Revolutionising the Lifecycle of
Pharmaceuticals
Eyeforpharma RWD conference
June 5, 2013
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Topics
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Introduction to CASMI
Current lifecycle and its issues
Forces shaping the future
Adaptive licensing and its consequences
Real world data and its role
Speculations about where we are headed
Lessons for today
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Topics







Introduction to CASMI
Current lifecycle and its issues
Forces shaping the future
Adaptive licensing and its consequences
Real world data and its role
Speculations about where we are headed
Lessons for today
3
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Centre for the Advancement of
Sustainable Medical Innovation
www.casmi.org.uk
=
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The Innovation Gap
progress
Bioscience – understanding
human biology and disease
= potential patient benefit
The Innovation Gap
Actual patient benefit
time
The danger of doing nothing
progress
Bioscience – understanding
human biology and disease
= potential patient benefit
- First ever industry
reduction in R&D
spend
- $4bn drop in overall
US spending in 2011
Actual patient benefit
time
What’s distinctive about CASMI?

Providing independent thought leadership, convening power - and so
acting as a catalyst for change

Embedded in UCL and Oxford, but networked with other European and
international centres

Interdisciplinary – Medical, Bioscience, Law, Ethics, Business, Economics,
Statistics etc

Convening all stakeholders: academia, industry,
regulators, policymakers, investors
Centre for the Advancement of Sustainable Medical Innovation
patient groups,
A Global Solution requires a Global Network
EFPIA
IMI
Other European
centres
Three core “gaps in translation” persist across the
value chain
Gap 2: Failure to gain approval
after costly development
• Basic bioscience
Translation to
clinical
candidates
Regulatory &
reimbursement
approval
• Innovations in
clinical trials
Gap 1: Failure to turn early stage
research into potential products
• Approved
products
Uptake by health
systems
Patient Benefit
• Innovations
used by patients
Gap 3: Failure to achieve widespread
use and patient adherence to treatment
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Topics





Introduction to CASMI
Current lifecycle and its issues
Forces shaping the future
Adaptive licensing and its consequences
Speculations about where we are headed
10
Current development path
PV & RM
I
II
IIIa
Review
Access
HTA
IIIb
FIM
PoC
Ph III entry
Key characteristics of current model
• Inflexible processes and method
• Expensive and increasing data demands
• Lack of early alignment between key parties:
• Segmented input & decision making
• Access needs not designed in
• Patient perspective not fully addressed
Regul. Subm. & approval
IV
P&R
Launch
External activities
Sponsor activities
Topics







Introduction to CASMI
Current lifecycle and its issues
Forces shaping the future
Adaptive licensing and its consequences
Real world data and its role
Speculations about where we are headed
Lessons for today
12
Forces shaping the future of biopharma
More flexible
regulatory
processes for
better targeted
drugs
Pressure to make
drugs more
affordable
Stratified
medicine ->
molecular
definition of
disease
Emergence of
regulatory
science and new
technology
Demand for real
world
(comparative)
effectiveness
evidence
Emergence of
tools to collect
clinical and
patient-reported
outcomes
Future of
Biopharma
Aspiration to
collect and
analyse Big Data
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Topics
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





Introduction to CASMI
Current lifecycle and its issues
Forces shaping the future
Adaptive licensing and its consequences
Real world data and its role
Speculations about where we are headed
Lessons for today
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Potential New Flexible Blueprint
Phase IV
PreclinicalR&D
Exploratory
Phase I
Phase 2
Phase
3
Confirmatory
trials
Regulatory
Review
PhV & B/R
Access Reviews
Patient Use
Basic division between exploratory and
confirmatory trials, rather than Phases I-IV
Reference: Athenaeum Group
Potential New Flexible Blueprint
Exploratory R&D
Review &
design
Confirmatory trials
Regulatory
Review
PhV & B/R
Access Reviews
Patient Use
Collaborative design step before the most
expensive confirmatory trials are
commissioned
Potential New Flexible Blueprint
Exploratory R&D
Review &
design
Confirmatory trials
Submit &
Regulatory
Confirm
Review
approval
Initial access
Ability/need to customise the model for
different benefit/risk/uncertainty profiles
PhV & B/R
Access Reviews
Patient Use
Potential New Flexible Blueprint
Exploratory R&D
Review &
design
Confirmatory trials
Submit &
Confirm
approval
Initial access
PhV & B/R
Access Reviews
Early access on
condition of
data collection
Patient Use
Ability to allow early, controlled patient access,
if justified by interim findings in
confirmatory trials
Potential New Flexible Blueprint
Exploratory R&D
Review &
design
Confirmatory trials
Submit &
Confirm
approval
PhV & B/R
Initial access
Early access on
condition of
data collection
Effectiveness/comparative studies
Subject to requirements for pharmacovigilance
and pharmaceconomic analyses before full
‘green light’ for wide access and longer term
reimbursement policy
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Key elements of the concept
Conditional
Approval (or
approval on
conditions)
Stakeholders:
-Sponsor
-Regulator
-HTA
-Patient org
Co-design of
confirmatory
trials
* MAPPs = Medicines Adaptive
Pathways for Patients
Adaptive
Licensing
= MAPPs*
Real world
effectiveness
tracking
EMA, based on
rapporteur
evaluation of
submission
Managed
Market Entry
Outcome, safety data
collection via reliable
network
Patients treated;
sponsor
reimbursed
Do you have a potential pilot? - draft pilot selection
criteria
1. A robust case for accelerated process – including unmet
clinical need.
2. Strong efficacy signal from initial trials; positive benefit/risk
profile likely
3. Sufficient numbers of patients that can be recruited.
4. Appropriate data collection mechanisms: robust trial
networks in the specific disease area with clinicians that are
interested in participating in research
5. Existing patient support mechanisms
6. Could be either a new NCE/NBE or one approved in another
indication
Topics
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





Introduction to CASMI
Current lifecycle and its issues
Forces shaping the future
Adaptive licensing and its consequences
Real world data and its role
Speculations about where we are headed
Lessons for today
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RCTs
 May be unnecessary, inappropriate, inadequate, or impractical
 Efficacy versus effectiveness
 Population: may not be available for sub-populations and
vulnerable populations
 Interventions: may not be able to assign high-risk interventions
randomly
 Comparators: may not represent standard care
 Outcomes: may report intermediate outcomes rather than
main health outcomes of interest
 Timing: may be too short in duration
 Setting: may not represent typical practice
 Expense and bureaucracy
Hierarchies of evidence should be replaced
by accepting—indeed embracing—a diversity
of approaches.
This is not a plea to abandon RCTs and
replace them with observational studies. Nor
is it a claim that the bayesian approaches to
the design and analysis of experimental and
non-experimental data should supplant all
other statistical methods.
Rather, it is a plea to investigators to
continue to develop and improve their
methods; to decision makers to avoid
adopting entrenched positions about the
nature of evidence; and for both to accept
that the interpretation of evidence requires
judgment.
Efficacy v effectiveness
 Efficacy
 patient benefit and harm in experimental and closely
monitored research studies, normally RCTs.
 major advantages in minimising bias
 generalisability questionable
 restricted entry criteria
 unrepresentative settings
 Effectiveness
 patient benefit and harm when the technology is actually
applied in everyday practice.
 pragmatic clinical trials
 adverse event reporting
 clinical audit
Groundbreaking RWD Study Launched in Salford
The Salford Lung Study is a unique collaboration between GSK,
North West e-Health (NWeH), The University of Manchester,
Salford Royal NHS Foundation Trust, NHS Salford, local GPs and
local community pharmacists.
Around 4,000 patients with COPD and 5,000 patients with asthma
from Salford, Greater Manchester, will be enrolled in the yearlong study.
It is the first time a large, ‘real-world’ study has been performed
on a pre-licence medicine, across a large population within one
geographical setting.
It will utilise Salford’s e-Health records infrastructure – a clinical
information system providing a single, integrated electronic
patient record across both primary and secondary care.
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Topics







Introduction to CASMI
Current lifecycle and its issues
Forces shaping the future
Adaptive licensing and its consequences
Real world data and its role
Speculations about where we are headed
Lessons for today
31
Consequences of these developments ….?
Sharper
definition of
patient
populations
Real world
data to
confirm/refine
B/R and value
CPRD and
related
e-health
developments
Increasing
pressure on
budgets and
prices
Adaptive
approaches to
pre-approval
trials
Big Data
insights on
routine use of
drugs
Increasing
focus on
outcomes
Industry is in the data business, not
just the product business
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Topics







Introduction to CASMI
Current lifecycle and its issues
Forces shaping the future
Adaptive licensing and its consequences
Real world data and its role
Speculations about where we are headed
Lessons for today
33
Topics







Introduction to CASMI
Current lifecycle and its issues
Forces shaping the future
Adaptive licensing and its consequences
Real world data and its role
Speculations about where we are headed
Lessons for today
34
Lessons for today
Ensure you’re well networked into industry bodies (like ABPI)
Have a medical information lead on board in your company
Ensure cross-functional dialogue
Consider AL/MAPPs for early stage projects (Phase 1
onwards)
 Monitor RWD developments (like GSK’s Salford project and
IMI’s GetReal) and their findings
 Find one or more centres (HERCs?) focused on relevant
therapeutic areas
 Consider creating a collaborative project to monitor and
evaluate your product’s outcomes
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