Disruptive Innovation in Health CareAdoption of Personalized Medicine and Beyond

Mara G. AspinallPresident and CEOVivirHealth

Diagnosis Save LivesDiagnosis Save Money

Monitoring Ensures Both

The Fundamentals

ValueFear Adoption

FundamentalsThree Stage Process of Adoption

Successful When it Leads to Innovation and Improves

Standard of Care.

Fails When We Settle for “Trial and Error” Medicine AS the Standard of Care.

Old Paradigm: Trial and Error Medicine

Personalized / Precision Medicine

Personalized / Precision Medicine

New Paradigm: Personalized MedicineLinking Tests to Action and Therapy

Observation Test Action PredictableResponse

Breaking The Cycle of Trial and Error Medicine

Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Mariotto A, Feuer EJ, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2002, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2002/, based on Nov 2004 SEER data submission, posted to the SEER web site 2005.

Precision Medicine Saves Lives

80 Years Ago

Leukemia or Lymphoma60 Years Ago

Chronic LeukemiaAcute LeukemiaPreleukemia

Indolent LymphomaAggressive Lymphoma

100 Years Ago

“Disease of the Blood”

Today

∼38 Leukemia types identified:Acute myeloid leukemia (∼12 types)Acute lymphoblastic leukemia (2 types)Acute promyelocytic leukemia (2 types)Acute monocytic leukemia (2 types)Acute erythroid leukemia (2 types)Acute megakaryoblastic leukemiaAcute myelomonocytic leukemia (2 types)Chronic myeloid leukemiaChronic myeloproliferative disorders (5 types)Myelodysplastic syndromes (6 types)Mixed myeloproliferative/myelodysplastic syndromes (3 types)

∼51 Lymphomas identified:Mature B-cell lymphomas (∼14 types)Mature T-cell lymphomas (15 types)Plasma cell neoplasm (3 types)Immature (precursor) lymphomas (2 types)Hodgkin’s lymphoma (5 types)Immunodeficiency associated lymphomas (∼5 types)Other hematolymphoid neoplasms (∼7 types)

5 YearSurvival

~ 0%

70%

Precision Medicine Saves MoneyHer2 Testing For Breast Cancer

$24,000savings

HER2 Test Delivers Healthcare Savings that are ~65x its Cost

* As measured by FISH and reimbursed by CMS, Los Angeles, 2007 ratesSource: Elkin et al. HER-2 Testing and Trastuzumab Therapy for Metastatic Breast Cancer: A Cost-Effectivensss Analysis. J Clin Oncol (2004) 22: 854-863; Genzyme analysis

$79,181

$54,738

Without HER2 Test With HER2 Test

Cost of Herceptin Therapy Per Patient

Fee

Price of HER2 testing per patient*

CPT Code Description

88368 Morphometric analysis, in situ hybridization (probe #1)

$183

88368 Morphometric analysis, in situ hybridization (probe #2)

$183

Total $366

Personalized MedicineFriend or Foe?

Personalized Medicine Needs to be a FriendPathologists Need to :

- Own Personalized Medicine - Source of expertise on all tests available- Interpreter and consolidator of all test results- Educator of all other physicians on diagnosis

Move Industry from Fear to Acceptance

Pathology Call to Action Need to Capture the Future

Present Future

Morphology Tests Molecular Tests

Stable Base of Technology Many New Emerging Technologies

Single Gene Tests Multi Gene / Multi Technology Tests

Tissue Samples Multiple Sample Types

Timeframe Controlled by Pathologist Point of Care Diagnostics Growth

Pathologist Initiates & Interprets Diagnosis

Molecular Lab Provides Diagnosis directly to Treating Physician

ASCO 2009 Theme - Personalizing Cancer Care

Vivir 11

Most Important “New” Approach:DNA Damage Repair

Most Promising New Technology: Circulating Tumor Cells

ASCO 2002Theme - Making a World of Difference

Vivir 12

Aspinall Personalized Medicine Presentation

“You have to be kidding”“We are oncologists – we personalize everything we do by definition”“Not Realistic”“We do not need diagnostics to tell us how to practice”

Classic Customer Adoption

# of New Customers

Time

EARLYADOPTER

EARLYMAJORITY

LAGGARDSLATE MAJORITY

Aware of New InventionsJournals, CME, Colleagues, Web

Skeptical Claim ≠ Reality

Never black or white – Typically ConservativeSubtleties matter

Protective of timeAlready >100%

PracticalWhat will I do differently?How does it impact me and my patients?

How do Physicians think about Innovation Adoption?

Clinical Practice Achievement

Clinical Procedure

Landmark Trial NHQR 2005 Years

Flu Vaccine 1968 63 % 37

Diabetic Eye Exam 1981 70 % 24

Mammography 1982 70 % 23

Cholesterol Screening 1984 67 % 21

Pneumococcal Vaccine 1997 54 % 8

Balas EA, Boren SA., Managing Clinical Knowledge for healthCare Improvement, Yearbook of Medical Informatins 2008

Slow Adoption - Not new problem

Eating Oranges Hand Washing

Doherty, S. History of evidence-based medicine. Oranges, chloride of lime and leeches: Barriers to teaching old dogs new tricks. Emergency Medicine Australasia (2005) 17, 314–321

1591 Lancaster documents value of Lime Juice

1747James Lind ‘RCT’of Oranges & Limes

1754 Lind publishes ‘Treatise of the Scurvy’

1794 British Admiralty adopts as standard

203

Yea

rs

1846 Ignatz Semmelweiss: puerperal fever is spread by OB’s

1848 Hand washing reduces mortality 76%

1891 Pasteur’s germ theory leads to adoption of standard

1861 Results published but rejected

45 Y

ears

Why MD’s ignore clinical innovations

• Their own clinical experience• Over reliance on a surrogate outcome• Natural history of the illness vs. study• Love of a wrong patho-physiological model• Ritual and mystique• A need to do something• No one asks the question• Patients’ expectation (real or assumed)

Doust J, Del Mar C. Why do doctors use treatments that do not work? BMJ 2004; 328: 474–5.

Key Opinion Leaders Present

JournalArticles

CompleteProduct

Developmentand

Launch

Standard of Care

Adopted

Stages to Full Adoption - Past

KeyOpinionLeadersPresent

TrialDesignDebate

TechnologyIntroduction

Pro/ConJournalArticles

Stages to full adoption - Today

PayorsWeigh In

SystemEconomics

Analysis

AHRQTechnologyAssessment

CompleteProduct

Developmentand Launch

PhysicianAssociationGuidelines

Phase 4Trials

PatientGroups

Weigh In

StandardOf CareAdopted

KeyOpinionLeadersPresent

TrialDesignDebate

TechnologyIntroduction

Pro/ConJournalArticles

Stages to full adoption - FuturePathology Impact

PayorsWeigh In

SystemEconomics

Analysis

AHRQTechnologyAssessment

CompleteProduct

Developmentand Launch

PhysicianAssociationGuidelines

Phase 4Trials

PatientGroups

Weigh In

StandardOf CareAdopted

PositiveEffect

BenefitNeutral(RR=1)

NEJM

J Clin Onc

Ca ResUltimate Estimate of RR

(or Predictive Value)

Adoption of a New BioMarker

Adapted from D. Hayes, in Prin. Molec. Oncol., Humana Press, 2000

J ImmunoHisto

NY Times“Next Nobel Prize”

Buffalo Evening News“Needs repeating”

Ann. Int. Med editorial“Doesn’t work & we knew

it wouldn’t 5 years ago”

J. Lab. Med. Editorial“Important in a small %

of patients”

NEJM“15 years after discovery,

Big Pharma announcesa breakthrough. While testinghas been available for 10 yearsit took until now to design and

obtain approval for a treatment.”

Personalized Medicine Diagnostic Adoption Years to $100 million in Revenue

22

Years Post Launch

Rev

enue

in M

illio

ns

0

20

40

60

80

100

120

0 1 2 3 4 5 6 7 8 9

Myriad

Genomic Helath

Best Practices to achieve Adoption• Acute/Serious (easier than chronic)• Clear description of desired change• High quality evidence• Simple decision-making • Simple to do • No new skills needed • Low cost• Fair compensation for MD time• Low collaboration required• No organizational change required• Compatible with existing values

Adapted from Grol R, Grimshaw J. From best evidence to best practice: effective implementation of change in patients’ care. Lancet 2003; 362 : 1225–30.

Personalized Medicine is a challenge• Acute/Serious (easier than chronic)• Clear description of desired change• High quality evidence• Simple decision-making • Simple to do • No new skills needed • Low cost but who gains? • Fair compensation for MD time• Little collaboration required• No organizational change required• Compatible with existing values

Where is the adoption of Personalized Medicine on the spectrum?

• Acute/Serious• High quality evidence• Low cost• Compatible with existing values

• Simple decision-making? • Simple to do? • New skills needed?• Collaboration?• Organizational change?• Clear description of change?• Compensation for MD time?

Physician EducationPathologists Lead

Data & Integration into the EMRPathologists Lead

Policy – Reimbursement and Regulatory

Pathologists Lead

Moving From Fear To Acceptance

Aspinall and Hamermesh, Harvard Business Review, Oct 2007

Moving from Fear to Acceptance Physician Education Imperatives

Increased Medical Education on Diagnosis15% of medical school have no genetics education

Enhanced Use of CME and Boarding Exams to Focus on DiagnosisAggressive Issuance of Guidelines for use of Personalized Medicine and New Diagnostics Publish, Publish, Publish

Moving from fear to acceptanceEducate Physicians

Laurie Demmer MD, et al., University Of Massachusetts Medical School, Department of Pediatrics and Office of Ethics

Practicing PhysicianViews on Genetic Testing

“I feel comfortable with my 18 %knowledge of available genetic tests”

“I have a standard for deciding 28 %when patients need to be informed

about the option of genetic testing”

Percent of Physicians Receiving Training inGenetic Testing During Medical School

8577

71

38

0

20

40

60

80

100

1990-1999 1980-1989 1970-1979 1940-1969Year of Graduation

Physician EducationPathologists Lead

Data & Integration into the EMRPathologists Lead

Policy – Reimbursement and Regulatory

Pathologists Lead

Moving From Fear To Acceptance

Aspinall and Hamermesh, Harvard Business Review, Oct 2007

Moving from Fear to AcceptanceRegulatory Policy Imperatives

Need Dedicated Federal expertise in diagnosticsRecognition of diagnostics’ unique needs

Action#1 Create a new FDA Center for Advanced Diagnostics Evaluation and Review (CADER)#2 Establish diagnostics-specific regulatory standards

Include appropriate use of “retrospective” – case controlled studies of archived samples

Mara G. AspinallCopyright 2008

Moving from Fear to AcceptanceReimbursement Policy Imperatives

Need Reimbursement based on Value not Activity Transparency and Clarity

Action#1 Create new reimbursement system that rewards Value #2 Create new market pricing system where diagnostic innovators choose and justify their price#3 Create new coding system with unique national identifying codes

Mara G. AspinallCopyright 2008

Physician EducationPathologists Lead

Data & Integration into the EMRPathologists Lead

Policy – Reimbursement and RegulatoryPathologists Lead

Change the Game

Moving From Fear To Acceptance

Aspinall and Hamermesh, Harvard Business Review, Oct 2007

Change Clinical Orientation fromSilos to Disease Pathway Teams

SpecialtySilos

Integrated Disease Team

• Pathologists not embracing personalized medicine tests

• Diagnosis ends pathologist involvement

• Communication one way• Treating MDs looking for more

explanation• Labs marketing Treating MDs

• Patient centered process • Pathologists create Team with

Treating MDs• Pathologists know and analyze all

new tests – and publicly comment• Diagnosis is supplemented with

active Monitoring • Decision making across team

Health Care TodayOrgan-Based Treatment Paradigm

Colon Cancer

Breast Cancer

Leukemia

Lung Cancer

Brain Cancer

Pancreatic Cancer

Health Care in the Future –Mechanism-Based Treatment Paradigm

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