title: Developing a Risk Score to Guide Individualized Treatment Selection in Attention Deficit/Hyperactivity Disorder.
abstract: OBJECTIVE
  To develop a risk score for treatment failure that could potentially be used to individualize treatment selection between lisdexamfetamine dimesylate (LDX) and osmotic-release oral system methylphenidate (OROS-MPH) in children and adolescents with attention deficit/hyperactivity disorder (ADHD).
  
  
  METHODS
  The study used data from patients with ADHD receiving LDX (N = 104) or OROS-MPH (N = 107) in a phase III randomized clinical trial. A prediction model was developed to estimate risk scores for failing OROS-MPH, where treatment failure was defined as less than 25% improvement in the ADHD Rating Scale IV total score from baseline. Patients were ranked by their predicted risks of OROS-MPH failure to define high-risk subpopulations. Outcomes of LDX and OROS-MPH were compared within subpopulations.
  
  
  RESULTS
  The prediction model for OROS-MPH failure selected seven predictors (age, disease duration, and five ADHD Rating Scale IV item scores) and had an in-sample C statistic of 0.860. Among all patients, LDX had a 17% (95% confidence interval 7.1%-27.8%) lower treatment failure rate than that of OROS-MPH; differences in failure rates ranged from 17% to 43% across subpopulations, increasingly enriched for high-risk patients. Similar heterogeneity across subgroups was observed for other efficacy measures.
  
  
  CONCLUSIONS
  In the overall trial population, LDX was associated with a lower rate of treatment failure compared with OROS-MPH in patients with ADHD. A more pronounced benefit of LDX over OROS-MPH was observed among subpopulations with a higher predicted risk of failing OROS-MPH. The present study showed the feasibility of individualizing treatment selection. Future research is needed to prospectively verify these results.
authors.affiliation: Shire Pharmaceuticals, Wayne, PA, USA. Electronic address: jsetyawan@shire.com.
authors.forename: Juliana
authors.initials: J
authors.lastname: Setyawan
authors.affiliation: Analysis Group, Inc., Boston, MA, USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yang
authors.affiliation: Analysis Group, Inc., Boston, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Analysis Group, Inc., New York, NY, USA.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Cai
authors.affiliation: Analysis Group, Inc., Boston, MA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Signorovitch
authors.affiliation: Analysis Group, Inc., New York, NY, USA.
authors.forename: Jipan
authors.initials: J
authors.lastname: Xie
authors.affiliation: Shire Pharmaceuticals, Wayne, PA, USA.
authors.forename: M Haim
authors.initials: MH
authors.lastname: Erder
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002652:Child Behavior / Q000187:drug effects; D017326:Clinical Trials, Phase III as Topic; D057186:Comparative Effectiveness Research; D003661:Decision Support Techniques; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage* / Q000009:adverse effects; D018579:Patient Selection; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D017211:Treatment Failure
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D000069478:Lisdexamfetamine Dimesylate
keywords: attention deficit/hyperactivity disorder; lisdexamphetamine dimesylate; personalized treatment selection; treatment individualization