Defining Bayley Scales of Infant and Toddler Development Third Edition (BSITD-III) meaningful change and item relevance in children with neuronopathic MPS II: a caregiver interview-based study

Neuronopathic mucopolysaccharidosis type II (MPS II) is a rare genetic disorder characterized by multisystem impairments that include profound cognitive and behavioral impairment and global developmental delay. Developmental function is considered a sensitive indicator of disease progression and a relevant outcome to evaluate the efficacy of existing and novel therapies. The Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) has been recommended by expert consensus to assess treatment effect in the disease. The current study aimed to better understand what constitutes a meaningful change on the BSITD-III in response to treatment of neuronopathic MPS II according to caregivers and to investigate the functional relevance of items on the BSITD-III to daily function. Ten semi-structured interviews were conducted with caregivers of children aged 2–6 years old in the UK and USA. The interviews included hypothetical vignettes describing a change on the BSITD-III in response to an intervention over 1 year. Caregivers were asked to rate the level of change, discuss whether the changes were clinically meaningful and to describe any relevance to daily function. Qualitative and quantitative analyses were undertaken. Interviews involved 12 caregivers of 11 children. Caregiver perceptions support a meaningful change on the BSITD-III being as small as a change of 1–2 months in Age Equivalent values: increases in age-equivalent scores of 2 months were reported to be associated with meaningful changes (Caregiver Global Impression of Change rating of minimal or greater improvement) over 1 year by 97.1% of caregivers (all subtests) and increases of 1 month for the Fine Motor and Expressive Communication subtests were considered meaningful by 81.8% and 90.9% of caregivers, respectively. Caregivers reported that the BSITD-III Cognitive, Expressive Communication, and Fine Motor items outlined in the hypothetical vignettes were functionally relevant to their children with MPS II and provided practical examples of item relevance in their child’s daily activities. These findings support the use of BSITD-III as an appropriate clinical outcome assessment for measuring changes in developmental skills in children with neuronopathic MPS II.