2013 OpenClinica Global Conference: June 21, 2013
KSLION
OpenClinica Enterprise for Clinical Trial in Japan
*Y Natsumeda, * T Osako and H Maniwa
Mount Fuji
Yokohama
Mitsui
Building
* Key Support for Life Innovation (KSLION)
Information Services International Dentsu (iSiD)
Kanagawa
Yokohama
Kawasaki
Tamagawa
River
Tokyo
Haneda/Tokyo Airport
Keihin Life Innovation Global Strategic Zone applied to the
Government by Yokohama, Kawasaki, Kanagawa (Sep 2011)
The focus of my talk is to demonstrate the importance and
value of the OpenClinica Enterprise in Japan.
Need: Japan has not fully addressed the promise of biotech,
health and life innovation, especially in clinical trials.
Value: Refinement of the clinical trial process in Japan will
promote tremendous innovation and, therefore, value in the
Japanese HealthCare System. I will describe recent efforts.
Vision: OpenClinica and related modification will streamline
the critical path, eliminate drug lag and device lag and revive
Japan in life innovation.
The focus of my talk is to demonstrate the importance and
value of the OpenClinica Enterprise in Japan.
Need: Japan has not fully addressed the promise of biotech,
health and life innovation, especially in clinical trials.
Value: Refinement of the clinical trial process in Japan will
promote tremendous innovation and, therefore, value in the
Japanese HealthCare System. I will describe recent efforts.
Vision: OpenClinica and related modification will streamline
the critical path, eliminate drug lag and device lag and revive
Japan in life innovation.
Japanese Clinical Trial System
1. High cost per patient
2 ～ 6 times more expensive than either USA or EU
2. Poor performance
Too many sites, too few patients per site per trial - requiring
J-GCP to enforce each trial site have independent IRB (1997).
3. Pharma and Biotech exclude Japan from global
development program until POC trial promising results.
Nine out of 10 compounds in clinical trials fail to get approved.
4. Poor experience in FIH, POC or international
collaborative clinical trials in Japan
Difficult to develop clinical trial leaders and infrastructure
5. Many trials designed to confirm overseas trials
Lack of enthusiasm of physicians
Success Rate (%)
Reality of New Drug Development
100
90
80
70
60
50
40
30
20
10
0
Safety
POC
Phase I
Phase II
Phase III
NDA
Approval
Stage of Development
Kola and Landis, Nature Review Drug Discovery, 2004 (3):711-715
Japan Lags behind Many Countries in
International Collaborative Trials
Japan ranked 60th among 87 countries
Total protocols: 413
Rank
Country
Protocol
%
Rank
Country
Protocol
%
1
USA
264
63.9
15
Hungary, Sweden
75
18.2
2
Canada
175
42.4
17
Argentina
73
17.7
3
Germany
171
41.4
18
South Africa
71
17.2
4
Spain
133
32.2
19
Brazil, Denmark
63
15.3
5
France
132
32.0
21
India
59
14.3
6
England
124
30.0
22
Korea, Taiwan
51
12.3
7
Poland
110
26.6
41
Hong Kong
27
6.5
8
Italy
108
26.2
47
Singapore
23
5.6
9
Belgium
106
25.7
50
China
18
4.4
10
Australia
105
25.4
54
Pakistan
10
2.4
11
Mexico
86
20.8
57
Indonesia
7
1.7
12
Czech Republic
83
20.1
60
Japan
6
1.5
13
Netherlands, Russia
79
19.1
68
Vietnam
2
0.5
＜Data from 2008 European Federation of Pharmaceutical Companies, PhRMA＞
Japanese clinical trials are designed to replicate and
validate previous studies, therefore, results cannot be
published in top medical journals.
Japan
Phase I lag
Phase I is initiated only after overseas POC shows promising.
Submission
Phase I
High cost/Poor performance
Approval
1.9 years
Review
1.8 years
Clinical trials 6.1 years
Phase I
Submission
USA
Approval
Clinical trials 4.5 years
Review
1.1 years
Drug lag
3.8 years
Asahi Newspaper June 9, 2010
Ranking of Basic and Clinical Research
Basic Research
Clinical Research
Nature Med, Cell, J. Exp. Med.
1993~97 1998~2002 2003~07
NEJM, Lancet, JAMA
1993~97 1998~2002 2003~07
3,097 (1)
2769 (1)
2674 (1)
3314 (1)
3695 (1)
2677 (1)
Germany
321 (3)
404 (2)
442 (2)
253 (6)
511 (3)
343 (4)
Japan
236 (6)
371 (3)
369 (3)
122 (12)
183 (12)
74 (18)
UK
365 (2)
352 (4)
314 (4)
920 (2)
1484 (2)
873 (2)
France
239 (5)
256 (5)
269 (5)
274 (5)
432 (5)
300 (5)
Canada
227 (7)
209 (6)
204 (6)
377 (3)
502 (4)
462(3)
Switzerland
244 (4)
209 (6)
166 (7)
166 (8)
261 (9)
252 (9)
Italy
132 (8)
132 (8)
155 (8)
236 (7)
374 (7)
279 (7)
Holland
109 (9)
114 (9)
127 (9)
277 (4)
410 (6)
294 (6)
Australia
97 (10)
106(10)
120(10)
155 (9)
282 (8)
260 (8)
China
1 (36)
8 (25)
53 (13)
20 (30)
59 (21)
102 (15)
15 (22)
39 (18)
－
－
USA
S. Korea
－
－
2011 Rankings
1 Hong Kong
1 USA
World Competitiveness Rankings by IMD*
3 Singapore
4 Sweden
5 Switzerland
World Competitiveness Rankings
6 Taiwan
7 Canada
8 Qatar
USA (1) Industry?
Where is innovative Japanese
9 Australia
Germany
Toyota, Honda, Nissan, Isuzu, Mitsubishi,10
Mazda,
Germany (8) 11 Luxemburg
12 Denmark
Subaru, Panasonic, SONY, Toshiba, Hitachi,
13 Norway
UK
(15)
SANYO, Fujitsu, Shiseido, Kikkoman, 14
Kirin,
Holland
15 Finland
Nintendo, Tamagocchi, SeijiJapan
Ozawa,
Tonegawa,
(17) 16 Malaysia
17 Israel
iPS by Yamanaka, Ichiro, Gozzila, etc?
18 Austria
19 China
France (19)
20 UK
21 New Zealand
22 South Korea
China (31)
23 Belgium
24 Ireland
25 Chile
26 Japan
27 Thailand
UAE
IMD*: International Institute for Management Development 28
29 France
Announcement started in 1989
30 Czech Republic
The focus of my talk is to demonstrate the importance and
value of the OpenClinica Enterprise in Japan.
Need: Japan has not fully addressed the promise of biotech,
health and life innovation, especially in clinical trials.
Value: Refinement of the clinical trial process in Japan will
promote tremendous innovation and, therefore, value in the
Japanese HealthCare System. I will describe recent efforts.
Vision: OpenClinica and related modification will streamline
the critical path, eliminate drug lag and device lag and revive
Japan in life innovation.
High cost
Poor performance
Excluded and isolated
Lack of global experience
Lack of leaders
Immature infrastructure
Drug lag & Device lag
2008
Education for clinical research
GCP training & seminars
PMDA/YCU joint graduate course
Public Private Partnership
International workshop
Revive Japan in Life Innovation
2012
Eliminate drug lag and device lag
KSLION
High performance
High quality
Low cost
Paperless
Remote
2013
Pre-PMDA consultation
Networking & Grouping
Central IRB
ICH-GCP
CDISC
FDA 21 CFR Part 11
Current Activities & Future Vision of DCRI:
Global Collaborations Such as HBD
Yokohama City University:
Clinical Research Seminar
December 20, 2008
Mitchell W. Krucoff MD, FACC
Professor of Medicine / Cardiology
Duke University Medical Center
Director, Cardiovascular Devices Unit
Duke Clinical Research Institute
Duke Clinical Research Institute
• > 1,000 faculty & staff
(205 faculty)
• > $100 M annual activity
(2/3 from industry)
• world’s largest ARO
• not for profit
• faculty interest-driven mission:
• academic & scientific integrity
• clinical care for unmet medical needs
• public health
• different culture from big CROs
CBMI Palaver Seminars: Members
 Center for Biomedical Informatics, Harvard Medical School
 Laboratory for Personalized Medicine, Harvard Medical School
 Harvard Molecular Technology Group & Lipper Center for
Computational Genetics, Harvard Medical School
Dr. P. Tonellato
 Regenerative Biology, Wisconsin University
 Great Lakes WATER Institute, Wisconsin University
 National Center for Biomedical Computing, USA
 The School of Biomedical Science, Tokyo Medical and Dental University
 Recombinant Data Corp. , USA
 Johnson & Johnson Corp. , USA
 The Partners HealthCare Center for Personalized Genetic Medicine, Harvard
Medical School
CBMI Palaver Seminars on Translational Medicine, 2009
Date
Speaker
Title
1
2009/9/28
2
2009/10/5
Takako Takai
Activities in education and research on translational
research at Tokyo Medical and Dental University, Japan.
3
2009/10/19
Vince Fusaro
Using Existing Data to Improve Translational Research
4
2009/10/26
Mark Boguski
5
2009/11/2
Dennis Wall
6
2009/11/16
7
8
9
10
Peter J. Tonellato Methodology and Infrastructure for Translational Science
Clinical and Educational Genomics -Personal experiences
with direct-to-consumer genotypingDisentangling autism through cross-disease computational
analysis
Sa'ndor Szalma TranSMART - data warehouse for translational research
Virtual Patient Population Convergence: A New Framework
for Translational Biomedical Informatics
2009/11/23
Structure of protein interaction network and their implication
Hiroshi Tanaka
on drug design
Status of translational and clinical research in Japan and
2009/11/30 Yutaka Natsumeda
YCU's vision
Akihiko Konagaya
2009/12/7 Vikas P. Sukhatme Promoting Translational Medicine
Vince Fusaro
11 2009/12/14
Peter J. Tonellato
Closing Remarks on the Fall '09 Palaver
Joint International Conferences on Translational Research
and Personalized Medicine in Yokohama
Feb 1, 2010 by YCU and HMS/CBMI
To Translate Extensive Basic Research Data into Clinical
Research and Practice
Feb 2, 2010 by TMDU, YCU and HMS/CBMI
The Opening of the Next Generation in Omics-based Medicine
Feb 3, 2010 by FDA, DCRI, HMS/CBMI, YCU
Strategy and Scientific Tools to Facilitate Processing Basic
Discovery Seeds to Meet Medical Needs
Minatomirai, Yokohama
Harvard Medical School, Mallinckrodt Professor of Pathology,
Dr. Jeffrey Saffitz March 3, 2010
Duke Clinical Research Institute, Chief Operating Officer,
Ms. Miriam Donohue
March 5, 2010
PMDA・YCU Joint Graduate Course
Started on April 1, 2010
http://www.pmda.go.jp/
Pharmaceuticals and Medical Devices
Agency
A Test Trial to Implement IntraLinks (Highly Secure
Cloud Storage System) into Clinical Trial Sites and
Central IRB
February ～ April, 2011
Name
Sponsor
Shionogi
CRO
LINICAL
Sites
Fukui General Hospital, other 10 sites in Fukui
prefecture
SMO
Sehma
IT Services
iSiD
Achieved in the trial
1.
2.
3.
4.
5.
6.
Feasibility search for the sites for the trial
Paperless IRB review and approval
Prompt and secure delivery of safety information
Remote source document verification (R-SDV)
Secure storage of the document
Delivery of the information only to the authorized members
Keihin Life Innovation Global Strategic Zone
KSLION
Adopted by the Japanese Government (Dec. 2011)
Mount Fuji
Yokohama
Mitsui
Building
Kanagawa
Yokohama
Kawasaki
Tamagawa
River
Tokyo
Haneda/Tokyo Airport
Keihin Life Innovation Global Strategic Zone
adopted by the Japanese Government (Dec, 2011)
The goals are to develop innovative medicines and
devices to achieve personalized medicine.
Strategic aims (selected):
• International collaborative clinical trials to eliminate
drug/device lag
• Pre-PMDA functions
Founded in June, 2012
• Efficacious clinical trial network
• Partnering and Matching between discovery seeds and
medical needs
• Construct a biobank integrated with the clinical information
database
Collaborations among 4 Major Sites
Tonomachi
Suehiro
Fukuura
YCU
RIKEN
Regenerative Medicine
YCU
Cancer/ Lifestyle diseases
YCU
Preventive Medicine
YCU
Medicine/Technology
Minatomirai
Conferences, Exhibitions
KSLION
26
Personalized preventive medicine/Innovative drugs
and medical devices/Creating new industries
Basic
Research
Pre-PMDA
KSLION
Academic
Pharmas
Bioventures
Devices
Clin trial NW
Central IRB
CRC support
PMDA
Joint graduate
course
YCU
2 YCU hospitals
Adv Med Res Center
Clin Pharm Center
GCP trainings
Seminars & workshops
FIH/Phase I
Low cost
High performance
Global standards
POC
International
collaborative trials
FDA/EMA
Keihin NW
Japan NW
Asian NW
US NW
EU NW
Keihin Life Innovation Global Strategic Zone
CDISC : Clinical Data Interchange Standards Consortium
• Paper work to electronic system
• Better, Faster, Cheaper
• Global standards
Global standard EDC
(Electronic Data Capture)
Commercial
source
・
・
・
Open source
・
28
OpenClinica Training Seminar
Dates: January 30
- February 1. 2013
Wednesday
9:30-13:00 - Business Administration
14:00-17:00 - Data Management
Thursday
9:30-12:30 - Data Management (con’t…)
13:30-14:30 - Monitoring
15:30-17:00 - Clinical Research Coordination / Data Entry
Friday
9:30-12:00 - Investigators / Data Specialists
12:00-17:00 - CRF Design/ Additional questions/tutoring
29
Influence of Nuclear Power Plant Disaster to the Residents in Fukushima
• A cohort study should be done and exact data should be collected on how the
residents are affected with the exposure.
• Japan is responsible for reporting the data to the world.
• OpenClinica could be used for the cohort study.
• Opportunity for the EDC to be implemented in the clinical trial networks all over
Japan
60,000 people moved out
from Fukushima.
A total of 94 Red Cross hospitals in Japan
Even if Japan closes all nuclear power plants;
• There are many nuclear power plants in East Asia.
• Fukushima data will tell how to reduce the risk.
Natural disasters in the world (1978 – 2008)
Nuclear Power Plants in East Asia
年代別
Natural disasters in Asia (1978 – 2008)
Disasters
Asia ３６６
（３７％）
Deaths
Asia 1.34 M
（59％）
Victims
Asia 977 M
（89％）
Damage
Asia $605 B
（45％）
被災者数（百万人）
被害額（億ドル）
（資料）CREI,アジア防災センター(内閣府）
31
A Project to Build Large Hospital Ships
Be ready for Natural Disaster
Activities at Non-Emergency Situation
• Medical Patrol around Medical Depopulated Area
• Extend the Medical Patrol to South Asian Countries
• Domestic/International Contributions
• Downsize/Reduce Weight of Therapeutic and Diagnostic Devices
• Promote Industry for Medical and Nursing Devices
• Training Young Talents
• Creating jobs
Yokohama
Mercy (USA)
70,000 tons, 273 m x 32 m
1,000 beds, 12 operation rooms
32
Building Realistic, Predictive Models of Disease:
Drug Repositioning and Personalized Medicine
Pharmacodiagnostics can Streamline
Clinical Development and Increase Value.
Traditional clinical
trials
Pharmacogenomicsbased trials
Broad patient
population
Responders
only
10-12 years
Cost of Development
Success Rate
Patients Per NDA
Value
5-7 years
>$1,000Million
5-10%
>2,000
Good
<＄500Million
25-50%
>600
Better
Source: Pharma 2010: The Threshold of Innovation.
History of Metformin
1922 Synthesized
1927 Shown blood sugar reducing effect in rabbit
1957 Shown anti-diabetic effect in diabetic patients
1958 Approved
2001 Mechanism to reduce blood sugar is shown to activate AMPK
Effect of Metformin on Colorectal Aberrant Crypt Foci
K Hosono et al. Cancer Prev Res 3:1077-1083, 2010
Plans to implement OpenClinica
• YCU oncology group working in 6 major hospitals in
Keihin area agreed to use it for their studies.
• Several other local clinical trial networks such as
red-cross, Shikoku, Kyushu, Tokyo metropolitan are
under consideration.
• Fukushima cohort study is under discussion.
• Yokohama city now supports financially KSLION.
• US-Japan collaborative clinical trials could be run
with OpenClinica.
• Japan needs close collaborations with OpenClinica
for training and Enterprise supports.
The focus of my talk is to demonstrate the importance and
value of the OpenClinica Enterprise in Japan.
Need: Japan has not fully addressed the promise of biotech,
health and life innovation, especially in clinical trials.
Value: Refinement of the clinical trial process in Japan will
promote tremendous innovation and, therefore, value in the
Japanese HealthCare System. I will describe recent efforts.
Vision: OpenClinica and related modification will streamline
the critical path, eliminate drug lag and device lag and revive
Japan in life innovation.
Thank you!