To develop a clinician-completed assessment specific to Phelan-McDermid syndrome (PMS) for assessing outcomes in clinical trials.

Evaluating symptoms specific and meaningful to patient populations is critical for determining potential benefit of treatment in clinical trials. The Clinical Global Impression (CGI) scales have been widely used as outcome measures in CNS trials and have favorable assay sensitivity. The CGI is a 7-point Likert rating scale that reflects expert clinical judgment to assess the severity of illness (CGI-S) and improvement in symptoms (CGI-I). It has become best practice in neurodevelopmental disorders (NDD) to develop syndrome-specific anchors to calibrate scoring (Busner, et al. 2009).

PMS is a rare genetic condition associated with NDD caused by a deletion or other change in the terminal end of chromosome 22 or a mutation of the SHANK3 gene. No medications are approved for the treatment of PMS.

Symptom areas that are functionally important were identified based on published literature from the PMS Natural History Study, input from patient advocacy organizations, and feedback from clinicians. Scoring anchors were developed and reviewed in an iterative process by a group of experts in PMS.

The anchors for the CGI were focused on the core, characteristic symptoms of PMS seen in all individuals: expressive communication, receptive communication, gross motor, fine motor, social interaction, self-care, and cognition/learning. For CGI-S, anchors provide a characterization of impairment that may be observed in each symptom domain. CGI-I anchors provide a framework for considering: 1) breadth of change; 2) magnitude of change; 3) breadth of contexts, and 4) impact on function. Clinicians provide an overall global severity rating and a severity rating for each domain.

The PMS-specific CGI is designed to assess the PMS phenotype and is a potential tool to assess treatment change. It will be used in a Phase 2 trial in PMS (NCT05025241).