This study was supported and funded by Shire, now part of Takeda. Medical writing support was also commissioned and funded by Shire, now part of Takeda
In this study, post-hoc correlation analyses were performed to investigate relationships between treatment-associated changes in measures of ADHD symptoms, functional impairment and health-related quality of life (HRQoL) in children (aged 6–12 years) and adolescents (aged 13–17 years) with ADHD.
Correlation coefficients were calculated for changes in symptom, functional impairment and HRQoL scores from baseline to endpoint in outcomes from one randomised placebo- and active-controlled trial of lisdexamfetamine (LDX) (osmotic-release methylphenidate [OROS-MPH] reference arm) and one of guanfacine extended-release (GXR) (atomoxetine [ATX] reference arm).
Pearson correlation coefficients were determined for efficacy outcomes by measuring changes from baseline to endpoint for the following:
- ADHD Rating Scale (ADHD-RS-IV) total score versus Child Health and Illness Profile–Child Edition: Parent Report Form (CHIP-CE:PRF)* domain T-scores (domains: Achievement, Risk Avoidance, Resilience, Satisfaction, Comfort) (LDX study only).
- ADHD-RS-IV total score versus Weiss Functional Impairment Rating Scale–Parent (WFIRS-P)† total score and WFIRS-P domain scores (domains: Family, Learning and School, Life Skills, Child’s Self-concept, Social Activities, Risky Activities) (both studies).
- CHIP-CE:PRF domain T-scores versus WFIRS-P total score and WFIRS-P domain scores (LDX study only).
A total of 317 participants (mean [standard deviation (SD)] age 10.9 [2.70] years; 72.2% were aged 6–12 years) were included in the full analysis set of the LDX study, of whom 191 completed the study (LDX: n=77; placebo: n=42; OROS-MPH: n=72). A total of 337 participants (mean [SD] age 10.8 [2.77] years; 71.8% were aged 6–12 years) were included in the full analysis set of the GXR study, of whom 272 completed the study (GXR: n=91; placebo: n=89; ATX: n=92).
Post-hoc analyses of efficacy outcomes from the two studies indicated that:
- There were weak-to-moderate correlations between changes in ADHD-RS-IV total score and CHIP-CE:PRF domain T-scores for the Achievement (OROS-MPH: r=-0.48, p<0.001) and Risk Avoidance (LDX: r=-0.44, p<0.001; OROS-MPH: r=-0.42, p<0.001) domains. All other correlations were weak or very weak.
- In the LDX study, there were moderate correlations between changes in ADHD-RS-IV total score and WFIRS-P total score (LDX: r=0.51, p<0.001; OROS-MPH: r=0.49, p<0.001). Correlations between ADHD-RS-IV total score and WFIRS-P domain scores were strongest for the Family domain in the LDX and OROS-MPH groups (LDX: r=0.55, p<0.001; OROS-MPH: r=0.52, p<0.001), and moderate correlations were observed for the Learning and School (r=0.43, p<0.001) and Risky Activities (r=0.44, p<0.001) domains in the LDX group only. All other correlations were weak.
- In the GXR study, a moderate-to-strong correlation was observed between changes in ADHD-RS-IV total score and WFIRS-P total score in the GXR group (r=0.56, p<0.001). Moderate-to-strong correlations between ADHD-RS-IV and WFIRS-P domain scores were also observed for the Family (r=0.54, p<0.001), Learning and School (r=0.46, p<0.001), Child’s Self-concept (r=0.48, p<0.001), Social Activities (r=0.52, p<0.001) and Risky Activities (r=0.46, p<0.001) domains in the GXR group only. The correlation was weak but nominally significant in the ATX group (r=0.38, p<0.001). All other correlations were weak but nominally significant (including all domains in the ATX group).
- For the LDX group, moderate-to-strong correlations were observed for change in total CHIP-CE:PRF Achievement score versus WFIRS-P total score (r=-0.65, p<0.001), and versus five WFIRS-P domain scores (Family: r=-0.50; Learning and School: r=-0.54; Child’s Self-concept: r=-0.40; Social Activities: r=-0.45; Risky Activities: r=-0.58; all p<0.001). Similarly, moderate-to-strong correlations were observed for changes in CHIP-CE:PRF Risk Avoidance score versus WFIRS-P total score (r=-0.62, p<0.001) and versus domain scores (Family: r=-0.50; Learning and School: r=-0.53; Child’s Self-concept: r=-0.55; Social Activities: r=-0.49; Risky Activities: r=-0.71; all p<0.001).
- For the OROS-MPH group, moderate-to-strong correlations were observed for changes in CHIP-CE:PRF Achievement score versus WFIRS-P total score (r=-0.59, p<0.001) and versus three WFIRS-P domain scores (Learning and School: r=-0.59; Child’s Self-concept: r=-0.43; Risky Activities: r=-0.40; all p<0.001); and for CHIP-CE:PRF Risk Avoidance score versus WFIRS-P total score (r=-0.62, p<0.001) and versus four domain scores (Family: r=-0.50; Learning and School: r=-0.46; Child’s Self-concept: r=-0.41; Risky Activities: r=-0.56; all p<0.001).
Limitations of this study were: 1) CHIP-CE:PRF data were included in the LDX study but not in the GXR study; 2) both studies were short-term and did not include data on functional or HRQoL improvements beyond the end of the study; 3) functional impairments and HRQoL deficiencies were not requirements for study inclusion; 4) ADHD-RS-IV was completed by investigators, whereas CHIP-CE:PRF and WFIRS-P were completed by parents; and 5) only two clinical studies were included in the post-hoc analyses.
The authors concluded that a reduction in child and adolescent ADHD symptoms during short-term pharmacological ADHD treatment may be associated with a reduction in functional impairments and an increase in HRQoL. Moreover, they proposed that their findings may be suggestive of factors other than reduction in ADHD symptom scores influencing improvements in functioning and HRQoL, and that these measures should be included as outcomes in future studies.
Read more about Pearson correlations between ADHD clinical study outcomes here
*CHIP-CE:PRF is a generic HRQoL instrument not specific to any disease or disorder
†WFIRS-P is a tool designed around functional impairments that are relevant but not limited to patients with ADHD
Coghill DR, Joseph A, Sikirica V, et al. Correlations between clinical trial outcomes based on symptoms, functional impairments, and quality of life in children and adolescents with ADHD. J Atten Disord 2017; Epub ahead of print.