1. Clinical Data – Dealing with the Chips as they Fall Patricia L. Ruppel, Ph.D. President, dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003

2. Paint the Picture dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 NDA Study 989

3. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Oh No !!!!!!

4. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Results – Not Positive Primary Outcome

5. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Spotfire DecisionSite Can Help

6. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 High Failure Rate in Drug Development Stage 10,000 250 10 1 Discovery Preclinical Clinical FDA Approval

7. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Reasons why 90% of compounds fail in clinical development Prentis et al, Br J Clin Pharm 1988

8. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 How Can Spotfire DecisionSite Help?  Rapid exploration through the data  Performed in team setting  Minimizes time and resources

9. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Case Study 3-Arm Double-blind Controlled Study in 466 Depressed Patients Placebo control N=161 patients Test compound N=151 patients Active control N=154 patients 5 Investigative Sites Ham-D Score %Pts Ham-D Responders

10. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Strategies for Exploring Results  Are there skewed / outlier data affecting results Correlation with other clinical endpoints  Are there site / investigator aberrations  Can efficacious subgroups be identified forward exploration backward exploration

11. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Scatter Plot of Ham-D Change from Baseline for each Treatment Group ActivePboTest

12. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Box Plots of Ham-D Change from Baseline for each Treatment

13. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Scatter Plot of Ham-D Change from Baseline vs. Madrs Change from Baseline

14. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Differences in Ham-D Response Across Investigators Active Pbo Test

15. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Ham-D Response Rates across Treatments and Investigators ActivePboTest

16. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Episode Rates across Investigators

17. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Data Quality vs. Quality of Response

18. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Active Pbo Test Ham-D Response Rate by Presence of Underlying Stress at Study Start

19. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Ham-D Response Rate by Episode Recurrance ActivePboTest

20. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Active Pbo Test Ham-D Response Rate by Age of Onset

21. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Backward Approach What differentiates responders vs non-responders

22. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Age of Onset Ham-D Non-Responders Ham-D Responders

23. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Age Primary Splitters for Test Treatment Ham-D Responders Episode Occupation Age AgeOnsetAge Living Situation AgeOnset

24. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Primary Splitters for Placebo Treatment Ham-D Responders AgeOnset Age Sex Occupation Episode

25. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Treatment Separators are not Enough Test Pbo All Patients Subgroup 1 Subgroup 2

26. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 Separating Desirable Bins from Undesirable Bins Test Responders Pbo Non-Responders Test Non-Responders Pbo Responders Focus is on “Active” Treatment Response

27. dKb Technologies 2003 Spotfire User Conference Boston, 28 October 2003 How Can Spotfire DecisionSite Help?  Rapid exploration through the data run through all collected variables univariately and mutivariately  Performed in team setting different knowledge and perspectives from members  different avenues of exploration  Minimizes time and resources also gives a deeper understanding of therapeutic area / drug response directions for future study designs