Functional impairment outcomes in clinical trials of different ADHD medications: post hoc responder analyses and baseline subgroup analyses

TY - JOUR

T1 - Functional impairment outcomes in clinical trials of different ADHD medications

T2 - post hoc responder analyses and baseline subgroup analyses

AU - Coghill, David R

AU - Werner-Kiechle, Tamara

AU - Farahbakhshian, Sepehr

AU - Bliss, Caleb

AU - Robertson, Brigitte

AU - Huss, Michael

N1 - Funding Information: We thank the participants and investigators involved in the studies. This post hoc analysis and the original studies were funded by the sponsor, Shire Development LLC, a member of the Takeda group of companies. Under the direction of the authors and funded by Shire International GmbH, a member of the Takeda group of companies, Dr MG Cottingham and Dr AL Jones of Oxford PharmaGenesis provided writing assistance for this publication. Editorial assistance in formatting, proofreading, copy editing and fact checking was also provided by Oxford PharmaGenesis. Although employees of the sponsor were involved in the study design, data collection, analysis and interpretation, and fact checking of information, the content of this manuscript, the interpretation of the data and the decision to submit the manuscript for publication in European Child and Adolescent Psychiatry was made by the authors independently. Dr C Bliss served as the statistical expert for this research. Publisher Copyright: © 2020, Shire Development LLC, a member of the Takeda group of companies and the Authors.

PY - 2021/5

Y1 - 2021/5

N2 - Several recent phase 3 clinical trials of attention-deficit/hyperactivity disorder (ADHD) medications have used the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P). Here, we assess WFIRS-P response in individual patients in two pivotal trials of lisdexamfetamine dimesylate (LDX) and guanfacine extended release (GXR). We also analysed pooled WFIRS-P data from seven phase 3 studies of ADHD medications to shed light on factors associated with baseline functional impairment. The proportion of patients with a change in WFIRS-P score that exceeded the minimal important difference (MID) criteria for response was greater for LDX than placebo in the Family, Learning and School, and Risky Activities domains, and was greater for GXR than placebo in the Social Activities, Learning and School, and Family domains. Responders had significantly worse baseline scores in all WFIRS-P domains (all p < 0.001) than non-responders. In the pooled analyses, baseline WFIRS-P scores in all domains were significantly worse in participants with oppositional defiant disorder (ODD) than in those without ODD. Having combined type or hyperactive-impulsive type ADHD, being enrolled into a study in Europe, being male and being younger also had modest negative effects on baseline WFIRS-P scores. The present analysis of WFIRS-P response shows that previously reported group-level improvements in WFIRS-P functional impairment score translated into clinically relevant improvements in many individual participants. Functional impairment is a diverse and subjective construct that is influenced by multiple factors. Optimal management of individuals with ADHD should involve monitoring improvements in functioning and quality of life, as well as symptomatic improvement.

AB - Several recent phase 3 clinical trials of attention-deficit/hyperactivity disorder (ADHD) medications have used the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P). Here, we assess WFIRS-P response in individual patients in two pivotal trials of lisdexamfetamine dimesylate (LDX) and guanfacine extended release (GXR). We also analysed pooled WFIRS-P data from seven phase 3 studies of ADHD medications to shed light on factors associated with baseline functional impairment. The proportion of patients with a change in WFIRS-P score that exceeded the minimal important difference (MID) criteria for response was greater for LDX than placebo in the Family, Learning and School, and Risky Activities domains, and was greater for GXR than placebo in the Social Activities, Learning and School, and Family domains. Responders had significantly worse baseline scores in all WFIRS-P domains (all p < 0.001) than non-responders. In the pooled analyses, baseline WFIRS-P scores in all domains were significantly worse in participants with oppositional defiant disorder (ODD) than in those without ODD. Having combined type or hyperactive-impulsive type ADHD, being enrolled into a study in Europe, being male and being younger also had modest negative effects on baseline WFIRS-P scores. The present analysis of WFIRS-P response shows that previously reported group-level improvements in WFIRS-P functional impairment score translated into clinically relevant improvements in many individual participants. Functional impairment is a diverse and subjective construct that is influenced by multiple factors. Optimal management of individuals with ADHD should involve monitoring improvements in functioning and quality of life, as well as symptomatic improvement.

KW - Adolescent

KW - Attention Deficit Disorder with Hyperactivity/drug therapy

KW - Child

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Male

KW - Quality of Life/psychology

KW - Treatment Outcome

KW - Functional impairment

KW - Attention-deficit/hyperactivity disorder

KW - Response

KW - Weiss Functional Impairment Rating Scale-Parent

UR - https://www.scopus.com/pages/publications/85088237433

U2 - 10.1007/s00787-020-01586-5

DO - 10.1007/s00787-020-01586-5

M3 - Article

C2 - 32691164

SN - 1018-8827

VL - 30

SP - 809

EP - 821

JO - European Child & Adolescent Psychiatry

JF - European Child & Adolescent Psychiatry

IS - 5

ER -