Pharmacoeconomic assessment of a drug, medical device, or other healthcare product can take on many forms and occur at multiple points in the development cycle. Cost-effectiveness analysis, a major component of pharmacoeconomic assessment, has traditionally occurred in the later phases of product development—either as a piggy-back to a phase III or pivotal clinical trial, or peri-authorization.

1. Welcome

2. Agenda for Today’s Webinar
2 Physician Led | Therapeutically Focused
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o Overview of pharmacoeconomic (PE) assessment
o Data collection for PE assessment
o PE assessment at different phases
o Implementing data collection at different phases
o Collection of real world PE data
o Future considerations
o Q&A

3. Overview of
PE Assessment

4. Why PE Assessment?
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o Need for product differentiation in competitive
market
o Challenging reimbursement requirements
o Blend scientific and marketing objectives to help
sponsors tell value story of their products
o Maximize potential return on investment
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5. Main Types of PE Assessment
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o Cost-minimization analysis
o Cost-effectiveness analysis
o Cost-utility analysis
o Cost-benefit analysis
o Budget impact modeling
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6. Cost-Minimization Analysis (CMA)
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o Compare costs of two or more drugs or therapies
to determine least costly option
o Baseline costs will always include acquisition
costs for drugs or therapies under consideration
as well as costs of preparation and administration
o Additional costs considered depend on
perspective of analysis
o Main benefit: cheaper and easier than cost-
effectiveness analysis
o Main drawback: assumption that two drugs or
therapies are used at equivalently effective doses
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7. Cost-Effectiveness Analysis (CEA)
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o More comprehensive than CMA in that it
considers both costs and effectiveness of two or
more drugs or therapies
o Costs measured in monetary units of interest (Eg,
$, £, €)
o Effectiveness generally measured using one or
more clinical outcome
 Examples:
• Years of life saved
• Hospitalizations averted
• Complications prevented
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8. Incremental Cost-Effectiveness Ratio (ICER)
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o ICER is main outcome of CEA
o ICER calculated as: (∆ Costs / ∆ Effectiveness)
 Examples:
• Incremental cost per life year saved
• Incremental cost per hospitalization averted
• Incremental cost per complication prevented
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9. Willingness to Pay Threshold
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o ICER is then compared against one or more
willingness-to-pay thresholds to determine if drug
therapy of interest is cost-effective, cost-saving, or
cost-neutral
o Can be plotted on cost-effectiveness plane
o Multiple comparisons can be conducted using
cost-effectiveness acceptability curve (CEAC)
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10. Cost-Effectiveness Plane
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∆Costs
∆ Effectiveness
Maximum
Acceptable
ICER
Accept
Reject
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11. Cost-Effectiveness Acceptability Curve
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ProbabilityCost-Effective
Threshold Cost-Effectiveness Ratio
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12. Cost-Utility Analysis (CUA)
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o CEA that accounts for quality of time gained or
lost
o Quality of life (QOL) measured using utility
 Generally ranges from 0 (dead) to 1 (perfect QOL)
 For some conditions (Eg, advanced ALS), negative
utility has been considered
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13. Quality-Adjusted Life Years (QALY)
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o Most common ICER assessed in CUA is cost per
QALY gained
 QOL increase of 0.5 to 0.75 for 4 years = 1 QALY
gained
o Depending on condition or therapy, other
timeframes can be used (Eg, month or day)
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14. Cost-Benefit Analysis (CBA)
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o Differs from CEA in that effectiveness is also
monetized
 Eg, year of life saved could be equated to year of
productive value to society, measured as per capita
GDP or average annual income
o Cost-benefit ratio calculated as:
(∆ Costs / ∆ Monetized Value of Effectiveness)
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15. Budget Impact Modeling (BIM)
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o CMA, CEA, CUA, and CBA often targeted toward
broader audiences
o BIM generally designed for specific audiences,
particularly third party payers
o Measures net cumulative treatment cost with drug
or therapy of interest for specified number of
patients in particular population
o Impact of particular drug or therapy is assessed
as effect on cost per member per month (PMPM)
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16. Perspective of PE Assessment
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o Who will pay for drug or therapy and who will
benefit?
o Potential perspectives include:
 Healthcare provider
 Third party payer
 Patient/Caregiver
 Society
o Different perspectives warrant different
considerations
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17. Time in Context of PE Assessment
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o Timeframe of disease (acute vs. chronic) and
therapy will determine time horizon for PE
assessment
o When in development cycle should PE
assessment be initiated and how long should it
continue?
 Contemporaneous with later Phase III is common
but can consider earlier Phase III or Phase II
 Collection of real world PE data?
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18. Data Collection for
PE Assessment

19. o Clinical Data
 Prospective
 Retrospective
o Claims Data
 Standalone
 Link with clinical data:
Carefully Consider
• Consent
• HIPAA
• Blinding
Data Sources – Clinical and Claims
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=
Payer
Trial
Payer Trial
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20. Cost Data
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o Primary
 CMS 1450 (UB04 Uniform Bill)
 CMS 1500 (Claim Form)
o Secondary
 CPT (AMA’s Current Procedural
Terminology), other codes
mapped to costs from payers
 RED BOOK
 Published Reports
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21. Collecting and Integrating Data from
Multiple Sources
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o Augment eCRF
 Additional form matching UB04/CMS 1500
 Instruct site on finding UB04/CMS 1500 in other file
 Ask site to complete UB04/CMS 1500 from scratch
o Code collected data in-house using CPT, or other
cost source
o Map MedDRA codes utilized as standard part of
clinical trial to CPT, or other cost source
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22. PE Assessment at
Different Phases

23. Drug Development Cycle
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24. Different Phases to Consider
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o Phase II
o Earlier phase III
o Phase III piggyback studies
o Peri-authorization
o Post-authorization / Real World
o Comparing and contrasting approaches for
smaller/mid-size relative to larger sponsors
 Developing a plan that encompasses all relevant
phases
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25. Implementing Data
Collection at
Different Phases

26. Best Practices for Changing the eCRF
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o Include all stakeholders in the decision
 Site feedback
 Statistical considerations
 Impact on regulatory submissions
o Plan and communicate cutover
o Design database to be flexible
 Dropdowns, normalized structure
o Off-line development and validation
o Cutover on weekend
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27. Collecting Real
World PE Data

28. Why Real World PE Data?
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o Differentiation in costly yet lucrative landscape
 $2.6 billion to bring new drug to market (Tufts CCSD)
 Global sales (2014) for top 25 pharmaceutical
companies were $548 billion (GlobalData)
o More robust data than literature-based models
o More relevant than earlier phase clinical data
o Timing a potential issue
 Prospective longer to conduct than ideal
 Retrospective later to collect than ideal
o True cost-effectiveness rather than cost-efficacy
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29. Are Payers the True Decision Makers?
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o Roles of FDA and payers, including Medicare and
Medicaid, are constantly evolving
o Drug approval becoming “easier” (Forbes)
 2008: 50% of new molecular entities (NMEs)
approved by FDA
 2014: 88% of NMEs approved
o US District Court ruling re: Amarin’s Vascepa®
o Increased emphasis on generation and
dissemination of evidence aimed at payers
 Real World Evidence/Outcomes liaisons at larger
sponsors
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30. Real World vs. Earlier PE Assessment:
Functional Considerations
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Study Activity Real World Earlier Phase
Study feasibility and
document collection
More likely remote More likely in-person
Site qualification and
initiation
More likely remote More likely in-person
Routine monitoring visits • Less frequent
• Data-driven
• More frequent
• Involves assessment
of protocol adherence
Source data verification More targeted Broader
Data review More centralized More dispersed
Cost data sources Targeted claims
databases
Various sources
Effectiveness data sources Targeted EHR Various sources

31. Target Data for Hybrid EHR Sourcing
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Problem data for
EHR systems
Stop dates
Scaled data
Surveys/PROs
Costs
Better data for
EHR systems
Coded for payments
Already transactional
(lab systems,
pharmacy)
Most problematic
data for sites
High volume
Complex
Query-prone
Research vs.
Healthcare
Labs
Meds
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32. Recruitment and Retention Considerations
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o Well-integrated EDC, EHR, and ePRO will
enhance retention of sites and patients
o Recruitment population for real world studies
differs from population for RCTs
o Real world studies tend to be longer, which has a
direct impact on site motivation and patient
retention
o Gauging and developing site experience and
motivation are essential in optimizing enrollment
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33. Site Training Considerations
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o Establishing study expectations from the outset is
essential
o Sites and Investigators:
 How are patient records structured?
• How find UB04, cost data?
 Capacity for integration with EDC?
 Research-naïve?
• Real world and/or PE research experience?
• Clinical trial experience?
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34. Regulatory and Safety Considerations
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o Regulatory requirements for non-interventional
studies are evolving and dependent on locality or
localities in which study conducted
o Emphasis on scientific credibility and data protection
o Good Pharmacoepidemiology Practice (GPP)
proposes minimum practices and procedures to
ensure data quality, integrity, and adequate
documentation
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35. Future
Considerations

36. Future Considerations
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o PE assessment in earlier and later phases,
including real world, are important supplements to
clinical trials
o Development cycle does not end with approval
o 51% of sponsors think in-house and outsourced
heath economics and outcomes research (HEOR)
studies will increase significantly or moderately by
2018 (Industry Standard Research, 2014)
o Flexibility is essential
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37. Thank You
Lee Walke
Vice President e-Clinical
h.walke@Medpace.com
Matthew J. Page, Ph.D., M.P.P.
Epidemiologist
m.page@Medpace.com

38. Q&A