Proposals of the Advisory Committee on
Administrative Reform：Lessons Learned
from Drug-Induced Hepatitis
What’s “the Advisory Committee on
Administrative Reform:Lessons Learned
from drug-induced hepatitis“?

June 5,2010
Ｍａｓｕｍｉ Ｍｉｎａｇｕｃｈｉ

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Ｔhe Advisory Committee on Administrative Reform:Lessons Learned from Drug-Induced Hepatitis

Ｔhe Advisory Committee on Administrative Reform：
Lessons Learned from Drug-Induced Established by the MHLW, based on a basic

 Two years’ deliberations（May 08-Apr 09)

agreement between national plaintiffs, their lawyers’
groups and the MHLW, concerning the drug-inducedhepatitis C litigation.

 Research group for verification

 Purpose:

To verify the Drug-Induced Hepatitis Disaster
Make practical proposals on administrative reform 20members, including 5 victims

2008: Interim draft, first proposal
2009: Final proposal

 survey for victims, company staff hearings
 Questionnaire survey※ my position

For PMDA/MHLW personnel
4

3

The monument of oath

Historical significanceWe keep the value of life to heart.
We hereby swear that we will make the utmost effort toensure the safety and efficacy of drugs, to prevent arecurrence of drug-induced disasters, such as Thalidomide,
SMON, drug-induced Creutzfeldt-Jakob, and drug-induced
AIDS.
More than 1000 patients were infected by tainted blood
products in the HIV scandal. We have established thismonument as a token of our reflection on this history.
5August 1999

Ministry of Health, Labor and Welfare

61”Form-policy-function” of pharmaceuticalclass actions in Japan

Recurrence of drug-induced disasters
and pharmaceutical class actions in JapanThe litigations’ purposes are Thalidomide SMON Dura mater infected with Creutzfeldt-Jakobdisease

Basic agreement
between plaintiffs and the MHLW HIV-tainted blood products

Ｐｈａｒｍａｃｅｕｔｉｃａｌ Cｌａｓｓ Ａｃｔｉｏｎｓ
ａｎｄ Ａｄｍｉｎｉｓｔｒａｔｉｖｅ Rｅｆｏｒｍｓ

A milestone for pharmaceutical class actions

 Thalidomide (1９６７)

This is the first time the MHLW has establishedan advisory committee for verification
purposes and administrative reform

ADR report system, drug re-evaluation system, ＧＭＰ
 SMON(１９７９)

Not only for compensation
But also to…
clarify the government’s responsibility
establish permanent measures for victims
find out the truthdevelop preventive measures

Reform of drug affairs law

Emergency order, relief systemｃｆ. Negotiations by victims and lawyers

 Drug-induced AIDS(1９９７)

Division of regulation bureau and promotion
Crisis management system

What’s possible?
- Verification beyond the lawsuit in question- Verification of present system- Wide range of reform measures proposed- NGOs and victims’ opinions reflected Drug-induced Creutzfeldt-Jakob Disease(2004)

Relief system for biological products
Education on drug-induced disasters

 Drug-induced Hepatitis C(2010)

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The composition of the report The e
Contents of the report
１ Introduction
２ DIH verification
3 Past systemic revisions4 Systematic reform proposals
5 Regulatory bureau reform proposals
6 Conclusion

The report

Questionnaire survey to PMDA/MHLWpersonnel
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Fundamental viewpoints
based on verification
Problem exists in decision making
True information has not reached doctors
and patients,
but has reached drug companies and theMHLW↓“a precautionary principle” is essential“drastic reform measures” needed for thewhole system including the PMDA and MHLW,
human resource development, and education

The Proposals

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Clinical Trials

Systematic reform proposals

Transparency/foundation independent fromthe influence of drug companies
 Clinical trial registration system should becompulsory
 Broad items for registration and disclosure Examinees’ rights should be legally defined Unified legal system through clinical trials
and other clinical research

１ Basic View
２ Clinical Trials
３ Approval Review
４ Post Marketing Safety Measures
５ Relief System for ADR
６ Medical institutions
７ Societies
８ Pharmaceutical companies
９ Regulatory bureau
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Drug lagand shortening of examination period

Approval Review
Safety and quick examinations
Transparency

 Cause of a drug lag is complicated.

- Drug companies’ strategy

 PMDA reviewers’ qualifications and quality shouldbe enhanced

 Only limited problems can be resolved by

 Conditions of approval and evaluations ofspeeding up examinations

performances and conditions should be checkedthoroughly Transparency, such as disclosure of the review
process before approval, should be improved.
 MHLW’s responsibility for package inserts indrugs should be clarified.

 Important to ensure safety

Lessons Learned from FDA
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Systematic Reform Proposals

Post-marketing safety measures

１ Basic View
２ Clinical Trials
３ Approval Review
４ Post Marketing Safety Measures
５ Relief System for ADR
６ Medical institutions
７ Societies
８ Pharmaceutical companies
９ Regulatory bureau

Construction of fundamental system forreview and distribution of information
 Harmonization of approval reviews andpost-marketing measures More pharmacoepidemiology measures
 Establishment of receipt database Regulations for unapproved drugs
 Reform of risk communication system
2019

Risk Communication

Package Insert - Paxil

Risk Communication
Before marketing approval/post marketing
Adequate collection and provision ofinformation
 Release essential points for PMS at time ofapproval Reform of regulation for package inserts（Please refer to the following clauses:"precautions concerning the drug’seffects", "important fundamentalcautions”, and "administering to a child." Enhance communication with patients
 Reform of advertising regulations
 Early communication

Overseas reports state that
following a comparative trial withplacebo, Paxil is not effective inpatients aged 7 to 18 years old withmajor depression, and that this drug
strengthens the risk of suicidal
behavior. Please be careful whenprescribing this drug to patients
under 18 with major depression.

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Risk Communication
Package Insert - Paxil

No warning for pregnant women!

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Risk Communication
Provision of Information for Patients
 PMDA website’s present condition

There have been reports thatbabies born of women who
used paroxetine have an
increased risk of congenital
anomalies. Women who are or
may be pregnant should use
Paxil only when thetherapeutic benefits outweigh
the risks. (see Use During
Pregnancy, Delivery,or Lactation ).

Drug guide for patients
Manual listing serious side effects
 Whole system needs to be transformed←access, contents, speed※ secure adequate human resources

Not noticeable !
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4

PMDA web site

Risk Communication
Drug Guide for Patients

Information for patients

What you should be careful of
before using this medicine:
There are reports that thisdrug has not been effective
on patients with major
depression and that itstrengthens the desire to die.
Patients under 18 with major
depression must consult a
medical practitioner.

No warnings
for pregnant women!
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Risk Communication
Drug Guide for Patients

Risk Communication
Drug Guide for Patients Revised in May.2010“There have been reports that babies born of women whoused paroxetine have an increased risk of congenital
anomalies….”

If .you are or may be
pregnant,
please consult your doctor

 Lag 4 years behind

Jan.2006 MHLW
Revision of package insert
Dec.2005 FDA
Category D

Any serious risk cannot beunderstood！
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Risk Communication
ADR report system from patients
 Establishment of an ADR report systemfrom patients is essential
 Issue raised by SSRI in UK

Risk of suicidal behavior
Why does yellow card system not work ?
BBC program and patients’ report（6５０００calls, 1400mails,1２４０００ web accesses)

5Ｒｉｓｋ Cｏｍｍｕｎｉｃａｔｉｏｎ
Advertising regulations
 Information such as scholarly

information/medical practitioners’ talks andreports/medical information for patients’associations
 Information for patients’ associations raisingexcessive expectations on effects and efficacy*definition of advertisingCharles Medawar
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31Relief System for ADR

Systematic Reform Proposals
１ Basic View
２ Clinical Trials
３ Approval Review
４ Post Marketing Safety Measures
５ Relief System for ADR
６ Medical institutions
７ Societies
８ Pharmaceutical companies
９ Regulatory bureau Familiarize doctors and patients with thesystem Examine the range of objects for relief:anti-cancer drug, fetus※ Petition33343536

Systematic Reform Proposals
１ Basic View
２ Clinical Trials
３ Approval Review
４ Post Marketing Safety Measures
５ Relief System for ADR
６ Medical institutions
７ Societies
８ Pharmaceutical companies
９ Regulatory bureau

6Regulatory Agency

Regulatory Agency
 Current － PMDA and MHLW The following points are essential

regardless of the organization

 Unify PMDA and MHLW, or maintaincurrent system ?
“Pharmaceutical Bureau” Plan
“Act for the Total Number of Civil Servants”※ Questionnaire survey
to PMDA/MHLW personnel
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・Government must take responsibility・ Harmonization of approval reviews and postmarketing safety measures
・Transparency and specialization
・Reflection of people/patients’ opinions
・Adequate funding to remain independent fromcompanies. Secure proper personnel
・ Continuous reviews of this organization

Establishment of a third party organization towatch and evaluate drug regulations

Establishment of a third party organization towatch and evaluate drug regulations

Aims to prevent drug-induced disasters

 Authority to inspect, admonish Whole administrative issue

Watches and evaluates entire drug regulations, 10 members

Admonishes and recommends that the MHLW regulate※ １９９７※ ２００３※ ２００９※ ２０１０38

JFBA statement
Medwatcher Japan proposal
Medwatcher request letter
JFBA opinion letter( victims, consumers,pharmacoepidemiologists, doctors,pharmacists, lawyers）
 Staff with specialized knowledge who areable to inspect, and support members.
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Establishment of a third party organization towatch and evaluate drug regulations
 Independence, expertise, mobility

Must be different from existing council
Position in organization law
Procedure for selection of members

The Future Re-review every three years

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Real value will be questioned in future Understand what the report proposes The establishment of a third party organization

is a breakthrough Basic Act for Drug Safety

Now, change the culture surroundingdrugs!
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