1. 1 Lotronex ® (alosetron HCl) Tablets Introduction Victor F. C. Raczkowski, M.D. Director, Division of Gastrointestinal and Coagulation Drug Products April 23, 2002

2. 2 Center for Drug Evaluation and Research (CDER) A CDER priority: –Assure that safe and effective drugs are available to the American Public Basis of regulatory decisions: –Laws and regulations –Scientific evidence –Judgement

3. 3 Need for Joint Advisory Committee Public debate over Lotronex –Safety of Lotronex –Access to Lotronex New data about Lotronex –Clinical-trial data –Post-marketing data

4. 4 Issues for this Joint Advisory Committee Can conditions be described for which benefits of Lotronex exceed the risks? –Describe patients –Describe physicians Does the GSK risk-management plan adequately ensure appropriate use of Lotronex?

5. 5 Issues (continued) How is the success of the plan best monitored or audited: –At the level of the patient? –At the level of the physician? –At the level of the pharmacist?

6. 6 Issues (continued) Describe criteria for success of the plan: –Process controls –Evaluation of outcomes

7. 7 FDA Presentations Clinical-Trial Experience Post-Marketing Experience Risk-Benefit Issues Risk-Management Program Summary and Conclusions Thomas Permutt, Ph.D. Ann Corken Mackey, M.P.H. Victor F. C. Raczkowski, M.D. Toni Piazza-Hepp, Pharm. D. Victor F. C. Raczkowski, M.D.