pharmacoeconomic assessment through market approval and beyond

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


Types of PE Assessment to be Discussedo Cost-minimization analysiso Cost-effectiveness analysiso Cost-utility analysiso Budget impact modeling


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


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


Cost-Effectiveness Plane

∆ Co

sts

∆ Effectiveness

Maximum Acceptable

ICER

Accept

Reject


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


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)


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


Drug Development Cycle


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?


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


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


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


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


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


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


RWPE Builds on Observational Epidemiology

o Registries are cohort studies

Specifically prospective and retrospective cohort studies


Different Results Based on Different Data

Implementing RWPE

Assessment


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


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



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



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)



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


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


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


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


Merging Data from Multiple SourcesCDISC Healthcare Link Initiative


Merging Data from Multiple SourcesFDA EHR Demonstration Project


Merging Data from Multiple SourcesNational Claims Database?


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


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


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?


Too Much of a Good Thing?


In Other Words…o … is RWPE worth the hassle?

o Blommenstein et al. conclude…

o In short, YES, if done properly and efficiently


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

Thank You

Matthew J. Page, PhD, MPPEpidemiologist

[email protected]

Questions?

pharmacoeconomic assessment through market approval and beyond

Health & Medicine