Abstract

Objectives

This study presents a novel method for estimating meaningful score differences (MSDs) and meaningful score regions (MSRs) for the Observer-Reported Communication Ability (ORCA) Measure for individuals with Angelman syndrome (AS).

Methods

The AS Natural History Study collected longitudinal data on an individual’s communication abilities on the ORCA Measure, Vineland Adaptive Behavior Scales-3, and the Bayley Scales of Infant and Toddler Development-4. In a separate Delphi-based study, caregivers provided MSDs and MSRs for the Vineland-3 and Bayley-4 scores. Leveraging the strong correlations between ORCA and these measures, mixed models with random intercepts were used to estimate ORCA MSDs and MSRs based on the previously derived Vineland-3/Bayley-4 MSDs and MSRs.

Results

The ORCA Measure was completed by 192 caregivers, with 113 also completing the Bayley-4 and 159 completing the Vineland-3. ORCA T-score MSRs for low, intermediate, and high communication ability were estimated for expressive, receptive, and pragmatic communication domains using the Vineland-3 and Bayley-4 previously derived MSDs and MSRs. ORCA MSDs varied depending on the MSR and ranged from 0.38-4.55 (based on Vineland-3) and 1.79-4.62 (based on Bayley-4).

Conclusions

We present a novel anchor-based methodological approach for deriving MSD and MSR thresholds for clinical outcome assessments. Although these MSD and MSR estimates for the ORCA measure are preliminary, our methods offer a strategy for establishing meaningful change thresholds in rare disease populations in which traditional longitudinal methods may be challenging to implement.