N of-1 trials for precision treatment of predefined genetic epilepsies

The ultimate goal of the n of 1 project is to improve individualized care of patients with rare, monogenic epilepsies by optimizing the assessment of therapies per patient. An n-of-1 trial methodological and ethical framework will be developed to support the use of this design in rare and complex epilepsies. The n of 1-project will focus on the following objectives:

1. Reviewing the use of precision treatments in patients with monogenic epilepsies across EpiCARE centres over the past 5 years.
2. Developing an ethical and methodological framework for N-of-1 trials tailored to rare and complex epilepsies.
3. Creating Bayesian hierarchical models for analyzing N-of-1 trials in monogenic epilepsy syndromes.
4. Adapting Patient-Centered Outcome Measures (PCOM) for use in epilepsy-specific N-of-1 designs.
5. Conducting proof-of-concept N-of-1 trials, including a study of everolimus in GATOR1-related epilepsy, led by the three coordinating centres.

Ongoing Actions

Multidisciplinary Expert Panel (MEP):
A collaborative EpiCARE and ECET initiative to evaluate proposed off-label precision treatments and assess the feasibility of N-of-1 trial designs.

Registry: 96 cases, 17 centres

Purpose of the MEP

For each submitted project, the MEP will assess:

• The risks and benefits of proposed off-label precision treatments
• The feasibility of N-of-1 study designs

The MEP will consist of experts in:
✔ Clinical trial design
✔ Clinical pharmacology
✔ Genetics
✔ (Pediatric) Neurology

Role of the MEP : will serve as an advisory team of external experts, providing guidance to local healthcare teams. It would not replace oversight procedures of clinical care at the local center conducting the N-of-1 strategy. 

Interested in Submitting a Project? If you are considering an N-of-1 study and would like support from the Expert Panel, please contact Sébile Tchaïcha.