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.

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.

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