How to Make Postmarket Surveillance More Cost Effective

June 16, 2016

Introduction

Post Market Surveillance Status in the Industry

Value Based Healthcare and Real World Evidence

Rising Costs and Opportunities for Cost Effectiveness

Case Studies

Agenda

Vicki Anastasi

Vice President and Global Head Medical Device and Diagnostics Research

ICON Medical Device and Diagnostics Research Group

4,300 + Europe, Middle East, Africa

2,000 + Asia Pacific

4,900 + The Americas

ICON: A market leader positioned for continued growth

Operating from 90 offices in 37 countries with 11,900 employees

PHD or Higher - 9%

Master Degree - 24%

Bachelor Degree - 39%

Diploma/Certificate - 13%

Other - 15%

Seren Phillips HTA training slides

ICON Expertise Over the Medical Device Lifecycle

Medical Device Clearance / Approval Process

Concept & Design

( 12 mo)

Pre-Clinical Development ( 24-36 mo)

Clinical Trials Proof of

Concept / Pivotal Trial

(Timing varies)

FDA Review (510K3-5 mo) (PMA 12 -24

mo)

Reimbursement Assignment ( 0-24 mo)

Post Market Activities

Regulatory strategy Pre-submission meeting Quality System support

Pre-clinical test plans Human factors testing

Study conduct & report preparation

IDE Submission 510K / PMA Submission

FDA discussion / negotiations

Post Market studies Registry studies

Product enhancements / new submissions Technology

Rise of Post Market Surveillance Global Impact

6

50% increase in the number of PMS studies conducted by top 5 medical device manufacturers between 2009 and 2015 (ClinicalTrials.gov analysis)

Worldwide requirements from regulators, payers To intensify under EU MDR/IVDR

Major changes proposed by the Commission Impact on non-grandfathered CE-approved products already on the market Effect of changes on diagnostics and companion diagnostics Changes in clinical evidence requirements Impact on the industry of increased requirements, as the number of Notified Bodies

is reduced

Costs are not the only challenge! Viability of product in the value-based healthcare environment will become paramount.

Value-Based Healthcare is Driving Increase in Post-Market Data

Global market launch needs to be aligned with future requirements

Requires a different framework to define value and commercial success

Bundled payment model: CMS Comprehensive Care for Joint Replacement

Model program delivers on CMS pledge to shift 50% of Medicare payments to ACOs and bundles by 2018

Expect the next area, based on volume and variance in per-procedure costs, to be cardiovascular

How does your product fit in to these programs? What is next?

7

Global Rationale of Value Driven Data Collection

What are the effects? (e.g., providers have targeted manufacturers for price concessions first, before reforming care protocols or delivery)

Lessons from UK [e.g., payments differ between indications, thus requiring careful choice of patient population (e.g., co-morbidities) as hospitals become smarter about codes]

Start earlier to accelerate true time-to-market: Arrival at regulatory clearance with limited evidence of real-world cost effectiveness and a suboptimal prioritization of payer targets will delay market access, restrain early revenue potential, and concede control of a products value story.

8

Broadening Opportunities for Real World Evidence

The "top programmatic priority" for the US Food and Drug Administration

(FDA), under Commissioner Robert Califf, is to leverage real world evidence

from the healthcare system to inform FDA decision making

Prospectively designed registries and cohort studies in the context of clinical practice are highly valuable, and randomized trials conducted in the context of clinical practice, often called a pragmatic clinical trial may be the most important source of knowledge in the future Robert Califf, FDA Commissioner

Food and Drug Law Institute's Annual Conference, May, 2016

First, both data sources and research methods must be optimized

9

http://www.raps.org/Regulatory-Focus/News/2016/03/10/24517/Real-World-Evidence-Can-it-Support-New-Indications-Label-Expansions/

Seren Phillips HTA training slides

Real World Evidence Solutions

As healthcare accelerates towards a patient-centric, value based approach, a new set of questions are emerging from key stakeholders : How will patients respond to your product when it enters the real world? How does its value proposition hold up within the competitive set and current

standards of care? Which subset of patients are likely to see the greatest benefit?

Reasons for optimism Digitization of healthcare continues to increase New technologies improving data capture, connectivity and access Numerous RWE data sources available

Seren Phillips HTA training slides

Robust RWE Strategy Drives Commercial Success

Preliminary Objectives Situational Assessment

Disease and subtype dynamics Treatment Landscape

Current standard of care, treatment algorithms Clinical and in market targets with indications current and anticipated profiles for

safety and efficacy Review of clinical research programs

Determine Opportunities and Potential Challenges How can these be better identified, quantified exploited and mitigated through RWE What is of primary importance and what can be addressed by secondary RWE data

Seren Phillips HTA training slides

Real World Evidence Solutions

Herein lies the challenge with Real World Evidence

Industry has a plethora, perhaps too many, real world evidence options to consider

How should companies go about navigating what should be generated de novo primary RWE (i.e. Registries) versus sourced, secondary RWE (available data)

Determining a sound RWE strategy requires a multifaceted approach

You need expertise in both realms as well as clinical, medical, operational, data and outcomes expertise, to define your RWE strategy

Real World Evidence Case Study

Maestro Rechargeable Systems approved based on Patient Preference Information

Real World Intelligence (RWE): drive R&D with insights from RWE that is

provided earlier in the process and across the usual clinicalmedical affairs

commercial divide (facilitates deeper payer and patient-centric insights into

optimal target indications, opportunities to improve care management, product

feature profiles that align to potentially non-obvious patient populations, viable

protocol designs, endpoint sensitivity, or recruitment strategies)

13

Key market Strategy Registry Plan: Design, Execution, and Communication

REPORTS

LEGAL, REGULATORY, IRB REVIEW

MATERIALS PRODUCTION AND DISTRIBUTION SITE RECRUITMENT AND TRAINING

PATIENT ENROLLMENT, OUTCOMES TRACKING,

DATA COLLECTION

SITE SUPPORT

ANALYSES

NEWSLETTERS

PUBLICATIONS ABSTRACTS, PRESENTATIONS

MEETINGS

STRATEGY

ANALYSIS PLAN COMMUNICATIONS PLAN

DATA COLLECTION FORMS, PROCESSES, AND LOGISTICS SCIENTIFIC ADVISORY PANEL

SITE IDENTIFICATION (FIELD INVOLVEMENT)

Sheet1

SITE SUPPORTPUBLICATIONSABSTRACTS, PRESENTATIONSREPORTS

ANALYSES

PATIENT ENROLLMENT, OUTCOMES TRACKING, DATA COLLECTIONMEETINGS

NEWSLETTERS

MATERIALS PRODUCTION AND DISTRIBUTIONSITE RECRUITMENT AND TRAINING

LEGAL, REGULATORY, IRB REVIEW

DATA COLLECTION FORMS, PROCESSES, AND LOGISTICSSCIENTIFIC ADVISORY PANELSITE IDENTIFICATION (FIELD INVOLVEMENT)

ANALYSIS PLANCOMMUNICATIONS PLAN

STRATEGY

Sheet2

Sheet3

Methodological Considerations: Patient Selection, Size & Scope

Target Population

Assessable Population

Intended Population

The population to which the study

findings are meant to apply

Subset of the target population available

for the study

Subset of the population sampled

according to the registry design

Patients who actually participate in the

registry

Identification of the target population All patients

Actual Population

Defining Registry Size & Scope: Design Considerations

Duration of the registry o Time needed to assess outcomes o Plan for evolution?

How many patients per site? o Size of overall patient population o Enrollment timeframe expectations o Level of engagement o Not too many to bias analysis, but enough to be interesting to sites o 5-10 is generally the rule

16

Patient registry success primarily hinges on a well-reasoned design and good data collection practices

Success Factors for Patient Registries Broad entry criteria Make sure entry criteria is not limited to specific treatments to facilitate comparisons

Ideal ration of incident vs. prevalent cases

It is key to strike the right balance between methodological purity (only newly diagnosed) vs. practicality (more eligible patients, if you allow previously diagnosed)

Targeted data collection

While you may have the ability to collect large amounts of data, sometimes it is a good idea to collect only what you know you plan to analyze

However, often very interesting questions can be addressed when collecting extra information (the drawback is that you risk losing sites and/or patients)

It is important to get both clinical data and patient-reported data, because neither can substitute for the other

Data collection automation Get objective medical information (e.g. labs, utilization information, Rx refill information, etc.) in an automated way, because it will greatly enhance your registry at a relatively low cost

Address known biases Address all known biases at the design stage, including Patient selection within sites and systematic

differences between sites (academic/community), because these may subsequently affect interpretation of the results

Data control Control access to the data by having a single team of analysts this guards against misinterpretation of the data and poor-quality analyses

Costs are Accelerating Best Practices for Management

Post-Market surveillance budgets rival clearance/approval budgets

Build an evidence generation roadmap

Consider all stakeholders needs are considered

Leverage Payer and Market Access available data

17

Opportunities to Increase Cost Effectiveness

Operational differences for post-market data collection

Site selection

Use of networks and EMR

Enrollment

Site management

Continual training

Monitoring

18

Opportunities to Increase Cost Effectiveness Technology

Site training Risk based monitoring Ease the burden of patient participation

Truly informed consent/eConsent Better informed participants

Reduce visits with mobile, cloud and wearables Types of sensors Data gathering Apps Patients vs healthy individuals what is available

Outsourcing is it a solution for your program?

19

Evidence Generation Roadmap: The role of real world data in the product lifecycle

20

LIFECYCLE

POST MARKET

NO PHASE RESEARCH

CONCEPT

PRECLINICAL & PHASE I

PRE-CLINICAL & FEASIBILITY

PHASE II

FIRST IN MAN

PHASE III

PILOT

REGISTRATION

PIVOTAL

Strategy Development

Strategy Development

Clinical Outcomes Assessment

Peri-Approval & Observational Research / Medical Device & Diagnostic Research

Health Economics & Epidemiology

PRODUCT LIFECYCLE

Patient / Physician surveys

Observational studies

Preference Studies (DCE / WTP)

Select or develop PROs / ClinROs / ObsROs, including linguistic validation

PRO measurement strategy - Efficacy endpoints and labelling

Regulatory interactions / submissions - Dossier development

PRO dissemination strategy

Regulated and non regulated clinical studies

Phase IIIB/IV Prospective Trials

Directed Use Programs

Registries (pharma /device/ commercial strategy)

Interventional / Non-Interventional Research

PASS, PAES

Comparative Effectiveness Research

Burden of Illness

Resource Use Studies

Epidemiology Characterisation of Disease & Treatment Patterns

Dynamic Transition Modelling

Economic Modelling

Meta-Analysis, NMA

PERI-POST APPROVAL

POST-APPROVAL

PHARMA:

DEVICE:

Case Study: Seamless Transition from PMA to Post-Market Study

Case Study: Rapid Post-Market Study Start-up

Accelerating Time to Market and Eliminating $5 Million in Development Costs through Adaptive Design

Your New Prescription for

Commercial Success

Peri-Approval & Observational Research

Global Pricing & Market Access

Healthcare Communications

Medical Device and Diagnostics Research

Clinical Outcomes Assessment

Market Research

Creative Digital Language Services

Content Call Center

ICON Commercialisation & Outcomes

Health Economics & Epidemiology

Real World Evidence

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How to Make Postmarket Surveillance More Cost EffectiveOMTEC-2016_Anastasi_Postmarket-SurveillanceHow to Make Postmarket Surveillance More Cost EffectiveAgendaICON Medical Device and Diagnostics Research GroupICON: A market leader positioned for continued growthICON Expertise Over the Medical Device LifecycleMedical Device Clearance / Approval ProcessRise of Post Market Surveillance Global ImpactValue-Based Healthcare is Driving Increase in Post-Market DataGlobal Rationale of Value Driven Data CollectionBroadening Opportunities for Real World EvidenceReal World Evidence SolutionsRobust RWE Strategy Drives Commercial SuccessReal World Evidence SolutionsReal World Evidence Case StudyKey market Strategy Registry Plan: Design, Execution, and CommunicationMethodological Considerations: Patient Selection, Size & ScopePatient registry success primarily hinges on a well-reasoned design and good data collection practices Costs are Accelerating Best Practices for Management Opportunities to Increase Cost EffectivenessOpportunities to Increase Cost Effectiveness TechnologyEvidence Generation Roadmap: The role of real world data in the product lifecycleCase Study: Seamless Transition from PMA to Post-Market StudyCase Study: Rapid Post-Market Study Start-upAccelerating Time to Market and Eliminating $5 Million in Development Costs through Adaptive DesignSlide Number 25

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