NINDS Workshop: Challenges in Epilepsy Clinical Trials

Fairmont Turnberry Isle Resort
Aventura, Florida
April 30, 2011

Agenda

Salon VIII

Purpose: Identify the key problems facing epilepsy clinical trials and propose new approaches (why do trials fail and what can we do to fix them?)

Methodology: Working groups formed in advance of the meeting will prepare a proposal to be presented to the larger group for discussion.

8:00 - 8:15 Welcome (Fureman and French)

Morning sessions: Issues with Trial Methodology

8:15-8:45 Overview: Current status (French)

• Inconsistent/incorrect phenotyping leads to variability (global site problem)
• Inclusion/exclusion criteria (global site problem)
• Reluctance to enroll patients when other approved meds available to try
• Retention problem
• Placebo response
• Pediatrics
• Acute vs chronic treatment

 

Session I: Inclusion/exclusion criteria

Working Group: Bergey, Perucca, Hesdorffer, (MaryAnn) Brodie, Versavel, Kossoff, Hirtz

Are currently used inclusion/exclusion criteria appropriate and effective? Will harmonization make trial results more comparable?

8:45-9:00: Presentation   

9:00-10:00: Open Discussion

Deliverable: Inclusion/Exclusion criteria

 

10:00-10:15: Coffee Break

 

Session II: Epilepsy/Seizure confirmation

What should be done to ensure appropriate adult and pediatric patients are enrolled? How should investigators be trained?

Working group: Friedman, Schachter, Glauser, Kwan, Kramer, LaFrance

10:15-10:30 Presentation

10:30-11:30: Open Discussion

Deliverable: Plan for screening of potential patients to ensure proper patients are enrolled

 

Session III: Seizure Diaries

Working Group: Fisher, Herman, Vogelsong, Vannest

What are the problems with existing diaries? What are new/alternative options? How should new methods be validated?  How should investigators be trained on seizure classification and diary evaluation?

11:30-11:45: Presentation

11:45-12:30: Open Discussion

Deliverables: Recommendation on seizure diaries, Plan for investigator training.

 

12:30-1:30: Working Lunch (Salon II)

 

Afternoon sessions: Issues with Trial Design

1:00-1:30: Overview of current status (Baulac)

Designs

• Clinical trial outcome measures
• Monotherapy trials
• Adaptive designs
• Non-inferiority trials
• Combination therapy trials
• Targeted population trials
• Modeling from prior trials

 

Session IV: Trial designs: Monotherapy

Working group:

Messenheimer, (Martin) Brodie, Baulac, Blum, Mintzer, Dlugos, Gilbert, Stables

Are current designs in Europe and the US feasible, interpretable, appropriate, acceptable? Is there an alternative design that would be acceptable to both EMA and FDA?

1:30-1:45: Presentation

1:45-2:30: Open Discussion

Deliverable: Considerations for monotherapy design for US and Europe

 

Session V: Trial designs: Add-on trial considerations

Working group: Ryvlin, French, Bagiella, Emir, Arzimanoglou, Elterman

Are current designs supportable, ethical? What are the alternatives? Should we consider time to event, adaptive designs, other solutions?

2:30-2:45: Presentation

2:45-3:30: Open Discussion

Deliverables: Novel Trial Design for adjunctive epilepsy trials

 

3:30: Wrap-up (Fureman and French)

 

4:15: Meeting concludes