Introduction Philip Sager, MD (Consultant/Stanford Univ) 

 Session I

CV Outcome Studies to Determine Drug Safety

Session Chairs:  Peter Kowey, MD and Jonathan Seltzer, MD 

·         Overview of their role, findings, impact, and challenges Peter Kowey, MD (Lankenau)

·         CV Safety Assessments

o   FDA Perspective Patrick Archdeacon, MD (Office of Medical Policy, FDA)

·         Low prevalence events when there is not a clear safety signal

o   The role of individual dedicated CV studies versus monitoring throughout drug development when prevalence rates are expected to be low; How much unknown risk is acceptable at the time of approval? Nancy Geller, PhD (NIH\NHLBI)  

o   Value of information analysis and statistical approaches to studying CV Safety Mark Hlatky, MD (Stanford University)

·         What factors should be considered when deciding if pre-approval outcome studies are required? William White, MD (University of Connecticut)

·         Benefit:risk analysis- qualitative vs quantitative analysis  William Hiatt, MD (University of Colorado)

*Discussion*

Session II

  Discussion of Specific Examples: Lower and higher risk populations [Each speaker to address a few specific questions (see end of agenda)].  Considerations- What do the past examples show? What can we learn to apply to future CV safety questions and their evaluation?

Session Chairs:  Philip Sager, MD and Bob Temple, MD

·         Why was a CV Outcomes trial not required for Aliskiren based on the Altitude trial results?  Mary Ross Southworth, PharmD (FDA)

·         Discussion of the CV safety approach for the assessment of varienicline (Champix) and potential implications. Judith Prochaska, PhD (Stanford)

·         Do the sibutramine data support the need to perform a CV Outcome Safety Studies for all drugs to treat obesity? Domenic Sica, MD (Medical College of Virginia)

·         Tegaserod: Is the data sufficiently compelling for a class effect and thus a CV Outcome Safety should be required for all 5HT-4 agonist for severe constipation? Jeff Anderson, MD (Intermountain Healthcare)

o   FDA Perspective Joyce A. Korvick, M.D., M.P.H.

·         Tiotropium: Do the findings of a CV safety signal in the meta-analyses have implications for all drugs to treat COPD?  Lorcan McGarvey, MD (Queen’s University)

o  FDA Commentary Sally Seymour , MD (FDA)

 ·         Do dronedarone data supported the need to perform a CV Outcome Safety Study?  Gerald Naccarelli, MD (Hershey Medical Center)

o  FDA Commentary Norman Stockbridge, MD, PhD      

·         Does the rosiglitazone experience and the new label lessons learned? Murray Stewart, M D (GSK)

*Discussion*

Session III

Alternative Approaches To Randomized Prospective CV Outcome Studies To Evaluate Drug Safety

Session Chair: Chairs: William White, MD (Univ of Connecticut), Rick Turner, PhD (Quintiles)

·   What is the potential for impact on Phase 3 development if CV Safety can be well defined in the early post-approval period?  How might new technologies impact assessment of the benefit: risk relationship Robert Temple, MD (FDA)

·   The approach and potential impact of the Sentinel effort on drug development  Marsha Reichman, MD (FDA)

·   The use of registries and electronic medical records to evaluate post-approval drug safety Kathleen Hewitt, MSN, RN

·   Observational studies- current examples Leroy LeNarz, MD (Eli Lilly)

*Discussion*