Date post: | 18-Jul-2015 |
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Increasing ageing population Prevalence of chronic debilitating diseases in over 65sCurrent therapies limited success
Increasing unmet medical needTendency for medicines to benefit smaller proportion of patient population
increasing emphasis on “Personalised Medicine”
Ability to deliver effective novel medicines to market declining
costs escalatingincreasing burden on healthcare budgets
“A Perfect Storm” in 21st Century Healthcare
2
Equates to growth from 3.5% to 8.5% GDP over
the same period
3
PricewaterhouseCoopers Reporthttp://www.pwc. com/gx/en/pharma-life-sciences/pharma-2020/pharma-2020- vision-
path.jhtml.
“
”
•We believe that, if the industry is to become more innovative and cut its R&D costs, four features will be vital: • A comprehensive understanding of how
the human body works at the molecular level
• A much better grasp of the pathophysiology of disease
• Greater use of new technologies to “virtualise” the research process and accelerate clinical development
• Greater collaboration between the industry, academia, the regulators, governments and healthcare providers.
What is Avicenna?
Ab Al al- usayn ibn Abd All h ibn Al-Hasan ū ʿ ī Ḥ ʿ āibn Ali ibn S nī ā
The Canon of Medicine 1025 AD In Silico Clinical Trials: How Computer
Simulation Will Transform The Biomedical Industry
An international research and development roadmap for an industry-driven initiative
EC funded Cooperation and Support Action
In silico clinical trials• The use of patient-specific computer modelling
and simulation applied in the research and development of new biomedical products, as well as in their evaluation and assessment
• Both clinical and pre-clinical. • From physiology-based pharmacokinetics to
collections of patient-specific dynamic models• Quantitative data, including medical imaging
and sensing• Dynamic system view
Not a “single hit” phenomenon
Arise from maladaptations
that reflect an alteration in the
state of a system
Driven by the reorganisation of
regulatory networks ->
defective system response
Correction requires
identification of key control
points focusing on
normalising system response
Complex Multifactorial Diseases
6
Complex Network Analytics
7
StatisticsBioinformatics
‘Omics Data
Signatures, Profiles, Associations, InferenceSignatures, Profiles,
Associations, Inference
Static ViewStatic View
Modelling & Simulation
8
Courtesy Prof Peter Sorger, Harvard Med Sch
New
Sim
ulat
ion
Refine ModelVerify Simulation
Verify Simulation
“Validated”ModelModel
“Validated”ModelModel
Dynamic not Static
Dynamic not Static
Mapping the territory: a new ISCT industry
Merging two existing sectors: • Clinical trial industry (provides design, execution and interpretation of clinical trials)
+• Virtual Prototype industry (provide in silico design and assessment for industrial sectors – aero-space, nuclear…)
Objectives
• Stakeholder engagement• Map processes -> CT• Identify points of CM&S application• Collect data from widest possible sources• Acquire opinions on key themes• Identify key areas & topics for action -> roadmap• Achieved using AO process- Schellingpoint LLP
Opinion Surveys
Producers
Spenders
Providers
Consumers Research
Regulators
Alignment Cycles gather and process the
four categories of opinion that drive our actions and inaction
Alignment Cycles gather and process the
four categories of opinion that drive our actions and inaction
2014-05-27 20:44Foundation Document
Sida 1 av 2https:/ /aot.schellingpoint.com/foundation_documents/1872/edit
F o u n d a t i o n D o c u m e n tF D T h e C u r r e n t S t a t e o f I n S i l i c o C l i n i c a l T r i a l s
T h e e n d o r s e d o p i n i o n s d e s c r i b i n g t h e c u r r e n t s t a t e , t r e n d s , a s s e t s a n d g u i d i n g p r i n c i p l e s a n d v a l u e s g u i d i n g t h e a d v a n c e m e n t o f I n S i l i c o C l i n i c a l T r i a l s
B e n e f i t - C T , B e n e f i t - P h a r m a , B e n e f i t s , B e n e f i t s - D e v i c eM a n y d e v i c e C T s t u d i e s i n v o l v e a l o w n u m b e r o f p a t i e n t s , l e a d i n g t o l o w q u a l i t y w i t h o u t a b r o a d b e n e f i t t o t h e d e v i c e i n d u s t r y .T h e a p p l i c a t i o n o f I S C T i s m i n i m a l w i t h i n t h e p h a r m a i n d u s t r y .T h e r e a r e e x a m p l e s o f s u c c e s s f u l I S C T .T h e r e i s e v i d e n c e o f u s e . C o n f u s i o n m a y a r i s e f r o m t h e u s e o f I S C T a n d a n . . . t h a t t h i s o n l y a p p l i e s t o c l i n i c a l t r i a l s a l o n e n o t d i s c o v e r y a n d p r e c l i n i c a lT h e r e i s g r e a t i n t e r e s t i n I S C T i n p h a r m a .
D e v i c e s , D i s e a s e s , W h e r e , W h e r e - D e v i c e sA n e c d o t a l e v i d e n c e s u p p o r t i n g t h e s e s t a t e m e n t s e x i s t s .D e v i c e C T f a i l u r e s o c c u r m o s t i n t h e l a s t 1 0 % o f t h e p i p e l i n e w h e r e 9 0 % o f t h e a c t i v i t y n e e d e d t o g e t t h e d e v i c e o u t t o m a r k e t t a k e s p l a c e .I S C T w i l l h e l p u s u n d e r s t a n d h o s t - d e v i c e r e s p o n s e u p t o 8 0 % .S o m e s i m p l e t a r g e t s w i l l a p p e a r i n b o t h t h e d e v i c e a n d t h e m e d i c i n e s a r e n aT h e r e a r e I S C T u s e d i n P K P D , p e d i a t r i c s , a n d f o r m u l t i - t r i a l s i n e l d e r l y , t h a t s h o w m o d e l - s p e c i f i c a s p e c t s o f t h e t r i a l .T h e r e w i l l b e g r e a t e r o p e n n e s s t o I S C T m e t h o d s i n a r e a s w i t h h i g h r e s e a r c h a c t i v i t y .
C a p a b i l i t i e sI S C T w i l l n e v e r r e p l a c e e n t i r e l y c l i n i c a l t r i a l s , b u t o n l y r e d u c e a n d r e f i n e t h e m .
D a t a , M o d e l i n g , M o d e l i n g - M e t h o d sA p o o r e x a m p l e o f u s i n g I S C T i s w h e r e g r o u p s a r e f o c u s e d o n s p e c i f i c a r e a s b u t d o n o t i n c l u d e t h a t i n t h e C T w o r k f l o w .A n e x c e l l e n t e x a m p l e o f I S C T i s w h a t i s b e i n g d o n e i n t h e v i r t u a l p h y s i o m e , b u t . . . i s s t i l l a l o t t o d o b e f o r e i t g e t s c l o s e t o w h a t ’ s g o i n g o n i n t h e b o d y .A t t e m p t s a r e b e i n g m a d e t o r e p l a c e s o m e o r g a n f u n c t i o n s i n s i l i c o u s i n g b i o m i m e t i c s .C o m b i n a t o r i a l c h e m i s t r y h a s e n h a n c e d d i s c o v e r y .C o m p u t e r b a s e d m o d e l s a r e b e i n g u s e d t o s t u d y t h e i n f l u e n c e o f p h a r m a c o g e n o m i c s .F o r I S C T t o u l t i m a t e l y w o r k , w e w i l l n e e d t o c r e a t e t h e S y s t e m s D y n a m i c s m o d e l o f t h e h u m a n b o d y .G o o d e x a m p l e s o f t h e p o t e n t i a l o f I S C T h a v e b e e n p r o t o t y p e d b y E n t e l o s , b u t n o t s u c c e s s f u l l y i m p l e m e n t e d .L a c k o f c l a r i t y r e g a r d i n g d a t a m g m t a n d i t s a p p l i c a t i o n i n t h e c l i n i c a l c o n t e x tM i c r o f l u i d i c s a n d n a n o t e c h n o l o g y a r e h u g e l y d i s r u p t i v e a n d w i l l r e s u l t i n c o n s e q u e n c e s f o r e x i s t i n g C T b u s i n e s s e s .M o d e l i n g a n d s i m u l a t i o n i s b e i n g u s e d b o t h i n a c a d e m i a a n d i n i n d u s t r y . C o n f u s i o n a r r i s e s o v e r t h e e m p h a s i s t h a t I S C T i m p l i e s o n c l i n i c a l t r i a l u s e .M o d e l i n g a n i m a l t o h u m a n - t h e r e h a v e b e e n w h o l e c o m p a n i e s e s t a b l i s h e d t o d o t h i s - b u t w i t h n o m a t e r i a l r e s u l t s .P h a r m a c o l o g y m o d e l s d o e x i s t f o r u n d e r s t a n d i n g c h e m i c a l i n t e r a c t i o n m o d e l i n g .P r o b l e m s t h a t h a v e b e e n e n c o u n t e r e d i n m a p p i n g r e a l i t y w i t h m o d e l l i n g o u t c o m e s i n p r o c e s s d e s i g n c a n b e u s e f u l t o d e v e l o p i n g I S C T .Q u a n t i t a t i v e s y s t e m s p h a r m a c o l o g y i s a n a r e a t h a t h a s e n j o y e d s o m e a d o p t i o n .
T h e r e a r e f e w e x a m p l e s o f m o d e l s t h a t c a n p r e d i c t d r u g a b s o r p t i o n , d i s t r i b u t i o n , m e t a b o l i s m , e x c r e t i o n a n d t o x i c o l o g y ( A D M E T ) .W e c a n b e g i n t o a d v a n c e I S C T w i t h t h e s c i e n c e a n d m o d e l i n g c a p a b i l i t i e s w e h a v e n o w - m o d e l i n g c a p a b i l i t i e s a r e n o t w h a t i s h o l d i n g u p p r o g r e s s .W e h a v e n o t y e t e x p l o i t e d t h e m o d e l s a n d s i m u l a t i o n s t h a t a l r e a d y e x i s t .W i t h m o r e a n d m o r e E H R i n c o u n t r i e s , t h e i n n o v a t i o n w i l l b e c o m e a c c e s s i n g h e a l t h o u t c o m e s d a t a .
U s e r s , V a l i d a t i o nO v e r - s o p h i s t i c a t i o n o f m o d e l s i s n o t t h e r e a s o n t o d a y ' s I S C T m e t h o d s s u f f e r l o w a d o p t i o n .T h e v a l i d a t i o n o f m o d e l s i s f a r f r o m s u f f i c i e n t n o w .
C o l l a b o r a t i o n , K n o w l e d g e T r a n s f e r , O t h e r C o m m u n i t i e sA c u l t u r e o f t r u s t a n d o p e n n e s s i s r e q u i r e d t o m a k e I S C T s u c c e s s f u l .I S C T i s h u g e l y m u l t i d i s c i p l i n a r y a n d c a n n o t b e d e l i v e r e d b y s m a l l g r o u p s w o r k i n g i n a l a b .M o d e l i n g a n d s i m u l a t i o n a p p r o a c h e s a r e c l e a r l y b e i n g u s e d w i t h i n b i o m e d i c a l . . . L a c k o f c o n v i n c i n g e v i d e n c e e x i s t s r e g a r d i n g w h e r e i t c a n b e o p t i m a l l y u s e d n o w .
C u l t u r e , F i n a n c e sP h a r m a c a n n o t a f f o r d t h e i n c r e a s i n g c o s t o f f a i l u r e a n d m u s t a d v a n c e I S C T .R e s i s t a n c e t o I S C T w i l l e x i s t f r o m b a s i c R & D t o r e g u l a t o r s u n t i l w e c a n s h o w t h a t i t h a s a r e m o t e c h a n c e o f s u c c e e d i n g .
a b o u t c o n t a c t u s a n d e r s s i g n o u t h o m e
m e a s u r e m a x i m i z e a d m i n Avicenna
The Alignment Cycle translated ‘We each think’
into -We are here
-We should go there-This is how to get there
The Alignment Cycle translated ‘We each think’
into -We are here
-We should go there-This is how to get there
Class Analysis• Alignment within a
class (balls)• Alignment between
classes (lines)• Green= excellent,
Yellow= good• Line thickness= level
of alignment• Table- detail of
alignment levels across categories
• Industry statistics show standard alignment index is in the order of 44-83•Avicenna is very high by comparison•Indicates strong basis for future collaboration
• Industry statistics show standard alignment index is in the order of 44-83•Avicenna is very high by comparison•Indicates strong basis for future collaboration
Summary of AO delivery
• What we have– A refined and comprehensive view of the
stakeholder landscape– A better understanding of what constitutes “ISCT”-
beyond Clinical Trials– Key, detailed data on topics and areas of focus
• How we are applying it– The foundation content to build the detailed
Roadmap– Building a time-phased action plan for implementing
the Roadmap
Biomedical Industry
clinical trialsindustry
clinical trialsindustry
Virtual Prototypeindustry
Virtual Prototypeindustry
IT industry
CAE tools
CRO
Regulatory
Engineering firms
Researchhospitals
“Engaged Discussants”Community of Practice
Roadmap Industrial Alliance
Informs
Alliance Objectives
• Prototype & build confidence in application of CM&S
• To lobby the EC to fund ISCT in H2020• Develop a mid/long term vision for
ISCT
Alliance Activities ➨• Develop and disseminate “Good Modelling Practices” for the
use, verification, validation, and accreditation of ISCT
• Promote events that foster interdisciplinarity and related training
• Promote, sustain, and disseminate data and model sharing
• Develop educational content and provide targeted training
• Maintain an observatory of all ISCT success stories
• Secure funding for ISCT research and technological development
• Drive necessary standardisation and interoperability efforts
Alliance: Lobbying & Influencing
• A European Trade Association for in silico medicine
• Market focused• A platform for industries and research
institutions to discuss bottlenecks to progress on in silico medicine
• The go-to Association for all things in silico in European Politics.
General Benefits for Members
• Targeted at all those with a vested interest in the in silico market eg: Pharma, Medtech, Cosmetics, Software industries, Research institutions
• Ability to set the policy and advocacy agenda of the Association in year 2
• Access to Rohde Public Policy expertise/VPH PAWG analysis of all Regulatory and policy issues affecting specific market interests
• Potential opportunity to create new funding streams for in silico research: Public Private Partnership
Public Private Partnership• EC conversation -> invitation to
consider more ambitious alternative to Alliance concept
• Work with industry to scope a plan and make a proposal
• Industry-driven, EC, Academics • Implications- financial (huge),
governance, oversight, legal and ethical, management
• Potential to move from demonstrating evidence of utility to full implementation and ultimately routine practice
Current Status
• Outreach to industry ongoing• Likely that key MEP will be honorary President
of the Alliance• First gathering of emerging Alliance partners in
Barcelona in June• Exploratory discussions with EMA held• Active discussions with EFPIA- link to IMI2 and
SGGs• Contact with EC ongoing to ensure feasible
timeline for PPP submission
“The Virtual Physiological Human (VPH) will revolutionise the way health knowledge is
produced, stored and managed as well as the way in which healthcare is currently delivered”
- European Commission
AVICENNAEVENT 5
Hosted by AQuASAgency for Health Quality and Assessment of Catalonia
4th and 5th June 2015, Barcelona, Spain
In Silico Clinical Trials: the future is now