1. Developing Payer-Focused Evidence:
The Role Of Post-Approval Programs
September 13, 2011
Compliments of
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2. Today’s Panel
Nathan White, CPC
Executive Director
Access & Reimbursement
Jeff Trotter
Executive Vice President
Phase IV Development
Lujing Wang, MD, MPH
Practice Area Lead
Pricing & Market Access
2 WE KNOW THE WAY IN HEALTHCARE > INVENTIV HEALTH

3. The Global Payer Market:
Programs To Support Managed
Market Strategies
Nathan White, CPC
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4. European Landscape
• Coverage largely through government
sponsored/managed insurance
• Well-defined health technology assessment
(HTA) process
• HTA/Payer relationship is strong (i.e. UK‟s NHS
& NICE)
• Emphasis on medical innovation: “me too”
products are not favored in HTA process
• HIT is a critical part of coverage and
reimbursement systems
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5. US Landscape
• Complex evidence development and utilization
• Many national payers and PBMs have developed in-house HTA‟s
› Research could be viewed as subjective
› Rely heavily on claims data and chart review
• CMS coordinates to some degree with AHRQ on evidence needs
› AHRQ-sponsored review of evidence for colorectal screenings
› NCD for treatment of actinic keratoses
• “Me-too” products still have market potential
• National HIT standards implementation
still has room for improvement
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6. US Payers Likely To Use PRO’s In Future Decisions
How likely are you to use PROs to make
coverage and reimbursement policy decisions
in the future?
(on a scale of 1 to 7 where
1=Not likely, 7= Very likely)
# of lives = 4,353,435 Mean 4.5
5%
# of lives = 19,701,655
26%
Very Likely
Likely
Not Likely
68% n=22
# of lives = 51,127,435 Source: 2011 inVentiv Health Payer Study
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7. US Payers Likely To Follow CMS Lead
If CMS publicly leverages the results of these
studies, how likely are you to follow CMS’s
lead in utilizing PRO’s to guide your
coverage decisions?
(on a scale of 1 to 7 where
1=Not likely, 7= Very likely)
1%
14%
Very Likely
Likely
Not Likely
86%
Source: 2011 inVentiv Health Payer Study
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8. Evidence Development: Pre- and Post-Approval
• Prospective
› Clinical study data
• May include PRO endpoints and cost-benefit analysis
› FDA approved label
• Retrospective
› Pharmacy claims analysis
› Chart review
› Budget impact modeling
› Cost effectiveness analysis (limited use in US)
› Registry
› Phase IV outcomes study with PRO
› Commercial marketing programs
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9. What Is This Evidence Used For?
• Determining relevant “access barrier” criteria
› Step therapy
› Prior authorization
› Quantity limits
• Deciding which benefit the therapy is placed in (medical v.
pharmacy v. specialty)
• Reimbursing at an appropriate rate
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10. Reimbursement Support Programs
TODAY TOMORROW?
 Focused on helping patients  Managed markets data could
with reimbursement access be used to better guide NAM
barriers and assisting the tactics
underinsured
 Could this program type be
 Used primarily as marketing integrated into a Phase IV study
initiative to reduce sponsor cost?
 Captures some data which  CHALLENGE: How do we get
could be valuable to managed all the stakeholders (vendor,
markets and brand teams brand teams, managed markets,
etc) to share the same vision?
 Typically doesn‟t capture PRO
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11. Patient Assistance Programs
TODAY TOMORROW?
 Focused on assisting the  PAPs could begin to collect
uninsured (PAP) adherence/compliance data
(especially IPAPs)
 Used primarily as corporate
awareness to the public  What confounding factors
would inhibit such an evolution
 Captures some data which (ex. IRS, study population bias,
could be valuable to managed misclassification)?
markets teams
 Would patient advocates
 Typically doesn‟t capture PRO object to muddying the waters of
a free drug program?
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12. Adherence Programs
TODAY TOMORROW?
 Focused on changing patient  Would patients be willing to
behavior and improving patient respond to PRO questionnaires
health outcomes in an opt-out program?
 Opt-out programs typically  How can manufacturers
administered through 3rd party partner with payers and
and use claims data to manufacturers to utilize PRO
intelligently message patients more effectively?
 High touch programs use a
clinical case management
approach
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13. Patient Support Programs:
The “Package” Approach
• Post-approval RCT sought to demonstrate superior effectiveness
of buprenorphine medication-assisted therapy paired with
interventional coaching (in opioid dependent patients)
• CAC and trained registered nurses conducted telephonic
interventions designed to encourage appropriate compliance &
persistency
• The study concluded that patients were more likely to take their
therapy every day and less likely to abuse, compared to controls
What can we learn from this example?
• Better patient support leads to better patient outcomes, reducing
overall payer spend
• Additional messaging to payers on total value of package (product
+ program)
Source: Supplement to Journal of Managed Care Pharmacy, Feb 2010
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14. Role of Commercial Programs In Evidence
Development
• The primary direct link to patients after approval
• Types of programs:
› Reimbursement
› Patient assistance
› Adherence
• Control arms could be added with a non-interventional survey or
interventional care coordination to demonstrate therapy or
therapy/program effectiveness to payers
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15. Observational Studies & Registries:
Strategic & Operational Considerations
Jeff Trotter
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16. Post-approval Research Today – Safety & Value
• Requirement
› In some countries, „real world‟ post-approval experience data must be
submitted to maintain market approval.
› Increasingly, some form of safety surveillance / risk management program
will be mandated and enforced.
• Responsibility
› Corporate accountability for post-approval safety is increasingly expected
by various constituencies.
› Documentation of clinical / economic / humanistic value is critical for
commercial acceptance and accelerated product uptake.
• Opportunity
› If managed proactively, safety surveillance obligation can be controlled.
› An observational study can be a cost-effective, high ROI mechanism for
fulfilling the post-approval obligation for both safety and effectiveness
data.
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17. Real World Perspectives, Real World Research
“The conditions under which products are
examined for regulatory approval are
generally not the conditions under which
they are actually used…”
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18. Who Needs Real World Data?
• Health authorities WellPoint's CER Guide Describes How It Will Determine
Usefulness Of Studies
• Pricing commissions Observational Studies Of "Real-World" Questions
The guidelines state that, "while randomized, controlled clinical trials remain the gold
• Payers standard for producing reliable efficacy and safety data, WellPoint recognizes that there
are circumstances in which RCTs alone may not be sufficient for decision-making.
Accordingly, a well-conducted CER or observational study may complement RCT-
• Regulatory based information by providing effectiveness data, or data on outcomes achieved
in a 'real-world' setting.“
authorities
• Physicians / German Pharma Law Require Firms to Prove Drugs' Value
providers Within a Year /
Germany's Comparative Effectiveness Debate Concludes;
Dossier Refinement Begins
• Policy makers
The holder of the marketing authorization will be required to hand in a comprehensive
• Patients dossier to the G-BA, which needs to contain information on:
• the authorized indications;
• the actual medical benefit of the product;
• the additional medical benefit of the product compared with existing therapies;
• the number of patients and patient groups for which the product is relevant;
• the cost of the therapy to the statutory health insurance funds; and
• requirements for quality-assured use of the product.
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19. Real World Studies & Registries Are Needed
Because…
►…RCTs can be too artificial in intent and design, and
therefore poorly reflective of actual medical practice
► Tight inclusion criteria
► Experimental protocol
► Tight procedural control
► Randomization, blinding, placebo, etc.
► Short in duration
► Homogeneous sites
►We need to know how a product is used and how it
“performs” under real world conditions
► Safety
► Clinical outcomes (CER)
► Economic value
► Humanistic value
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20. But The Real World Can Be Really Messy!
►What are we trying to prove?
►What can we prove?
►Should we be trying to “prove” anything?
►Considering…
►Not typically testing a hypothesis
►Potentially shaky statistical foundation
►Inexperienced research sites
►Liberal inclusion criteria
►Strong likelihood of various biases
►Imperfect ability to identify all confounders
►Hawthorne effect
►Inconsistent understanding of observational research
…is there a “perfect” observational study? Probably not…
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21. Different Conditions Require Different Processes
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22. Key Components
RCT Component Observational Study
Support for approval Strategic Goal Support for “real world” data
Efficacy Measures Safety, effectiveness, value
Randomization, Controls Inclusion/exclusion
inclusion/exclusion criteria,
protocol, monitored
Sample size based on Statistical Power Possibly, based on expected
hypothesis event rate, but often lacking
Investigators, subjects Participants Practitioners, patients
Consent, EC/IRB, privacy Approval Consent, EC/IRB, privacy
(notification)
As short as necessary Timeframe Longer-term (“sustain
and maintain”)
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23. Operational Issues & Challenges
• Site selection • Data management
• Site training and start-up › Accommodating multiple
measures
• Site “interaction”
› EDC issues
(monitoring) and
management › Data quality
• SDV
› Site motivation
› Protocol “adherence” • Analysis
• Inclusion › Biases, etc.
• Procedures › Findings
› Reporting (communications
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24. Observational Studies Are A Different Animal
So, who “owns” it…?
• HEOR
• Epidemiology
• Medical Affairs
• Marketing / Product Management
• Clinical Operations
• Development
• Safety / PV
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25. Highlights From Study On Observational Research
• Motivation: “Schizophrenic” RFPs
› i.e., uncertainty, inconsistency, imprecision, over-engineering, etc.
• Many functional areas have some involvement in observational research
studies
• Many different purposes underlie these studies
• “Observational research” goes by many names
• Sponsors have varying levels of “comfort” with observational research
• Most sponsors do not have defined processes for observational studies
› Design, Procurement, Operational, Analytical, etc.
• Sponsors have varying expectations for the “conclusiveness” of findings from
observational studies
• Sponsors are concerned that regulatory/health authorities “don‟t get it”
• Sponsors plan to become increasingly involved in observational research
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26. Operational Planning:
Building The Study From The Ground Up
PUBLICATIONS ABSTRACTS, PRESENTATIONS
• What are the strategic REPORTS
goals underlying the ANALYSES
study?
SITE
› Direct impact on how the SUPPORT MEETINGS
PATIENT ENROLLMENT,
project/study should be
OUTCOMES TRACKING,
„operationalized‟
DATA COLLECTION
NEWSLETTERS
• Direct impact on budget
and ROI
• Work backwards from MATERIALS PRODUCTION AND DISTRIBUTION SITE RECRUITMENT AND TRAINING
the deliverable LEGAL, REGULATORY, IRB REVIEW
• Don‟t consider any DATA COLLECTION FORMS,
SCIENTIFIC ADVISORY PANEL
SITE IDENTIFICATION (FIELD
PROCESSES, AND LOGISTICS INVOLVEMENT)
individual component in
a vacuum ANALYSIS PLAN COMMUNICATIONS PLAN
STRATEGY
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27. Observational Research & Registries: Best Practices
• Be realistic in study planning
• Set appropriate expectations (internally and externally)
› Observational study as part of overall “portfolio”
• Strive for organizational inclusiveness and consensus
• Develop guidelines addressing study design and SOPs addressing unique
operational requirements
• Interact with stakeholders during planning stages (and concurrently)
• Maintain a collaborative stance with research partners
› Minimize operational constraints
• Expect change: “shift” happens
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28. Payer Utilization Of Value
Evidence
Lujing Wang, MD, MPH
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29. Pros and Cons of Late Stage Evidence Generation
Late-stage evidence generation should aim to demonstrate how a product can provide meaningful
benefits to fulfill a justifiable need, at a reasonable and predictable cost
Evidence Analysis
Very
Evidence
X
Generation
Relevance
Slight Very
Pros Cons
 Real-world data with  Intuitive suspicion of
balanced demographics manufacturer-
Y  Long-term outcomes sponsored studies
Slight
Repositioning in a large population  Lack of credible
 Ability to address adjudication of
Credibility payers‟ concerns methodology
 Ability to define specific  Perceived subjectivity
What to generate: patient (sub)population of patient-reported
study endpoints outcomes measures
 Partnership to boost
credibility of results  Limited actionability of
How to generate: study results
study design
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30. Payer Communication of Value Evidence
Successful communication with payers requires following three principles.
Principles of Payer Communication
I Simplicity II Transparency III Credibility
 A complete story that  Avoidance of “black  Well-accepted
can be told in a box” design and methodology and
definite time window subjective validated design
assumptions
 Concise and crisp  Third-party
takeaways that can  Key foundations for endorsement and
stay in memory audience to interpret KOL partnership
study results
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31. Stakeholder Engagement
The right value evidence needs to be delivered to the right audience at the right time by the right
people. Stakeholder mapping and engagement is pivotal in rolling out the study outputs efficiently
and effectively.
Potential Access
Stakeholder Groups Stakeholder Profiles Engagement Plan
PULL
THROUGH
Pharmacy
Stakeholders
Roles and What messages to
responsibilities communicate
Provider Stakeholders
Evolving interests How to deliver the
and incentives messages
Financial Stakeholders
Interaction and Who to own the
Operational
influence relationship
Stakeholders
Attitudes and When to engage
Key Opinion Leaders
perceptions PUSH the stakeholders
THROUGH
Societies and
Advocacies
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32. Organizational Requirements
The right value evidence needs to be delivered to the right audience at the right time by the right
people. Stakeholder mapping and engagement is pivotal in rolling out the study outputs efficiently
and effectively.
Hypothesis Evidence Value
Validation Generation Communication
Strategic Visionary Rigorous Scientist Credible Ambassador
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33. Panel Discussion
Nathan White, CPC
Jeff Trotter
Lujing Wang, MD, MPH
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34. Panel Contact Information
Nathan White, CPC
Executive Director, Access & Reimbursement
inVentiv Patient Access Solutions
(703) 662-1851
nwhite@inventivhealth.com
Website: www.inventivhealth.com/patientaccess
Jeff Trotter
Executive Vice President, Phase IV Development
PharmaNet / i3
(847) 943-2508
jtrotter@pharmanet.com
Website: www.pharmanet.com
Lujing Wang, MD, MPH
Practice Area Leader, Pricing & Market Access
Campbell Alliance
(973) 967-2300 ext. 2343
lwang@campbellalliance.com
Website: www.campbellalliance.com
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