Contemporary Trends, IT Systems and Technologies in Clinical Trials

1. Contemporary Trends, IT Systems and Technologies in Clinical Trials Dr. Sandeep Bagga, PhD Scientific Advisor

2. Interactive Voice Response (IVR) • Multiple native languages • Operate continuously • Global access • Cost effective

3. IVR System • Streamlines and expands the patient enrollment process • Automates and implements even the most complex randomization to ensure both participant and data integrity • Tracks and monitors drug inventory helping to manage drug costs, production, and supply • Collects recorded and electronic patient reported outcomes.

4. Case Report Form • Case Report Form (CRF) is the name given to the collection of forms used to record data obtained during a clinical study -Completed by the investigator or study staff -Based on data from source documents -Reviewed by the monitor -Entered into the computer - Must be completed as designed, so NO CHANGES to the CRF may be made by the study site

5. Case Report Forms for FDA office

6. Why Electronic Record Keeping - Increases Speed of Information Exchange - Reduces Errors - Data Integration - Improves Process Control -Economical Data Management -Easy Accessibility

7. Case Report Form (Web Browser Interface) • Standard Pages -Simplifies CRF completion -Identical or similar formats for multiple studies - Demographics - Inclusion/Exclusion Criteria - Physical Exam - Medical History - Laboratory Analysis - Adverse Events - Concomitant Medications

8. Case Report Form (Web Browser Interface) • Study Specific Pages -Designed specifically for an individual study - May be a ‘standard’ type of page, but designed specifically for a particular study - Efficacy Evaluations - Drug Accountability

9. Document Imaging • A true paperless environment • Transform documents into instantly accessible files • Save on physical storage space • Reduce retrieval time and lost files

10. ICR/OCR/OMR technology • ICR – Intelligent Character Recognition Reads human hand printed text • OCR – Optical Character Recognition Reads computer generated text • OMR – Optical Mark Recognition Reads mark sense fields such as check boxes

11. Regulatory Requirements for Clinical Trials Record • IND regulations 21 CFR 312 - 312.62(b) Prepare and maintain adequate and accurate case histories -312.68 Permit FDA to have access to, and copy and verify any records or reports required under 312.62(b) -21 CFR 11 applies if the above are electronic

12. Challenges in Defining Standards - Uneven levels of technology - Different regulatory practices/procedures - Reaching internal (co.) consensus on configuration - Development and transition costs • Rewriting regulations, SOPs & retraining personnel - Communicate to policy makers - Crucial to maintain flexibility and openness to change - Avoid jargon (easy to understand by all) - Cutting edge technology is often not a motivation for change

13. Data Review • CRFs are coded • Data entered into computer system • Diagnostics are developed • Data review conventions are developed • Internal data review • Computer-assisted review • Corrections made to data • Corrected data sent for analysis

14. SAS Reporting Tools SAS is a registered trademark of SAS Inst., Inc., in United States of America and other countries • Reading external data • Processing SAS data sets • Storing SAS data sets • Sorting SAS data sets • Documentation and coding

15. SAS XPORT • Processed by: -XPORT engine in V6 & beyond • Why XPORT? -Ease of use in Pharmaceutical/Biotech industry -Well tested by US FDA and industry -Data transfer to/from common DB systems -ASCII based -It is computer platform independent

16. Corresponding Transport Files Data Sets To/From XPORT Processing • Extension Identifies File Type

17. SAS System Viewer

18. Efficacy and Safety Results (Examples)

19. Incidence of Adverse Events by Treatment GroupsDisplayed by Body System

20. Conclusion Computer Assisted NDA • Electronic data capture • Data readily available on screen • Electronic linking of documents • SAS datasets with programs • Submission

21. Seeking Vacation !

22. Not Approvable Letter (314.120) • The FDA believes the NDA is insufficient to justify approval • The letter describes the deficiencies • Within 10 days, the Sponsor must do one of the following: -Amend, or notify the FDA of an intent to amend, the NDA -Withdraw the application -Ask for a hearing -Ask for an extension so the sponsor can consider options -If a Sponsor fails to respond within 10 days, the FDA will automatically withdraw the application

23. US FDA Action Letters Approvable Letter (314.110) • The application substantially meets the requirements for marketing approval • The agency thinks it can approve the application if specific additional information or material is submitted or specific condition are agreed to by the applicant • Most often the FDA requests changes in proposed labeling and safety update reports

24. Approval Letter (314.105) • Drug is approved as of the date of the letter • The Sponsor is required to submit final printed labeling

25. Finally, thank you for attending! My email address is: sbagga@visionpointsystems .com URL: www.visionpointsystems.com Address: 10201 Lee Highway, Suite 224 Fairfax, VA 22030