Peking University Asia Pacific Economic Cooperation Regulatory Sciences Center of Excellence APEC CENTER OF EXCELLENCE PILOT WORKSHOP

Transcription

1 Peking University Asia Pacific Economic Cooperation Regulatory Sciences Center of Excellence APEC CENTER OF EXCELLENCE PILOT WORKSHOP MULTI-REGIONAL CLINICAL TRIALS AND INCORPORATING GCP-RELATED CONSIDERATIONS July, 2016 Peking University, Beijing, China Workshop Program

2 Pre-workshop reading materials Mandatory reading 1. ICH E6 Guideline for Good Clinical Practice 2. ICH E8 Guideline for General Considerations for Clinical Trials 3. ICH E9 Guideline for Statistical Principles for Clinical Trials 4. ICH E10 Guideline for Choice of Control Group and Related Issues in Clinical Trials 5. Essential Elements of US FDA Drug Review Process 6. Article on Evidence vs. Access by J Woodcock 7. Presentation: Notable Topics of the Review Process (by Bob Temple, Bob O Neill and Justina Molzon) 8. Presentation: Design of Clinical Trials (by Bob Temple) 9. Presentation: A Perspective on the Acceptance of Foreign Clinical Data and the MRCT (by Bob O Neill) 10. Basis of MRCT Essential information for MRCT - Disease prevalence (Epidemiological Data) - Healthcare System and Medical Practice - Medical needs - Utilization of IT The CTD and relevant ICH Guidelines for MRCT 11. ICH E17 Guideline for General principles on planning/designing Multi-Regional Clinical Trials Optional / Supplementary reading 1. Overview of Clinical Trial Framework Pharmaceuticals, Biologics and Radiopharmaceuticals 2. CDER Clinical Investigator Training Course 3. CDER 21st Century Review Process Desk Reference Guide 4. Presentation: A Perspective on the Science of Regulatory Statistics (by Bob O Neill) 5. Presentation: Statistical Analysis of Clinical Trials (by Catherine Njue) 6. Article on From Medical School to Secondary School (by K Ranga Krishnan) 7. Basic principles on Global Clinical Trials ( 8. Basic Principles on Global Clinical Trials (Reference Cases) ( 9. Handbook for Good Clinical Research Practice (

3 Day 1, July 12 9:00am Open Remarks Prof. Qimin Zhan, PKU CFDA 9:10am Welcome, Introduction to PKU APEC Health Science Academy Prof. Xiaoying Zheng, PKU 9:20am Welcome, Introduction to CoE Pilot, and the Workshop Prof. Yangfeng Wu, PKU Session 1: Trends of Clinical Development for Medicinal Products 9:30am Regulator s viewpoint Challenges and opportunities for regulatory strengthening CFDA 10:00am Industry s view point - Current issues and expectations Dr. Karen D. Weiss, J&J 10:30am Break Session 2: Science basis for MRCT- how to justify for a MRCT proposal Speaker: Dr. Yoshiaki Uyama, PMDA, Dr. Chenyan Gao, CFDA Facilitator: Dr. Feng Guo, Merckserono 11:00am Interactive lecture a) Brief introduction of the 2015 CFDA MRCT guidance b) Review strategy for MRCT application in China c) Introduction of ICH E17 guideline (draft) d) Review experiences of MRCT data for drug approval in Japan e) The difference and similarity among MRCT regulatory guidelines 12:30pm Lunch 1:30pm Case Study a) World-wide drug development strategy b) East Asia-based drug development strategy Session 3: Special considerations for Asian population in MRCT Speaker: Professor Yuji Kumagai, Kitasato University Facilitator: Dr. Joan Shen, Xi an Janssen 3:00PM Interactive lecture a) Basics of clinical pharmacology - Dose-effect relationship - Basic knowledge of pharmacokinetics (ADME) - Phamacodaynamics and efficacy based on PK b) Ethnic difference in drug development - Intrinsic and extrinsic factors - Pharmacokinetic factors - Adverse effects - Case study of tolterodine (Korea-Japan Study)

4 4:00pm 4:30pm 6:00pm - Case study of rosvastatin (PK difference) Break Case Study - APECSTATIN End

5 Day 2, July 13 Session 4: MRCT Design, Statistical Analysis and Interpretation Speaker: Dr. Daphne Lin, FDA Dr. Gang Chen, R&G Facilitator: Dr. Hong Wang, PKU Dr. Xiang Guo, MSD 9:00am Interactive lecture a) MRCT concept and issues b) Scientific rigor requirement in the design and execution of MRCT regulatory and industry perspectives. c) Current existing regulatory guidance: USFDA/EMA/PMDA/CFDA d) Consistency consideration in the design and interpretation of MRCT results: global vs. local e) Current statistical methods considered in the design of MRCT to full fill global & regional registration requirement - Non-inferiority - Weighted Method - Bayes Method f) Sample size considerations in MRCT for regional registration consideration g) Some remarks 10:30am Break 11:00am Interactive lecture a) Protocol Design, Statistical Analysis Plan and examples in the Multi-Regional Clinical Trials, regulatory perspectives. b) Update on ICH E17 document General Principles on Planning/Designing Multi-Regional Clinical Trials 12:00am Lunch 1:30pm Interactive lecture Subgroup analyses in MRCTs: what/why/how and assessing heterogeneity in treatment effect across subgroups (or regions) with cases: two NDAs: Toprol-XL and Brilinta (Ticagrelor) as examples. 2:00pm Break 2:30pm Case Study a) Brilinta (Ticagrelor) b) How to design MRCT, type of design, sample size consideration c) How to interpret the results d) Different Efficacy findings between regions e) Different safety findings between countries/regions 5:30pm End

6 Day 3, July 14 Session 5: How to handle Adverse Drug Reaction (ADR) and manage the risk in MRCT Speaker: Mr. Daisuke Sato, PMDA Ms. Shohko Sekine, PMDA Dr. Daisuke Tanaka, WHO Dr. William Collins, Novartis Facilitator: Dr. Xue Tang, Pfizer 9:00am Interactive lecture a) Handling ADR - Setting an ADR Report timeline - Evaluating ADR reports and the impact on clinical trial conduct - Safety signal detection Signal detection and generation, and methods for signal refinement Meta-analyses for safety and level of evidence b) Risk management plan (RMP) - Reviewing the RMP early in the Development Stage Avoiding failure in product development Safety signal management - Optimising RMP for a Market Authorization Application c) WHO s activities on Pharmacovigilance WHO Programme for International Drug Monitoring Current focus and Future Perspective d) Importance of Pharmacovigilance Industry perspective - Sharing of PV models and processes 10:30am Break 11:00am Case Study/Panel 12:00pm Lunch Session 6: GCP Findings in the Review of MRCT Speaker: Ms. Karen Takahashi, FDA Ms. Laura Pioppo, EMA Facilitator: Jun Li, J&J 1:30pm Interactive lecture a) Identifying the significant deviations and the potential impact b) Real-world sharing of inspection experiences by FDA, and EMA. c) Assessing the deviations in GCP and implications of reports on regulatory decision-making d) Assessing the outcomes of an GCP inspection 3:30pm Break 4:00pm Case Study/Panel

7 5:30pm End Day 4, July 15 Session 7: Ethical Considerations in MRCT Speaker: Asst Prof Bruce Burnett, Duke University (confirmed) Prof. Yali Cong, PKU (confirmed) Facilitator: Dr. Haihong Zhang, PKU (confirmed) 9:00am Interactive lecture a) General Principles on Ethical Review of Clinical Trials - Declaration of Helsinki - Belmont Report (Principles) - ICH-GCP E6 Principles b) Special Challenges in Ethical Review of MRCT - Law - Different regulatory framework on MRCT - Culture - Context-based Comparison among varied cultural background: e.g. informed consent, health care system and medical insurances - Practice - Analysis of real world problems: e.g. Doctorpatient relationship 10:30am Case Study 11:30am Break 12:00pm Q&A with Faculty and Facilitator 12:30pm Post-workshop feedback 13:00pm Lunch