Transcript Risk Communication in Medical Writing

Risk Communication in
NDA (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 Topics
Why do we need:
1. Clinical trials ?
2. Regulatory body ?
3. Risk communication ?
“New Drug” reminds you of・・・
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Newspaper Articles
Tough Diseases: HIV, Cancer
High-Techs in Medicine
Severe Adverse Effects
Mega Pharma Companies
Clinical Trials
Why do we need clinical trials ?
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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 need
our own human data.
You never want dog or cat food
on your dinner menu.
The same with your drug.
Are you happy with
alternative medicine only?
You probably need drugs whose
data have been scientifically
reviewed.
Human Experiment Era
Today’s Topics
Why do we need:
1. Clinical trials ?
2. Regulatory body ?
3. Risk communication ?
Benchmarking of Drugs: Who does it ?
Independent Body
Regulatory Authority
•PMDA
•FDA
•EMEA
In your home
country?
MHLW
JPMA
ICH
EMEA
EFPIA
FDA
PhRMA
ICH
International Conference on
Harmonisation of Technical Requirements
for Registration 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
Tuesday, 8 June 2004
Time
Code
8:00 am - 9:00
CTD-CG
am
Topic
CTD Implementation Coordination Group
各種分科会がある
9:00 am - 5:00
ICG
pm
Industry Coordination Group
9:00 am - 5:00
Regulators
pm
Regulators Meeting
9:00 am - 5:00
M1P
pm
MedDRA PtCWG
9:00 am - 5:00
M2
pm
Electronic Standards for Transfer of Information (eCTD)
9:00 am - 5:00
E2B
pmEWG Electronic Submission in Individual Case Safety Reports
9:00 am -10:30
S7B/E14
am
Safety Pharmocology Qt Prolongation/Clinical Qt Prolongation
10:30 am - 5:00
S7Bpm
Safety Pharmocology Qt Prolongation
9:00 am - 5:00
S8pm
Immunotoxicology
10:30 am - 5:00
E14pm
Clinical Qt Prolongation
12:00 pm - 5:00
Q4 pm
Pharmacopoeial Harmonization
9:00 am - 5:00
Q5E
pm
Comparability of Biotechnological/Biological Products
9:00 am -10:30
Q8/Q9/QS
am
GMP Plenary
10:30 am - 5:00
Q8pm
Pharmaceutical Development
10:30 am - 5:00
Q9pm
Risk Management
9:00 am - 5:00
QSpm
Quality Systems
12:00 pm - 5:00
PDG
pm
Pharmacopoeial Discussion Group
9:00 am- 12:00
PDG/Q4
pm
Pharmacopoeial Discussion Group/Pharmacopoeial Harmonization
9:00 am - 5:00
GT
pm
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
ADH
Japanese
Whites
Welcome Acceptable Hate
Active
Partial
Deficient
56
40
4
100
0
0
Warfarin for NVAF
Japan
US
Coagulation factor mutation
SARS & HLA typing
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
Importance
of ethnic differences
• Intrinsic
PK/PD, genetic analysis (in future), etc.
• Extrinsic
differences in clinical practice, etc.
Japan
MHLW
approval
Universal health insurance
coverage
国民皆保険
USA
Health insurance
system A
FDA
approval
Health insurance
system B
Health insurance
system C
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
CURRICULUM VITAE FORMAT
FOR
TENURE 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:
Disclosure & accountability is essential.
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 application
 Common ground of
communication
 Key for disclosure and
accountability
Time to approval
PMDEC/MHLW NDA
FDA (CDER)
Standard NDA
approved
year
approvals
median
months to
approval
approvals
median
months to
approval
1997
1998
1999
2000
2001
2002
40
58
71
84
57
52
33.6
36.6
30.6
18.8
15.5
15.8
101
65
55
78
56
67
15.0
12.0
13.8
12.0
14.0
15.3
Today’s Topics
Why do we need:
1. Clinical trials ?
2. Regulatory body ?
3. Risk communication ?
Our Mission
Risk
Benefit
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
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
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
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 CoGood Drugs for People
Not conflict but
Cooperation
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)
Stop Confrontation
Drug Co.
Citizens
Media
Government
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