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Presentation on theme: "STANDARD COURSE IN CLINICAL TRIAL PIENGTHONG NARAKORN May 23, 2008."— Presentation transcript:


2 OUTLINE: March 24, 2008  From R&D product to licensing  Study design & research methodology for clinical trials  Proposal development  Grant hunting, fund management, research administration & human resource management  Management of multi-center trials

3 OUTLINE: March 25, 2008  GCP&ICH-GCP  Tools for conducting GCP  Challenges with large-scale, phase III  Principle of electronic data management  Role of CRO&CRA  Common pitfalls in pharmacy  Common pitfalls in GLP

4 OUTLINE: March 26, 2008  Symposium: Challenges in ethical approval of clinical trials  International clinical trial registration  Symposium: Practical points of IRB review in clinical trials  Investigational new drug  Interactive session: Case study& common pitfalls of GCP trial

5 From R&D to product licensing  Requirements on Quality –Active substance  General information, Manufacture  Control of active substance, Stability –Finished product  Formulation product  Control of excipients and finished product, stability

6  Registration application for generic product require: –Product quality –Literature references –Bioequivalence study From R&D to product licensing

7  Innovator products should be fulfilled all these tests: –Pharmaceutical tests –Non-clinical test –Clinical trials –Potential environment risks From R&D to product licensing

8 Study design&methodology  Descriptive study  Epidemiology study  Analytic study  Intervention study  Experimental study:phase I,II, III  Observational study:phase IV (Non-experimental)

9 Study design&methodology  Efficacy: phase III  Effectiveness ( ประสิทธิผล ): phase IV  Efficiency ( ประสิทธิภาพ ):

10 Clinical trials  Phase I –PK, safety, healthy volunteers  Phase II –Placebo controlled design, dose-response relationship, short-term safety, patients  Phase III –Larger patient groups, efficacy, short & long term safety  Phase IV –Post marketing surveillance

11 Clinical trials  Research Involving Children –The research might not equally well be carried out with adults –The purpose of the research is to obtain knowledge relevant to the health needs of children –A parent or legal representative of each child has or given permission –Children’s refusal to participate or continue in the research will be respected

12  Good Idea: target, question  Good Timing: 3-6 months  Good Presentation: What, Why, How, Outcome  Good Support: Mentors, Collaborators, General reader  Good Luck  Good Grantsmanship Proposal Development

13  General & background information  Trial objectives & purpose  Benefits  Study location  Trial design  Selection and withdrawal of subjects  Treatment of subjects  Assessment of Efficacy  Assessment of Safety  Statistics  Project plan  Timeline  Direct access to source data/documents  Quality Control  Ethics  Data handling & record keeping  Instruments  Financing and insurance  Publication policy  CV of investigators  Institutional declaration

14 Finding Grants  Pharmaceutical Companies –Ready-made protocols –Investigator-initiated  National Research Council of Thailand  International Organizations –U.S. NIH –U.S. CDC –WHO –Japanese government –Wellcome Trust –Bill&Melinda Gates Foundation

15 Management of Multicenter Trial  Sample size>1000 subjects  > 10 sites  Timely and In-time result is needed-speed  Many people involved  Central Coordinator Center; PI, Co- Investigator, IRB, Administrative support, Data systems, Project Coordination, Statistical analysis, Computer support,  Study Protocol & Design

16 Management of Multicenter Trial  Pre-study Activities; Investigator selection, Site qualification, Pre-study visit  Monitoring  Close out visit  Database management issues  Statistical considerations  Sponsor reports  Investigator reports  Budget & contract  Data Safety and Monitoring Board  Rewards & Incentives

17 To set globally applicable standards for the conduct of such biomedical research on human subjects Good Clinical Practice ( การปฏิบัติการวิจัยทางคลินิกที่ดี )

18 GCP GLP S-Scientific valid E-Ethically oriented A-Accuracy T-Traceability Good Clinical Practice

19  ICH GCP:1-13 (Principles, IRB/IEC, Investigator, Sponsor, Protocol, IB, IP  Process in a Clinical Trial; –Developing a study protocol  Blinded study (Single, Double, Triple)/Open  Randomization  Comparative  Co-intervention –Ethical approval –Sign a contract –Get FDA approval –Pre-trial meeting –Screening/enrollment –Complete CRF

20 Good Clinical Practice  Process in a Clinical Trial; –Monitoring –Audit of trail –Data cleaning, entering –Data analysis: interim, final –Compliance/Adherence –AEs, SAEs –Data and Safety Monitoring Committee –Standard Operating Procedure (SOP) –Intention-to treat Analysis –Per Protocol Analysis –Contamination: community trial –Writing report –Presentation & publication

21 Tools for Conducting a clinical trial  Protocol  CRF; record within 48 hrs  Source documents -hospital records, Lab. note, -memorandum -subject’s diaries -questionnaires -pharmacy dispensing records -recorded data from automated instruments -x-rays film  Records & reports  IB  Product insert

22 Informed consent  กระบวนการที่ยืนยันความสมัครใจของอาสาสมัคร ในการตัดสินใจเข้าร่วมในโครงการวิจัยภาย หลังจากได้รับข้อมูลเกี่ยวกับการวิจัยอย่างละเอียด  ใช้ภาษาที่บุคคลทั่วไปเข้าใจได้ง่าย  ควรหลีกเลี่ยงการใช้ศัพท์ทางการแพทย์  ควรขอความยินยอมจากเด็ก ( ถ้าต้องวิจัยในเด็ก )  ควรระบุไว้ด้วย ว่า “ การไม่เข้าร่วมโครงการไม่ถือ เป็นความผิด ”  งานวิจัยที่ยกเว้นการขอความยินยอม : พฤติกรรม ทางเพศ ยาเสพติด งานวิจัยในชุมชนบางแห่งของ ประเทศกำลังพัฒนา

23 Informed consent  A copy should be offered to the subject  Purpose of the research  Procedures that will be followed, including total time  Risks and discomforts  Benefits of the research  Compensation, if any  Alternatives to participation

24 Principle of Electronic Data Management in Clinical Trials  Good Data Management Practices: 21 CFR 11  Data manager  CRF development: –Started when draft protocol became available –6 week –100% reflect protocol –Use multiple choice –Medical term  Data Entry  Start data cleaning ASAP  Medical review  Data review meeting  Database lock

25 Role of Investigator  Conduct clinical trial; high responsibility, medical training &experience, have sufficient time, facilities, compliance with GCP & Protocol, potential for recruiting  Contact with IRB  Review protocol  Take an informed consent  Know Lab. Specimens  Record & report to sponsor/IRB/Regulatory authorities  Provide medical care of subjects  Write final report and submit to sponsor/IRB/Regulatory

26 Role of CRO  Contract Research Organization (CRO); CT plan, site management, monitoring  1110 CROs, 6 biggest companies (Quintiles, Covance, PPD, Charles River Labs., Parexel, MDS Pharma)  Provide speed, larger enrollment (China, India), efficiency  Younger work force than academic  IATEC & CUIPIF:Ratchadamri Rd.

27 Role of CRA  Protocol editing  Writing patient information/consent form  Site identification  Lab. identification  CRF editing  Regulatory document collection & submission  Ordering & shipping IP  Pre-study, Initiation, Monitoring, Close out visit  AEs/SAEs follow-up  CRA cannot take on investigator responsibilities, patients care

28 Responsibilities of research pharmacist  Ordering; companies/import  Storage; temp., humidity  Inventory control; monthly check  Distribution; control storage condition  Dispensing & Accountability  Disposal

29 Practical Points of IRB Review in Clinical Trials  Competent and properly trained committees  Managing of Conflicts of Interest  Compliance with related SOPs  Independent review –Appropriateness of the scientific design of a study –Subject selection –Risk & benefit –Informed consent: free from pressure –Data protection plan –Examine qualifications of investigators & staff –Evaluate study site –Continuing review  High risk: very 4 months  Moderate risk: every 6 months  Minimal risk: every 1 year  Retain all records 3 years after completion

30  AEs –Any untoward medical occurrence, not related to the medicinal product –Do not include:  Medical or surgical procedures  Pre-existing disease or conditions present at the start of the study Safety & the Safety Reporting Process

31  SAEs –Results in death –Is life-threatening –Require/prolong hospitalization –Results in incapacity –Is a congenital anomaly/birth defect

32 Investigational New Drug Regulation  Might allow parallel application with EC submission : จุฬาฯ ศิริราชฯ รามา ฯ มช. มอ. มข. เวชศาสตร์เขตร้อน กรมแพทย์ทหารบก กระทรวงสาธารณสุข  Need: –Drug label –Drug leaflet –IB –Patient information sheet –Clinical Trial Protocol –Information on Drug Quality & GMP  Requirement: –GCP –GMP  Accepted ECs  GCP Inspection

33 International Clinical Trial Registration  To promote public awareness  To ensures that the results of all trials can be tracked down  To reduce unnecessary duplication of research  Manuscript to be reviewed by International Committee of Medical Journal Editors (ICMJE)  All interventional clinical trials should be registered  PI/lead PI is responsible for registering  Chula IRB review now includes a section asking whether a clinical trial has been or will be registered  Eligible registries for ICMJE – (USA): – (UK) – (Australia) – (Netherlands)

34 Common Pitfalls of GCP Trials  Safety reporting  Consent: Wrong ICF, no date, time, witness  Inclusion/Exclusion criteria  Investigational product: storage, accountability

35 Common Pitfalls in Pharmacy  Protocol out of date, incomplete  Incomplete prescription  Correction made without signature/date  Mixed-up between active stock & expired stock  Easy access for unauthorized persons  Temp./humidity out of range  Error correction


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