Precision treatments In moNogenic ePilepsies: Observational regIstry and N-of-1 Trial recommendations (PINPOINT)

PINPOINT aimed to create a shift in the therapeutic approach of rare epilepsies by providing an alternative to upgrade the quality of evidence on treatment efficacy using single-patient (n-of-1) trials. We partnered with University of Amsterdam (JASP) and Neuroventis BV to deliver digital tools to support the implementation of n-of-1 trials. 

Epilepsy is a debilitating brain condition affecting approximately 70 million individuals worldwide. More than 30% of patients with epilepsy suffer from treatment resistant seizures. While treatment guidelines are available for some forms of epilepsy, in practice individuals may respond differently to treatments or be burdened by comorbid symptoms. Personalized treatment selection, suited to the underlying cause of epilepsy or to specific symptoms, is a promising alternative requiring a systematic approach to assess therapy efficacy objectively.  

N-of-1 strategies, in which an individual follows a predefined treatment plan alternating between treatments of interest in several cycles, can provide a systematic manner to assess efficacy of a therapy for a patient. Single-patient trials are well-suited for use in research and by practitioners searching for the optimal treatment for those with rare conditions, and when treatments effects or symptoms are highly variable between patients. Lack of methodological expertise and clarity on ethical oversight procedures have limited the use of n-of-1 strategies.  

PINPOINT developed tailored n-of-1 methodology which can be adapted to a range of epilepsies to improve individualized treatment selection. To enhance the quality of n-of-1 trials two user-friendly tools were developed: a patient-centered outcome measurement embedded in a mobile-health application and statistical analysis scripts. PINPOINT published an ethical framework to define oversight and quality standards for n-of-1 strategies. When finalized, the PINPOINT project will exemplify personalized treatment selection in proof-of-principle n-of-1 trials using tailored n-of-1 methodology, a digital application to gauge patient experience, and a practical statistical module for clinicians.