TY - JOUR
T1 - Development of a Composite Primary Outcome Score for Children with Attention-Deficit/Hyperactivity Disorder and Emotional Dysregulation
AU - Johnstone, Jeanette M.
AU - Leung, Brenda M.Y.
AU - Srikanth, Priya
AU - Hatsu, Irene
AU - Perez, Leanna
AU - Gracious, Barbara
AU - Tost, Gabriella
AU - Aman, Michael G.
AU - Gadow, Kenneth D.
AU - Findling, Robert L.
AU - Bukstein, Oscar
AU - Arnold, L. Eugene
N1 - Funding Information:
1Helfgott Research Institute, National University of Natural Medicine, Portland, Oregon. 2Department of Child and Adolescent Psychiatry, Oregon Health & Science University, Portland, Oregon. 3Faculty of Health Sciences, University of Lethbridge, Lethbridge, Alberta, Canada. 4School of Public Health, Oregon Health & Science University-Portland State University (OHSU-PSU Program), Portland, Oregon. 5Department of Human Sciences, The Ohio State University, Columbus, Ohio. 6Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, Ohio. 7Orange Park Medical Center, Orange Park, Florida. 8The Nisonger Center UCEDD and Department of Psychology, The Ohio State University, Columbus, Ohio. 9Department of Psychiatry, Stony Brook University, Stony Brook, New York. 10Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland. 11Department of Psychiatry, Boston Children’s Hospital, Boston, Massachusetts. *Current affiliation: Virginia Commonwealth University, Richmond, Virginia. Funding: The TOSCA study: Funding was provided by the National Institute of Mental Health (NIMH) to The Ohio State University (R01 MH077907), Case Western Reserve University (R01 MH077750), the University of Pittsburgh (R01 MH077676), and Stony Brook University (R01 MH 077997). The project was supported by an NIH General Clinical Research Center grant M01RR10710 (State University of New York, Stony Brook) and Clinical and Translational Science Awards from the National Center for Advancing Translational Sciences: grants UL1TR002733 and 8UL1TR000090-05 (The Ohio State University) and UL1 RR024153 and UL1TR000005 (University of Pittsburgh). Funding for the Micronutrients for ADHD in Youth study was provided by the Gratis Foundation; the Foundation for Excellence in Mental Health Care; the National Institutes of Health (NIH) National Center for Complementary and Integrative Health (NCCIH) 5R90AT00892403 (to National University for Natural Medicine); and NIH NCCIH T32 AT002688 (to OHSU), Department of Child and Adolescent Psychiatry, OHSU, supported the study. At OHSU, NIH, UL1TR000128, UL1TR002369; at Ohio State UL1TR002733 and 8UL1TR000090-05; and the Department of Behavioral Health and Psychiatry, Nationwide Children’s Hospital, supported the study. At the Canadian site, the Nutrition and Mental Health Research Fund, administered by the Calgary Foundation; and Emmy Droog Endowed Chair in Complementary and Alternative Healthcare supported the study.
Funding Information:
Dr. L. Eugene Arnold has received research funding from Forest, Lilly, Noven, Otsuka, Shire, Supernus, Roche, and YoungLiving (as well as NIH and Autism Speaks); has consulted with Pfizer, Tris Pharma, and Waypoint; and been on advisory boards for Arbor, Ironshore, Otsuka, Pfizer, Roche, Seaside Therapeutics, and Shire.
Publisher Copyright:
© Copyright 2020, Mary Ann Liebert, Inc., publishers 2020.
PY - 2020/4
Y1 - 2020/4
N2 - Objective: Study goals were to (1) provide a rationale for developing a composite primary outcome score that includes symptom severity for attention-deficit/hyperactivity disorder (ADHD) and emotional dysregulation, plus symptom-induced impairment; (2) demonstrate weighting methods to calculate the composite score using a sample of children diagnosed with ADHD and aggression; and (3) identify the optimal weighting method most sensitive to change, as measured by effect sizes. Methods: We conducted secondary data analyses from the previously conducted Treatment of Severe Childhood Aggression (TOSCA) study. Children aged 6-12 years were recruited through academic medical centers or community referrals. The composite primary outcome comprised the ADHD, oppositional defiant disorder, disruptive mood dysregulation disorder, and peer conflict subscales from the Child and Adolescent Symptom Inventory (CASI), a DSM (Diagnostic and Statistical Manual)-referenced rating scale of symptom severity and symptom-induced impairment. Five weighting methods were tested based on input from senior statisticians. Results: The composite score demonstrated a larger (Cohen's d) effect size than the individual CASI subscales, irrespective of the weighting method (10%-55% larger). Across all weighting methods, effect sizes were similar and substantial: approximately a two-standard deviation symptom reduction (range: -1.97 to -2.04), highest for equal item and equal subscale weighting, was demonstrated, from baseline to week 9, among all TOSCA participants. The composite score showed a medium positive correlation with the Clinical Global Impressions-Severity scores, 0.46-0.47 for all weighting methods. Conclusions: A composite score that included severity and impairment ratings of ADHD and emotional dysregulation demonstrated a more robust pre-post change than individual subscales. This composite may be a more useful indicator of clinically relevant improvement in heterogeneous samples with ADHD than single subscales, avoiding some of the statistical limitations associated with multiple comparisons. Among the five similar weighting methods, the two best appear to be the equal item and equal subscale weighting methods.
AB - Objective: Study goals were to (1) provide a rationale for developing a composite primary outcome score that includes symptom severity for attention-deficit/hyperactivity disorder (ADHD) and emotional dysregulation, plus symptom-induced impairment; (2) demonstrate weighting methods to calculate the composite score using a sample of children diagnosed with ADHD and aggression; and (3) identify the optimal weighting method most sensitive to change, as measured by effect sizes. Methods: We conducted secondary data analyses from the previously conducted Treatment of Severe Childhood Aggression (TOSCA) study. Children aged 6-12 years were recruited through academic medical centers or community referrals. The composite primary outcome comprised the ADHD, oppositional defiant disorder, disruptive mood dysregulation disorder, and peer conflict subscales from the Child and Adolescent Symptom Inventory (CASI), a DSM (Diagnostic and Statistical Manual)-referenced rating scale of symptom severity and symptom-induced impairment. Five weighting methods were tested based on input from senior statisticians. Results: The composite score demonstrated a larger (Cohen's d) effect size than the individual CASI subscales, irrespective of the weighting method (10%-55% larger). Across all weighting methods, effect sizes were similar and substantial: approximately a two-standard deviation symptom reduction (range: -1.97 to -2.04), highest for equal item and equal subscale weighting, was demonstrated, from baseline to week 9, among all TOSCA participants. The composite score showed a medium positive correlation with the Clinical Global Impressions-Severity scores, 0.46-0.47 for all weighting methods. Conclusions: A composite score that included severity and impairment ratings of ADHD and emotional dysregulation demonstrated a more robust pre-post change than individual subscales. This composite may be a more useful indicator of clinically relevant improvement in heterogeneous samples with ADHD than single subscales, avoiding some of the statistical limitations associated with multiple comparisons. Among the five similar weighting methods, the two best appear to be the equal item and equal subscale weighting methods.
KW - ADHD
KW - aggression
KW - composite primary outcome
KW - emotional dysregulation
KW - irritability
KW - symptom severity and impairment
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U2 - 10.1089/cap.2019.0179
DO - 10.1089/cap.2019.0179
M3 - Article
C2 - 32101469
AN - SCOPUS:85082780404
VL - 30
SP - 166
EP - 172
JO - Journal of Child and Adolescent Psychopharmacology
JF - Journal of Child and Adolescent Psychopharmacology
SN - 1044-5463
IS - 3
ER -