Development of a Composite Primary Outcome Score for Children with Attention-Deficit/Hyperactivity Disorder and Emotional Dysregulation
Dr. Michael G. Aman has received research contracts, consulted with, served on advisory boards, or done investigator training for CogState, Inc.; CogState Clinical Trials, Ltd.; Confluence Pharmaceuticals; J & J Pharmaceuticals; MedAvante-ProPhase; Otsuka Pharmaceutical Development & Commercialization, Inc.; Ovid Therapeutics; ProPhase LLC; Supernus Pharmaceuticals; and Zynerba Pharmaceuticals. He receives royalties from Slosson Educational Publications. 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. Dr. Oscar Bukstein has received honoraria from Routledge Press, Wolters Kluwer Health, and Guilford Press. Dr. Robert L. Findling receives or has received research support, acted as a consultant, and has received honoraria from Acadia, Aevi, Akili, Alcobra, Allergan, Amerex, American Academy of Child and Adolescent Psychiatry, American Psychiatric Press, Arbor, Bracket, Daiichi Sankyo, ePharmaSolutions, Forest, Genentech, Ironshore, KemPharm, Luminopia, Lundbeck, Merck, NIH, Neurim, Noven, Nuvelution, Otsuka, PCORI, Pfizer, Physicians Postgraduate Press, Purinix, Receptor Life Sciences, Roche, Sage, Shire, Sunovion, Supernus Pharmaceuticals, SyneuRx, Teva, TouchPoint, Tris, and Validus. Dr. Kenneth D. Gadow is shareholder in Checkmate Plus, publisher of the Child and Adolescent Symptom Inventory. Dr. Barbara Gracious receives or has received research support, research contracts, acted as a consultant, or received honoraria from the American Academy of Child and Adolescent Psychiatry, American Psychiatric Association, AstraZeneca, Brain and Behavior Foundation, Novo Nordisk, the Stanley Medical Research Institute, and Otsuka.
Journal of Child and Adolescent Psychopharmacology
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.
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Johnstone, J. M., Leung, B. M., Srikanth, P., Hatsu, I., Perez, L., Gracious, B., ... & Bukstein, O. (2020). Development of a composite primary outcome score for children with attention-deficit/hyperactivity disorder and emotional dysregulation. Journal of child and adolescent psychopharmacology.