A Study of Label Compliance for Attention Deficit/Hyperactivity Disorder (ADHD) Medications in Japan

Attention Deficit/Hyperactivity Disorder (ADHD) Medications in Japan: A Retrospective Cohort Study of Label Compliance

The purpose of this study is to document the extent of on-label and off-label use of Methylphenidate (MPH) (Concerta), MPH (Ritalin), Atomoxetine (ATO), and Guanfacine (GFC) in Japan.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Disorder With Hyperactivity
• Intervention / Treatment: Drug: MPH (Concerta); Drug: MPH (Ritalin); Drug: Atomoxetine (ATO); Drug: Guanfacine (GFC)

• Study Type: Observational
• Enrollment (Actual): 17418

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Titusville, New Jersey, United States, 08560
      • Janssen Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study population will comprise of population (participants with attention deficit/hyperactivity disorder [ADHD]) described in the Japan Medical Data Center (JMDC) database which has data available through 1 January 2005 to 30 September 2018.

Description

Inclusion Criteria:

• Participants have been in the database for greater than or equal to (>=) 30 days
• Have received, between 1 January, 2013 and 30 September, 2018, a prescription for Concerta, Ritalin, Atomoxetine (ATO) or Guanfacine (GFC)

Exclusion Criteria:

- Participants who received an unspecified Methylphenidate (MPH) formulation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

14

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort T1: Methylphenidate (MPH) (Concerta); Analysis of data will be performed for participants who have had first exposure of MPH (Concerta) and who were never exposed to MPH (Ritalin) between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure.	Drug: MPH (Concerta); MPH (Concerta) is approved for the indications of ADHD and Narcolepsy in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from Japan medical data center (JDMC) database.
Cohort T2: MPH (Ritalin); Analysis of data will be performed for participants who have had first exposure of MPH (Ritalin) and who were never exposed to MPH (Concerta) between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure.	Drug: MPH (Ritalin); MPH (Ritalin) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T3: MPH (Concerta and Ritalin); Analysis of data will be performed for participants who have had exposure to Concerta and Ritalin during the time in the cohort between 1 January 2013 and 30 September 2018 and has continuous observation of at least 30 days prior to the exposures.	Drug: MPH (Concerta); MPH (Concerta) is approved for the indications of ADHD and Narcolepsy in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from Japan medical data center (JDMC) database.; Drug: MPH (Ritalin); MPH (Ritalin) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T4: Atomoxetine (ATO); Analysis of data will be performed for participants who have had first exposure of ATO between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure.	Drug: Atomoxetine (ATO); Atomoxetine (ATO) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T5: Guanfacine (GFC); Analysis of data will be performed for participants who have had first exposure of GFC between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure.	Drug: Guanfacine (GFC); Guanfacine (GFC) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T6: MPH (Concerta and Ritalin), ATO, or GFC; Analysis of data will be performed for participants who had have MPH (Concerta or Ritalin), ATO, or GFC first exposure between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure. These are all exposures to any study drug(s) among the participants with an exposure to at least one of the study drugs.	Drug: MPH (Concerta); MPH (Concerta) is approved for the indications of ADHD and Narcolepsy in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from Japan medical data center (JDMC) database.; Drug: MPH (Ritalin); MPH (Ritalin) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.; Drug: Atomoxetine (ATO); Atomoxetine (ATO) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.; Drug: Guanfacine (GFC); Guanfacine (GFC) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T7: MPH (Concerta or Ritalin); Analysis of data will be performed for participants who had have MPH (Concerta or Ritalin) first exposure between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior. These are the first exposure to any MPH among the participants with who had some exposure to MPH.	Drug: MPH (Concerta); MPH (Concerta) is approved for the indications of ADHD and Narcolepsy in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from Japan medical data center (JDMC) database.; Drug: MPH (Ritalin); MPH (Ritalin) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T8: MPH (Concerta) All Exposures; Analysis of data will be performed for participants who have had all exposures of MPH (Concerta) and were never exposed to MPH (Ritalin) between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure.	Drug: MPH (Concerta); MPH (Concerta) is approved for the indications of ADHD and Narcolepsy in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from Japan medical data center (JDMC) database.
Cohort T9: MPH (Ritalin) All Exposures; Analysis of data will be performed for participants who have had all exposures of MPH (Ritalin) and were never exposed to MPH (Concerta) between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure.	Drug: MPH (Ritalin); MPH (Ritalin) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T10: ATO All Exposures; Analysis of data will be performed for participants who have had all exposures of ATO between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure.	Drug: Atomoxetine (ATO); Atomoxetine (ATO) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T11: GFC All Exposures; Analysis of data will be performed for participants who have had all exposures of GFC between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure.	Drug: Guanfacine (GFC); Guanfacine (GFC) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T12:MPH(Concerta and Ritalin),ATO,orGFC All Exposures; Analysis of data will be performed for participants who have had all exposures of MPH (Concerta or Ritalin), ATO, or GFC between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure. These are all exposures to any study drug(s) among the participants with an exposure to at least one of the study drugs.	Drug: MPH (Concerta); MPH (Concerta) is approved for the indications of ADHD and Narcolepsy in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from Japan medical data center (JDMC) database.; Drug: MPH (Ritalin); MPH (Ritalin) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.; Drug: Atomoxetine (ATO); Atomoxetine (ATO) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.; Drug: Guanfacine (GFC); Guanfacine (GFC) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T13: MPH (Concerta or Ritalin) All Exposures; Analysis of data will be performed for participants who have had all exposures of MPH (Concerta or Ritalin) between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure. These are all exposures to any MPH (Concerta or Ritalin) among the participants with an exposure to MPH (Concerta or Ritalin).	Drug: MPH (Concerta); MPH (Concerta) is approved for the indications of ADHD and Narcolepsy in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from Japan medical data center (JDMC) database.; Drug: MPH (Ritalin); MPH (Ritalin) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.
Cohort T14: MPH (Concerta and Ritalin) All Exposures; Analysis of data will be performed for participants who have had all exposures of MPH (Concerta and Ritalin) between 1 January 2013 and 30 September 2018 that also has continuous observation of at least 30 days prior to exposure. These are all exposures to any MPH (Concerta or Ritalin) among the participants with an exposure to MPH (Concerta) during the study period and to an exposure to MPH (Ritalin) during the study period.	Drug: MPH (Concerta); MPH (Concerta) is approved for the indications of ADHD and Narcolepsy in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from Japan medical data center (JDMC) database.; Drug: MPH (Ritalin); MPH (Ritalin) is approved for the indication of ADHD in Japan. This is a non-interventional study and no drug will be given as part of this study. Analysis will be performed from data taken from JDMC database.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Stratified on Age, Sex, and Medication	The percentage of participants stratified on age, sex, and medication (Methylphenidate [MPH] [Concerta], MPH [Ritalin], Atomoxetine [ATO], Guanfacine [GFC]) will be reported. The data will be taken from Japan Medical Data Center (JMDC) database for analysis.	Up to 5.8 years
Percentage of the Specialty of the Department of the First Prescriber who Prescribe MPH (Concerta), MPH (Ritalin), ATO, or GFC	The percentage of specialty of the department of the first prescriber for each first dispensing of each study medication will be reported. The data will be taken from JMDC database for analysis.	Up to 5.8 years
Percentage of Participants whose First Prescription for MPH (Concerta), MPH (Ritalin), ATO, or GFC was Associated with an On-label Diagnosis	The percentage of participants whose first prescription for MPH (Concerta), MPH (Ritalin), ATO, or GFC was associated with an on-label diagnosis, that is, a diagnosis of Attention Deficit Disorder with Hyperactivity (ADHD) for MPH (Concerta), ATO or GFC; or a diagnosis of narcolepsy for MPH (Ritalin) will be reported. The data will be taken from JMDC database for analysis.	Up to 5.8 years
Percentage of Participants who Received More than Maximum Recommended Dose of MPH (Concerta), MPH (Ritalin), Methylphenidate (Concerta and Ritalin), ATO, or GFC	The percentage of participants who received more than the maximum recommended dose of MPH (Concerta), MPH (Ritalin), Methylphenidate (Concerta and Ritalin), ATO, or GFC will be reported. The data will be taken from JMDC database for analysis.	Up to 5.8 years
Percentage of Participants not Meeting Age Criteria at the Time of Receiving Medication	Percentage of participants who at the time of receiving the medication were outside the approved age range will be reported. The data will be taken from JMDC database for analysis.	Up to 5.8 years
Percentage of Participants not Meeting Medication Criteria at the Time of Receiving Medication	Percentage of participants who at the time of receiving the medication had other contraindications will be reported. The data will be taken from JMDC database for analysis.	Up to 5.8 years
Percentage of Participants whose Prescriptions were Consistent with all Aspects of the Label that was Current at the Time of the Prescription	Percentage of participants whose prescriptions were consistent with all aspects of the label that was current at the time of the prescription will be reported. The data will be taken from JMDC database for analysis.	Up to 5.8 years
Percentage of Participants with Shopping Behavior as a Marker of Misuse of Medications	Percentage of participants whose use pattern of MPH (Concerta), MPH (Ritalin), MPH (Concerta and Ritalin) or ATO included prescriptions from three or more departments within any 18-month period will be reported. This describes "shopping behavior", which is a marker for misuse or abuse of medications. The data will be taken from JMDC database for analysis.	Up to 5.8 years
Time Trends in Percentage of Participants Compliant with all Label Requirements	The time trends in the percentage of participants whose prescriptions complied with all requirements of the label for MPH (Concerta), MPH (Ritalin), MPH (Concerta and Ritalin), ATO, and GFC will be reported. The data will be taken from JMDC database for analysis.	Up to 5.8 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Fife D, Voss EA, Hardin J, Rofael H, Solomon ID, Ryan PB, Stang P. Medications for attention-deficit/hyperactivity disorder in Japan: A retrospective cohort study of label compliance. Neuropsychopharmacol Rep. 2021 Sep;41(3):385-392. doi: 10.1002/npr2.12191. Epub 2021 Jun 28.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): January 10, 2020
• Study Completion (Actual): January 10, 2020

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (Actual): October 2, 2019

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 21, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Adrenergic Uptake Inhibitors; Methylphenidate; Atomoxetine Hydrochloride; Guanfacine
• Other Study ID Numbers: CR108692; PCSESP001604 (Other Identifier: Janssen Research and Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No