Early Global Developmentfrom Sponsor’s Point of View

Clinical Research, Pfizer Japan Inc.
Tomoko Hirohashi
Feb 19th, 2011

Objective
To discuss points to consider for Japan to join
G-FIH (Global First-In-Human) study with
Western countries, which will be a base for
future global Ph2 and Ph 3 development plans

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Agenda• Strength and Weakness of Japan• Eligible Study Site for FIH Study– Performance– Ability of study sites– Ability of investigators/staff– Extra values• Non-clinical work
• Investigator Initiated Trials (IITs)• Regulatory Challenges• Summary

10th Anti-Tumor Drug Development Forum, Feb 19th, 2011

3Strength of JapanThe number of published articles indicate strength in certain DAs1)
Disease Areas
Japan China Korea India
USOncology

62

6

4

11,446

A&R(Allergy & Respiratory)

13

310233

Neurology

7512511,185

Pain

201054

CVMED

484

60

28

76,535

Inflammation

22

310339Immunology

799421,247

Vaccine251121575

1. Papers published in either Nature or Science
Cumulated results from 2005 to 2010 (as of Nov 18, 2010) 4

10th Anti-Tumor Drug Development Forum, Feb 19th, 2011

Many Japanese researchers arecollaborating with global researchers

Japan is a key global player
in basic research

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5

Weakness of Japan

Genome science

Social science
Epidemiology

FIH

Cancer clinicalresearch
Exploratory treatment
Clinical trial

Investigator Initiated Trial(using unapproved drug）

Standardization of medicine

Reverse TR

Therapeutics andengineering

Clinical TR

Cellular biology

Pre-clinical TR

Molecularbiology

Cancer TR

Establishment of next generation therapy

Cancer basicresearchLong term study
Analysis of side effect
Personal medicine
Research ofpredictor/responsive marker

がん研究の現状と今後のあり方について（平成22年6月25,ライフサイエンス委員会,がん研究戦略作業部会）改変
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Lack of experience in
G-FIH study and IITs,
coming from / resulting in few
TR activities

Japan is not yet a key global
player in TR and clinical research

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Eligible Study Site for FIH Study (1)• Performance– Enrollment speed in various tumor types• Constant enrollment throughout the study period– CRF data entry (especially AE)• Ability of study sites– Handling unexpected AEs (dermatology, cardiology etc)
– Imaging technology, tissue sampling etc.
– Acceptance of innovative/flexible study design• Ability of investigators/staff– Deep discussion with W-investigators in English– In depth knowledge of target molecule10th Anti-Tumor Drug Development Forum, Feb 19th, 20118

Enrollment Speed-Number of Patients/site in Global StudiesPts/Site

1.40
US1

3.2

25

Japan
1.20

2

4.9

13Korea

3

9.4

4DJJapanAsiaEUUSCanada/LA/AfME
EU & USA

1.00(No. of studies = 13)

0.80
0.60
0.40
0.20

10th Anti-Tumor Drug Development Forum, Feb 19th, 2011

RCCP2LC
NSCLC
P2

NSCLC
P3

NSCLC
P2

NSC

GC

P3

P2RCCP3LC
NSC

CRC

P2

P2

HCCP3

CRC

nc

P2

pa

P3

BC

0.00

P3

Randomized/Region/Month

Rank ofPts/Site

Rank forEnroll

1.60Country

9Source: Pfizer Japan data

Enrollment in Japan is competitive in Ph2/3
For FIH study…
Can we enroll various types of tumors?
Can we constantly enroll patients throughout
the study period?

Establish a network with affiliate sites

10th Anti-Tumor Drug Development Forum, Feb 19th, 201110Speed of Data Entry: AE Module-Median Number of Days in Global Studies(2009DEC - 2010NOV)

Data Entry Speed Median (days)

80

AE_median2010

70
60
50
40
30
20
1000_All

JAPAN

CHINA

KOREA

HONG KONGCountryCountries
10th Anti-Tumor Drug Development Forum, Feb 19th, 2011

TAIWAN

UNITED
STATES(No. of studies = 13)
11

Source: Pfizer Japan dataSpeed of Data Entry: AE Module
40500

35450400

30350

25300

20250

15200150

10The number of AEs

Data Entry Speed (Day)-Median Number of Days and Number of AEs in a Global Ph1-10055000JAPAN (8)KOREA(14)Country (# of subject)(No. of studies = 1)

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Source: Pfizer Japan dataWhy Prompt Data Entry is Important?

ALCOA Standard
Accurate

正確であることLegible

判読可能であること

Contemporaneous 同時であること
Original

オリジナルであること

Attributable

属性を持つこと，起因性（誰が記載したか、audit trail）

http://www.fda.gov/OHRMS/DOCKETS/98fr/04d-0440-gdl0002.PDF
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Data entry, record, and update must happen
at same time.
time.
Data should be recorded once it is generated
in order to maintain high quality.

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Eligible Study Site for FIH study (2)• Performance– Enrollment speed in various tumor types• Constant enrollment throughout study period– CRF data entry (especially AE)• Ability of study sites– Handling of unexpected AEs (dermatology, cardiology etc)
– Imaging technology, tissue sampling etc.
– Acceptance of innovative/flexible study design• Ability of investigators/staff– Deep discussion with W-investigators in English– In depth knowledge of target molecule10th Anti-Tumor Drug Development Forum, Feb 19th, 201115

If these eligibility criteria are met,
Japan can become a player in global studies

Sites with extra values are selected

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Extra Values: Proactive research• Proactive involvement in optional tumor samplingand diagnosis assessment (IHC, gene expression
profile, etc)
• Conduct of additional non-clinical pharmacologystudies for other potential indications and/ortreatment concepts

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Extra Values: Proactive Research- ProposalEstablish collaborations among clinical site,
non–non–clinical Sites, and Sponsor

Clinical study sites

Science fromJapan/AsiaSponsor

TR

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Academia
Basic research sites(non-clinical site)18

Extra Values: Investigator Initiated Trials (IITs)• Overseas, IITs are conducted after FIH or POM• In Japan, examples of IITs using new agents arelimited– Difficult to get an agreement on IITs from globalcompany• Hard for global company (HQ) to understand Japan insurance
system and clinical research system– Little knowledge of study sites capable of conducting
IITs with new agents under ICH-GCP

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• Study sites should establish a system for IITs
• PMDA/MHLW and sites should appeal theirability/acceptability of conducting IITs

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Regulatory Challenges
Current situation• Few examples of G-FIH study with Western countries inJapan due to concern on ethnic differences– Korea can Join G-FIH study with any country• Data on recommended dose in Japanese is required• Concern on safety in Japanese population• Separate J-IND/ Protocol is required when core protocol
elements are amended• Study objective, design, target population, etc. arefrequently modified based on emerging clinical data

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Sponsor, study sites, and PMDA should work
together for Japan to join GG-FIH study

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Summary• Strength and weakness of Japan– Japan is a key global player in basic research, but not yet in TR andclinical research• Eligible study site for FIH study– Improvement in performance and ability of study sites/investigators/staff
is required to be selected for FIH study site

• Extra values such as non-clinical work and IITs
– Proactive involvement in optional tumor sampling and diagnosis
assessment (IHC, gene expression profile, etc)
– Conduct of additional non-clinical pharmacology studies for otherpotential indications and/or treatment concepts– Investigator Initiated Trials• Regulatory challenges– Sponsor, study sites, and PMDA should work together for Japan to join
G-FIH study
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Thank you for your attention！
ご静聴ありがとうございました。

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Quality of Data Entry-Number of Queries in Global StudiesSWITZERLAND
NETHERLANDSAUSTRIASINGAPORE
INDIA
AUSTRALIACANADA
UNITED KINGDOMRUSSIAN FEDERATION
SPAIN
ITALY
GERMANYCHINA
POLANDFRANCETAIWANKOREA, REPUBLIC OFJAPANUNITED STATES0.00

0.05

0.10

0.15

0.20

0.25

Number of Queries/CRF page
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0.30

0.35

0.40

(No. of studies = 13)
25

Source: Pfizer Japan dataImprovement in Perception of Clinical Trials• Education of patients– Understand difference between research and treatment– Balanced expectation on efficacy and safety• In some cases, single agents may not show efficacy• Fair message on clinical research from media

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