1 / 18

Development and Approval of Drugs and Devices EPI260 Lecture 6: Late Phase Clinical Trials May 5, 2010 Richard Chin, M.

Development and Approval of Drugs and Devices EPI260 Lecture 6: Late Phase Clinical Trials May 5, 2010 Richard Chin, M.D. Overview Outline. GXP Protocol design and writing Case report forms Investigators brochure Operations Budget; staff training Safety reporting

hollye
Download Presentation

Development and Approval of Drugs and Devices EPI260 Lecture 6: Late Phase Clinical Trials May 5, 2010 Richard Chin, M.

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Development and Approval ofDrugs and DevicesEPI260 Lecture 6: Late Phase Clinical TrialsMay 5, 2010Richard Chin, M.D.

  2. Overview Outline • GXP • Protocol design and writing • Case report forms • Investigators brochure • Operations • Budget; staff training • Safety reporting • Site initiation, monitoring and closeout • Data management and data analysis • Report writing • Regulatory requirements for approval; NDA/BLA and pre-NDA meeting

  3. GXP • Good clinical practice • Good manufacturing process • Good laboratory process

  4. GCP • Goal: to protect • Patient safety • Patient rights • Data integrity • What is it? • Instructions on how to responsibly conduct a study • Process, not outcome • SOPs on all aspects of study conduct • Must exercise control over study • Must document • Must take corrective action as needed

  5. GMP • Similar but more strict than GCP • Criminal liabilities for failure • Even for intentional failures • Guilty until proven innocent • Focus on how a drug is manufactured • Lots of documentation

  6. Protocol design • Best to have CRF before protocol • Keep it short • Keep it simple • Minimize number of procedures • Minimize data collection (unless you are an academician) • Keep instructions clear • Don’t ask for more precision than you need • Work with a statistician

  7. Key Drivers of Study Design • Patient population • Dose • Endpoint

  8. Key documents • Investigators Brochure • Must list all adverse events • Protocol • CRF • ICF

  9. Operations • Project management • Multinational studies • Key personnel • Medical director • Clinical operations • Statistician • Data manager • Programmer • Project leader • Project manager • Regulatory • Safety • CMC • Pharmacology • Pharmacoeconomics • Quality • Compliance • Contracts • Finance

  10. Operations • Budget • $10,000 - $200,000 per patient • Per patient costs increase with smaller study size, longer duration, more procedures, certain specialties, number of sites, number of countries • Timeline • 12 months or more for Phase 1 • 18 months or more for Phase 2 or 3 • Key drivers for timeline: drug labeling, IRB approval, regulatory approval, contracts, enrollment, follow-up

  11. Safety Reporting • Adverse event reporting • Adverse event monitoring • Pharmacovigilance systems • Reconciling with clinical database • Breaking the blind

  12. Site Monitoring • Feasibility study • Site identification • Site qualification • Site initiation • Investigators meeting • Monitoring visits • Drug storage • ICF • Adverse events • Audits • Site closeout visits • Drug accountability

  13. Data Management and Analysis • Case report form • Statistical Analysis Plan • Data Quality Plan • % target query resolution • Maintaining the blind • DSMB • Adaptive design • Administrative looks • Safety unblinding • Electronic Data Capture • Double data entry • Query generation and resolution

  14. Data Management • Validation • IT system and CFR Part 11 • Program installation • Data listings and tables • Double programming • Dummy data • Sensitivity analysis • Imputations for missing data • Data management costs are about 25% of trial costs

  15. Report Writing • Clinical Study Reports • Integrated summary of efficacy and safety • Tables, Listing, Graphs • Trial Conduct Report

  16. Regulatory Requirements for Approval • Requirements • Risk/Benefit • Accelerated approval • Pre-NDA/BLA meeting • MAA

  17. Regulatory Requirements for Approval • Common Technical Document Format • Administrative and prescribing information • Overview and summary of modules 3 to 5 • Quality (pharmaceutical documentation) • Safety (toxicology studies) • Efficacy (clinical studies) • REMS • Filing • Rolling submission • Acceptance of filing

  18. Regulatory Requirements for Approval • PDUFA requirements • Major amendment • Advisory Committee Meeting • Approval vs. Complete Response

More Related