radical

Results:

1. Radical inventions are largely based on existing

knowledge vs. new knowledge

2.Radical inventions are induced by the

recombination over more knowledge domains.

3. The combination of knowledge from domains

that might usually not be connected seems to

deliver more radical inventions.

Edges, Limits, Interfaces and Boundaries

Innovation often (best) occurs at the edges or

limits of a domain or space

edge = limit to overcome, as challenge,

as a place to go beyond

Innovation often (best) occurs at the interface

between 2 or more often disparate fields

Creative interaction and mixing of ideas from

normally separate (siloed, i.e. boundaries

traditionally defined) domains

Technologies

Stretchable Electronics

High performance electronics that are ultra-thin,

stretchable, and conformal

36

Core Building Block 1: Stretchable Electrode Arrays

(Islands and interconnects

fabricated together and

transferred to PDMS)

Nature Materials March 7, 2011

24-Dec-14 38

Balloon Angioplasty/EP Smart Catheters

µLEDs

(On-off switching of each

cell)

Wavelengths: 600-900 nm

(near UV)

LEDs on balloon catheter enable:

• Highly localized delivery of photoactivated pharmaceuticals

Electronics Across Substrates

Integration on wide variety of substrates & shapes

Paper Leather

FabricVinyl

Skin

Stretchable Electronics – Smart Skins

UltrathinBreathableConformalStretchableMulti-sensor

ECG, HR, Pressure, Flow, Material Properties – tissue stiffnessHydration status, edemaMotion – multiple degrees of freedomAnalytes

Monitoring Patch Requirements

• Comfortable

• Ultra Compact, Discreet

• Multi-Sensor Capability

• Disposable (decreases clinic visits)

• Wirelessly Transmit Data in Real Time

Physiological Parameters

• ECG

• Temperature

• Hydration

• Heart Rate

• Respiration Rate

• Activity

Monitoring Patch

MC10 Inc.

Electronics that match

Elastic modulus

Bending stiffness of skin

Binding based on

van der Waals adhesion

“Mechanically” invisible

Incorporates:

ECG, Pressure

Temp

Strain

Transistors, LED,

Photodetectors

Rf Inductors

Capacitors

Oscillators

Solar cells

Wireless coils

Kim et al Science 333:838, 2011

Sensor arrays on sheets

Conformal to epicardium

Measure:

Electrical activity

Temperature

Mechanical strain

Pressure

Physical contact

Kim et al PNAS 109:19910, 2012

Visualization of High Density Mapping

Cardiovascular Implants

Other than EP devices – largely passive

or Active without feedback

In-Stent Restenosis

Stent Thrombosis

Smart Stents: “Do More” TechnologyExamples

Stent “Auto Diagnostic” InformationPressure, FlowLumen narrowing/intimal thickeningMass build-up

New Stent Function - DxLong term Event Monitoring (ECG/Arrhythmia)Analyte - electrolyte, cholesterol, drug/toxin level,

inflammatory/protein markers, infection

New Stent Function - TxSelf cleaning or Biodegradation on demandDrug delivery - pulsatile, temporal sequence

Implant

Sensor

Memory

Actuator

SynCardiaTM

Total Artificial Heart System’

Implantable

Full Cardiac Replacement

Full Normalization of Hemodynamics

CE Approved - Europe

FDA approved - USA

Transient/Biodegradable Electronics

Electronics = Magnesium, Thin Iron, Ultra-thin Silicon

Substrate = Biodegradable polymers – Natural, Synthetic

Hwang et al Science 337:1640, 2012

Transient Bioelectronic Contruct

Hwang et al Science 337:1640, 2012

Polymeric Endoluminal

Paving and Sealing

Smart Paving Layers

Multiple Bioelectronic Functions:

SensingActuationTelemeteringData storageTherapeuticsDegradation

PiezoElectric ConformalBiomaterial Energy Harvesting

Dagdeverin…Slepian, Rogers PNAS 2014 doi 10.1073/pnas.1317233111

PiezoElectric Biomaterial Energy Harvesting: Cardiac Motion

Dagdeverin…Slepian, Rogers PNAS 2014 doi 10.1073/pnas.1317233111

DATA KNOWLEDGE

Insight

Big Data + Innovation

Big

Data

Volume

Velocity Variety

Veracity

Value

The 5th V

Big Data: Innovation Opportunities

1. Creating the Model/Hypothesis Generation

- Domain expertise

2. Computer Science Advances –

Enhanced Data Capture

Data Transformation

Computational “Hooks and Interlinks”

3. Predictive Analytics

4. The Service

Big Data in Healthcare: Opportunities

Pattern Recognition

Trends

Model building and Hypothesis Generation

Mechanisms of Disease

Precipitants of Clinical Events

Understanding Disease Progression

Medical errors

Disease recurrence

Readmission

Mortality

Normalize

Store

BioMedical Data-Mining Application Architecture Framework

Text

Distributed

programming

An Illustrative Example: Lyticas Data Platform (Apurba Technologies)

RichXML

RichXML

LytAP

Content Processing and Normalization

Control

FilesDB

LytAP API

File BasedAPI

Programmatic API(SOAP web Service)

WebAgents

RDBMSBased API

Categorizer

Semantic Tagging

Language ID

Headline Generation

Classifier

Extraction Modules

Language Classifier

Templates

Categorization Manager

LytAPDeveloper/Modeler

Languages Configuration

Key ConceptsConfiguration

LytAP Studio

RichXML

External Feed

Configuration & Monitoring

Console

Cloud Manager

Inference Modules Generate Inference

Global Mapping Modules LytAP Knowledge Base

Domain Experts

NLP Stack

Structured DataDB

Unstructured Data XML DB

Open Source Proprietary

XML

ControlAPI (Application

Programming Interface)

Integrated Electronic Biomaterial Systems

Skin patch

Catheter

Sheet/Array

PPM

ICD

Smart Stent

VAD/TAH

Big Data

Summary

Despite dramatic advances in Dx/Tx Medicine remains under increasing pressure – multiple stresses

Innovation as a science & methodology is a key adaptive mechanism yielding new solutions for emerging challenges

Despite varying economic climates medical device approaches have been a steady means of rapidly developing translational Txics which address unmet needs

The combination of new advances in biomaterials, polymerchemistry, microelectronics, robotics, fluid mechanics, Rx delivery will yield many novel, cost-effective Dxics/Txicin the years to come.

Novel innovations may help not only the patient, but medicine, the economy and society as a whole

Slepian Lab

Funding

NIH Quantum U01 RFA-EB-09-003 Optimizing

Cardiovascular Device Thrombogenicity for

Eliminating Anticoagulants

NIH R21 1R21HL111990-01A1

American Heart Association

Bio 5 Pilot Grant - University of Arizona