Feasibility, reliability, and clinical validity of the Test of Attentional Performance for Children (KiTAP) in Fragile X syndrome (FXS)

Abstract

BackgroundAttention and inhibition are core executive-function deficits in FRagile X syndrome (FXS). This pilot study evaluated the feasibility, reproducibility, and clinical relevance of the KiTAP, a computer-based pictorial measure of attention and inhibition with an enchanted-castle theme, in an FXS cohort.MethodsThe 8-subtest KiTAP battery (as many subtests as each could perform) was given to 36 subjects with FXS, of variable age and cognitive/behavioral functioning, and 29 were retested, with an interval of 2 to 4 weeks between sessions. Subjects were rated by parents on the Aberrant Behavior Checklist-Community Edition (ABC-C) and Behavior Assessment System for Children, Second Edition (BASC-2). Feasibility, ceiling and basal effects, and data range and distribution analyses were used to eliminate outliers and invalid data points. Reproducibility of scores was analyzed using intraclass correlation coefficients (ICCs) and validity/clinical relevance was assessed by correlating KiTAP scores with ABC-C and BASC-2 scores.ResultsMost of the participants with FXS were able to complete the Alertness, Distractibility, Flexibility, and Go/NoGo subtests.About 50 to 60% completed the Visual Scanning and Vigilance subtests, and 20 to 25% completed the Sustained Attention and Divided Attention subtests. A panel of seven scores from four subtests were identified as feasible for most subjects, lacked excessive ceiling, basal, or learning effects, exhibited an acceptable range and distribution of scores, had good reproducibility (ICC > 0.7), and correlated with behavioral ratings for hyperactivity or attention (P < 0.01). Only minor differences in performance on the KiTAP were seen between mental age-matched cohorts of subjects with FXS and non-FXS intellectual disability.ConclusionsThe KiTAP can be administered to cohorts with FXS over a wide range of function with valid reproducible scores. With additional validation, it could represent a useful outcome measure for assessment of attention/executive-function abilities in clinical trials targeted to these core deficits in FXS.

The NIH Toolbox Cognitive Battery for intellectual disabilities: three preliminary studies and future directions

“…Based on our prior work on the feasibility, reliability, and validity of the KiTAP in FXS [49], we chose the flexibility, go/no-go, and distractibility subtests, which include reliable and validated scores matching well with several NIH-TCB constructs.…”

Fragile X Syndrome and Targeted Treatment Trials

“…Only a subset of outcome measures utilized in recent trials have shown good feasibility and validity (Berry-Kravis et al 2006, 2008a, b, 2009). Thus, recently investigators have begun to develop templates for pretrial feasibility, reproducibility, and validity assessment (Berry-Kravis et al 2008a, b; Hessl et al 2008; Knox and Berry-Kravis 2009; Scaggs et al 2011). The choice of outcome measures must also balance the use of standard accepted behavioral measures with precedent for use in drug registration/FDA approval, which are generally caregiver rating scales (such as the ABC), versus use of novel measures (Hessl et al 2008; Knox and Berry-Kravis 2009; Scaggs et al 2011) that are more quantitative and may objectively measure core phenotypes (such as eye tracking or PPI), thus advancing treatment science, but have no precedent for registration and are not yet known to predict a specific functional outcome.…”

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

“…Only a subset of outcome measures utilized in recent trials have turned out to fulfill the majority of these criteria (Berry-Kravis et al, 2006) suggesting better, FXS-specific measures are needed. Only recently have investigators begun to develop templates to test the feasibility, reproducibility, and validity assessment before using the measure in a trial (Berry-Kravis et al, 2008b;Hessl et al, 2009;Knox and Berry-Kravis, 2009;Farzin et al, 2011). Choice of outcome measures must also balance use of accepted behavioral measures, which are generally caregiver rating scales (such as the ABC), with precedent for use in drug registration/FDA approval versus use of novel measures Knox and Berry-Kravis, 2009;Farzin et al, 2011) that are more quantitative and may objectively measure core phenotypes and electrophysiology (such as eye tracking or PPI).…”

“…Only recently have investigators begun to develop templates to test the feasibility, reproducibility, and validity assessment before using the measure in a trial (Berry-Kravis et al, 2008b;Hessl et al, 2009;Knox and Berry-Kravis, 2009;Farzin et al, 2011). Choice of outcome measures must also balance use of accepted behavioral measures, which are generally caregiver rating scales (such as the ABC), with precedent for use in drug registration/FDA approval versus use of novel measures Knox and Berry-Kravis, 2009;Farzin et al, 2011) that are more quantitative and may objectively measure core phenotypes and electrophysiology (such as eye tracking or PPI). These novel quantitative measures advance treatment science, but have no precedent for registration, do not clearly predict a specific functional outcome, and are often expensive and difficult to run at multiple sites.…”