the 2 nd clinical data management training innovative drug research and development (...
TRANSCRIPT
The 2nd Clinical Data Management Training
Innovative Drug Research and Development (创新药品的研发过程)
Frank Shen (沈志华) , Ph.D.
Head of Biometrics and Clinical Management
生物统计数据和临床管理负责人罗氏药品开发中国中心
August 30, 2010
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My Objective is…
The Global The Global InnovativeInnovative Pharmaceutical Industry Pharmaceutical IndustryThe Complexity of Drug Development and The Complexity of Drug Development and
Clinical ResearchClinical ResearchThe Role of Data Manager played in Clinical The Role of Data Manager played in Clinical
ResearchResearchChallenges and Opportunities in ChinaChallenges and Opportunities in China
After this talk, you will have some good understandings about:
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Top Line, Bottom Line, Pipeline and Regulated Industry
Pharmaceutical Automobile
Sales 100 100
Cost of Sales 28 75
Marketing 30 7
R&D 10 3
Administration &Overhead
7 8
Net income before tax
25 7
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Drug Discovery to Drug Development: A Ten-Year Bet
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Drug Discovery: Finding A Right Target and Picking Winners
Identify a disease Identify a disease target:target:
Cell Biology Cell Biology
GenomicsGenomics
Mass-screening for Mass-screening for hits:hits:
High-Throughput High-Throughput Screening (HTS)Screening (HTS)
MiniaturizationMiniaturization
Identify a key:Identify a key:
Combinatorial Combinatorial chemistrychemistry
Natural ProductsNatural Products
Compound AcquisitionCompound Acquisition
Quantitative-Structure Quantitative-Structure Activity Relationship Activity Relationship (QSAR)(QSAR)
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Early Phase Development: Use Clinical Pharmacology (CP), Pharmacokinetics (PK) and Pharmacodynamics (PD) to find A Right Drug
Early Phase Development: Use Clinical Pharmacology (CP), Pharmacokinetics (PK) and Pharmacodynamics (PD) to find A Right Drug
PK: What the body does to the drug
PD: What the drug does to the body
0
2
4
6
8
10
12
0 0.5 1 2 3 4 6 8 10 14 18 24
Time (h)
Conc
cent
ratio
n (n
g/m
L)
AUC
Cmax
Tmax
Drug Exposure (DOSE)
Res
pons
e (E
ffec
t)
Max Effect
50% Effect
50% Effect Dose
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Process Development
Formulation/Stability
File IND Phase I Phase II
Clinical Trials
Phase III
File NDA
APPROVAL
Metabolism
Toxicology
Late Phase Development: Finding A Right Clinical Plan
Drug DiscoveryPreclinical
(II-B)(II A)
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““ If it were not for theIf it were not for the great variability among great variability among individualsindividuals,,medicine might as well medicine might as well be a science and not an be a science and not an art”art”
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Dilemmas in Modern MedicineDilemmas in Modern Medicine
““ Every day, doctors diagnose Every day, doctors diagnose patients and prescribe the most patients and prescribe the most appropriate drug, and yet in many appropriate drug, and yet in many cases, the drug won’t work or will cases, the drug won’t work or will trigger miserable side effects”trigger miserable side effects”
- - The Wall Street JournalThe Wall Street Journal
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Relative signal/noise in drug studies due to inter-subject Relative signal/noise in drug studies due to inter-subject variability (noise)variability (noise)
Phase 1Phase 1 Phase 2Phase 2 Phase 3Phase 3
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Evidence-Based Medicine is a Statistical-Based Medicine
Populationsample Inferences
based on the sample
Extrapolate
e.g. patients with high cholesterol
e.g. 150 patients with high cholesterol in a clinical trial
e.g. statin reducescholesterol
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Hypothesis (Scientific belief)
Data Collection
Data Analysis
Interpretation
•Confirm/Reject
•Refine
Design of Scientific Experiments (e.g., Clinical Trial)
Objective (Signals/endpoints)
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Clinical Trials of New DrugsClinical Trials of New Drugs
A high-noise/low yield endeavor Requires great care in design and execution
for success Expectations often not realized 50% of phase III trials failed to show positive
results Investment needs to be protected Buy A Good Insurance Policy and
Execute with High Quality
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Four Elements of Clinical ResearchFour Elements of Clinical Research
Data and MonitoringPatient
Protocol
Biostatistics
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Protocol DesignStudy Setup & Conduct
Data Base Lock
Analysis & Report
Draft/Design
Review
CRF/Form Design
Signoff
FPFV
Database design & verification
LPLV
CRF Lock
Data Review, Query & Cleaning
Clinical Trial and Protocol Life
STAGE
TASKData Entry/ CRF Processing
Data Q&R
External Data
Statistical Analysis Plan
Data Review Plan
Data Presentation Plan
Medical Encoding
Clinician/Statistician CRA/DM Statistician/ClinicianDM/CRA/ClinicianRoles
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Drug Development in China
Due to the large volume of generics, regulators (sFDA) concentrate mostly on drug manufacturing quality
Minimal experience in true innovation-based R&D processes
Complex regulatory processes subject to frequent policy changes and political environment
2005 US FDA Chinese sFDA
# of New Drugs 20 1,113*
# of Generics 344 8,075
# of Reviewers 1,800 120
* Include formulation changes
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Preclinical
Phase I
Phase III
Phase II
Marketing Authorizati
on
Global
CTA Clinical Trial IDP
Chinese
Launch in
China
0 1 2 3 4 years
CPP
4 years behind!
Routine Registration Map in China (Imported Drugs)
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China’s Rapid Pharmaceutical Market Growth
Source: IMS Audit China Hospital Market 2010
• Projected to be 3rd largest market by 2013, 2nd largest by 2020
• CAGR +20% 2002 to 2011 driven by generics, branded generics and innovative medicines
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1919
There will be an increasing need for new medicines in ChinaChanging Demographics in China 1995 - 2030
1995 2010 2030 19
(166M) (342M)
2020
Great Opportunities for Professional Growth Come From
1. Outsourcing strategy from global companies and CRO to support global projects
2. R&D center from global companies focused on penetrating China’s high potential market
3. New Professions: Biostatistics, Programming (SAS and DBA), Data Management, Pharmacometrics, etc…
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We Innovate Healthcare
The 2nd Clinical Data Management Training
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