TY - JOUR
T1 - Rare diseases – rare outcomes
T2 - Assessing communication abilities for the developmental and epileptic encephalopathies
AU - Berg, Anne T.
AU - Kaat, Aaron J.
AU - Zelko, Frank
AU - Wilkening, Greta
N1 - Funding Information:
We are grateful to the many families who participated in the Ability Study. The study was funded by a grant from the Pediatric Epilepsy Research Consortium, Dallas Tx and received support from the precision medicine program at Lurie Children’s Hospital. We also thank Gerry Nesbitt of CLIIRINX©, Dublin, Ireland, who designed the web-based infrastructure that made this study possible. We also thank Abigail Van Nuland for her assistance during the data collection phase of the study.
Publisher Copyright:
© 2022
PY - 2022/3
Y1 - 2022/3
N2 - Objective: Developmental and epileptic encephalopathies (DEE) entail moderate to profound communication and other impairments that are poorly measured by typical clinical outcomes assessments (COA). We examined the potential of alternative approaches, specifically, the use of raw scores and COAs outside of their intended age ranges. Methods: In a cross-sectional survey, 120 parents of children with Dravet Syndrome, Lennox–Gastaut syndrome, KCNQ2-DEE, KCNB1-DEE, and SCN2A-DEE (ages 1–35 years) completed the Adaptive Behavior Assessment System-3 for ages 0–5 years, modified checklist for autism (mCHAT), communication and social behavior scales (CSBS), communication matrix (CM), and several parent-reported classifiers of communication. Adaptive Behavior Assessment System communication and social raw scores were the primary and adjunctive outcomes. Floor and ceiling effects, dispersion and convergence with related measures were assessed with appropriate parametric and nonparametric statistical techniques. Results: Median chronological age (CA) was 8.7 years (Interquartile range (IQR): 5.3–13.5). Adaptive Behavior Assessment Systemcommunication and social age equivalents were 12.5 months (IQR 7.5–28) and 16.5 months (IQR 9–31). Most raw scores corresponded to standardized scores indicating performance <3 standard deviations below the general population mean. Adaptive Behavior Assessment System raw scores demonstrated minimal floor and ceiling effects (<1–2.5%). In linear regression models, scores correlated with age under 6 years (communication, p = 0.001; social, p = 0.003) but significantly flattened out thereafter. Scores varied substantially by DEE group (both p < 0.001) and decreased with higher convulsive seizure frequency (communication, p = 0.01, social, p = 0.02). There was good convergence with mCHAT, CSBS, and CM scores (all r > 0.8). Significance: Raw scores and out-of-range COAs may provide measures that are sensitive at the very limited levels of functioning typical of profoundly impaired, older patients with DEEs. To ensure that targeted trial outcomes are responsive to meaningful change, development of these approaches will be essential to clinical trial readiness for novel therapies for rare DEEs.
AB - Objective: Developmental and epileptic encephalopathies (DEE) entail moderate to profound communication and other impairments that are poorly measured by typical clinical outcomes assessments (COA). We examined the potential of alternative approaches, specifically, the use of raw scores and COAs outside of their intended age ranges. Methods: In a cross-sectional survey, 120 parents of children with Dravet Syndrome, Lennox–Gastaut syndrome, KCNQ2-DEE, KCNB1-DEE, and SCN2A-DEE (ages 1–35 years) completed the Adaptive Behavior Assessment System-3 for ages 0–5 years, modified checklist for autism (mCHAT), communication and social behavior scales (CSBS), communication matrix (CM), and several parent-reported classifiers of communication. Adaptive Behavior Assessment System communication and social raw scores were the primary and adjunctive outcomes. Floor and ceiling effects, dispersion and convergence with related measures were assessed with appropriate parametric and nonparametric statistical techniques. Results: Median chronological age (CA) was 8.7 years (Interquartile range (IQR): 5.3–13.5). Adaptive Behavior Assessment Systemcommunication and social age equivalents were 12.5 months (IQR 7.5–28) and 16.5 months (IQR 9–31). Most raw scores corresponded to standardized scores indicating performance <3 standard deviations below the general population mean. Adaptive Behavior Assessment System raw scores demonstrated minimal floor and ceiling effects (<1–2.5%). In linear regression models, scores correlated with age under 6 years (communication, p = 0.001; social, p = 0.003) but significantly flattened out thereafter. Scores varied substantially by DEE group (both p < 0.001) and decreased with higher convulsive seizure frequency (communication, p = 0.01, social, p = 0.02). There was good convergence with mCHAT, CSBS, and CM scores (all r > 0.8). Significance: Raw scores and out-of-range COAs may provide measures that are sensitive at the very limited levels of functioning typical of profoundly impaired, older patients with DEEs. To ensure that targeted trial outcomes are responsive to meaningful change, development of these approaches will be essential to clinical trial readiness for novel therapies for rare DEEs.
KW - Clinical outcome measure
KW - Clinical trial readiness
KW - Communication
KW - Epilepsy
KW - Functional impairment
UR - http://www.scopus.com/inward/record.url?scp=85124630553&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85124630553&partnerID=8YFLogxK
U2 - 10.1016/j.yebeh.2022.108586
DO - 10.1016/j.yebeh.2022.108586
M3 - Article
C2 - 35158285
AN - SCOPUS:85124630553
SN - 1525-5050
VL - 128
JO - Epilepsy and Behavior
JF - Epilepsy and Behavior
M1 - 108586
ER -