1 / 19

AED IX: an antiepileptic drug meeting

AED IX: an antiepileptic drug meeting . Jacqueline A. French, M.D. Department of Neurology University of Pennsylvania. AED meeting: The beginning. Meeting began in 1991, as a practical “how to” course on performance of AED trials Emphasis on regulatory, contracts, hiring co-ordinators, etc.

tarmon
Télécharger la présentation

AED IX: an antiepileptic drug meeting

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. AED IX: an antiepileptic drug meeting Jacqueline A. French, M.D. Department of Neurology University of Pennsylvania

  2. AED meeting: The beginning • Meeting began in 1991, as a practical “how to” course on performance of AED trials • Emphasis on regulatory, contracts, hiring co-ordinators, etc

  3. The Present “With nine new AEDs already approved, there is a unique opportunity to learn from the past as we move into the future. This symposium will bring together representatives from academia, industry, the NIH, and the FDA to review what has been learned and to discuss strategies to enhance AED development.” www.aedtrials.com

  4. Format • 3 day freestanding meeting • 25-30 faculty • 150-200 participants • Support: • Registration fee • Independent grants from Pharma, device companies

  5. Format • 20 minute talks • Long discussion sections • Round-tables • Final day: Drugs in Development and “CNS/Epilepsy company Forum” • Partnership & Financing Opportunities in Epilepsy and CNS: Corporate and VC Perspectives

  6. From the first meeting, the following elements were present: • Basic scientists involved in translation • Thoughtful presenters who were involved in active clinical trials • Europeans and US • Industry representatives • FDA representation • NIH

  7. Written Output • 2 Books • French, J.A., Dichter, M.A., Leppik, I.E. (eds) Elsevier 1993. New Antiepileptic Drug Development: Preclinical and clinical aspects. Epilepsy Research Supplement 10, 1993. • French, J.A., Leppik, I.E., Dichter, M.A. (eds) Lippincott-Raven Advances in Neurology:Volume 76, 1997, Antiepileptic Drug Development • Conference Proceedings • Epilepsy Research, Volume 68 pp19-94, 2006

  8. Topics that have been emphasized • Animal Models: Translation to human studies • Proof of principle trials • Outcome measures • Special populations • Women • Elderly • Children • Drugs in the pipeline • Monotherapy

  9. Animal Models • Relationships of effective dose in animal models vs human trials • Validation of new animal models • Anti-epileptogenesis

  10. Proof of Principle • How to determine: • Brain penetration • Effect on epileptic activity • Spectrum of activity • Appropriate dose range • Before moving to larger trials

  11. Outcome measures • Is seizure counting enough? • Seizure severity • Quality of Life • Mood

  12. Special Populations • Elderly • Are trials necessary? • How do metabolism, absorption differ?

  13. Children • What is ethical in regards to studies in infants? • What are current FDA regulations? • How to get pediatric exclusivity

  14. PEDIATRIC EXCLUSIVITY(Russ Katz, 2002) • TYPICALLY, WE HAVE ASKED FOR ONE OR TWO CONTROLLED TRIALS, SAFETY DATA, PHARMACOKINETIC DATA • PHARMACOKINETIC DATA TYPICALLY CAN COME FROM FORMAL STUDIES OR FROM THE CONTROLLED TRIAL(S) • EXCLUSIVITY IS INDEPENDENT OF THE RESULTS OF THE TRIAL(S)

  15. Monotherapy • Approval of new AEDs as monotherapy lagging behind general approval • Reason: conflict between rigorous scientific methodology and ethics/feasibility • Placebo-control, and “superiority studies are preferred, but not ethical

  16. HISTORICAL CONTROL • Instead of using placebo as control group, use “expected” behavior of placebo, based on prior trials • Not the same as “natural history”, because it is linked to a specific trial design and population. • Acceptable (barely) to FDA • We looked at existing data from trials to generate a historical control, to validate use of active control equivalence studies

  17. • T 40 • A % seizure free Treatment • HC

  18. Historical control: Current status • FDA has confirmed that if new AED beats the “bar” in a properly conducted historical control study, they will grant monotherapy.

  19. In summary, why is it useful? • Bouncing ideas off each other • Bouncing ideas from basic scientists to clinicians (and back) • Bouncing ideas off FDA

More Related