Vlad Dragalin
Vlad Dragalin
Vlad Dragalin
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bn1
Benefit from the expertise, databases,
and infrastructures of consortium
partners
€1.638 bn Partnership €1.425 bn
• Access to databases and best funds - in-kind
practices cash 2014 - 2024 invest-
✓
ments
Credibility and visibility of IMI's
projects in Europe and globally
• Enviable platform to promote change
and best practices to healthcare
Average resources for projects: ~20-40M€ +
systems across the world matching in-kind investments from
collaborating pharma companies
IMI2 vision – towards integrated healthcare solutions
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IMI2 - Major Axes of Research
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New models: Paradigm shift in R&D,
licensing, access and healthcare delivery
1. Re-engineer Conditional 2. Clarify/align data/methodology
Authorisation mechanism for all stakeholder B/R assessment
needs, pre- and post-approval
Confirmatory trials
Submit &
Review &
Explore R&D design
Confirm
approval
Early access on
condition of
Initial access data collection
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7 priority themes and enablers = 7 SGGs
Neuro-degeneration
Leads: Janssen, Lilly, Abbvie
Immune-Mediated diseases
Leads: GSK
Metabolic Disorders
Leads: Sanofi, Lilly, Servier
Translational safety
Leads: Sanofi, Bayer, Janssen, Novartis
Data and Knowledge Management
Leads: Janssen, Pfizer
Medicines Adaptive Pathways to
Patients
Leads: Amgen, Janssen
Infection control
Leads: AstraZeneca
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SGG DKM WS2 - Therapeutic Development Optimization
Members
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SGG DKM WS2 - Therapeutic Development Optimization
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Expected outputs from the new SGG process
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SGG DKM is aiming at defining an ambitious program and initiatives
related to Adaptive Designs in Drug Development to launch calls in
2016
Topic definition
Stage 1 Stage 2 Negotiation phase
phase
Academic
research Hospitals
teams Applicant
consortium
Industry Mid-size
Regulators
enterprises
consortium
Industry
Patients’ consortium
SMEs
organisations
Source: IMI 11
Adaptive Design Refresher
Adaptive Design is defined as a multistage study design that uses
accumulating data to decide how to modify aspects of the study
without undermining the validity and integrity of the trial
Trial Level Program Level Portfolio Level
Seamless Adaptive
Designs: Combining
• Number of Subjects Conventional Phases in • Compound Finder
• Study Duration a Single Trial
• Indication Finder
• Treatment Duration
• Basket Trial
• Patient Population • Seamless Phase I/II
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Seamless Adaptive Designs
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Types of Adaptive Designs at the Program Level
• SAD or MAD combined with Biomarker-based Efficacy
Phase I/II Design • To identify the Optimal Safe Dose
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Types of Adaptive Designs at the Portfolio Level
• The fixed aspect of the trial is the indication (e.g., breast cancer) and the
Population Finder treatment (e.g., epidermal growth factor receptor inhibitor)
• The design aims to establish which subset of the population benefits most
• The competing options are several different compounds for the same
indication
Compound Finder • The design aims to identify the compound with the most impressive
therapeutic index
Population Finder • The design aims to dynamically change the allocation of new patients with
a given signature to different compounds
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Adaptive Platform Benefits
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Alzheimer’s
GBM Global
LUNG-MAP
Ebola
UK MATRIX
BATTLE
I-SPY 2
MICAT
On-going Platform Trials
• Many cancers
• Alzheimer’s
• Ebola
• Antibacterials
• CVOT for testosterone
gel
• Community acquired
pneumonia
• Scleroderma
*Berry DA. The Brave New World of clinical cancer research: Adaptive biomarker-driven trials
integrating clinical practice with clinical research. Molecular Oncology 9(2015):951-959.
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U.S. Congress bill:
21st Century Cures
One pager: TITLE III – MODERNIZING CLINICAL TRIALS
• “Encouraging broader utilization of efficient, flexible trial designs
… would help modernize the development and assessment of
potential new treatments”
http://energycommerce.house.gov/sites/republicans.energycommerce.house.gov/
files/114/Analysis/Cures/20150127-Cures-Discussion-Document.pdf
One pager: http://energycommerce.house.gov/sites/
republicans.energycommerce.house.gov/files/114/Analysis/Cures/20150127-Cures-
Discussion-Document-One-Pager.pdf
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Summary
• Adaptive designs offer much more than just sample size re-
estimation and early stopping
• Adaptive designs enable more effective decision-making
throughout the whole development process of a compound
• Adaptive designs assist and enhance the decision on which
compound to develop for which population
• The adoption of an adaptive design strategy across the drug
development process brings a number of important benefits:
– increased R&D efficiency,
– increased R&D productivity,
– increased probability of success at phase III
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