Draft Agenda

Monday, August 19, 2013   (starts at 1:00pm)

Day 1: The DSMB and Clinical Trials 

                * Purpose, role, responsibilities, and scope of authority of  a DSMB  

            * Overview of clinical development plans in neurological disorders

            * Pre-clinical studies- identifying biomarkers, target validation, potential safety signals

            * Learning phase questions and studies- dosing, safety and efficacy signals in early phase
               research

            * Confirming phase questions and studies

            * Panel discussion – what preclinical studies should you do, when do you have enough data to go
               into humans, how do you determine dose, how do you identify safety and efficacy signals, how
               do you juxtapose safety and efficacy in balancing risk and benefit, how do you maintain vigilance
               thru early and late stage development


Tuesday, August 20, 2013

Day 2: DSMB and Trial designs

                * Protocol design – Different types of designs and relevant issues

            * Statistical issues – Basic Principles – sample size calculations, hypothesis testing vs estimation,
               different analytic techniques, when do you apply each one, issues of hierarchy, issues of control
               for multiple observation

            * Statistical issues – Novel approaches –– Adaptive Design (CRM, dose ranging, futility, sample
               size re-estimation, triggering new trials), multiple endpoints

            * FDA interactions (IND, end of phase 2, SPA, how the FDA operates)

            * Panel – When to use specific study designs, which statistical approach to use, how to interact
               with the FDA, role of interim analysis for safety, efficacy, futility and for planning future studies,
               role of sensitivity analysis

Wednesday, August 21, 2013   (Ends at 1:00pm)

Day 3: DSMB organization and operations 

                  * Regulatory guidance on DSMBs

            * Organization – structure, charter, how to choose members, training, legal issues

            * Operational issues – what data to look at, how does it work, interaction with sponsor, regulatory,
               IRB, confidentiality, should reviews be blinded or unblinded, who to report to, what to report

            * DSMB in studies with adaptive design – what is the role and how are decisions made

            * Case studies and panel –stopping early for efficacy, stopping for reverse efficacy/safety, dropping
               a dose for safety, stopping a study for futility, resisting stopping for efficacy, breaches of
               confidentiality