EXCITE International:

A Global Collaboration to Pull Impactful Technologies into Health Systems Through

Expedited Pathway

May 2018

Leslie Levin MD

Chief Executive and Scientific Officer

EXCITE International

• Complicated two step pathway to adoption; regulatory and coverage

• Expectations differ:

• Regulators oversee entry into market. Payers choose from the marketplace as commitment to health of their beneficiaries

• Regulators require proof of claim and safety (Changing)

• Payers require evidence on which to base funding

• Payer evaluation late in the cycle often with less-relevant evidence

• Inefficient pathway a concern:

➢Patent protection difficult: market exclusivity 18 months

➢ Increased risk to investors – low confidence

➢Companies focus on regulation and cheaper studies; hit the brick wall when seeking coverage approval

➢Consultants feed on complexity - ? How effective

• 55-95% first pass rejection of FDA approved technologies

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The Issue

The Solution: The EXCITE Model

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EXCITE: Collaborative Approach to Streamline and De-Risk Pathway from Innovation to Adoption

Innovation Development Evaluation Adoption

• Collaboration of regulators, payers, KOLs, clinical trials experts, and patients (Key Stakeholders) to drive innovation to adoption by de-risking the pathway

• Early and continuous engagement improves adoption

• Addresses concerns of all stakeholders and allows companies direct continuous access to insights and expertise of stakeholders

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Protocol, trial design,outcomes

Execution

Results

RegulatorPayers/Health System

HTA/ Comparative Effectiveness

Adoption

RejectionStatus Quo

EXCITE InternationalPayers/Health System

HTA/ Comparative Effectiveness

/Patients/ Experts

Adoption

Rejection

Regulator

Industry Protocol, trial design,outcomes that meet multi-stakeholder needs & expectations upstream

Execution

• Evidence polices adoption• Limited payer

involvement• Higher first pass rejection • Higher investment risk

• Evidence drives adoption• Pivotal payer and other

stakeholder involvement• Lower first pass rejection

rates• Lower investment risk• Expedited adoption

Industry

Results

Process Overview

• Early communication improves positive coverage decisions

• Attempts to combine evidence development for regulatory and coverage decisions:

➢FDA Parallel Review, FDA Payer Communication Task Force,NEST, Evidence Street BCBS, Green Park Collaborative CMTP (US) Accelerated Access, NICE Scientific Advice, Office of Market Access (UK)

➢EXCITE: Holds interest of key stakeholders across entire pathway in multiple countries expedites global reach and reduces costs

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EXCITE Value-Add to Current Efforts

Lessons Learnt from National EXCITE Model

• Addresses local v international opportunities (1% v 70% of world market)

• Fails to take into consideration regulatory and payer perspectives from countries in which adoption is sought

• Fails to deal with technologies from other countries

• Excludes participation in international expertise and trends in technology evaluation and development

• Compromises investment opportunities, given small market

• 14 technologies since 2012 in pilot EXCITE program (previous 140 post-market EBAs for policy development 2002-2014)

• First Case EXCITE Study• High volume sleep lab tests (2008)

• Payer (Ministry) requested simpler technology (2009)

• BresoTec developed disposable mask; microchip records apnoeicepisodes. Home based, no supervision (2013)

• MaRS EXCITE evaluated 2014-2016: Completed RCT (n>250). Full stakeholder engagement upstream: Positive study

• Implementation by commenced immediately results were available

• Game changer – Open letter from Ontario Ministry of Health

“The Ministry is committed to …...ensure EXCITE technologies that receive a positive recommendation …......are considered for (expedited) adoption and diffusion into the Ontario healthcare system…....” Deputy Minister October 31st 2016

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Case Study from MaRS EXCITE

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EXCITE International (EI)

• World-leading policymakers, payers/ health systems, innovation thinkers have joined forces through EXCITE International: incorporated not for profit March 2016

• Established to address problems with national approach and following encouragement by senior U.S. interests

• Game-changing initiative:

- Jointly select impactful technologies: USA, Canada, UK, Europe

- Common protocol accelerates global adoption

- Built on excellence in each country, respecting uniqueness, needs, and independence, governance

- International excellence selected and shared

- Forum to share perspectives, expertise and ideas

Structure and Functions of EXCITE International

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ECRI (Human factors)Clinical Trials (Kaiser, CROs ? Mayo)Yale Medical School CORE, BaimResearch Institute, HarvardMDICBlue Cross Blue Shield, Kaiser, Aetna, CMS, AnthemFDAIndustry:

AdvaMedMDMA

CMTP

US UK

N

EUROPE

Netherland

Nordic

(France, Spain)

Canada

IDEAL (Surgical quality)Govt. Office of Life SciencesNHSNICE Academic Health Science NetworksIndustry: Association of British Healthcare IndustriesBoard representative

MaRS EXCITE & 4 Academic Methodology Centers with 24 Research HospitalsClinical Trials OntarioGlobal eHealth (Human Factors)Ontario Ministry of Health Industry (MEDEC) OHTACHealth Canada

NorwayNorway Health TechGovernmentInnovation NorwayBoard representativeNetherlandsRadBoud UMC

EU Clinical trials networkEarly HTA and decision analysisPatient engagement

GovernmentFrance and SpainMedpass (Early development)

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EI Coalition

Secretariat

CEO and CSO Les Levin

Secretary Treasurer Dan Wright

International

Scientific

Collaboration

Chair Bryan Luce

Executive Board:Rick Kuntz (Chair) Sir Bruce

Keough Anne KolbeSean Tunis. Ilse Treurnicht

Carl Gilhuus-Moe Richard Ivey Les Levin

NL Rep

Advisory BoardChair Anne Kolbe

Hubs:US, UK, Canada,

Norway Netherlands

• Clinical trials • Contextualization• Links to industry,

regulators, payers, KOLs, academia, patients

Payers’ Advisory

CommitteeChair Naomi

Aronson

Patient Included Initiative

Lead Lucien Engelen

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EI: Governance

IndustryAdvisoryCommitteeIn developmentChair Rick Kuntz

• Anne Kolbe Chair New Zealand• William Charnetski Health Ministry

Ontario, Canada• MDIC US• Brian O’Rourke CADTH Canada• Carey Agnew Health Canada• Chris Henshall Consultatnt, UK• Jo Carol Hiatt Kaiser Permanente US• Joe Gatewood VP AdvaMed US• Louis Jacques Consultant: Past

Medical Director, CMS US• Mark Leahey CEO Medical Devices

Manufacturers Assoc US• Murray Sheldon FDA US• Naomi Aronson, Chair

Payers’Advisory Committee & ED Clinical Evaluation, Innovation and Policy BCBS US

• Neil Fraser CEO Medtronic, Canada• Office of Life Sciences UK• Peter Ellingworth CEO Assoc British

Healthcare Industries UK• Rafi Hoffstein CEO MaRS Innovation

Canada• Shirlee Sharkey Health System

Canada• Trent Haywood Chief Medical

Officer, BCBS Association US• Yves Verbovan MedTech Europe

Belgium• Shaihira Bhimani, Director MaRS

EXCITE Canada;• Netherlands TBA• Pall Jonsson NICE UK• Bryan Luce, Chair SC; President

Evidera USA• Kathrine Mhyre CEO Norway

HealthTech Norway

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EI Advisory Council

• Membership:• Chair Naomi Aronson (BCBS Association)• Kaiser Permanente• AETNA• ANTHEM (ex-senior executive)• CMS (Observer status)• ? United (TBD)• Canada: Ministry of Health, Ontario• NHS UK• NICE UK• Ministry of Health Netherlands (TBD)• Ministry of Health Norway (TBD)

EI Payers / Health System Advisory Committee

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Payers’ Advisory Committee (PAC) Objectives

• Advises EI Board on selection for review

• Early advice to industry on relevance to Payers at proof-of-concept (Early Technology Review)

• Input into protocol development to meet payer expectations

• Share high level decision principles

• Drive innovation pipeline

• NB: PAC is advisory. Cannot recommend funding

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15PROPRIETARY & CONFIDENTIAL 15

• Bryan Luce - Chair; Immediate past CSO, PCORI USA• Peter McCulloch, Professor of Surgery; Fellow Trinity College Oxford

University and John Radcliffe Hospital, Oxford. Head of IDEAL, UK• Naomi Aronson - Executive Director of Clinical Evaluation, Innovation, and

Policy, Blue Cross and Blue Shield Association USA• Rod Taylor - Professor of Health Services Research, University of Exeter, UK• Peter Juni - Director Applied Health Research Centre (AHRC) Li Ka-Shing

Institute St. Michael’s Hospital; Professor of Medicine Univ Toronto Canada• Amit Oza – Director, Clinical Trials and Head Medical Oncology PMH, CEO

Ozmosis, Professor of Medicine, Uiv Toronto Canada• Joseph Ross - Center for Outcomes Research and Evaluation, Assoc Professor

of Medicine, Yale School of Medicine USA• Mike Argentieri, ECRI – Usabiity/Human Factors USA• Danica Marinac-Dabic – Director Division of Epidemiology (FDA) USA• Elise Berliner – Director, Technology Assessment Program (AHRQ) USA• Maroeska Rovers, Evidence Synthesis RadBoud/MedValue, Netherlands • Joe Caffazio, UHN – Director Global e-Health (Usability) Canada• Fiona Miller – Qualitative/ Patient preference Univ Toronto Canada• Gheorghe Doros - Professor Biostatistics, Boston University USA• Rachel Fleurence MDIC (NEST Program) USA• PCORnet TBA USA

EI Scientific Collaboration (SC)

SC Membership Expertise

• Discipline/technical expertise• Epidemiology, • Biostatistics

• Bayesian statistics• Economics• Health Policy• Operations research• Qualitative research• Data analytics• Meta-analysis• Clinical trial design

• Adaptive designs• Pragmatic designs

• Trial management• Quality assurance• Economic modeling• Patient engagement• Patient preference research• Barriers to uptake research• Human Factors

• Clinical Expertise/Experience as required

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Scientific Collaboration Objectives

Flexible trial platform approach that……..

• Must:• Meet regulatory requirements • Provide evidence that the technology is value-add compared

to funded alternatives

• Flexible platform to seamlessly transition:• From explanatory to pragmatic design• From pre- to post-market conditions• Use of patient outcomes data

• Adaptable for:• Technical modifications• Additional indications• Different populations• Different settings, cultures, practice patterns, comparators

• Efficiency and affordability paramount

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Patients Included Initiative

• Increasing emphasis

• EI Patients Included Initiative. Charter under development, with initial focus in NL and then scale up

• Protocol development:• Define primary/secondary outcomes • Ethical considerations • Recruitment strategies• Balance risks and benefits

• Drive innovation pipeline based on patient needs

• No interest in window-dressing or to be “politically correct”

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Offerings: EXCITE International

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Company

SC with GMRCPACUsability Patients IncludedRegulator perspectiveEarly HTA; RadboudEnd-User safety/QAPatient outcomes data Qualitative research

Clinical TrialGMRC & EXCITE networks :RadboudNOCRI (U.K.)Baim Institute (U.S.)MaRS EXCITENordic Proof

informed by SC and PAC

ncluding economic analysis

Synchronous adoption through EXCITE Hubs

EI Algorithm

VCAcceleratorMultinational

Proof of Concept

Radboud

EI: EARLY Technology Review

• Agreed-to Framework

• Key stakeholder advice:• Ecosystem e.g comparators, target population, deployment • Benchmarking and downstream effects on costs and events• Potential barriers/facilitators to adoption• QA, safety, usability • High level advice on POC and clinical trial

• Part of evidence continuum

• Company engagement with Regulators to establish requirements

• Company involved throughout the 16 week process

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“The FDA will advance the use of real-world experience to better inform patient care and provide more efficient, robust and potentially lower-cost ways to develop clinical data that can inform product review and promote innovation.

“The FDA will establish a new capability, including the development of data and analytical tools, to conduct near-real-time evidence evaluation down to the level of individual electronic health records for at least 10 million individuals in a broad range of U.S. healthcare settings.”

Scott Gottlieb FDA Commissioner February 2018

Protocol Development: Example Keeping Ahead of the Curve

Protocol Development: Real World Data:

Partners: Discussion Phase

• PCRF/PCORI - Washington

• CORE – Yale

• MDIC/NEST/FDA – Washington

• PAC

• Methodological Opportunities

• Propensity score matching

• Bayesian

• Adaptive design:• Change in indications, prototype, target population• Continuous data

Data capture: • Proof of concept to pivotal• Explanatory to pragmatic• Pre to post market

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Industry & Innovators

✓ Early selection

✓ Expectations addressed early

✓ Lead time for adoption

✓ Decreased costs

✓ Value-based outcomes

✓ Influence innovation pipeline

✓ Share in broader Payer conversation on technology

✓ De-risk & prioritize investment

✓ Opportunity to dialogue with others involved in pathway from innovation to adoption

✓ Early advice from stakeholders along pathway to adoption de-risks innovation and investment

✓ Single platform

✓ Improves coverage decision

✓ Expedited global adoption

✓ Value-based outcomes

Payers & Health Systems

VC

Patients: Faster access to technologies with proven outcomes

✓ Grow innovation economy: with global reach

Economy

EXCITE International Value Propositions

www.exciteinternational.comFor additional information Email:

LesLevin@Exciteinternational.com