Kazumichi Kobayashi
R&D Head Club / Office of Pharmaceutical Industry Research (OPIR)
Clinical Trial Environment and Capabilities in Japan
12th Kitazato-Harvard Symposium
Session 3: Review of Past Effort and Exploring the Future Possibilities in New Drug Development
May 14, 2013
Outline
R&D Head Club Clinical Trial
Survey in 2012
OPIR Web Survey on Attitude of
Investigators (Japan, Korea, US)
2
Quality: A variety of Understandings
High Quality Clinical Trials; • Data Accuracy ? • GCP/SOP compliance • Follow up (Adherence, Low Drop-out Ratio) • Ethical Consideration to the Subjects • Scientific Level (Level of Study Design, Free
from Bias, Variability of the Evidence)
3
R&D Head Club Clinical Trial Survey in 2012
R&D Head Club has conducted the clinical trial performance survey in Japan every year since 2004. Survey in 2012 is managed by Following Working Group Members and Data Center, under supervising Professor Takeuchi, Kitasato University.
Working Group Members Yuji Kawamura (Astellas) Manabu Okamoto (MSD) Kayoko Ikawa (GlaxoSmithKline) Yoshiko Inada (Chugai) Hiroshi Yamaguchi (Pfizer) Kayo Abe (Pfizer) Hitoshi Maruyama (Janssen)
Data Center
Research Center for Clinical Pharmacology in Kitasato University (Masahiro Takeuchi, Professor, School of Pharmacy, Kitasato)
4
Participating Companies
Survey in 2012 is collaborated by following 19 companies.
Abbott Japan Co., Ltd.
Astellas Pharma Inc.
Astra Zeneca K.K.
Bayer Yakuhin, Ltd.
Bristol-Myers K.K.
Chugai Pharmaceutical Co., Ltd.
Daiichi Sankyo Co., Ltd..
Eisai Co., Ltd.
Eli Lilly Japan K.K.
GlaxoSmithKline K.K.
Janssen Pharmaceutical K.K.
MSD K.K.
Nippon Boehringer Ingelheim Co., Ltd.
Novartis Pharma K.K.
Otsuka Pharmaceutical Co., Ltd.
Pfizer Japan Inc.
Shionogi & Co., Ltd.
Takeda Bio Development Center Ltd.
Takeda Pharmaceutical Company Ltd.
Note: Member companies of R&D Head Club in green 5
Survey 2012-1 Number of Protocols by Starting Year
1 4
1320
3542 39
43
5752
87
42
8
0
10
20
30
40
50
60
70
80
90
100
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
# o
f pr
oto
cols
Year of start
Total number of protocols for analysis = 328
(137)(109)(82)
(# of protocols)
6
Survey 2012-2 Background of Protocols
5.9%
6.4%
6.1%
8.8%
23.9%
20.7%
6.6%
3.7%
11.0%
15.6%
12.2%
16.9%
13.8%
17.1%
19.1%
13.8%
17.1%
15.4%
6.1%
16.2%
20.2%
17.1%3.7%
2.8%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
09-11 (136)
07-08 (109)
Disease Area 05-06 (82)
(# of protocols) Infec. Onco. Bone Neuro. Metabo. CV Resp. Other
69.3%78.0%
89.0%
30.7%22.0%
11.0%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
09-11 (137)07-08 (109)
Global Trial 05-06 (82)
(# of protocols) Domestic only Global
85.4%67.0%
24.3%
14.6%33.0%
75.7%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
09-11 (137)07-08 (109)
EDC 05-06 (74)
(# of protocols) Yes No
5.8%
3.6%
94.2%
96.4%
100.0%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
09-11 (137)
07-08 (83)
SDV 05-06 (7)
(# of protocols) Sampling SDV 100% SDV
7
14
14
14
6
11
11
35
56
49
85
101
112
110
109
82
48
60
53
0 50 100 150 200 250 300 350 400
09-11 (2933)
07-08 (2245)
05-06 (1680)
Days (Median)
Trial application - IRB IRB - Contract Contract - FPI FPI - LPI LPI - LPO LPO - CRF fix
(# of sites)
Survey 2012-3 Trial Speed (Trial Application-CRF fix)
8
Survey 2012-4 Trial Speed (Trial Application-CRF fix excluding LPI-LPO)
14
14
14
18
6
11
11
14
35
56
49
64
85
101
112
131
48
60
53
72
0 50 100 150 200 250 300 350
09-11 (2933)
07-08 (2245)
05-06 (1680)
00-03 (1626)
Days (Median)
Trial application - IRB IRB - Contract Contract - FPI FPI - LPI LPO - CRF fix
9
5 5 5
3 3 3 3
4 4 5
4 4 3
6
3
5 5 5 5
6 5
7 8 8
0
2
4
6
8
10
12
14
16
05-06 (2120)
07-08 (3088)
09-11 (3501)
05-06 (225)
07-08 (340)
09-11 (250)
05-06 (197)
07-08 (290)
09-11 (219)
05-06 (154)
07-08 (240)
09-11 (314)
05-06 (23)
07-08 (45)
09-11 (62)
05-06 (232)
07 -08 (389)
09-11 (275)
05-06 (615)
07-08 (843)
09-11 (1110)
05-06 (674)
07-08 (941)
09-11 (1271)
(# o
f sub
ject
s)
(# of sites)
Survey 2012-5 Number of Enrolled Subjects per Site by Type of Site
National / Public U.
Private U.
Clinic
ALL
Private HP
Public HP
◆ Median
National HP except for
NHO
NHO 10
¥0
¥500
¥1,000
¥1,500
¥2,000
¥2,500
¥3,000
¥3,500
¥4,000
¥4,500
¥5,000
05-06 (1949)
07-08 (2701)
09-11 (2757)
05-06 (190)
07-08 (264)
09-11 (169)
05-06 (173)
07-08 (234)
09-11 (156)
05-06 (139)
07-08 (212)
09-11 (183)
05-06 (23)
07-08 (43)
09-11 (31)
05-06 (210)
07-08 (357)
09-11 (231)
05-06 (575)
07-08 (734)
09-11 (882)
05-06 (639)
07-08 (857)
09-11 (1105)
Cos
t per
Sub
ject
: Yen
(# of sites)
Survey 2012-5 Cost per Enrolled Subject by Type of Site
National / Public U.
Private U.
Clinic
ALL
Private HP
Public HP
◆ Median
National HP except for
NHO
NHO
(X 1,000)
11
1212121313141515
171717
202223
2527
2930313232
3845
4863
6666
7779
9192
128
0 20 40 60 80 100 120 140
TurkeyGreekJapanCzech
New ZealandPeru
S. AfricaNorwayTaiwan
S. KoreaPortugalHungary
FinlandRussia
DenmarkMexicoAustria
SwitzerlandSweden
ArgentineBrazil
PolandNetherland
AustraliaSpain
ItalyBelgium
FranceUK
GermanyCanada
US
12
Number of Phase II, III Global Studies for JNDA approved from 2006 to 2011 (by countries)
(Studies)
OPIR News, No. 37, K.Genda「国内新薬における創出企業の国籍と治験実施国」, p46, fig 6, 2012 (Modified)
Total : 214 trials out of 948 (22.6%)
OPIR Web Survey on Attitude of Investigators working in the Japan, Korea and the US
①Survey Method： Web Survey (Internet) ②Investigators： Principal/Sub Investigators ③Experience： Participate more than 5 trials in the
preceding 3 years ④Number of Drs： 300 (100 of each country) ⑤Web Survey Period： Japan （2012/11/8-11/16） Korea（2012/11/12-11/28) US (2012/11/9-11/28) ⑥Internet Research Agency: Nielsen ⑦Researchers: Koichi Genda, Shingo Haseto (OPIR)
13 Source: OPIR News （政策研ニュース）, No. 38, p24-30, 2013
OPIR Survey-1 Background of Institutions of each investigator
22
5
22
10
18
45
14
17
5
24
49
19
30
11
9
0 20 40 60 80 100
Japan
Korea
US
State/Regional University
Private University
State/Regional Hospital
Private Hospital
Clinic
（人）
14 Source: OPIR News （政策研ニュース） No. 38, p25, fig.1, 2013
OPIR Survey-2 How many hours can you spend for the clinical trials?
28
8
4
52
44
36
15
35
42
2
10
12
1
4
2
3
2
0 10 20 30 40 50 60 70 80 90 100
Japan
Korea
US
Less than 1hr 1～5hr 5～15hr 15～25hr 25～35hr More than 35hr
(人)
15 Source: OPIR News （政策研ニュース） No. 38, p28, fig.7, 2013
(/week)
0 50 100 150 200 250
Gain access to the cutting-edge information
Earn research funds
Submit research papers
Contribute to the instituion or boss
Credit as own track record in medical society
Lead to own skill development in the future
Have enough time
Have many target patients
Protocol is simple and easy to understand
Target disease has few therapy options
Able to gain staff cooperation
Japan
Korea
US
OPIR Survey-3 What would make you more proactively participate in the clinical trials? Priority gives selection of five items, 1-5POINT sequentially. (Items below are excerpted from the original.)
16
(point)
Source: OPIR News （政策研ニュース） No. 38, p28, fig.4, 2013 (Modified)
0 10 20 30 40 50 60 70
Directly contact or visit trial sponsors and ask for trial participations
Make the hospital website rich with clinical trial information
Host presentations of clinical trial information (track records, facilities, etc.)
Publish clinical trial records at conferences etc
Other
Japan (15)Korea (38)US (75)
OPIR Survey-4 Do you make special efforts on a personal level to gain CTs? What kinds of effort?
17 Source: OPIR News （政策研ニュース） No. 38, p28, fig.6, 2013
(人)
OPIR Survey-5 Have you ever participated in training related to clinical trials except for GCP?
18 Source: OPIR News （政策研ニュース） No. 38, p29, fig.11, 2013
0 10 20 30 40 50 60 70
Bioethics/ Research ethics
Related laws and regulations
Drug development process/strategy
Data management
Statistical analysis
Cost related to clinical trials
Compensation for the health damage to subjects
GCP/Regulatory Authority audit
None
Japan
Korea
US
(人)
Quality Clinical Trials in Japan Strengthen or Weakness?
Over-Reaction
Over-Quality Important to improve Weakness • Cost Performance • Productivity • Speed
More important to conduct “Quality CTs”
• Minimizing Bias • Providing good environment/Infra-structure • Quality Clinical Plan & Strategy from
scientific/business point of view • Educated staff
19
