Clin Eval 33（3）2006
Session 2: National system and policy on T.R. at academy/university hospital

Translational research in Japan:
Opportunities and obstacles
Masanori Fukushima, Director, Dept Clinical Trial Design and Management,
Kyoto University Translational Research Centerof cancer in each country. Fortunately for this year,
Professor Masanori Fukushima, M.D.,
Ph.D. Director, Dept Clinical Trial
Design and Management, Kyoto
University Translational ResearchCenter; Translational ResearchInformatics Center at Kobe

we will have the 11th US-Japan Clinical Trial Summit Meeting. This meeting is focusing on multiple
myeloma. This is a very unique and very important project not only for the two countries, US andJapan, but also for the whole world because wehave determined a very unique and important

1. Introduction

prognostic factor for multiple myeloma. And thisFirst of all, I would like to express my plea-

meeting will be organized by Dr. Takashi

sure to hold this very extraordinary and uniqueUchiyama, the Director of the Kyoto University

meeting - Franco-Japanese First Translational Re-

Hospital, and will be held on April 7-9, 2006 at

search Initiative, today. I would also like to thankKyoto Miyako Hotel during the cherry blossom

Mr. Roy and Mr. Higuchi for their great effort inblooming season.

bridging the relationship between Saint LouisMy talk today is about the national system andHospital and Kyoto University Hospital. Also, mypolicy on translational research at academy andgreat thanks go to Professor Calvo and Saint Louis

university hospital. My talk is relatively the same

Hospital Director Professor Lajonchere. Thisas those presented by Professor Lajonchere. Whenmeeting was made possible by the quick decision-

we plan to collaborate or harmonize with othermaking of Professor Lajonchere when we visitedcountries, we must first understand and learn theSaint Louis Hospital last August and very friendly

healthcare systems which differ from country todiscussion with Professor Calvo. Many thanks.

country.

This very unique Franco-Japan Translational
Research Initiative reminds me of my visit to the

2. Healthcare system in Japan

United States some fifteen years ago when I met

This slide (Fig. 1) gives a short description

Dr. Charles A. Coltman, Jr. He is the chairman ofof the healthcare system in Japan. Our system isSouthwest Oncology Group, one of the biggest andvery unique in the world. We have a universal in-

the most active cancer clinical study group in thesurance system. Patients under this system usuallyworld. When we met in Houston, we agreed to start

pays very small amount of money in co-payment

a 10-year program for the review and exchange ofcompared to other countries. We have very uniqueinformation about clinical trials on a broad range

point system of reimbursement. Under this point− 499 −

臨 床 評 価 33巻 3号

2006system, the Japanese government allocates equiva-

to have opportunities detecting early stage diseases,

lent points for each medical procedure in order toFor example, detection rates of stage ¿ cancers

ensure equal opportunity for each patient and aim-

are substantially high. This is a very unique sys-

ing for equal results. This is quite different othertem. So I think it is important to learn thecountries. We also have free access system mean-

healthcare system of the country before discuss-

ing all doctors regardless of their specialty caning anything else.

treat see all patients. For example, gynecologists
or internists can see children or surgeons can see
dermatology patients. In the same vein, every

3. Translational Research Centersin Japanpatient can visit every doctor. Again this is quite

In 2001, the Ministry of Education, Science,different. This system guarantees diagnosis-Culture and Sports (MEXT) built two translational

oriented patient care and achieve early detection

research centers in Japan, one in Kyoto Univer-of diseases. Those systems allow Japanese patientssity and one in Tokyo University (Fig. 2). Following the year, four other translational research centers were built, in Osaka, Kobe, Kyushu, andFig. 1 Health Care System in Japan

Japan・Universal Insurance − small co-payment
・Dot System reimbursment
・Free Accessq Diagnosis oriented
q Early Detection
increase stage ¿Nagoya. Now, we have five university translational
research centers and one institute. There are otheruniversities which also challenge translational
researches - Chiba University, Keio University andTokyo University.
Each translational research center has different approach in clinical research and each TRC

Fig. 2 Translational Research Centers inJapan -1 Established by MEXT

has its own collection of seed compounds in different stages of clinical development (Table 1). Soquite frankly, the system is not well organized, but

5 Univ. Hosp. & 1 Res. Inst.

the five university translational research centersand one institute agreed to meet every year to hold2001 Tokyo, Kyoto
2002 Kobe
OsakaNagoya
Kyushudiscussions and exchange information. Each TRC
has a cell processing center (CPC) but only Kobe
TRC has a full GMP-level CPC. Unfortunately rightnow, Kyoto University Hospital CPC, which will
be presented later on by Professor Maekawa, isnot yet a full GMP-level CPC.
Table 1 TRC in Japan -2
1．Each TRC takes different approaches.
2．Each TRC has several seeds for clinicaldevelopment.
3．Each TRC has Cell Processing CTR (CPC).
TRC at Kobe has full GMP level CPC.

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Clin Eval 33（3）2006

The Common Operational Guideline is a kind

4. Kyoto University Translational
Research Initiativesof an amendment of government-issued Ethics
Committee regulation (Table 3). This was devel-

Kyoto University Hospital has taken initiative

oped by TR Consulting Group, an autonomous

to build infrastructure for translational researchgovernance initiative consisting of 5 leading uni-in terms of developing operational guideline ofversity hospitals and one research institute whichethical committee, data center and basis for clinicalI mentioned you earlier. This guideline was acti-practice (Table 2). This is a very important issuevated in 2004 and is scheduled for revision either

in Japanese university hospital, especially in our

this year or next year.

hospital. We have also taken initiative to carry out

Our hospital is currently undertaking many

investigator-sponsored IND registered trial. This

activities of new drug clinical development (Fig.

is really critical step to promote translational3). These activities include PGE analog and HGF

research in our country. In Europe and the Unitedwhich are IND-registered trials. We also haveStates, all translational research should be regis-

research on leptin, ghrelin and thioredoxin. Leptin

tered. Kyoto University Hospital has finallyand ghrelin are peptides and Phase 2 trials forachieved breakthrough to carry out investigator-

these peptides are ongoing. We are also now pre-sponsored IND registered trial, with ongoing trials

paring thioredoxin for IND-registered trial. bFGF

on Hepatocyte Growth Factor (HGF) and Prostag-is a regenerative medicine, and the results of trialslandin-E Receptor 4 Agonist.

in this area have been very successful. The six

Table 2 TRC at Kyoto Univ. Hospital takes
initiative

Table 3 Common Operational Guideline for theEthical Review of Translational Researchk To build infrastructure for TR in terms ofdeveloping operational guideline of EC, data centerand clinical practice basis.
kTo carry out investigator sponsored IND registeredtrial.
ex. HGF, and PGER4 agonist

Developed by the TR Consulting Group an autonomous
governance initiative consisting of 5 leading Univ.
Hospitals and 1 Res. Inst.
Activated in 2004.4.1
Scheduled revision 2006.4.1

Fig. 3 Ongoing Translational Researches at KUHP
2006.1classspecies

No. of trials

・Chemical

1

PGE analog

1・Hormone

2

leptin, ghrelin

3・Biologics

3thioredoxin, HGF , FGF

5・Cellular

2BMC, DC

2Total8＊：IND Registered

11＊＊

color：Regenerative Medicine− 501 −

臨 床 評 価 33巻 3号

2006

patients with peripheral artery obstructive disorderwith the joint funding from MEXT and Kobe City.

who received slow released bFGF treatment haveThis is the organization of the Translationalalready recovered. We also have the DC trial,Research Informatics Center at Kobe (Fig. 5). The

which is a trial on anti-cancer immunotherapy.

center has 4 medical supervisors, 6 biostatisti-

This is being conducted by Professor Uchiyama

cians, 8 protocol managers, 3 project and P/Cusing bone marrow cell. It is also currently ongoing.

managers, 8 registration/data managers, 2 staff
managing information distribution, 3 IT adminis-

5. Kobe Translational Research
Initiatives

trators (this is a very important position), and two
IT specialists system engineers. We also have 2Kobe city has a biomedical research instituteand a translational research informatics center

clinical database developer, one genetic databasedeveloper, and 2 secretariats.

(Table 4). The mission of this center is to supervise

At the Institute, we conduct more than 70

10 cancer translational research projects nation-

trials including phase 1, 2 and 3 clinical trials andwide and to disseminate translational researchoutcomes research, as well as genetic/biomarkers

methodology. These projects include cancer vaccine,and diagnostic studies or PET scan projects (Tablecellular therapy, viral therapy and molecular tar-5). Many of these projects are cancer trials.

geting therapy. One of these projects is thegamma-delta T-cell project which is conducted byFig. 4

Professor Minato at the Kyoto University.

Translational Research Informatics
Center at Kobe Founded in 2002

This photo shows the Kobe Translational Research Informatics Center built in 2002 (Fig. 4)

Table 4

Translational Research Informatics
CTR at Kobe has responsibilityk To supervise nation wide 10 cancer TR projects including cancer vaccine, cellular therapy, viraltherapy and molecular targeting therapy.
k To disseminate TR methodology.

Fig. 5 TRI Kobe Operation Team46Med. Supervisor

Biostatistician8Protocol Development

3Project & P/C Manager

3
Information Distributor

2

8Registration/DM2

IT Administrator

Clinical DB Developer

34Secretariat

Genetic DB Developer− 502 −Clin Eval 33（3）2006

Table 5 Ongoing & Protocol developing Trials& Studies at KUTRC & TRI Kobe

6. Major obstacles in translational
research in Japan2005.1We still have many obstacles to overcome toaccelerate clinical research and promote transla-Phase ¿Phase ¿−ÀPhase ÀPhase ÁOutcomes
Genetic/Biomarker
Diagnostictional research in Japan (Table 6). One majorobstacle is the lack of legislation to protect humantrial subjects. Also, we lack an established quality
assurance in investigator-initiated clinical trials
because many of these trials are non-registeredtrials. A solution to overcome these obstacles isTotal
21527
1421
63Cancer
2322
815
638859to encourage investigator-sponsored IND-registered trial (Table 7). Therefore, we need to har-Table 6 Major obstacles in Japan

monize our translational research activities withk Lack of law which protect human subjects.

those of the Europe and US.

k Lack of quality assurance in investigator initiatedclinical trial. (non-registered)

7. Translational research - National
strategy
In terms of national strategy (Table 8), toTable 7 Direction towards next 5 years

accelerate new drug development, we need tok Encourage investigator sponsored IND registeredtrial

encourage investigator-sponsored registered trial,
develop academia-industry complex as a new busi-→ harmonization of TR with EU & US

ness scheme just as France is doing. But we needto establish our own business scheme which is different from EU and US because Japan s business

Table 8 TR−National Strategy

culture is quite different from other countries. WeWhich should be taken to accelerate
new drug development.
k Encourage
Investigator Sponsored Registered Trialk Form Academia-Industry complex
as New Business schemek Enforce Laws for■ Protection of Human Subjects■ Assurance of Medical Practice Quality

also have to establish and enforce laws for protection of human subjects participating in clinical trials and establish quality assurance of medical practice. These last two points are very effective and ifthey are achieved, then Japan s translational
research activities can be harmonized with the EU
and the US. Thank you.

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