pharmacoeconomic assessment through market approval and beyond: theory and operations

Welcome

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Agenda for Today’s Webinar

Physician Led | Therapeutically FocusedCopyright© 2015

o Overview of pharmacoeconomic (PE) assessmento Data collection for PE assessment o PE assessment at different phaseso Implementing data collection at different phaseso Collection of real world PE datao Future considerationso Q&A

Overview of PE Assessment

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Why PE Assessment?o Need for product differentiation in competitive

marketo Challenging reimbursement requirementso Blend scientific and marketing objectives to help

sponsors tell value story of their productso Maximize potential return on investment


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Main Types of PE Assessmento Cost-minimization analysiso Cost-effectiveness analysiso Cost-utility analysiso Cost-benefit analysiso Budget impact modeling


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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Cost-Effectiveness Analysis (CEA)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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Incremental Cost-Effectiveness Ratio (ICER)o ICER is main outcome of CEAo 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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Willingness to Pay Thresholdo 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 planeo Multiple comparisons can be conducted using

cost-effectiveness acceptability curve (CEAC)


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Cost-Effectiveness Plane

∆ Co

sts

∆ Effectiveness

Maximum Acceptable

ICER

Accept

Reject


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Cost-Effectiveness Acceptability CurvePr

obab

ility

Cost

-Eff

ectiv

e

Threshold Cost-Effectiveness RatioPhysician Led | Therapeutically Focused

Copyright© 2015

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Cost-Utility Analysis (CUA)o CEA that accounts for quality of time gained or

losto 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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Quality-Adjusted Life Years (QALY)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

gainedo Depending on condition or therapy, other

timeframes can be used (Eg, month or day)


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Cost-Benefit Analysis (CBA)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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Budget Impact Modeling (BIM)o CMA, CEA, CUA, and CBA often targeted toward

broader audienceso BIM generally designed for specific audiences,

particularly third party payerso 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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Perspective of PE Assessmento 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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Time in Context of PE Assessmento 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?


Data Collection for PE Assessment

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o Clinical Data Prospective Retrospective

o Claims Data Standalone Link with clinical data: Carefully Consider

• Consent• HIPAA• Blinding

Data Sources – Clinical and Claims

=

PayerTrial

Payer Trial


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Cost Datao 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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Collecting and Integrating Data from Multiple Sourceso 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


PE Assessment at Different Phases

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Drug Development Cycle


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Different Phases to Considero Phase IIo Earlier phase IIIo Phase III piggyback studieso Peri-authorizationo 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


Implementing Data Collection at

Different Phases

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Best Practices for Changing the eCRFo 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 structureo Off-line development and validationo Cutover on weekend


Collecting Real World PE Data

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Why Real World PE Data?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 modelso More relevant than earlier phase clinical datao 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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Are Payers the True Decision Makers?

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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Real World vs. Earlier PE Assessment: Functional Considerations

Physician Led | Therapeutically Focused Copyright© 2015

Study Activity Real World Earlier PhaseStudy 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 adherenceSource data verification More targeted Broader

Data review More centralized More dispersedCost data sources Targeted claims

databasesVarious sources

Effectiveness data sources Targeted EHR Various sources

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Target Data for Hybrid EHR Sourcing

Problem data for EHR systems

Stop datesScaled data

Surveys/PROsCosts

Better data for EHR systemsCoded for paymentsAlready transactional (lab systems, pharmacy)

Most problematic data for sitesHigh volumeComplexQuery-prone

Research vs.Healthcare

LabsMeds


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Recruitment and Retention Considerationso Well-integrated EDC, EHR, and ePRO will

enhance retention of sites and patientso Recruitment population for real world studies

differs from population for RCTso 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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Site Training Considerationso Establishing study expectations from the outset is

essentialo 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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Regulatory and Safety Considerations

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 protectiono Good Pharmacoepidemiology Practice (GPP)

proposes minimum practices and procedures to ensure data quality, integrity, and adequate documentation


Future Considerations

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Future Considerationso PE assessment in earlier and later phases,

including real world, are important supplements to clinical trials

o Development cycle does not end with approvalo 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


Thank You

Lee WalkeVice President e-Clinical

[email protected]

Matthew J. Page, Ph.D., M.P.P.Epidemiologist

[email protected]