Download Strategic Considerations - American Statistical Association

Value to Outcomes (V2O) in Oncology Drug
Development
Dr. John J. Doyle
June 17, 2016
™
© Copyright 2014 Quintiles
Pharmaceutical companies are making remarkable
investments in cancer research
Number of pipeline products in R&D
Source: Lloyd. Citeline Pharma R&D annual review 2015 - PharmaProject Jan 2015
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For example, the PD-1/PD-L1 pipeline is intensely
competitive across major oncology markets
Phase I-III trials for PD-1 and PD-L1
Keytruda
(43 trials)
Opdivo
(42 trials)
Atezolizumab
(28 trials)
Launch 2017
MEDI-4736
(23 trials)
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There are 143 oncology trials spanning 23 markets and 39 trials are phase III
5 trials
1 trial
3
Source: BioMedTracker September 2015, Quintiles Analysis
These efforts are improving the prognosis for patients
5 Year Relative Survival, US 1990-2010
Source: SEER Survival Statistics, Period Analysis for 2010 – IMS Global Oncology Trend Report 2015
4
… but this innovation comes at a price that places a
strain on health care budgets
$ Billion
Worldwide Prescription Drug & OTC Sales, by therapeutic area
1200
Oncology
1,029
Anti-diabetics
1000
153.1
CAGR
+ 11.6%
Anti-rheumatics
Anti-virals
781
Vaccines
79.2
Bronchodilators
800
Sensory Organs
Anti-hypertensives
600
MS therapies
Immunosuppressants
400
Anti-coagulants
Dermatologicals
Anti-hyperlipidaemics
200
Anti-fibrinolytics
Anti-bacterials
Other
0
2014
2020E
5
Especially in the US, cancer drug prices have been
rising steadily
Monthly and median costs of cancer drugs at the time of FDA approval, 1965-2015
Source: Peter B Bach, MD Memorial Sloan-Kettering Cancer Center – Available from:
https://www.mskcc.org/research-areas/programs-centers/health-policy-outcomes/cost-drugs
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There is a bright spotlight on value
7
Prices have been criticized not only by payers, but also
by oncologists
8
How do we solve for value in cancer care?
9
The Value Cascade
How do we define and measure unmet
need?
• No unmet need implies no
value unless the aim is to
drive cost reduction
What is the consequence of
addressing the unmet need?
• Improved health outcomes,
reduced mortality, reduced cost
How good is this intervention
at addressing the unmet
need ?
• Clinically meaningful improvement of
outcomes in a defined patient
population vs an appropriate
comparator
How good is our
evidence of this?
• Does uncertainty detract from the value
How do we
value the
improved
outcomes?
• Does the value of this improved performance match
the increased cost? (product price less cost offsets)
• Different health systems take different approaches
to value
$
• How does the value translate into price?
10
Value-based assessment frameworks have emerged as
a means to appraise oncology products to control costs
US based Frameworks
ASCO framework to
assess the value of cancer
treatment options
NCCN Evidence Blocks
Combines a long-term
perspective on value
through CE analyses with
short-term affordability
considerations
Value-based pricing
calculations based on 6
modifiable components using
web-based tool DrugAbacus
EU based Frameworks
The European Society for Medical
Oncology Magnitude of Clinical
Benefit Scale ESMO-MCBS
NHS Cancer Drug Fund
(UK)
NVMO PASKWIL Criteria
(Netherlands)
11
Historical Evolution of Drug Evaluation in the US
1970
1980
1990
1972
1985
Congress
establishes Office of
Technology
Assessment (OTA)
1968
ECRI Institute
established
OTA Health
Policy staff
focuses on need
for HTA
1989
RAND call for health
1990
quality measures and
clinical effectiveness
guidelines
AHRQ (Agency
for Healthcare
Research and
Quality)
established
1982
Begins HTA; WHO Collaboration
Center
1985
Government
Select Evidence Based Practice Center (EPC)
Select Private
2000
Blue Cross Blue Shield
Association establishes
Technology Evaluation
Center (BCBSA TEC)
1992
1995
Congress
budget decision
closes OTA
1997
Tech. DEcIDE AHRQ EvidenceAssessbased Practice
ment
Centers (EPCs)
group
established
1997
1993
2005
John M. Eisenberg
Center established
2003
HTAIS HTA database Named AHRQ EPC Designated
CMS advisor
1997
1993
Kaiser
Permanente
collaboration
1993
1994
ICSI
Hayes
Inc.
Source: US Federation Scientists OTA Archive; Agency websites; Company
websites; NPC report “Current Evidence Based Medicine Landscape
Named AHRQ EPC
1997
Oregon EPC
formed
VA TAP
2003
Network of 14 states
form DERP
2003
2004
United
InHealth
Biosource
Consumer Reports
Best Buy Drugs
12
12
Other countries struggle to determine how to value drugs
•
•
•
•
UK undertook a process to
redefine drug price methodology
for PPRS
• VBP (Pricing)
• Renamed VBA (Assessment)
Initiative failed last year due to
debate over how to measure value
Issues over differential value for
different people
Arbitrary “multiplier” for Burden of
Illness and Wider Social Impacts
not justifiable according to critics
13
Value framework implicaitons for drug manufacturers
Clinical Trial Design
Payer Access
Pricing Strategy
Provider Usage
• Certain outcomes
(e.g., OS) are
valued more
highly than others
(e.g., Response
Rate)
• Major payers (e.g.,
Aetna) have
acknowledged the
potential utility of
value-based
frameworks for
coverage decisions
• Preliminary and
interim clinical
data will indicate
outputs from
value-based
frameworks
• Oncologists have
expressed
discomfort with
discussing the
cost or value of
treatments with
patients
• NCCN and
DrugAbacus have
metrics for data
quality and
consistency
(multiple trials are
preferred over one
larger trial)
• Power shifts to
Pharmacy Benefits
Managers and
Accountable Care
Organizations have
placed a premium
on specialty drug
value
• Increased
scrutiny on drug
prices may lead
to the use of
value-based
frameworks as
guideposts for
drug costs
• Providers will rely
on manufacturers
to contextualize
value outputs in
a way that is
useful for patients
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The healthcare system is moving from volume to value
…. to outcomes.
15
The Healthcare System is migrating from volume to
value … to outcomes (V2O)
Policymaker
• Balance of quality and cost
• Societal considerations
• Health system statutes
and guidelines
Patient
• Need to maintain health
• Benefit/risk tradeoffs
• Affordability of care
Rx & Dx
Manufacturer
•
Incentives to develop
evidence
•
Reimbursement
commensurate
with value
•
Return on investment
•
Reward for innovation
Laboratory
• Better, faster, cheaper
• Staff resource requirements and
turn around
• Managing with a budget
V2O
Healthcare
System
Payer & HTA
• Balance of quality and
cost
• Evidence-based care
• Provision of appropriate
care to appropriate
populations
• Balancing care across
the population
Provider & Hospital
• Provision of appropriate care
• Provision of reimbursed
services
• Financial efficiency & viability
• Managing with a budget
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Different stakeholders have various views on risks,
benefits and value
Industry
Regulators
Payers
Physicians
Market / Patient
Access
Drug/Device
Candidates
• Improve patient
outcomes
• Prove value
• Secure coverage
and reimbursement
• Enhance
understanding
of unmet patient
needs
• Explore new
indications
Patients
• Delineate riskbenefit profile
• Detect safety
signals
• Ensure long-term
safety and
effectiveness
• Appraise value for
coverage and
reimbursement
decisions
• Monitor usage
within criteria
• Evaluate
comparative- and
cost-effectiveness
•
•
•
•
Evaluate evidence
Advance science
Improve care
Ensure continued
reimbursement
• Generate
publications
• My own health—
what choices
do I have?
• What are the
risks/benefits?
• Which treatment
will improve my
quality of life?
• Which treatment
is safer, more
convenient and
affordable?
17
Risk-benefit analysis is also becoming personal
PERSONALIZATION
OF CARE
RISING TIDE OF
CONSUMERISM
MINDING THE
(SYSTEM) GAPS
DEMOCRATIZATION
OF CARE
18
How do we integrate RWE in cancer drug development
development?
19
Real-world evidence plays an increasing role across the
product lifecycle
Incorporate real-world data needs earlier in the R&D process
Development
Growth Phase
Post marketing
commitments
(safety, etc)
Budget Impact
Evidence
Required
Mature Phase
Long-term
clinical
outcomes
Utilization/
prescribing
patterns
Patient recruitment
Effect of switching
on outcomes
Head to head
comparative
effectiveness
Adherence
Unmet need/
disease burden
Differentiation in subpopulations
Usage
Difference
Target populations
Differentiate with or vs.
protected formulation
Understand
standard of care
Trial design
Launch
Now
Pricing
Review
New
Competition
Past
New
Formulation/
Indication
Competitor
Goes Generic
Source: Ref. modified from EMA Adaptive Pathways Pilot Presentation at STAMP
http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2015/11/WC500196727.pdf
- Confidential -
20
RWE can be generated through a variety of study
designs
Evidence Development Options
Minimally
interventional
trials designed to
include more
representative
populations,
comparators and
endpoints
predicted for
product use
Enriched studies
designed with
experimental and
observational elements
to track real-time riskbenefit and spawn
further research
Retrospective
Research
Pragmatic
RCTs
Enriched
Prospective
Studies
RWE databases evaluated to
characterize treatment patterns and
clinical disease patterns; also useful
for informing prospective study
design features
Enriched
Retrospective
Observational
Prospective
Studies
Enriched retrospective studies
conducted to strengthen
secondary data analyses with
information from patients and
clinicians
Disease registries established
early to investigate real-world
practice patterns and outcomes
21
Cost/Time Sensitive Approaches
Changing real world research evidentiary landscape
Database & Hybrid Registries
Pragmatic
Pragmatic Ph IV trials
• High external validity
• Large sample size
• Simple design
• Diverse settings
• Real world late
phase operations
• High internal validity
• Smaller sample size
• Sophisticated design
• Controlled environment
Explanatory trials (RCT)
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Engage Early
Early evidence for better outcomes
REIMBURSEMENT
APPROVAL
PRODUCT DECISION
Regulators
BioPharma
Preclinical
Clinical Development
Phase I
Phase II
Phase III
Regulatory
Submission
Payers
Providers Patients
Healthcare Delivery
Phase IIIB/IV
Product Development Services
Real World & Late Phase Research Services
Evidence for Regulators, Providers, Payers, Patients
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Healthcare System Goals
Equity
Economics
Effectiveness
Improve Enhance
Population Patient
Outcomes Experience
Efficiency
What
Success
Looks
Like
Reduce
Costs
System Levers
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