2013 OpenClinica Global Conference: June 21, 2013OpenClinica Enterprise for Clinical Trial in Japan

*Y Natsumeda, * T Osako and H Maniwa

Mount Fuji

Yokohama

KawasakiTokyo

Haneda/Tokyo AirportTamagawa

River

KanagawaYokohama　 Mitsui Building

KSLION

Keihin Life Innovation Global Strategic Zone applied to the Government by Yokohama, Kawasaki, Kanagawa (Sep 2011)

Information Services International Dentsu (iSiD)* Key Support for Life Innovation (KSLION)

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.

1. High cost per patient

2. Poor performance

3. Pharma and Biotech exclude Japan from global development program until POC trial promising results.

4. Poor experience in FIH, POC or international collaborative clinical trials in Japan

5. Many trials designed to confirm overseas trials

2 ～ 6 times more expensive than either USA or EU

Nine out of 10 compounds in clinical trials fail to get approved.

Too many sites, too few patients per site per trial - requiringJ-GCP to enforce each trial site have independent IRB (1997).

Lack of enthusiasm of physicians

Difficult to develop clinical trial leaders and infrastructure

Japanese Clinical Trial System

Reality of New Drug Development

0102030405060708090

100

Su

cces

s R

ate

(%)

Phase I Phase II Phase III NDA Approval

Stage of Development

　　　 Kola and Landis, Nature Review Drug Discovery, 2004 (3):711-715

POC

Safety

Japan　Lags　behind　Many　Countries　in　International　

Collaborative　Trials

＜Data　from　2008　European　Federation　of　Pharmaceutical　Companies,　PhRMA＞

Japan　ranked　60th　among　87　countries　　　　　　　　　　　　　　　Total　protocols:　413　

Rank

CountryProtoco

l%

1 USA 264 63.9

2 Canada 175 42.4

3 Germany 171 41.4

4 Spain 133 32.2

5 France 132 32.0

6 England 124 30.0

7 Poland 110 26.6

8 Italy 108 26.2

9 Belgium 106 25.7

10 Australia 105 25.4

11 Mexico 86 20.8

12Czech　

Republic83 20.1

13Netherlands,　

Russia79 19.1

Rank

CountryProtocol

%

15Hungary,　Sweden

75 18.2

17 Argentina 73 17.7

18 South　Africa 71 17.2

19 Brazil,　Denmark 63 15.3

21 India 59 14.3

22 Korea,　Taiwan 51 12.3

41 Hong　Kong 27 6.5

47 Singapore 23 5.6

50 China 18 4.4

54 Pakistan 10 2.4

57 Indonesia 7 1.7

60 Japan 6 1.5

68 Vietnam 2 0.5

Phase I Submission

Approval　　

Clinical trials 6.1 years

Phase I

Clinical trials 4.5 years Review1.1 years

Drug lag3.8 years

SubmissionApproval

Review1.8 years

1.9 years

Japan

USA

　　

　　

Phase I lag Phase I is initiated only after overseas POC shows promising.

Asahi Newspaper June 9, 2010

High cost/Poor performance

Japanese clinical trials are designed to replicate and validate previous studies, therefore, results cannot be

published in top medical journals.

Ranking of Basic and Clinical Research　　　 Basic Research Clinical Research

Nature Med, Cell, J. Exp. Med. NEJM, Lancet, JAMA 1993~97 1998~2002 2003~07 1993~97 1998~2002 2003~07

USA 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)

S. Korea － 15 (22) 39 (18) － － －

World Competitiveness Rankings by IMD*

IMD*: International Institute for Management DevelopmentAnnouncement started in 1989

　World　Competitiveness　Rankings 　USA　

(1)Germany　(8)　UK　(15)

　Japan　(17)

　France　(19)　China　(31)

2011 Rankings 1 Hong Kong 1 USA 3 Singapore 4 Sweden 5 Switzerland 6 Taiwan 7 Canada 8 Qatar 9 Australia10 Germany11 Luxemburg12 Denmark13 Norway14 Holland15 Finland16 Malaysia17 Israel18 Austria19 China20 UK21 New Zealand22 South Korea23 Belgium24 Ireland25 Chile26 Japan27 Thailand28 UAE29 France30 Czech Republic

Where is innovative Japanese Industry?Toyota, Honda, Nissan, Isuzu, Mitsubishi,

Mazda, Subaru, Panasonic, SONY, Toshiba, Hitachi, SANYO, Fujitsu, Shiseido, Kikkoman,

Kirin, Nintendo, Tamagocchi, Seiji Ozawa, Tonegawa, iPS by Yamanaka, Ichiro, Gozzila,

etc?

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 performanceExcluded and isolatedLack of global experienceLack of leaders Immature infrastructure Drug lag & Device lag

Pre-PMDA consultationNetworking & GroupingCentral IRBICH-GCPCDISCFDA 21 CFR Part 11

Education for clinical researchGCP training & seminarsPMDA/YCU joint graduate coursePublic Private Partnership International workshop

High performanceHigh qualityLow cost PaperlessRemote

Eliminate drug lag and device lag

Revive Japan in Life Innovation

KSLION

2008

2012

2013

Current Activities & Future Vision of DCRI: Global Collaborations Such as HBD

Current Activities & Future Vision of DCRI: Global Collaborations Such as HBD

Mitchell　W.　Krucoff　MD,　FACC

Professor of Medicine / Cardiology

Duke University Medical Center

Director, Cardiovascular Devices Unit

Duke Clinical Research Institute

Mitchell　W.　Krucoff　MD,　FACC

Professor of Medicine / Cardiology

Duke University Medical Center

Director, Cardiovascular Devices Unit

Duke Clinical Research Institute

Yokohama City University: Clinical Research Seminar

December 20, 2008

Yokohama City University: Clinical Research Seminar

December 20, 2008

Duke Clinical Research InstituteDuke Clinical Research InstituteDuke Clinical Research InstituteDuke 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: 　 MembersCBMI 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

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

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

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

Dr. P. Tonellato Dr. P. Tonellato

Date Speaker Title

1 2009/9/28 Peter J. Tonellato Methodology and Infrastructure for Translational Science

2 2009/10/5 Takako TakaiActivities 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 BoguskiClinical and Educational Genomics -Personal experiences with direct-to-consumer genotyping-

5 2009/11/2 Dennis WallDisentangling autism through cross-disease computational analysis

6 2009/11/16 Sa'ndor Szalma TranSMART - data warehouse for translational research

72009/11/23

Akihiko KonagayaVirtual Patient Population Convergence: A New Framework for Translational Biomedical Informatics

8 Hiroshi TanakaStructure of protein interaction network and their implication on drug design

9 2009/11/30 Yutaka NatsumedaStatus of translational and clinical research in Japan and YCU's vision

10 2009/12/7 Vikas P. Sukhatme Promoting Translational Medicine

11 2009/12/14Vince Fusaro

Closing Remarks on the Fall '09 PalaverPeter J. Tonellato

CBMI Palaver Seminars on Translational Medicine, 2009CBMI Palaver Seminars on Translational Medicine, 2009

Joint International Conferences on Translational Research and Personalized Medicine in Yokohama

Feb 1, 2010 by YCU and HMS/CBMITo Translate Extensive Basic Research Data into Clinical

Research and PracticeFeb 2, 2010 by TMDU, YCU and HMS/CBMI

The Opening of the Next Generation in Omics-based MedicineFeb 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

Pharmaceuticals and Medical Devices Agency

http://www.pmda.go.jp/

　 PMDA ・ YCU Joint Graduate Course Started on April 1, 2010

February ～ April, 2011

Name

Sponsor Shionogi

CRO LINICAL

Sites Fukui　General　Hospital,　other　10　sites　in　Fukui　prefecture

SMO

IT　Services

Sehma

iSiD

Achieved in the trial1. Feasibility　search　for　the　sites　for　the　trial2. Paperless　IRB　review　and　approval　3. Prompt　and　secure　delivery　of　safety　information4. Remote　source　document　verification　(R-SDV)　5. Secure　storage　of　the　document6. Delivery　of　the　information　only　to　the　authorized　members

A　Test　Trial　to　Implement　IntraLinks　(Highly　Secure　Cloud　Storage　System)　into　Clinical　Trial　

Sites　and　Central　IRB　

Mount Fuji

Yokohama

KawasakiTokyo

Haneda/Tokyo AirportTamagawa

River

KanagawaYokohama　 Mitsui Building

KSLION

Keihin Life Innovation Global Strategic ZoneAdopted by the Japanese Government (Dec. 2011)

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• Efficacious clinical trial network• Partnering and Matching between discovery seeds and

medical needs• Construct a biobank integrated with the clinical

information database

Founded in June, 2012

26

Regenerative Medicine

Cancer/ Lifestyle diseases

Preventive Medicine

Collaborations among 4 Major SitesTonomachi Suehiro Fukuura

YCU

YCU

MinatomiraiMedicine/Technology

KSLION

YCU

YCU

Conferences, Exhibitions

RIKEN

Personalized preventive medicine/Innovative drugs and medical devices/Creating new industries

Keihin　Life　Innovation　Global　Strategic　Zone　

　　YCU 2 YCU hospitalsAdv Med Res Center Clin Pharm CenterGCP trainingsSeminars & workshops

Joint graduatecourse

PMDAFDA/EMA

Pre-PMDA

KSLIONClin trial NWCentral IRB

CRC support

FIH/Phase I

POC

Keihin 　NW　

Japan　NWAsian　NW

US　NW

EU　NW

Low costHigh performanceGlobal standards

Inte

rnat

ion

al

coll

abo

rati

ve t

rial

s

Devices

Basic Research

Academic

Bioventures

Pharmas

・Open source・・

Commercial source

・

Global standard EDC (Electronic Data Capture)

•　 Paper work to electronic system•　 Better, Faster, Cheaper• Global standards

CDISC　　:　Clinical　Data　Interchange　Standards　Consortium

28

OpenClinica　Training　Seminar

Dates: January 30 - February 1. 2013

Wednesday9:30-13:00 - Business Administration14:00-17:00 - Data Management Thursday 9:30-12:30 - Data Management (con’t…)13:30-14:30 - Monitoring15:30-17:00 - Clinical Research Coordination / Data Entry Friday 9:30-12:00 - Investigators / Data Specialists12:00-17:00 - 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.

年代別

（資料） CREI,アジア防災センター( 内閣府）

Disasters

Asia　３６６（３

７％）

DeathsAsia　

1.34　M（ 59％）

VictimsAsia　977　

M（ 89％）

DamageAsia　

$605　B　　（ 45％）

被災者数（百万人）

被害額（億ドル）

Nuclear Power Plants in East AsiaNatural disasters in the world (1978 – 2008)

31

Natural disasters in Asia (1978 – 2008)

32

A Project to Build Large Hospital ShipsBe ready for Natural DisasterActivities 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 m1,000 beds, 12 operation rooms

Building Realistic, Predictive Models of Disease: Drug Repositioning and Personalized Medicine

Pharmacodiagnostics can Streamline Clinical Development and Increase Value.

Broad patient population

Responders only

Cost of DevelopmentSuccess RatePatients Per NDAValue

>$1,000Million5-10%>2,000Good

< ＄ 500Million25-50%>600Better

Source: Pharma 2010: The Threshold of Innovation.

Traditional clinicaltrials

Pharmacogenomics-based trials

10-12 years 5-7 years

History of Metformin 1922 Synthesized 1927 Shown blood sugar reducing effect in rabbit 1957 Shown anti-diabetic effect in diabetic patients1958 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!