Transcript drug
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 My Objective is… After this talk, you will have some good understandings about: The Global Innovative Pharmaceutical Industry The Complexity of Drug Development and Clinical Research The Role of Data Manager played in Clinical Research Challenges and Opportunities in China 2 Top Line, Bottom Line, Pipeline and Regulated Industry Sales Pharmaceutical Automobile 100 100 Cost of Sales 28 75 Marketing 30 7 R&D 10 3 7 8 Administration &Overhead Net income before tax 7 25 3 Drug Discovery to Drug Development: A Ten-Year Bet 4 Drug Discovery: Finding A Right Target and Picking Winners Identify a key: Mass-screening for hits: Identify a disease target: Combinatorial chemistry High-Throughput Screening (HTS) Cell Biology Natural Products Compound Acquisition Quantitative-Structure Activity Relationship (QSAR) Miniaturization 5 Genomics Early Phase Development: Use Clinical Pharmacology (CP), Pharmacokinetics (PK) and Pharmacodynamics (PD) to find A Right Drug PD: What the drug does to the body Response (Effect) Conccentration (ng/mL) PK: What the body does to the drug 12 Cmax 10 8 6 AUC 4 2 Tmax 0 0 0.5 1 2 3 4 6 8 10 14 18 24 Max Effect 50% Effect 50% Effect Dose Time (h) Drug Exposure (DOSE) 6 Late Phase Development: Finding A Right Clinical Plan Process Development Formulation/Stability File IND Drug Discovery Preclinical Clinical Trials Phase I Phase II (II A) Phase III (II-B) Metabolism Toxicology 7 File NDA A P P R O V A L “ If it were not for the great variability among individuals, medicine might as well be a science and not an art” 8 Dilemmas in Modern Medicine “Every day, doctors diagnose patients and prescribe the most appropriate drug, and yet in many cases, the drug won’t work or will trigger miserable side effects” - The Wall Street Journal 9 Relative signal/noise in drug studies due to inter-subject variability (noise) Phase 1 Phase 2 10 Phase 3 Evidence-Based Medicine is a Statistical-Based Medicine Extrapolate Population e.g. patients with high cholesterol sample e.g. 150 patients with high cholesterol in a clinical trial 11 Inferences based on the sample e.g. statin reduces cholesterol Design of Scientific Experiments (e.g., Clinical Trial) Hypothesis (Scientific belief) Objective (Signals/endpoints) Interpretation Data Collection •Confirm/Reject •Refine Data Analysis 12 Clinical 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 13 Four Elements of Clinical Research Data and Monitoring Patient Protocol Biostatistics 14 Clinical Trial and Protocol Life STAGE Roles Protocol Design Clinician/Statistician Study Setup & Conduct CRA/DM Data Review, Query & Cleaning DM/CRA/Clinician Statistician/Clinician CRF/Form External Design Data Draft/Design TASK Review FPFV Database design & verification Signoff Analysis & Report CRF Lock Data Entry/ CRF Processing Data Q&R Medical Encoding Data Review Plan LPLV Statistical Analysis Plan Data Presentation Plan 15 Data Base Lock Drug Development in China 2005 US FDA Chinese sFDA # of New Drugs 20 1,113* # of Generics 344 8,075 # of Reviewers 1,800 120 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 * Include formulation changes 16 Routine Registration Map in China (Imported Drugs) 4 years behind! Global Preclinical Phase I Phase II Phase III CPP Marketing Authorization 1 0 CTA Chinese 17 2 Clinical Trial 3 4 years IDP Launch in China China’s Rapid Pharmaceutical Market Growth • 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 18 Source: IMS Audit China Hospital Market 2010 18 There will be an increasing need for new medicines in China Changing Demographics in China 1995 - 2030 (166M) 1995 2010 19 (342M) 2030 19 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… 20 We Innovate Healthcare 21 The 2nd Clinical Data Management Training Click to edit company slogan .