Risk%20Communication%20in%20NDA%20(New%20Drug%20Application)

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Risk Communication inNDA (New Drug Application)

• Massie Ikeda MD, PhD
• Chief Medical Reviewer
• Pharmaceuticals and Medical Devices Agency

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Standard Disclaimer

• This is not an official PMDA/MHLW guidance or
  policy statement.
• No official support of endorsement by PMDA/MHLW
  is intended or should be inferred.

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Todays TopicsWhy do we need

1. Clinical trials ?
2. Regulatory body ?
3. Risk communication ?

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New Drug reminds you of

• Newspaper Articles
• Tough Diseases HIV, Cancer
• High-Techs in Medicine
• Severe Adverse Effects
• Mega Pharma Companies
• Clinical Trials

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Why do we need clinical trials ?

• Is it OK with animal data only ?
• Let safe drugs only go into the market?
• Are clinical trials dangerous?
• Let us leave to the doctors?
• Why do we need placebo ?

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We humans needour own human data.You never want
dog or cat food on your dinner menu.The same
with your drug.
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Are you happy withalternative medicine only?You
probably need drugs whose data have been
scientifically reviewed.
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Human Experiment Era
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Todays TopicsWhy do we need

1. Clinical trials ?
2. Regulatory body ?
3. Risk communication ?

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Benchmarking of Drugs Who does it ?
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Independent BodyRegulatory Authority

• PMDA
• FDA
• EMEA

In your home country?
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MHLW
JPMA
ICH
FDA
EMEA
PhRMA
EFPIA
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ICHInternational Conference on Harmonisation of
Technical Requirements for Registration of
Pharmaceuticals for Human Use
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International Conference on Harmonisation of
Technical Requirements for Registration of
Pharmaceuticals for Human Use

• Japan, USA, EU
• To make common regulations and share data on
  clinical trials
• It is not an academic conference
• Working on drugs but not on devices

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(No Transcript)
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QE5????????
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What is ICH E5 for?

• For providing good drugs faster to everybody in
  the world, especially ICH resions.
• It is not intended to bypass important domestic
  clinical studies.

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Importance of ethnic differences

• Intrinsic
• PK/PD, genetic analysis (in future), etc.
• Extrinsic
• differences in clinical practice, etc.

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Ethnic Difference in Alcohol Dehydrogenase
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Warfarin for NVAF
Japan
US
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Coagulation factor mutation
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SARS HLA typing
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An example of difference among Asians SARS
HLA typing
HLAB46 Jpn 4.4 Krn 4.4 Vtnm 13.2 Sngp 15.1 Kanton
15.4
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Importance of ethnic differences

• Intrinsic
• PK/PD, genetic analysis (in future), etc.
• Extrinsic
• differences in clinical practice, etc.

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Japan
USA
Health insurance system A
FDA approval
MHLW approval
Health insurance system B
Universal health insurance coverage ?????
Health insurance system C
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CTD(Common Technical Document)as CV of the Drug

• Our common ground to analyse the benefits and
  risks of the drug

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CTD as a CV of the new drug
CURRICULUM VITAE FORMATFORTENURE AND PROMOTION
DOSSIERS NAME __________________________________
_________________________ (Last) (First) (Initial
) EDUCATION UNDERGRADUATE _____________________
___________________ GRADUATE ___________________
____________________________POST DOCTORAL
_________________________________________ ACADEMI
C APPOINTMENTS (inclusive dates) OTHER
APPOINTMENTS AND PROFESSIONAL CONSULTANTSHIPS
(including other remunerated employment)
LICENSURE AND CERTIFICATION

• Disclosure accountability is essential.

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CTD as CV of the Drug

• Disclosure Accountability
• It is not a brochure or propaganda
• Disclosure of not only the benefit
• Explain why
• The drug is indicated to the target
• The drug overcomes the rivals

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CTD is

• CV of the drug application
• Common ground of communication
• Key for disclosure and accountability

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Time to approval
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15.8
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Todays TopicsWhy do we need

1. Clinical trials ?
2. Regulatory body ?
3. Risk communication ?

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Our Mission
Risk
Benefit
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No bad news is bad news

• when people are not aware of its shadow.

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Why not share the bad news ?
because it comes out sooner or later.
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Difficulties in risk communication

• Liability
• Conflicts of interests
• Uncertainty Variety
• Adverse events Drug-related on not
• One understands A causes B but others do not
• Changes as time goes by

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But we have to share bad news because

• It will come out, anyway.
• Early intervention before disaster
• Stay calm avoid panic
• To correct the system effectively
• To make no scapegoat

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Common Flaws in NDA

• Focus only on efficacy instead of safety
• Insisting on safety
• No significant difference compared with the
  placebo
• No causal relationship
• Very low frequency
• No similar case in PMS outside Japan

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Our Common Aim-Regulatory Authority Pharma
Co-Good Drugs for People

• Not conflict but Cooperation

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The sooner, the better ?The lessons from
Rofecoxib ( Vioxx)

• Cox2 Inhibitor
• Stomach-friendly super aspirin
• FDA approved in May 1999
• Voluntary withdrawal in September 2004
• Due to an increased risk of cardiovascular events
  (including heart attack and stroke)

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Stop Confrontation
Drug Co.
Citizens
Media
Government
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Future Issues

• Synthesizing data on safety
• Pharmacovigilance system
• Harmonization on safety data
• Safety and order-made medicine, e.g. SNP
• Media Relation
• Risk Communication with lay press people