japan’s activities and challenges to promote multi ... · japan’s activities and challenges to...

31
Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director, Ministers’ Secreatriat, MHLW

Upload: lamngoc

Post on 03-Aug-2018

223 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Japan’s Activities and Challengesto promote Multi Regional Clinical Trials

Shinobu UZUInternational Planning Director,Ministers’ Secreatriat, MHLW

Page 2: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Action plan to promote clinical trials

Contents

Activities to promote MRCT in consideration of ethnic factors

Page 3: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

3

Regulatory Authorities in JAPAN

Pharmaceuticals & Medical Devices AgencyScientific Review for Drugs & Medical DevicesGCP, GMP InspectionConsultation on Clinical Trials etc.

Pharmaceuticals and Food Safety Bureau, MHLWFinal Authorization of applicationsPublishing GuidelinesAdvisory committeeSupervising PMDA Activities

PMDA MHLW

Page 4: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

95

7154 52

63

4360 60 56

96105 107 109

722

500

406 391

463424 438

361414

497 504530

495

0

100

200

300

400

500

600

700

800

0

50

100

150

200

250

300

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008(by MHLW)

First IND INDNew GCP publication

New GCP enforcementICH E5: Ethnic  Factors in the Acceptability of Foreign Clinical Data

First INDIND

3‐Years Clinical Trial Activation 

Plan(prolonged 1 year)

New5‐Years 

Clinical Trial Activation 

Plan

Number of IND Notifications

4

Page 5: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

New 5‐Years Clinical Trial Activation Plan

(1) Clinical Study Infrastructure Building

(2) Human Resource Development for Clinical Research

(3) Public Promotion of Clinical Trial and Encouraging Participation

(4) Efficient Clinical Research Management 

5

Targets:

Build nationwide infrastructure to perform innovative and valuable clinical research in a smooth manner

Network core clinical research sites where research skills and resources are highly integrated

Page 6: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Core

TR

Major

Network of clinical research centers

Core

Major

Expedite trial performance

Total 750M\ / year (approx. 7.5M$ / year)

10 Core clinical research centers 30 Major clinical trial institutionsTotal 1,000M\ / year (approx. 10M$ / year) Infrastructure

improvement

Alliance with related trial sites and accumulate trial subjects

Ensure timely access to new drug from clinical trial stage(satisfy unmet needs)

Promote innovation of new drug

Institutional reinforcement of staff and IT environment to support trials

Build site networking to accumulate subjects → cost down and speed‐up

○ Train human resources in-house and in the institutions in the net work

○ Strengthen IRB capacity○ Consolidate data management system○ Plan, Do, Assess clinical research

○ Secure Recruiting CRCs and other trial supporting staff

○ Support promotion of common IT plat home

Page 7: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

MCRC is a  center to smoothly perform trials (MHLW)

MCRC is a  center to smoothly perform trials (MHLW)

7

Nation‐wide network of TR/clinical trial centers

Local Trial Network(based on clinical trial promotion program)

TR CentersMajor Clinical Research CentreCore Clinical Research Centre

CCRC is able to plan and manage multi‐center trials (MHLW)CCRC is able to plan and manage multi‐center trials (MHLW)

TR center is to translate basic medical research to clinical trial (MEXT)

TR center is to translate basic medical research to clinical trial (MEXT)

Page 8: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

8

(2) Human Resource Developmentfor Clinical Research 

1.Training Programs (FY 2009)‐ CRC(basic, Advanced)‐ Local Data Manager‐ IRB member

2. e-Learning Systems for Clinical Researchers, CRC etc.

http://icrweb.jp/icr/ https://etrain.jmacct.med.or.jp/

Page 9: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

9

Page 10: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

10Drug Information Associationwww.diahome.org

(4) Efficient clinical research management

Harmonize administrative document formatsStreamline administrative work share between hospitals and sponsors

Page 11: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Action plan to promote clinical trials

Contents

Activities to promote MRCT in consideration of ethnic factors

Page 12: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Trends of MRCTs including Japan-% of MRCTs in Clinical Trial Notifications-

0

5

10

15

20

25

0

50

100

150

200

250

300

% o

f MR

CTs

Num

bers

of A

ll C

TN

Late FY2007

EarlyFY2007

(Apr-Sep)

Late FY2008

EarlyFY2008

EarlyFY2009

(Oct-Mar) (Apr-Sep) (Oct-Mar) (Apr-Sep)

Late FY2009

(Oct-Mar)

EarlyFY2010(Apr-Jul)

Page 13: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Source: PMDA

Increasing trend toward multi‐centered trials

PMDA’s trial consultation basis

1119

40

76

101 99

5.7 8.7

13.9

27.0

32.1 29.6

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

0

20

40

60

80

100

120

140

2004 2005 2006 2007 2008 2009

Ratio of m

ulti‐cen

tered trials (%

)

Num

ber o

f con

sultations

Page 14: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

12.4%

55.8%

15.0%

16.8%

Operational Regions of Global Clinical trials in FY2009

East-Asia Only

Japan+US/EU

World-Wide

Unknown

FY2009

Page 15: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

15

Global Core Research Center

M M

Core

M M MM

Network of core/basic medical facilities for activating clinical research/trials

Core

Execution support system

Goal: Reinforcement of clinical trial institution in Japan and promotion of  simultaneous global development of innovative drugs

・ System for smoothly working out English contract and accounting based on international standards

・ Central ethical review function・ International research planning/data 

analysis (Senior data managers and computer technicians can be secured)

・ Setup as a domestic exploratory clinical research center (securing doctors, test technicians, radiologic technicians, etc.) 

・ Fostering of doctors to become international research support personnel and supply the personnel to the sites and bases

・ To secure human resources for constructing systems and strategies for the management of intellectual property.

・ Accumulation and organizational coordination of case information.

Functions to be provided

Started in 2009 with budget of \400 million

KEIO KITASATO

Global Core Research Center for Clinical Trial

Foreign Clinical Research Network

Foreign Clinical Research Network Joint research 

& collaboration

Page 16: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

How to extrapolate Foreign Data‐ Suitable Doses can be different among regions ‐

Arnold FL et al , Clin Pharmaco Therapeut., 87: 714-720, 2010

For 32 % of drugs, US/EU dose was > 2 times higher than Japanese dose Approved drugs in 2001-2007

Page 17: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

The purpose of ICH E5 GuidelineEthnic Factors in the Acceptability of Foreign Clinical data • To describe the characteristics of foreign

clinical data that will facilitate their extrapolation to different populations and support their acceptance as a basis for registration of a medicine in a new region*.

• To describe regulatory strategies thatminimize duplication of clinical data and facilitate acceptance of foreign clinical data in the new region.

• To describe the use of bridging studies*, when necessary, to allow extrapolation of foreign clinical data to a new region.

• To describe development strategies capable of characterizing ethnic factor influences on safety, efficacy, dosage and dose regimen.

Page 18: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Usual Bridging Strategy- Shorten Drug Lag but still -

2 3 4 5 6 7 8 9year

JAPANPhaseⅠ

Foreign Data

PhaseⅠⅡ

Approval

Approval

Review

NDA

NDA

18

Review

Bridging Study

Review

NDA ApprovalExtrapolate

Shorten

Compare PK/PD, Dose finding

“Drug Lag”

Page 19: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Sponsor

Simultaneous Global Clinical Trial

Applications will be submitted in Each Country at the same time and early

Approved in Each Country at the same time and early

If MRCT doesn’t consider ethnic factors such as intrinsic & extrinsic, -----

Not approved in some Countries without additional clinical data

Page 20: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

ICH E5 GL. Q&A (R1) 2006

A. (extract)The bridging study would allow extrapolation of an adequate data base to the new region. It would seem possible, and efficient, to assess potential regional differences as part of a global development program, i.e. for development of data to occur simultaneously in various regions, rather than sequentially. For example, if multi-regional trials had a sufficient number of trial subjects from the new region, it might be possible to analyze the impact of ethnic differences in those studied, to determine whether the entire data base is pertinent to the new region.

Q.1 I am planning to develop my new drug globally. Does E5 provide guidance for this approach?

Page 21: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

21

No Phase ⅢMRCT

Foreign

Japan

Phase I

Phase I

Phase ⅡMRCT(Dose finding)

Accessing whether Ethnic factors are significant/critical or not

NDA

Concept of simultaneous drug development

Phase III

Phase III

Yes

Page 22: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

English:http://www.pmda.go.jp/operations/notice/2007/file/0928010-e.pdf

Guidance: Basic Principles On Global Clinical Trials :MHLW’s notification

Providing basic principle for the design & conduct global clinical trials in 12 Q&As

Dose finding study in Japan is necessary?How to determine a sample size & proportion of Japanese subjectsIn case foreign evaluation index is not established in JapanIn case active control drugs are not approved in JapanIn case concomitant medications/therapies are not identical manner among regions

PMDA consultation for individual case

Page 23: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Collaboration in East-Asia

• Ethnic Similarities in China/Korea/Japan East-Asia– Genetic similarities– Cultural similarities (e.g.; chopsticks countries)

• Improvement of clinical trial environment in East-Asia• Emerging drug market in East-Asia

Background:- In the era of globalization of Drug Development- The necessity of evaluation on ethnic factors- East Asian Situation

To develop better drugs through collecting clinical data efficiently in East-Asia, Regulatory collaboration is important

Page 24: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

1 Activities of Japan

- FY2008 Collecting available PK data of Chinese, Korean and Japan and review the data

- FY2009-2010 Conducting Prospective PK study Including Chinese, Korean and Japanese in order to compare ethnic difference more precisely

Activities on ethnic factor research in East Asia

2 Activities of Korea, China & Japan Tripartite Cooperation

Collecting available data and

discussing ethnic factors

3 Japanese Perspective

To develop consideration for

collecting East Asian clinical

data in MRCT

PK Data Clinical Data

Clinical Data

Clinical Data

Clinical Data

Clinical Data

Clinical Data

Page 25: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Symposiums related to MRCT

1. Korea, China and Japan Tripartite CooperationEast Asian Pharmaceutical Regulatory Symposium 2008Japan-Korea-China Drug Clinical Trial Symposium 2009Multi-Regional Clinical Trials Seoul Workshop, highlighting Korea, China and Japan Tripartite Symposium 2010

2. China-Japan Symposium; May 2010China-Japan Symposium on Global Clinical Trials and

Ethnic Factors 20103. APEC-LSIF; 2009 & 2010

Multi-Regional Clinical Trials Seoul Workshop

Continuous activities are necessary

Strategic Approach is helpful

Page 26: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Source: APEC

APEC LSIF(Life Science Innovation Forum)

Leaders Meeting

Ministerial Meeting

Senior Officials Meeting

Committee onTrade and Investment

LSIF

Regulatory Harmonization Steering Committee (RHSC)

Regulatory Member: Canada, China, Japan, Korea, Peru, Chinese Taipei, Thailand, USA

Page 27: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Goal:Implementation of ICH E5 guideline and Promoting

harmonization on Regulatory Procedures on MRCT in order to facilitate MRCT and acceptance of foreign clinical data for drug review.

Best Practices Roadmap to Promote MRCT- Agreed in principle at RHSC in Sendai -

Activities:Economy Step-by-Step Implementation

Step1:AssessmentStep2:Training/workshopStep3:Assessment for training /workshopStep4:Training/workshop to reach the goal

Page 28: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Conclusions

It is important -

To improve circumstances to conduct Clinical trial

To design MRCT whose data can be utilized by regulatory authorities

To promote international cooperation

Page 29: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

Homepages,MHLW Homepage:  http://www.mhlw.go.jp/english/index.htmlPMDA Homepage:   http://www.pmda.go.jp/english/index.html

Page 30: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

ICH (International Conference of Harmonization)

JAPAN

MHLW/PMDA・JPMA

EU

EC/EMEA・EFPIA

USA

FDA・PhRMA

Observer: WHO, Health Canada, EFTA

Secretariat: IFPMA

Beyond ICH1. Global Cooperation Group (GCG: 1999‐)2. Regulators Forum (2008. 6 ‐ )

Page 31: Japan’s Activities and Challenges to promote Multi ... · Japan’s Activities and Challenges to promote Multi Regional Clinical Trials Shinobu UZU International Planning Director,

GCP activities under Regulators Forum

BackgroundICH-E6 (GCP) was identified as primary area of interest in the Regulators ForumDiscussion Group was established

ObjectivesIdentify critical factors for a proper implementation of ICH-GCPPropose a practical way to improve a proper implementation of ICH-GCP