PATIENCE Individual Patient DATa Network Meta-AnalysIs of the Efficacy aNd aCceptability of Attention-Deficit/Hyperactivity Disorder (ADHD) mEdication

Lead Investigator: Samuele Cortese, University of Southampton
Title of Proposal Research: PATIENCE Individual Patient DATa Network Meta-AnalysIs of the Efficacy aNd aCceptability of Attention-Deficit/Hyperactivity Disorder (ADHD) mEdication
Vivli Data Request: 7846
Funding Source: All researchers are employed by their respective University
Potential Conflicts of Interest: AT has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), and Angelini Pharma. Angleini Pharma are not involved in the current project. Potential conflicts of interest will be mitigated by declaring them in any subsequent publications. AC has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), and Angelini Pharma. Angelini Pharma are not involved in this project, nor are their compounds. Potential conflicts of interest will be mitigated by declaring them in any subsequent publications.

Summary of the Proposed Research:

Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common neurodevelopmental disorder and one of the most common diagnoses in child and adolescent mental health services. It has been estimated that the worldwide prevalence of ADHD is in the order of 5-7% in children [2] and 2.5% in adults [3]. ADHD is a heterogeneous disorder, primarily characterised by developmentally inappropriate inattention and/or hyperactivity-impulsivity to a degree that adversely affects schooling, work, and/or relationships. The disorder usually becomes apparent in early childhood [1] and, for approximately 70% of people, impairing symptoms continue into adulthood [4], disrupting the lives of patients and those around them.

For ADHD, as for many other disorders, clinicians, patients and parents/carers are faced with a range of possible medications to choose from. In the absence of evidence-based biomarkers and clinical predictors of response or adverse effects, currently treatment selection in the clinical practice often relies on trial-and-error.

Individual Patient Data Network Meta-Analyses (IPD-NMAs) analyse patient-level rather that group-level data. This type of analysis also has the capacity to provide estimates of the effects of medication on subgroups of patients with specific characteristics, such as previous exposure to medications, severity of symptoms and comorbidities which could moderate the effects of medications.

An IPD-NMA can help to inform guidelines, which in turn will have an impact on the treatment of ADHD, by enabling clinicians, patients and parents/carers to take patients’ personal characteristics into account when selecting medications. The results will inform clinical treatment guidelines on the management of ADHD.

Requested Studies:

Bain EE, Robieson W, Pritchett Y, et al. A randomized, double-blind, placebo-controlled phase 2 study of 42 agonist ABT-894 in adults with ADHD. Neuropsychopharmacology. 2013;38(3):405-413 (Bain2013). Drug: ABT-894
Data Contributor: AbbVie
Study ID: NCT00429091

Wilens TE, Gault LM, Childress A, et al. Safety and efficacy of ABT-089 in pediatric attention-deficit/hyperactivity disorder: results from two randomized placebo-controlled clinical trials. J Am Acad Child Adolesc Psychiatry. 2011;50(1):73-84 e71 (Wilens2011). Drug: BT-089
Data Contributor: AbbVie
Study ID: NCT00528697

Python packages: numpy (1.13.3) -> numpy (1.16.2 or above) pandas (0.20.3) -> pandas (1.0.5 or above) seaborn (0.8) -> seaborn (0.9.0 or above) scikit-learn (0.19.0) -> scikit-learn (0.21.0 or above) JAGS, installed from http://mcmc-jags.sourceforge.net/ and the following R packages: rjags meta R2jags stringr netmeta taRifx mice MCMCvis igraph mitools jomo missMethods R additional packages pcaMethods, plotfunctions, itsadug, LaplacesDemon Within the Python 3.8.1 environment, have the latest version of these packages os, datetime, time, tempfile, matplotlib, numpy, pandas, seaborn, sklearn, scipy, Jupyter Notebook Within the Python 3.8.1 environment, the following packages need to be install using pip, not conda TensorFlow 2.4.1+ (pip install –upgrade tensorflow), this need Microsoft Visual C++ Redistributable for Visual Studio 2015, 2017, and 2019 support which can be downloaded from https://support.microsoft.com/en-us/topic/the-latest-supported-visual-c-downloads-2647da03-1eea-4433-9aff-95f26a218cc0 tensorflow_docs (pip install git+https://github.com/tensorflow/docs) tensorflow-probability (pip install –upgrade tensorflow-probability) tensorflow-addons (pip install tensorflow-addons)
Data Contributor: I WILL BRING MY OWN
Sponsor ID: Packages

A Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Titration Study to Evaluate the Efficacy and Safety of CONCERTA (Methylphenidate HCl) Extended-release Tablets in Adults With Attention Deficit Hyperactivity Disorder at Doses of 36 mg, 54 mg, 72 mg, 90 mg, or 108 mg Per Day.
Data Contributor: Johnson & Johnson
Study ID: NCT00326391
Sponsor ID: CR011560

A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Response Study to Evaluate Efficacy and Safety of Prolonged Release (PR) OROS Methylphenidate (54 and 72 mg/Day) in Adults With Attention Deficit/Hyperactivity Disorder
Data Contributor: Johnson & Johnson
Study ID: NCT00714688
Sponsor ID: CR014566

A Placebo Controlled Double-Blind, Parallel Group, Individualizing Dosing Study Optimizing Treatment of Adults With Attention Deficit Hyperactivity Disorder to an Effective Response With OROS Methylphenidate
Data Contributor: Johnson & Johnson
Study ID: NCT00937040
Sponsor ID: CR015058

A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Response Study To Evaluate the Safety And Efficacy Of Prolonged Release OROS Methylphenidate Hydrochloride (18, 36 and 72 mg/Day), With Open-Label Extension, In Adults With Attention Deficit/Hyperactivity Disorder
Data Contributor: Johnson & Johnson
Study ID: NCT00246220
Sponsor ID: CR002479

A Double-blind, Placebo-controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of JNS001 in Adults With Attention-Deficit/Hyperactivity Disorder at Doses of 18 mg, 36 mg, 54 mg, or 72 mg Per Day
Data Contributor: Johnson & Johnson
Study ID: NCT01323192
Sponsor ID: CR017755

A Double-Blind Placebo-Controlled Asian Study of Atomoxetine Hydrochloride in the Treatment of Adult Patients With Attention-Deficit/Hyperactivity Disorder (ADHD)
Data Contributor: Lilly
Study ID: NCT00962104
Sponsor ID: 12107

Evaluation of Continuous Symptom Treatment of ADHD: A Placebo-Controlled Double-Blind Assessment of Morning-Dosed or Evening-Dosed Strattera
Data Contributor: Lilly
Study ID: NCT00486122
Sponsor ID: 7972

Phase IV Placebo-Controlled Study of Atomoxetine Hydrochloride in the Treatment of Adults With ADHD and Comorbid Social Anxiety Disorder
Data Contributor: Lilly
Study ID: NCT00190879
Sponsor ID: 9855

A Randomized, Double-Blind Comparison of Placebo and Atomoxetine Hydrochloride Given Once a Day in Adults With Attention-Deficit/Hyperactivity Disorder: With a Secondary Examination of Impact of Treatment on Family Functioning
Data Contributor: Lilly
Study ID: NCT00190775
Sponsor ID: 9043

Efficacy and Safety of Once-Daily Atomoxetine Hydrochloride in Adults With ADHD Over an Extended Period of Time (6 Months); With a Brief Evaluation of Executive Cognition
Data Contributor: Lilly
Study ID: NCT00190736
Sponsor ID: 9040

A Double-Blind Study of Atomoxetine Hydrochloride Versus Placebo for the Treatment of ADHD in Young Adults With an Assessment of Associated Functional Outcomes
Data Contributor: Lilly
Study ID: NCT00510276
Sponsor ID: 10803

A Double-Blind Study of Functional Outcomes With Atomoxetine-Hydrochloride and Placebo in Adult Outpatients With DSM-IV Attention-Deficit/Hyperactivity Disorder
Data Contributor: Lilly
Study ID: NCT00190931
Sponsor ID: 7066