# Beyond Seizures as an Outcome Measure: A Global Severity Scoring System for CDKL5 Deficiency Disorder

## TL;DR

Researchers developed a global severity score for CDKL5 deficiency disorder to better assess disease severity and improve clinical trials.

## Contribution

A validated global severity score for CDKL5 deficiency disorder was created using structural equation modeling.

## Key findings

- The global severity score was calculated using multiple assessments and correlated with biomarkers and quality of life.
- Motor and communication measures were the most significant contributors to the severity score.

## Abstract

Background: CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy (DEE) associated with multiple impairments and comorbidities. Outcome measures for disease‐modifying clinical trials for DEEs should measurably capture a spectrum of caregiver priorities and be externally validated.

Methods: The International CDKL5 Clinical Research Network was the data source for this observational study. A Structural Equation Model was constructed with latent, exogenous variables related to observed clinical features to calculate a global severity score from the following assessments: the CDKL5 Clinical Severity Assessment‐Clinician and ‐Caregiver, Communication and Symbolic Behavior Scales Developmental Profile Infant Toddler Checklist and the Sleep Disturbance Scale for Children. Quantitative EEG power was measured as a biomarker. The Quality of Life Inventory—Disability measured quality of life.

Results: Acceptable fit statistics for models were obtained using data from 206 subjects (median [range] age 6.8 [3 months to 40] years). Motor and communication measures were the most important weighted contributors to the global severity score which correlated well with the biomarker and quality of life to support external validation.

Conclusions: The resultant global severity score provided evidence that the assessments formed a coherent set of measures that reliably and meaningfully captured the diversity of severity in CDD. The models illustrated how the symptoms form a measurable network of relationships which may be suitable as an outcome measure for CDD and DEEs more broadly in clinical trials.

A validated global measure of severity for CDKL5 deficiency disorder was obtained from structural equation modeling that enables clinical trial readiness.