Clinical Trial Data Set Re-use With Statistical Methodologies Tailored for Clinical Trials in Rare Diseases

Tuberous sclerosis complex (TSC), affecting 1 in 6.000 live births, is characterized by the development of multisystem tumors. Seizures are frequent up to 80% of individuals. They usually start in infancy and are often drug resistant, with a high risk of intellectual disability and autism spectrum disorders. In animal models, preventive treatment before seizures onset significantly decreased the risk of epilepsy as well as associated comorbidities. EPISTOP randomized clinical trial (RCT) aimed to validate the effect of preventive therapy in patients with TSC diagnosed before clinical seizures with abnormal EEG, versus late standard therapy of epilepsy, administered after the seizures onset. This preventive therapy resulted in a significant better outcome in seizures and co-morbidities. However, this trial included few patients and did not allow to fully explore the secondary endpoints. Our goal within EPISTOP-IDEAL project is to benefit from joining clinical expertise of EPISTOP project and experts from IDEAL EU project on methodologies for CTs in small populations in order to consolidate the results of EPISTOP CT using uncertainty evaluation of the existing data of randomized and observational arms and adding important information from external data collected after EPISTOP ended. This collaboration aims to an optimal use of all available data (RCT, observational and external data collected with the same protocol). The goal is to demonstrate the added value of these methodologies in TSC CT and to their further use to rare epilepsies, and other rare diseases.

Sex

All

Minimum age

4 Months

Maximum age

2 Years

Inclusion Criteria:

1. Patients followed from 2013 to 2021 at the reference center for rare epilepsies with a diagnosis of tuberous sclerosis of Bourneville (based on Roach criteria and/or pathogenic variant identified in TSC1 or TSC2)
2. Start of follow-up at the reference center for rare epilepsies before the age of 4 months
3. Absence of epileptic seizures observed by relatives or on video EEG until inclusion

Exclusion Criteria:

1. objection from their legal representatives
2. Antiepileptic treatment before or at the time of study entry
3. Seizure occurrence prior to the inclusion visit