Download Main title slide header

THE COLLABORATIVE
ADVANTAGE OF
BIOPHARMA COMPANIES
AND GLOBAL SERVICE
PROVIDERS
October 26, LA JOLLA, CA
Ubavka DeNoble
CONFIDENTIAL
© 2016 PAREXEL INTERNATIONAL CORP.
AGENDA
• Drug development trends
• The growing significance of
Genomics and biomarkers
• The importance of the real-time
data access and predictive
analytics
• How trial design complexity
impacts the service provider
• Future critical alignment elements
between biopharma and the
service provider
© 2016 PAREXEL INTERNATIONAL CORP. / 2
CONFIDENTIAL
TOKYO, JAPAN
DRUG
DEVELOPMENT
TRENDS
© 2016 PAREXEL INTERNATIONAL CORP. / 3
CONFIDENTIAL
FDA APPROVAL FOR ORPHAN DRUG
SETS RECORD AGAIN IN 2015
• Improving NAS
approval trend;
highest since 1997
• Many first-in-class
medicines
• Orphan therapy
approvals also
increasing
Sources: FDA.gov and Jefferies Report, February 2016
© 2016 PAREXEL INTERNATIONAL CORP. / 4
CONFIDENTIAL
ONCOLOGY AND SPECIALTY DRUGS GAIN MOMENTUM
Sources: Citeline, Express Scripts,2013, Drug Trend Report; IMS Health
Report, 2014; JPM Healthcare Technology Report, 2013; Wells Fargo Report,
2013, PwC Specialty drug report, Fierce Biotech, DCAT, Cowen – Therapeutic
Categories Outlook (Feb 2015), Strategy& analysis
• Biopharma companies’ pipelines are shifting to oncology
and other areas of specialty medicine
– High unmet medical need
Source: “Medicine Use and Spending in the U.S.: A Review of 2015 and Outlook
to 2020,” IMS Institute for Healthcare Informatics, April 2016
• Significant growth in approvals
for targeted oncology products in recent years
• Targeted therapies expected to make up 91% of novel
active substances (NAS) in oncology in 2016–2020
– Better margins
– Leaner operating model
• By 2020, >225 new medicines will be introduced,
one-third for cancer
• 2/3 of drug sales will be for specialty drugs vs. 1/3 currently
© 2016 PAREXEL INTERNATIONAL CORP. / 5
CONFIDENTIAL
TAIPEI, TAIWAN
THE GROWING
SIGNIFICANCE OF
GENOMIC & BIOMARKERS
© 2016 PAREXEL INTERNATIONAL CORP. / 6
CONFIDENTIAL
BIOMARKERS ARE INCREASINGLY BEING UTILIZED
IN STRATIFYING CLINICAL TRIALS
The proportion of stratified trials is increasing
Percent oncology trials selecting or stratifying using biomarkers
• 73% of all ongoing/planned trials
using biomarkers are oncology
related; 94% of all patient
reselection /stratification trials
are cancer related
Top sponsors of ongoing/planned oncology trials
using biosimilars to select or stratify patients
• Approvals rose for programs
utilizing biomarkers for patient
selection to 25.9%, 3x higher
than development programs not
utilizing biomarkers (8.4%), per
a BioMedTracker analysis
Sources: Citeline’s Trialtrove - data accessed January - April 2015
© 2016 PAREXEL INTERNATIONAL CORP. / 7
CONFIDENTIAL
GENOMICS ARE BECOMING MORE CRITICAL
IN DRUG DEVELOPMENT
Target
Preclinical
Target Validation
Drug Metabolism, Transport
Drug Repositioning
© 2016 PAREXEL INTERNATIONAL CORP. / 8
Clinical
Launch
PostMarket
Differentiated Medicines
Differentiated Medicines
Patient Enrichment
Patient Enrichment
Patient Stratification
Patient Stratification
Efficacy
Efficacy
Safety
Safety
CONFIDENTIAL
REGULATORS SEEK GENOMIC INFORMATION TO
INFORM DECISION-MAKING
Definitions
SAD: single ascending dose
MAD: multiple ascending
dose
PK: pharmacokinetic
PD: pharmacodynamic
DDI: drug-drug interaction
PGx: pharmacogenomic
CYP: cytochrome P450
TQT: Thorough QT study
© 2016 PAREXEL INTERNATIONAL CORP. / 9
CONFIDENTIAL
IDENTIFYING DRUG REPURPOSING OPPORTUNITIES
Background:
Drug repurposing can accelerate medicine
development. While in pharma, we worked
with our clinical colleagues to identify
additional indications for an existing medicine.
Atopic Dermatitis Acne
What we did:
Our experts conducted a comprehensive,
clinical transcriptomics analysis across
multiple dermatologic conditions.
Value we added:
Our experts identified additional dermatology
indications for this medicine, discovered
mechanistic connections between skin
diseases and generated new hypotheses
to accelerate medicine development.
PAREXEL Genomic Medicine
can advise clients on lifecycle
management strategies
Drug Discovery Today (2014) 19 (9): 1364-71
© 2016 PAREXEL INTERNATIONAL CORP. / 10
CONFIDENTIAL
Psoriasis
BERLIN, GERMANY
THE IMPORTANCE
OF THE REAL-TIME
DATA ACCESS AND
PREDICTIVE
ANALYTICS
© 2016 PAREXEL INTERNATIONAL CORP. / 11
CONFIDENTIAL
CAPITALIZING ON REAL-TIME DATA
DESCRIPTIVE –
REPORTING
INVESTIGATIVE –
DIAGNOSTIC
PREDICTIVE –
SIMULATION
What happened?
Why did it happen?
What could happen?
© 2016 PAREXEL INTERNATIONAL CORP. / 12
CONFIDENTIAL
THE SOLUTION
Speed and Simplify Your Journey to Market
NOVEL
TECHNOLOGY
© 2016 PAREXEL INTERNATIONAL CORP. / 13
EXPERT
SERVICES
CONFIDENTIAL
INDUSTRY
STANDARDS
IMPACT CLINICAL DEVELOPMENT PLATFORM
END TO END CLINICAL PROCESS
CONVERGENCE
Country
Allocation
Site
Start-Up
Randomization
Trial Supply
Management
Clinical Trial
Management
System
Electronic
Data Capture
Imaging
Patient
Reported
Outcomes
Protocol
Deviations
Data-Driven
Monitoring
LEVERAGE OF SMAC TECHNOLOGIES
Social
Mobile
Analytics
Cloud
About How We Interact
About Big Data and Analytics
 Patients
 Sites
 Clinical Services Teams
 Access to Digitized Information
 Combined Insight
 Right Decisions
© 2016 PAREXEL INTERNATIONAL CORP. / 14
CONFIDENTIAL
Regulatory
Platform
BENEFITS TO THE BUSINESS
DRIVE DOWN
COSTS
ACCELERATE
DEVELOPMENT
TIMES
Reduce monitoring
costs while
enhancing quality
Make better
decisions faster
IMPROVE
COMPLIANCE
Turning data
into knowledge
Moving from transactional
to transformational
© 2016 PAREXEL INTERNATIONAL CORP. / 15
CONFIDENTIAL
PEOPLE,
PROCESS &
TECHNOLOGY
Focus on your
core competency
BOSTON, MASSACHUSETTS
HOW TRIAL DESIGN
COMPLEXITY IMPACTS THE
SERVICE PROVIDER
© 2016 PAREXEL INTERNATIONAL CORP. / 16
CONFIDENTIAL
INCREASING TRIAL COMPLEXITY
• Major shift in
business mix
toward more
complex studies
(e.g., oncology)
• Patients for
targeted indications
more difficult to find
• Specialized centers
with internal IRBs*
delay startup
$194
*Institutional Review Boards
Source: Medidata PICAS database score for therapeutic areas: high>70, medium= 20-70, low<20
© 2016 PAREXEL INTERNATIONAL CORP. / 17
CONFIDENTIAL
CLINICAL DEVELOPMENT OPTIMIZATION
= PAREXEL Optimization Innovations
DYNAMIC PLANNING
DESIGN
START-UP
EXECUTE
SUBMIT
Commercialization and
Outcomes Plan
Regulatory and Ethical
Approval
Recruitment and
Retention
Data Management /
Statistics Aggregation
Regulatory Strategy
Investigator Grants and
Contracts
Adaptive
Monitoring
Regulatory
Services
Study Training
Data Surveillance
Clinical Study Report
Site Regulatory
Documentation
Trial Management
and Analytics
Publications
Critical Path
Management
Imaging and
Spirometry
Study Transparency /
Disclosure
Clinical Trial
Logistics
Payments
Cross Data Analysis
Quantitative Clinical
Development
Protocol
Optimization
Country and Site
Selection
Risk Assessment
End-to End Data Standards and Trial Master Storage
First Protocol
Approval
First Subject First
Visit (FSFV)
Last Subject Last
Visit (LSLV)
DYNAMIC PLANNING
© 2016 PAREXEL INTERNATIONAL CORP. / 18
CONFIDENTIAL
Clinical Study
Report Approved
PROTOCOL OPTIMIZATION - HOW DOES THIS WORK?
OUR GOAL
5
4
Help clients develop
multiple study designs
in order to find
the optimal one.
3
2
1
A
Standard
Building
Blocks in
Every Study
Considerations
for Each
Building
Block
Leverage
30 Years of
PAREXEL
Experience
& Data
Interrogate
Relevant
Building
Blocks
Scenarios
that assist
Clients
with tradeoff
decisions
B
C
D
E
© 2016 PAREXEL INTERNATIONAL CORP. / 19
CONFIDENTIAL
THE PHILOSOPHY BEHIND BETTER INFORMED
DECISION MAKING
INVESTIGATOR
& PATIENT VOICE
THE BIG DATA
ENGINE
The Power to Identify
the “right countries,
sites & patients”
Bringing in
the Investigator
& Patient Voice
PREDICTIVE
ANALYTICS
Turning Data
Into Knowledge
CLIENT
DISCUSSIONS
& ACTIONABLE
DECISIONS
Effective Strategy
Planning by
Understanding Risk
DATA-DRIVEN INSIGHTS TO YIELD
CONSENSUS ON ACCEPTABLE RISK
20
© 2016 PAREXEL INTERNATIONAL CORP. / 20
CONFIDENTIAL
TAIPEI, TAIWAN
FUTURE CRITICAL
ALIGNMENT
ELEMENTS BETWEEN
BIOPHARMA AND THE
SERVICE PROVIDER
© 2016 PAREXEL INTERNATIONAL CORP. / 21
CONFIDENTIAL
BIOPHARMA
FACE ENORMOUS
PRESSURES
• Demonstrating proof-of-concept
• Creating Target Product Profiles
with endpoints that support
regulatory approval
• Identifying the right partner for
protocol design, site selection and
data collection/integrity
PERCENT OF R&D ORIGINATED
OUTSIDE THE TOP 25
PHARMACEUTICAL COMPANIES
• Managing ever-changing regulatory
and reimbursement landscapes
80%
© 2016 PAREXEL INTERNATIONAL CORP. / 22
CONFIDENTIAL
KEY ELEMENTS FOR
SUCCESS
Whether you seek to license
your compound, reach proof-ofconcept, or enter the clinic
and commercialize, the PAREXEL
BioPharm Unit’s flexible model
will help you extract maximum value
from your compound or portfolio by:
• Enhancing internal capabilities
• Helping reach faster go/no-go
decisions
• Increasing compound value by
demonstrating PoC and understanding
regulatory and reimbursement
landscape
• Accelerating study start-up and
site selection
• Ensuring logistical planning and
execution is integrated into the entire
trial process
© 2016 PAREXEL INTERNATIONAL CORP. / 23
CONFIDENTIAL
BENEFITS OF
PARTNERING
To reach your goals faster, the
PAREXEL BioPharm unit:
• Assigns a senior PAREXEL executive
to lead a dedicated team
• Develops a strategy to minimize
complexity, accelerate timelines,
and reduce fixed costs
• Designs commercialization solutions to
accelerate development, substantiate
value and vet evidence
• Provides access to sites and patients
across Europe, Asia and the Americas
• Differentiates your company and
compound in the eyes of potential
investors and partners
• Helps you derive the most value from
your compound
© 2016 PAREXEL INTERNATIONAL CORP. / 24
CONFIDENTIAL
THANK YOU
© 2016 PAREXEL INTERNATIONAL CORP. / 25
CONFIDENTIAL
ONGOING VIRTUALIZATION OF BIOPHARMA INDUSTRY
• Small-to-midsize companies,
including virtual companies, rely
heavily on outsourced services:
• Large, established companies
increasingly willing to extend the
range & breadth of outsourced
services:
• Executing clinical trials
• Expanding regulatory and commercial
capabilities
• Regulatory
• Managing cost and time to market
• Clinical IT
© 2016 PAREXEL INTERNATIONAL CORP. / 26
CONFIDENTIAL
• Commercial
Virtualization of
Biopharma
ACCELERATED REGULATORY PATHWAYS
•
64% used
at least one
accelerated
pathway
•
More than a third
used multiple
accelerated
pathways
Drug Pipelines and
Specialty Products
© 2016 PAREXEL INTERNATIONAL CORP. / 27
CONFIDENTIAL
HEALTHCARE SPENDING OUTPACES GDP AND WAGES
INDEXED GROWTH IN HEALTHCARE SPENDING,
GDP AND WAGES IN FOUR COUNTRIES
350
300
250
200
150
100
19921997200220072012
350
300
250
200
150
100
19921997200220072012
350
300
250
200
150
100
19921997200220072012
350
300
250
200
150
100
19921997200220072012
Healthcare
Spending
G
DP
• Healthcare spend growing at
an unsustainable pace
• Limited objective data on
value
• Biopharmaceutical
companies face external
pressures to reduce drug
costs
• Biopharmaceutical products
help bend cost curve down
Wage
s
Note: Index on basis of local currency Sources: BCG Analysis; OECD Health Data 2009; EIU, GBE (Gesundheitsberichterstattung des Bundes),
CMS, INSEE, Office for National Statistics UK; All data indexed to 100
Importance of Payers
© 2016 PAREXEL INTERNATIONAL CORP. / 28
CONFIDENTIAL
REAL-WORLD EVIDENCE PLATFORM
• Advances in computing power
to integrate real-world data
Patient
Population
from
Secondary
Data Assets
Patient Population from Clinical Trials
Phases
I-III
Approv
al
© 2016 PAREXEL INTERNATIONAL CORP. / 29
Post-Approval
Research
CONFIDENTIAL
• Allows study of
heterogeneous patient
populations beyond those
studied in clinical trials
• Age groups
• Disease
progression
• Patient lifestyle variance
• Compliance
PERSONALIZED MEDICINES ARE BECOMING
MORE AVAILABLE
138 FDA approved
drugs with
biomarker
information on their
label
20% of FDA
approvals in 2014
were for targeted
therapies
Adapted from Pharmaceutical Research and Manufacturers' Association (PhRMA):
Value of Personalized Medicine (2015)
© 2016 PAREXEL INTERNATIONAL CORP. / 30
CONFIDENTIAL
55% OF PERSONALIZED MEDICINES ARE WITHIN
ONCOLOGY/HEMATOLOGY AND PSYCHIATRY
© 2016 PAREXEL INTERNATIONAL CORP. / 31
CONFIDENTIAL
MARKET DRIVERS INFLUENCING NEED FOR GENOMIC MEDICINE
SERVICES
Decision Maker
Decision Drivers
Clients
Looking for information to drive drug development
decision making
Regulators
Seek pharmacogenomic information to understand who
will benefit or be harmed by the drug
Payers
Want companies to demonstrate value over current
medicines
Patients
Want medicines that work for them and don’t cause
side effects
© 2016 PAREXEL INTERNATIONAL CORP. / 32
CONFIDENTIAL
INTEGRATED MULTI-OMICS APPROACHES FOR NOVEL
TARGET DISCOVERY
Transcriptomics: IL23 vs IL12
Proteomics: IL23 vs. IL12
200
150
Comp.2 [12.25%]
100
50
0
-50
-100
-150
-200
-300
-200
-100
0
100
200
300
Comp.1 [25.66%]
Integrated Multi-omics Network
Causal Reasoning & Inference
Novel Target Candidates
J Immunol (2014) 192: 2527-8
EBI Immunogenomics Conference 2015
Background:
While working in pharma, we partnered
with pre-clinical scientists to develop
and implement a multi-omics strategy to
discover novel, specific drug targets in
the IL23 pathway.
What we did:
Our experts supported multi-omics
strategy design and applied cuttingedge methodologies (e.g., causal
reasoning, advanced network analysis)
to analyze, integrate, and interpret the
multi-omics experimental findings.
Value we added:
In close collaboration with our bench
scientist colleagues, we discovered
novel drug targets that are validated in
follow-up experiments.
PAREXEL Genomic Medicine can
help clients select and validate drug targets.
CONFIDENTIAL
© 2016 PAREXEL INTERNATIONAL CORP. / 33
ADME GENETICS EXPLAINS EXPOSURE DIFFERENCES
Drug X plasma concentrations over time by
CYP2B6 genotype
• In a Phase I drug-drug interaction study, a
subset of healthy volunteers had elevated
levels of Drug X when administered with the
client’s medicine.
• Drug X is primarily metabolized by CYP2B6.
Our experts assessed genetic variation in
the CYP2B6 gene to determine if genetic
variants leading to reduced CYP2B6
enzyme activity might account for increased
exposure of Drug X.
• The poor metabolizer CYP2B6 *6/*6
genotype was associated with elevated
exposure of Drug X. The client’s medicine
did not impact Drug X exposure; however,
Drug X increased metabolism of the client’s
medicine (data not shown) so dose
adjustments of the client’s medicine are
recommended.
© 2016 PAREXEL INTERNATIONAL CORP. / 34
CONFIDENTIAL
QUANTITATIVE CLINICAL DEVELOPMENT
• Model based development is critical to take the right steps to get into IND –
pave the way for successful Phase I (the right data without surprises)
A fit-for-purpose modeling tool, always
Create definable value in early development
Cost avoidance, focus only on what is truly needed
Enhancement of pharmacology data with focus on exposure response, occupancy
Clear definition of “target” or “candidate”
Establishing high-confidence stopping rules, eliminating clouded judgment
Successful modeling helps sponsors create optimal Proof-of-Principle and
Proof-of-Concept studies, delivering more valuable data earlier in
development cycle
Exposure to
Target
© 2016 PAREXEL INTERNATIONAL CORP. / 35
Binding to
Target
CONFIDENTIAL
Expression of
Pharmacology
SMALL AND MIDSIZED CLIENTS
YEAREND CASH AT SMALL/MIDSIZED
BIOPHARMA ($ IN BILLIONS)
$78
$62
• Industry as a whole has
approximately $350 billion of cash
• New business from segment remains
strong
$48
$33
• Despite recent slowdown in funding,
smaller biopharma companies have
about $78 billion of cash
$38
• Willing and ready to deploy capital
2011 2012 2013 2014 2015
Grow the Core
Source: Chestnut Partners
© 2016 PAREXEL INTERNATIONAL CORP. / 36
CONFIDENTIAL
DATA CAPTURE
& MANAGEMENT
Typical challenges
• Timely availability of a data capture
framework prior to first patient in
• Cost effectively capture data
• Leveraging ‘real time’ clinical data
PAREXEL® solution
Customer results:
Largest study
16,000+
SUBJECTS ENROLLED IN
1,900+
SITES
© 2016 PAREXEL INTERNATIONAL CORP. / 37
 Robust technology platform and
infrastructure supporting large trials
 Allow rapid study-build process with
design specification generation
 DataLabs closely integrated with
Data-Driven Monitoring to improve
study oversight
CONFIDENTIAL
SOURCE DATA
VERIFICATION &
SOURCE DATA REVIEW
Typical challenges
• Capturing, reviewing and analyzing
patient data in timely manner
• Managing multiple source of information
• Reporting and exporting of data
• Inspection ready SDV and SDR
PAREXEL® solution
Customer results:
20%
SDV & SDR THRESHOLD
for some studies
 Focus SDV within EDC to
critical elements
 Efficiently document SDR in CTMS
via customizable checklists
 Dashboard view of site and patients
 Improved patient data surveillance
enhances data quality safety
© 2016 PAREXEL INTERNATIONAL CORP. / 38
CONFIDENTIAL
PAYMENT MANAGEMENT
Typical challenges
• Effective control and management of
contracts and trial budgets
• Greater visibility into committed costs
vs. projected budgets
• Projecting under/over spend areas
throughout the process
Customer results: Impact
CTMS
880,000+
SUBJECTS ENROLLED IN
PAREXEL® solution
 Dynamically forecast and adjust
spend in real time
25,000+
 Easy generation of proposed payments
for hundreds of sites at once
STUDIES
 Straightforward interfacing with
Accounts Payable systems
© 2016 PAREXEL INTERNATIONAL CORP. / 39
CONFIDENTIAL
INVESTIGATOR
PERFORMANCE
Typical challenges
• Lengthy study start-up times
• Difficulty selecting and managing
investigators
• Maintenance of investigator database
impairs planning and study timelines
Customer results: Impact
CTMS
380,000+
70+
SITES IN
COUNTRIES
© 2016 PAREXEL INTERNATIONAL CORP. / 40
PAREXEL® solution
 Reduce the cost and risk of clinical
trial study start-up
 Have confidence that you are using
the right investigators in your study
 Expedite site selection and
patient recruitment
CONFIDENTIAL
DATA DRIVEN
MONITORING
Typical challenges
• Addressing cost pressure without
compromising data quality
• Regulatory pressure
• Maximizing the value of limited
resources
• Timely ability to monitor quality
and safety issues
Customer results:
10-25%
reduction in
STUDY
MONITORING
COSTS
© 2016 PAREXEL INTERNATIONAL CORP. / 41
PAREXEL® solution
 Reduce costs by assessing workload
to drive site visits
 Enhances study data integrity and
scientific credibility
 Predictability of outcomes that
withstand regulatory scrutiny
CONFIDENTIAL
TRIAL TRACKING
& MANAGEMENT
Typical challenges
• Site recruitment takes too long
• Large number of global sites
and patients
• Lack of centralized information
management for Clinical Operations
PAREXEL® solution
 Timely access to enrollment
and milestones
 Track submissions, approvals
and the study start-up process
 Focus on the sites that need
attention with on-screen filtering
and drill-through to action items
© 2016 PAREXEL INTERNATIONAL CORP. / 42
CONFIDENTIAL
EXAMINING RULE BASED VS MODEL BASED DESIGN
ACCRUAL NUMBER FOR ILLUSTRATIVE PURPOSES ONLY
Data on treatment
effect + LBM
Biomarker
+ 15 LBM5 LBM+ | 5 LBM-
7 (16)
3
+ 10 LBM+
+ 20(?) LBM
T Accrual = 35
T Accrual = 55
3
OBD
All Tox
Enrichment data
Reduced timeline
Exploring efficacy
Reduce P2b $$
~$55K/Pat*
$3.1M
3
Model
Based
3
T Accrual = 55
3
3
40
3(15)
3
Rule
Based
No MTD
DLT?
Exploring safety
~$43K/Pat*
$2.4M
No data on
treatment effect
3
3
1
2
3
4
5
6
Timeline in Months
© 2016 PAREXEL INTERNATIONAL CORP. / 43
CONFIDENTIAL
7
8
9
* Operation fees only
WELL POSITIONED FOR PHASE IIB
•
•
•
•
Reduce timeline to acquire efficacy data
Reducing risk of 2b design with defined patient enrichment
Increase Investigator interest in 2b (improved enrolment)
Reduce $ Investment for Phase 2b and time to Phase 3
Data on treatment
effect + LBM
Biomarker
+ 15 LBM5 LBM+ | 5 LBM-
7 (16)
3
+ 10 LBM+
+ 20(?) LBM
T Accrual = 35
T Accrual = 55
OBD
All Tox
Enrichment data
Exploring Efficacy
~$55K/Pat
$3.1M
3
Prospective
hypothesis testing
Confirm LBM
Response rate
3
3
3
1
2
3
© 2016 PAREXEL INTERNATIONAL CORP. / 44
4
5
6
CONFIDENTIAL
7
8
9
REGULATORS SEEK GENOMIC INFORMATION TO
INFORM DECISION-MAKING
Graphic courtesy of:
Issam Zineh
Office of Translational Sciences
CDER
U.S. Food and Drug Administration
FDA, EMA and PMDA have all recognized the importance of genomic sampling in clinical
trials:
– published guidance to industry on pharmacogenomics
– ICH guideline E18 on genomic sampling and management of genomic data has been released for
public consultation
© 2016 PAREXEL INTERNATIONAL CORP. / 45
CONFIDENTIAL
DRUG DEVELOPMENT
CHALLENGES
• Clinical studies are becoming
more complex
• Cycle times too long
• Cost pressure
• Lack of real-time and standardized
data and analytics
© 2016 PAREXEL INTERNATIONAL CORP. / 46
CONFIDENTIAL
PHASE III FAILURES
Success Rates by Phase,
2010 vs. 2011 vs. 2012 vs. 2013
(lead and secondary indications)
Approximately
40% fail!
Source: Korieth, Karyn.. “Facing protocol amendments head-on.” The CenterWatch Monthly 23.4 (April 2016): 1-13. Print
© 2016 PAREXEL INTERNATIONAL CORP. / 47
CONFIDENTIAL
PHASE III FAILURES
- Recent PAREXEL analysis,
we collected and evaluated
data on 38 Phase III failures
from mid-2012 through 2015
from a variety of publicly
available sources
- Failed to meet primary or
secondary efficacy endpoints
- Phase III trials that failed due
solely to safety issues are
not included
- These 38 failed trials
collectively enrolled nearly
150,000 patients
© 2016 PAREXEL INTERNATIONAL CORP. / 48
CONFIDENTIAL
ADAPTIVE DESIGNS
TRADITIONAL DESIGN (CARGO)
ADAPTIVE DESIGN (PASSENGER)
How could these designs reduce amendment & failure risk?
Prospectively planned opportunity to revisit initial assumptions based on
interim data –
e.g., Drop a dose arm that is ineffective or adapt sample size
based on observed treatment effect differences
© 2016 PAREXEL INTERNATIONAL CORP. / 49
CONFIDENTIAL
HOW DO WE FIND THE RIGHT INVESTIGATIVE SITES?
A COMPREHENSIVE
PICTURE OF THE
INVESTIGATOR
AND SITE
LANDSCAPE
DATA QUALITY
DIAGNOSTICS
EXPERIENCE
PATIENT
POPULATION
SITE PERFORMANCE
DATA IN THE
BROADEST
SENSE
ENROLLMENT
INVESTIGATOR
VOICE
RESPONSIVENESS
© 2016 PAREXEL INTERNATIONAL CORP. / 50
CONFIDENTIAL
A SEA OF DATA
CTMS
Geo Profiling
Imaging
Validation of
instruments
IRB
Clinical Trial
Data
Surveys
Lab Data
© 2016 PAREXEL INTERNATIONAL CORP. / 51
IVRS
CONFIDENTIAL
Audits
IDENTIFYING SIGNALS FROM THE NOISE
INTERNAL &
EXTERNAL
DATASETS
• Master the
datasets
− Investigator
− Study
− Site
© 2016 PAREXEL INTERNATIONAL CORP. / 52
NORMALIZE
THE DATA
• Compare to the
median performance
on the same study
in the same country
TURNING
DATA INTO
KNOWLEDGE
• Gain real
insights
CONFIDENTIAL
INCREASED STUDY
PREDICTABILITY
• Get the right sites,
countries and
patients for your
study
ACCESSIBLE DATA
REGIONAL AND COUNTRY HEAT MAPS WITH SITE LEVEL DRILL-DOWN
Filter for Best Sites in Japan
© 2016 PAREXEL INTERNATIONAL CORP. / 53
CONFIDENTIAL
DO THE PATIENTS EXIST?
Electronic Health Records (EHR) Insights
Early identification of potential issues with protocol inclusion
and exclusion criteria will enable a risk based approach to
feasibility and clinical trial management
Most Challenging
Eligibility Criteria
Number of Record
Queries
Independent
Criteria Impact
18,536 (100%)
Criteria 1
16,152 (87%)
Criteria 2
17,996 (97%)
Criteria 3
© 2016 PAREXEL INTERNATIONAL CORP. / 54
Identifying the impact certain criteria
will have on the patient pool allows
management of risk sharing
5,795 (32%)
CONFIDENTIAL
18,536
16,152
15,612
2,871
Potential patient
population
for study
CLINICAL TRIAL INTELLIGENCE
Industry
benchmark
data
Competitive
site landscape
MAGNITUDE
OF EXISTING
TRIAL DATA
Previous study
outcomes
© 2016 PAREXEL INTERNATIONAL CORP. / 55
CONFIDENTIAL
Study and drug
pipelines
Study duration
and timelines
DIGITAL LISTENING: PROVIDES UNCENSORED INSIGHT
DIGITAL LISTENING is Data Collected in Real-time via Social Media
to Support Better Decision-Making
• Analyze conversations
• Understand and advise clients
TWITTER
BLOGS
Key Benefits
 Develop strategies to mitigate
potential challenges
NEWS
FORUMS
• Engage patients and/or influencers
• Understand Sentiment – assess what is said,
whether good, bad or neutral
What We Learn from Digital Listening: Examples
Understanding Patient
Perceptions
Tracking Top Physicians
and Patient Influencers
Patients speak openly about
illnesses, conditions and drugs on
social media
Social media influencers range
from top doctors to recent cancer
survivors to authors and more
 Accurate insight into
patient/medical staff
experiences
 Target bloggers/tweeters to
push information
 Cost effective
 Global reach
© 2016 PAREXEL INTERNATIONAL CORP. / 56
CONFIDENTIAL
COUNTRY DECISION MAKING
SUPPORTED BY PREDICTIVE ANALYTICS
A data-driven approach to country selection takes into account key parameters
to gain a better awareness of the risks associated with country selection
SELECT THE
RIGHT COUNTRIES
DATA-DRIVEN
ALLOCATION
Identify the most desirable
countries from the beginning
Use the data to drive allocation
of countries
Validate protocol feasibility with
local clinical operations
Enforce indication and protocol
specific assessment
STRATEGY
TRANSPARENCY
Allow efficient and effective
conversations on country
allocation
RESULTS
RESULTS
RESULTS
Increase quality of country
selection
Increase predictability of country
performance
Increase sponsor confidence in
country selection capabilities
© 2016 PAREXEL INTERNATIONAL CORP. / 57
CONFIDENTIAL
RISK ASSESSMENT
Feasibility allows us to maximize what we know, firm up what
we suspect, and minimize what we don’t know
Undiscovered
Knowledge
Feasibility
Undiscovered
Knowledge
Feasibility
What We
Do Know
What We
Don’t Know
What We
Don’t Know
What We
Suspect
What We
Suspect
Feasibility will never be perfect. There will always be risk in the delivery of clinical trials.
Reducing risk to an acceptable level is the goal.
© 2016 PAREXEL INTERNATIONAL CORP. / 58
CONFIDENTIAL
ADAPTIVE TRIAL DESIGN CAN POTENTIALLY REDUCE
COST OF FAILURE
• About 50%
of Phase III
trials fail
• Average cost
of $20 M makes
it an expensive
problem
• Root cause
attributed to
traditionally rigid,
inflexible design
• Adaptive trial
design (ATD)
allows to
revisit initial
assumptions
and change
course
© 2016 PAREXEL INTERNATIONAL CORP. / 59
CONFIDENTIAL
REAL-TIME DATA AND PREDICTIVE ANALYTICS
TRANSFORMING STUDY EXECUTION
Value
Adaptive Trials
Strategic Planning
Proactive Interventions
Modelling Normality
Data Driven Interventions
Data Aggregation
Maturity
Resource required
Silo’ed
Systems
Data Driven
Interventions
Alerts
Raw
Data
Modelling
Normality
Anomaly
Detection
Proactive
Decisions
Actionable
Information
# People/Study
Monitored
© 2016 PAREXEL INTERNATIONAL CORP. / 60
CONFIDENTIAL
DATA-DRIVEN FEASIBILITY REQUIREMENTS
TURNING DATA INTO KNOWLEDGE
UNDERPINNING BIG
DATA ENGINE
INVESTIGATOR AND
PATIENT VOICE
PREDICTIVE
ANALYTICS
Power to identify the “right countries, right sites, right
patients”
Supporting Solutions
Analysis and
Scenario Modeling +
Visualization
A Single Intelligence Platform
CRO
Site Forecast
CTMS
EDC
Medical
Imaging
RTSM /
IRT
External Data
Sources
DATABASE 2
DATABASE 3
Site
Optimization
DATABASE 4
© 2016 PAREXEL INTERNATIONAL CORP. / 61
Investigator
Surveys
Pre-Screening
Platform
CONFIDENTIAL
What We
Do Know
What
we Risk
Patient Feasibility
Survey
DATABASE 1
Decisions based on
consensus of
acceptable risk
Country Allocation
Digital Listening
EHR INSIGHTS
UNDERSTANDING
RISK
Study
Optimization
Risk
Management
THE IMPACTS
CHURN?
COSTS?
DELAYS?
A big factor
contributing to delay
is the 'churn rate’
among investigators.
In some estimates,
over 50% of
investigators have
only completed
one study.
The average cost to
develop and gain
marketing approval
for a new prescription
medicine, a process
often lasting longer than
a decade, is now
$2.56 billion dollars.*
On average, 2-3
protocol amendments
can delay a trial by
2 months, with each
amendment adding
$500,000 in
additional costs.*
* Tuft CSDD Outlook 2015
* Tufts May 12, 2014, International
Journal of Environmental Research
And Public Health.
HOW TO MITIGATE THESE
CHALLENGES WITH BETTER
DATA- DRIVEN DECISIONS
© 2016 PAREXEL INTERNATIONAL CORP. / 62
CONFIDENTIAL
INDUSTRY CHALLENGES
Site landscape
is highly
fragmented
with variable
performance
40% of
participating
Investigators
never conduct
another FDA
regulated study
About 30% of
sites don’t
enroll a single
patient
Source: CenterWatch Reports
© 2016 PAREXEL INTERNATIONAL CORP. / 63
CONFIDENTIAL
Studies don’t
meet their
enrollment
timelines 80%
of the time
POSITIVE TREND IN FDA APPROVALS CONTINUES
NME Approvals
Total
Orphan
First-in-class
Breakthroughs
50
45
41
39
40
30
30
24
27
26
21
18
20
10
0
2007
•
2008
2009
2010
2011
2012
2013
2014
2015
Growth in the number of approvals is observed for orphan drugs
FIPCOs defined as companies with annual R&D spend of $500 million or over. SEBPCO defined as companies with annual R&D of less than $500 million.
Sources: www.fda.gov. Pink Sheets 2010 -2015. PAREXEL Biopharmaceutical R&D Statistical Sourcebook 2016/2017. Michael Lanthier, Kathleen L. Miller, Clark Nardinelli
and Janet Woodcock; “An Improved Approach To Measuring Drug Innovation Finds Steady Rates Of First-In-Class Pharmaceuticals, 1987-2011,” Health Affairs, 32, no.8
(2013):1433-1439
© 2016 PAREXEL INTERNATIONAL CORP. / 64
64
CONFIDENTIAL