Assessing Communication Impairments in a Rare Neurodevelopmental Disorder: The SCN2A Clinical Trials Readiness Study

Area of Science:

• Neuroscience
• Genetics
• Clinical Trials

Background:

• SCN2A-related disorders (SCN2A-RDs) cause severe impairments, including communication deficits.
• These deficits represent potential nonseizure outcomes for clinical trials.

Purpose of the Study:

• To evaluate the fitness for purpose of clinical instruments for assessing communication in SCN2A-RD participants.
• To compare standardized and alternative scoring methods, including out-of-age-range measures.

Main Methods:

• Cross-sectional and longitudinal study involving parents of children with SCN2A-RDs.
• Utilized Vineland Adaptive Behavior Scale (VABS-3), ABAS, Communication Matrix, and CSBS.
• Analyzed floor/ceiling effects, reliability, discrimination, and sensitivity to clinical aspects.

Main Results:

• 84% of participants were ineffective communicators; standardized scores showed significant floor effects and poor discrimination.
• Alternative scores (e.g., Vineland GSV, ABAS, Matrix, CSBS raw scores) had minimal floor effects and better discrimination.
• Alternative scores were sensitive to epilepsy severity, unlike standardized scores which decreased longitudinally.

Conclusions:

• Age-standardized scores (e.g., Vineland SS) are not fit for purpose in SCN2A-RD clinical trials due to floor effects and insensitivity.
• Alternative scoring methods and assessments show superior measurement profiles for SCN2A-RDs.
• GSVs and alternative scores should be considered for future precision medicine trials in SCN2A-RDs and similar rare diseases.