pharmacoeconomic assessment through market approval and beyond
TRANSCRIPT
Pharmacoeconomic Assessment through
Market Approval and Beyond:
Theory and Operations
Presented by:Matthew J. Page, PhD, MPP
Epidemiologist
2 Physician Led | Therapeutically Focused
Agenda for Today’s Presentationo Eat Luncho Try to Stay Awake!!!o Overview of Pharmacoeconomic (PE) Assessmento Planning PE Assessmento Real World PE (RWPE) Assessmento Implementing RWPE Assessmento Working with Datao Closing Considerationso Questions
Overview of PE Assessment
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Types of PE Assessment to be Discussedo Cost-minimization analysiso Cost-effectiveness analysiso Cost-utility analysiso Budget impact modeling
5 Physician Led | Therapeutically Focused
Cost-Minimization Analysis (CMA)o Compare costs of two or more drugs or therapies
to determine least costly option Baseline costs include acquisition costs as well as
costs of preparation and administration Additional costs 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
6 Physician Led | Therapeutically Focused
Cost-Effectiveness Analysis (CEA)o Considers both costs and effectiveness of two or
more drugs or therapies Costs measured in monetary unit of interest (Eg, $) Effectiveness generally measured using one or more
clinical outcome (Eg, years of life saved)o Main outcome is incremental cost-effectiveness
ratio (ICER): (∆ Costs / ∆ Effectiveness) Eg, incremental cost per life year saved
o ICER compared against willingness-to-pay (WTP) thresholds to determine if cost-effective, cost-saving, or cost-neutral
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Cost-Effectiveness Plane
∆ Co
sts
∆ Effectiveness
Maximum Acceptable
ICER
Accept
Reject
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Cost-Utility Analysis (CUA)o CEA accounting for quality of time gained or losto Quality of life (QOL) measured using utility
Generally ranges from 0 (dead) to 1 (perfect QOL)o Most common ICER assessed in CUA is cost per
quality-adjusted life year (QALY) gained
9 Physician Led | Therapeutically Focused
Budget Impact Modeling (BIM)o 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)
10 Physician Led | Therapeutically Focused
Perspective of PE Assessmento Who pays for treatment and who benefits?o Potential perspectives include:
Healthcare provider Third party payer Society
o Different perspectives mean different considerations
Planning PE Assessment
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Drug Development Cycle
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PE Assessment at Different Phaseso Phase IIo Earlier phase IIIo Phase III piggyback studieso Peri-authorizationo Post-authorization
o Contemporaneous with later Phase III is common but can consider earlier Phase III or Phase II
o Collection of RWPE data?
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Planning PE Assessmento Plan must consider:
Disease area• Acute vs. chronic vs. oncology?• Recurrence timeframe?
All relevant phases Sponsor budget
• CEA for publication vs. BIM for use with payers?
RWPEAssessment
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Why RWPE?o Differentiation in costly yet lucrative landscape
$2.6 billion to bring new drug to market (Tufts CCSD)o Development cycle does not end with approval
Real world research, including RWPE, can drive new earlier phase research, in turn driving new real world research
Sustain value across product lifecycleo Collect extensive effectiveness and safety data
More relevant than literature-based models More robust than earlier phase clinical data
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 Correcting Signals for Innovation in Healthcare Medicaid expansion under Affordable Care Act
o Drug approval becoming “easier” (Forbes)? 2008: 50% of 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
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o Three recommendations:1. Replace tax exclusion for employer-provided health
insurance with tax credit2. Strengthen Medicare coverage determination
process3. Experiment with reference pricing for certain
therapies in Medicareo RWPE can inform last two recommendations
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Epidemiologic Study Designs (by Traditional Strength of Evidence)
1. Randomized controlled trial2. Community trial3. Prospective cohort study4. Retrospective cohort study5. Case-control study6. Cross-sectional study7. Ecologic study8. Case report or case series
Observational
Interventional
Descriptive
Analytic
Strength of evidence: ability to establish causal link
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Real World/Observational Epidemiologyo Data gathered in naturalistic (real world) settingo Variables of interest include:
Exposure• Harmful (Eg, behavior) or protective (Eg, drug, vaccine)
Outcome• Disease or health state• Time to event
Potential confounderso If treatment involved, prescribed in usual manner
Therapy assignment not decided in advance by protocol No diagnostic or monitoring procedures other than those
ordinarily applied
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RWPE Builds on Observational Epidemiology
o Registries are cohort studies
Specifically prospective and retrospective cohort studies
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Different Results Based on Different Data
Implementing RWPE
Assessment
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RWPE Means Dynamic Data Collection and Analysiso Specifically, continually updated data streams
allow for refinement of CEA and BIMs to reflect most up-to-date data, providing consistently refreshed ICER and PMPM cost estimates
o How is this implemented? Dedicated processes
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Dedicated Processes for RWPE
o Protocol must describe study challenges and methods for resolution, while addressing (Giezen et al. 2009, Kiri 2012): Ecological validity Achievable study objectives Tailored operational processes
Study Design and Protocol
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Dedicated Processes for RWPE
o Ensure straightforward navigation for electronic case report forms (eCRFs)
o Provide guidance for online querieso Design database to be flexible and easy to useo Include all stakeholders in design as well as any
changes Sites Analysts Submissions team (if relevant)
eCRF Design and Development
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Dedicated Processes for RWPE
o Obtain permissions and licenses o Validate per FDA guidanceo Address HIPAA and security concernso Plan for incorporating PRO data into PE
assessment Ie, primary EQ-5D scores are preferred source of
utility data for NICE
Patient Reported Outcomes (PROs)
28 Physician Led | Therapeutically Focused
Dedicated Processes for RWPE
o Incorporate alerts into analysis dataset programso Use templates designed for repeated deliveryo Design output programs with locked, validated
modules as well as modules that are intended to evolve and change
o Structure eCRF rules to promote easy updates o Normalize dataset design and use of metadata to
support multiple data cuts
Programming and Data Governance
Working with Data
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Merging Data from Multiple Sources
o RWPE involves coordination with healthcare providers and payers to collect regularly refreshed, relevant data such as electronic health records (EHR), PROs, and costs/reimbursements
o Timing and costs of implementation are concerns o Therefore, data collection must be as efficient as
possible Efficiency derives from well-designed and well-
integrated electronic data capture (EDC) system
The Crux of the Matter for RWPE
31 Physician Led | Therapeutically Focused
Cost/Reimbursement Data Sourceso Patient records at doctor’s office
CMS 1450 (UB04 Uniform Bill) o Claims databases
Medicare and privateo Coding
CPT, other codes o RED BOOKo Published literatureo Government reports
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o Real world effectiveness study Prospective cohort Retrospective cohort
o Claims data Standalone Link with study data
Data Sources: Effectiveness and Claims
=
PayerStudy
Payer Study
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Merging Data from Multiple SourcesCDISC Healthcare Link Initiative
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Merging Data from Multiple SourcesFDA EHR Demonstration Project
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Merging Data from Multiple SourcesNational Claims Database?
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Merging Data from Multiple Sources
o Standardize any coding as well as definitions of events and outcomes (Abbing et al. 2010, Blake et al. 2012, Andrews et al. 2012)
o Foster harmonization across multiple sources by using common data model (Coloma et al. 2011) Standardized input files can be created from each
database, linked via patient ID, and managed locallyo Develop storage system making individual databases
accessible from common platform as anonymized data at appropriate level Based on common data model in compliance with
guidelines relevant for each database (Trifirò et al. 2014) Process should involve stakeholders for each database
Some Thoughts
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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
ClosingConsiderations
39 Physician Led | Therapeutically Focused
Recruitment and Retentiono Well-integrated EDC, EHR, and ePRO will
enhance retention of sites and patientso Recruitment populations for RWPE studies differ
from populations for interventional trialso RWPE studies tend to be longer
Direct impact on site motivation o Gauging and developing site experience and
motivation are essential in optimizing enrollment Establishing study expectations from outset Capacity for integration with EDC? Training?
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Too Much of a Good Thing?
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In Other Words…o … is RWPE worth the hassle?
o Blommenstein et al. conclude…
o In short, YES, if done properly and efficiently
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Future Considerationso Product development cycle does not end with
approvalo PE assessment in earlier and later phases,
including RWPE, is essential to demonstrating product value
o Real world research, including RWPE, can drive innovation
o RWPE demonstrates market leadershipo Flexibility is essential
Questions?