K. Shimatani/ K-H Symposium/ October 22-23, 20011 What Impact Will Globalization Have on Bridging...

K. Shimatani/ K-H Symposium/ October 22-23, 2001 1

What Impact Will Globalization Have on Bridging Studies

Katsuyoshi Shimatani

J-Clin, Pfizer


Number of Consultation for Bridging Studies

Kikoh Mr. Mori (07 October 2001)

Successful cases: >20

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1997 1998 1999 2000

Number of applications

Number of consultations for BS


Drug Approved Through the Use of Overseas Data (1)

Indication of Drug Date of Approval Overseas Data forErectile dysfunction January 1999 EvaluationAlzheimer's disease October 1999 Evaluation

Influenza December 1999 ReferenceDepression, Panic disorders August 2000 Reference

Allergy August 2000 EvaluationBreast cancer December 2000 Evaluation

Influenza December 2000 EvaluationBreast cancer April 2001 Reference

Bronchial asthma June 2001 ReferenceMigraine June 2001 Evaluation

(NCE)


Drug Approved Through the Use of Overseas Data (2)

(NCE)

YearNumber of Approvals

Approvals with Overseas Data

Evaluation ReferenceTotal

1999 39 3 (7.7%) 2 (5.1%) 1 (2.6%)

2000 39 4 (10.3%) 3 (7.7%) 1 (2.6%)

2001* 13 4 (25%) 2 (8.3%) 2 (16.7%)

Total 91 11 (11.1%) 7 (6.6%) 4 (4.4%)

*: as of October 1


Were the objectives of the bridging study achieved?

Was study duplication minimized?

Studies not done in Japan for CCDPPhase II: 1

Phase III: 5

Long term study: 3

Special study: 3


Were the objectives of the bridging study achieved?

Was the time-lag (drug-lag) between J and W reduced?

Time difference of approval between J and WErectile dysfunction: 11 MAlzheimer’s disease: 36 MInfluenza: 15 MAllergy: 55 MBreast cancer: 65 MMigraine: 111 M, 52 M

Average 49 M


Observations in Bridging Studies (1)

Are 20 successful consultations and 11 approval drugs in 3 years sufficient numbers?

The drug-lag has shortened but has not disappeared

“Bridging” is broadly defined Would it be better to define bridging more narrowly?

Most of the drugs that have been approved are ones that meet special medical needs



Dosage differences

There are no set results for determining dosage in bridging studies

Should dose response studies be conducted using the same dosage range as that used in the West, or a dosage range that is one step lower?

Japan is said to use lower dosages than the West, but is it really that the dosages are scientifically low, or is this simply a matter of culture/ custom?



Bridging is intended to mainly pursue similarity only, but has it been possible to adequately obtain the information required for Japanese prescribers and patients?

Is it necessary to re-confirm efficacy of the drugs in Japanese?

There are a lot of cases in which extrinsic factors have been a bigger problem than intrinsic factors



There are therapeutic areas for which bridging is difficult

The use of placebo in psychiatry

It is necessary to have a large sample size in order to calculate the true end points in CV area

Conducting only 1 bridging study is very risky. Depending on the therapeutic area, reproducibility may be low. Wise way to use overseas data should be considered in order to reduce duplication


Bridging Study Benefits

1. Drugs for which it would be difficult to obtain approval based only on the Japanese data have been approved through the use of overseas data

2. The duplication of clinical data has been minimized through the use of overseas data

3. The time required for development has been reduced

With the introduction of the new GCP

4. The quality of Japanese clinical studies has improved

5. Awareness of clinical studies has improved among investigators, sponsors, and others


Bridging Study Transitions

Retrospective bridging

The bridging of similar aspects based on studies already

conducted or underway in the West and Japan

Prospective bridging

The design and conduction of new studies in Japan that

are similar to studies already conducted in the West

Advanced bridging

The design and conduction of new studies in both the

West and Japan for the purpose of bridging


Future options of clinical trials under Globalization

1. Advanced bridging studies

2. Global studies


Advanced Bridging Studies (1)

( 1 ) Protocols of overseas studies should be designed aiming to bridge Japanese studies.

Japan must input to overseas protocols.


Advanced Bridging Studies (2)

( 2 ) Even if Japan start later, the NDAs can be simultaneous

West

Japan Phase I Phase II Phase III

Phase I Phase II

Simultaneous NDA

This strategy could be applied for the therapeutic

areas: No difference in medical practices End points already validated (precedent) Easy to get consistent results


Global StudiesWhy Global Studies?1) ICH recommend to avoid redundancy of clinical studies

which have been already done in overseas

However, MHLW/ Japanese prescribers need to see Japanese data

Global studies Simultaneous NDA

2) There are difficult areas to conduct clinical studies in Japan

Small patient population (cancer and others) Mega-trial (cardiac events, bone fracture) Difficult to have consistent result (psychiatry and others)


Points to be discussedin Global studies

Speed and Quality

Sample size

Similarity

Dosage

Study design

Medical practice


Speed and Quality

Has the Japanese clinical trialenvironment improved?

Collaboration with Asian Countries

YES, but…….


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Sample size/ Similarity

Is it possible to reduce sample size? Is it necessary to prove efficacy only in Japanese

patients?

Bridging Global study

1,000

200400

1,000

W J

Similarity

Prove efficacy

Proveefficacy

Prove efficacySimilarity


Similarity


Dosage

From PK profile

West L M H

Japan option 1 L M H

option 2 l L M

option 3 conduct Phase IIa


Study design/ Medical practice

To allow some flexibility in designing of protocol in

order to satisfy with local needs

- Diagnosis- Diagnosis - Primary endpoints- Primary endpoints

- Severity- Severity - Secondary endpoints- Secondary endpoints

- Demography- Demography - Dosage- Dosage


Bridging studies minimize the duplication of studies and increase the chances of approval

Summary (1)

Differences in extrinsic factors are more important than intrinsic factors in bridging studies


Summary (2)

As an important alternative to bridging studies, we should think to conduct global studies. In particular, we should be aggressive in looking into this for therapeutic areas in which clinical studies are difficult to conduct in Japan alone. In such cases, we should be flexible in choosing sample sizes and protocol designs that will allow both the global objectives as well as the local objectives to be achieved.

We need to explore options that would allow us to collaborate with other countries in Asia when conducting global studies

K. Shimatani/ K-H Symposium/ October 22-23, 20011 What Impact Will Globalization Have on Bridging...

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