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Risk Communication inNDA (New Drug Application)
Massie Ikeda MD, PhD
Chief Medical Reviewer
Pharmaceuticals and Medical Devices Agency
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.
Today’s TopicsWhy do we need:
1. Clinical trials ?
2. Regulatory body ?
3. Risk communication ?
“New Drug” reminds you of・・・
• Newspaper Articles
• Tough Diseases: HIV, Cancer
• High-Techs in Medicine
• Severe Adverse Effects
• Mega Pharma Companies
• Clinical Trials
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 ?
We humans needour own human data.
You never want dog or cat food on your dinner menu.
The same with your drug.
Are you happy withalternative medicine only?
You probably need drugs whose data have been scientifically
reviewed.
Human Experiment Era
Today’s TopicsWhy do we need:
1. Clinical trials ?
2. Regulatory body ?
3. Risk communication ?
Benchmarking of Drugs: Who does it ?
Independent BodyRegulatory Authority
•PMDA
•FDA
•EMEAIn your home country?
MHLW JPMA
FDA
PhRMA
EMEA
EFPIA
ICH
ICHInternational Conference on Harmonisation of Technical Requirements for Registrat
ion of Pharmaceuticals for Human Use
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
各種分科会があるTuesday, 8 June 2004Time Code Topic8:00 am - 9:00 am CTD-CG CTD Implementation Coordination Group
9:00 am - 5:00 pmICG Industry Coordination Group9:00 am - 5:00 pmRegulators Regulators Meeting
9:00 am - 5:00 pmM1P MedDRA PtCWG9:00 am - 5:00 pmM2 Electronic Standards for Transfer of Information (eCTD)9:00 am - 5:00 pmE2B EWG Electronic Submission in Individual Case Safety Reports9:00 am -10:30 amS7B/ E14 Safety Pharmocology Qt Prolongation/ Clinical Qt Prolongation10:30 am - 5:00 pmS7B Safety Pharmocology Qt Prolongation9:00 am - 5:00 pmS8 Immunotoxicology10:30 am - 5:00 pmE14 Clinical Qt Prolongation12:00 pm - 5:00 pmQ4 Pharmacopoeial Harmonization9:00 am - 5:00 pmQ5E Comparability of Biotechnological/ Biological Products9:00 am -10:30 amQ8/ Q9/ QSGMP Plenary10:30 am - 5:00 pmQ8 Pharmaceutical Development10:30 am - 5:00 pmQ9 Risk Management9:00 am - 5:00 pmQS Quality Systems12:00 pm - 5:00 pmPDG Pharmacopoeial Discussion Group9:00 am- 12:00 pmPDG/ Q4 Pharmacopoeial Discussion Group/ Pharmacopoeial Harmonization9:00 am - 5:00 pmGT Gene therapy
QE5分科会参加者名簿
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.
Importance of ethnic differences
• Intrinsic
PK/PD, genetic analysis (in future), etc.
• Extrinsic
differences in clinical practice, etc.
Ethnic Difference in Alcohol Dehydrogenase
Alcohol Welcome Acceptable HateADH Active Partial DeficientJapanese 56 40 4Whites 100 0 0
Warfarin for NVAF
Japan
US
Coagulation factor mutation
SARS & HLA typing
An example of difference among Asians
SARS & HLA typing
HLAB46Jpn 4.4Krn 4.4Vtnm 13.2Sngp 15.1Kanton 15.4
Importance of ethnic differences
• Intrinsic
PK/PD, genetic analysis (in future), etc.
• Extrinsic
differences in clinical practice, etc.
Japan USA
MHLW approval
Universal health insurance coverage国民皆保険
FDA approval
Health insurance system C
Health insurance system B
Health insurance system A
CTD(Common Technical Document)
as CV of the Drug
Our common ground to analyse the benefits and risks of the drug
CTD as a CV of the new drug
Disclosure & accountability is essential.
CURRICULUM VITAE FORMATFORTENURE AND PROMOTION DOSSIERS
NAME: ___________________________________________________________ (Last)(First)(Initial)EDUCATION: UNDERGRADUATE: ________________________________________ GRADUATE: _______________________________________________POST DOCTORAL: _________________________________________
ACADEMIC APPOINTMENTS (inclusive dates):
OTHER APPOINTMENTS AND PROFESSIONAL CONSULTANTSHIPS (including other remunerated employment):
LICENSURE AND CERTIFICATION:
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
CTD is
CV of the drug applicationCommon ground of
communicationKey for disclosure and
accountability
Time to approval PMDEC/MHLW NDA FDA (CDER)
Standard NDAapproved year
approvals
median months to approval
approvals
median months to approval
1997 40 33.6 101 15.01998 58 36.6 65 12.01999 71 30.6 55 13.82000 84 18.8 78 12.02001 57 15.5 56 14.02002
67 15.352 15.8
Today’s TopicsWhy do we need:
1. Clinical trials ?
2. Regulatory body ?
3. Risk communication ?
Our Mission
BenefitRisk
No bad news is bad news
when people are not aware of its shadow.
Why not share the bad news ?
because it comes out sooner or later.
Difficulties in risk communication
LiabilityConflicts of interestsUncertainty & Variety
Adverse events: Drug-related on notOne understands A causes B but others do notChanges as time goes by
But we have to share bad news because:
It will come out, anyway.Early intervention before disasterStay calm & avoid panicTo correct the system effectivelyTo make no scapegoat
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
Our Common Aim-Regulatory Authority & Pharma Co-
Good Drugs for People
Not conflict but Cooperation
The sooner, the better ?The lessons from Rofecoxib ( Viox
x)• 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)
Stop Confrontation
Drug Co.
Citizens
Government
Media
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