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Clinical Trial
. 2022 Mar;26(5):696-705.
doi: 10.1177/10870547211020073. Epub 2021 Jun 4.

Clinically Meaningful Improvements in Early Morning and Late Afternoon/Evening Functional Impairment in Children with ADHD Treated with Delayed-Release and Extended-Release Methylphenidate

Timothy E Wilens  1   2 , Stephen V Faraone  3 , Paul G Hammerness  2   4 , Steven R Pliszka  5 , Cassandra L Uchida  6 , Norberto J DeSousa  7 , Floyd R Sallee  8 , Bev Incledon  7 , Jeffrey H Newcorn  9
Affiliations
Clinical Trial

Clinically Meaningful Improvements in Early Morning and Late Afternoon/Evening Functional Impairment in Children with ADHD Treated with Delayed-Release and Extended-Release Methylphenidate

Timothy E Wilens et al. J Atten Disord. 2022 Mar.

Abstract

Objective: The Before School Functioning Questionnaire and Parent Rating of Evening and Morning Behavior-Revised assess early morning (BSFQ, PREMB-R AM subscale) and late afternoon/evening (PREMB-R PM subscale) functional impairment in children with ADHD. Clinically meaningful improvements were identified and applied to a trial of delayed-release and extended-release methylphenidate (DR/ER-MPH) in children with ADHD (NCT02520388) to determine if the statistically-determined improvements in functional impairment were also clinically meaningful.

Method: Clinically meaningful improvements in BSFQ/PREMB-R were established post hoc by receiver operating characteristics curves, using anchors of Clinical Global Impression-Improvement (CGI-I) = 1 and CGI-I ≤ 2. Percentages of participants achieving these thresholds were calculated.

Results: Thresholds for CGI-I = 1/CGI-I ≤ 2, respectively, were 27/20 (BSFQ), 5/3 (PREMB-R AM), and 9/5 (PREMB-R PM)-point decreases. More children achieved clinically meaningful improvements with DR/ER-MPH versus placebo (all p < .05).

Conclusion: DR/ER-MPH increased proportions of children achieving clinically meaningful improvements in BSFQ and PREMB-R.

Keywords: ADHD; BSFQ; PREMB-R; functional impairment; methylphenidate.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Timothy E. Wilens has received grant support from the National Institute on Drug Abuse (NIDA); he has been a consultant for Ironshore Pharmaceuticals & Development, Inc., KemPharm, Inc., Otsuka America Pharmaceutical Inc., NIH (NIDA), Gavin House and Bay Cove Human Services (Clinical Services), U.S. National Football League (ERM Associates), and U.S. Minor/Major League Baseball; he has co-edited the books Straight Talk About Psychiatric Medications for Kids (Guilford Press), ADHD in Children and Adults (Cambridge Press), Massachusetts General Hospital Comprehensive Clinical Psychiatry (Elsevier), and Massachusetts General Hospital Psychopharmacology and Neurotherapeuics (Elsevier); and he is the co-owner of and has a licensing agreement with Ironshore Pharmaceuticals & Development, Inc. for the Before School Functioning Questionnaire. Stephen V. Faraone received income, potential income, travel expenses, continuing education support, and/or research support from Takeda, OnDosis, Tris, Otsuka, Arbor, Ironshore, Rhodes, Akili Interactive Labs, Enzymotec, Sunovion, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child’s Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is Program Director of www.adhdinadults.com. Paul G. Hammerness published the books ADHD, Biographies of a Disease (Greenwood Press), Organize Your Mind, Organize Your Life (Harlequin Press/Harvard University), and Straight Talk About Psychiatric Medications for Kids (Guilford Press); and he is the co-owner of and has a licensing agreement with Ironshore Pharmaceuticals & Development, Inc. for the Before School Functioning Questionnaire. Steven R. Pliszka was a consultant/advisory board member for and received research support from Ironshore Pharmaceuticals & Development, Inc.; he was also an expert witness for AstraZeneca. Cassandra L. Uchida is an employee of Highland Therapeutics Inc. Norberto J. DeSousa and Bev Incledon are employees of Ironshore Pharmaceuticals & Development, Inc. Floyd R. Sallee is an employee of Ironshore Pharmaceuticals Inc. and serves on the advisory board/board of directors of P2D Bioscience. In the past year, Jeffrey H. Newcorn is/has been a consultant/advisory board member for Adlon, Arbor, Eisai, Medice, Myriad, NLS, OnDosis, Rhodes, Shire/Takeda, Supernus and the US National Football League. He was a DSMB member for Sunovion, and received research support from Otsuka, Shire/Takeda, Supernus, NIDA, and the National Institute of Child Health and Human Development (NICHD). He also has received speaker fees from Shire/Takeda for disease-state presentations.

Figures

Figure 1.
Figure 1.
ROC analysis of change from baseline to Week 3 in BSFQ, PREMB-R AM, and PREMB-R PM scores in participants reaching CGI-I anchors. Note. BSFQ = Before School Functioning Questionnaire; CGI-I = Clinical Global Impression–Improvement; PREMB-R AM = Parent Rating of Evening and Morning Behavior–Revised, Morning subscale; PREMB-R PM = Parent Rating of Evening and Morning Behavior–Revised, Evening subscale; ROC = receiver operating characteristics.
Figure 2.
Figure 2.
Cumulative percentage of participants with specified changes from baseline in BSFQ score anchored to CGI-I after 3 weeks of treatment.a Note. BSFQ = Before School Functioning Questionnaire; CGI-I = Clinical Global Impression–Improvement; CI = confidence interval; DR/ER-MPH = delayed-release and extended-release methylphenidate. aNegative score change indicates improved early morning functional impairment, as measured by the BSFQ.
Figure 3.
Figure 3.
Cumulative percentage of participants with specified changes from baseline in PREMB-R AM score anchored to CGI-I after 3 weeks of treatment.a Note. CGI-I = Clinical Global Impression–Improvement; CI = confidence interval; DR/ER-MPH = delayed-release and extended-release methylphenidate; PREMB-R AM = Parent Rating of Evening and Morning Behavior–Revised, Morning subscale. aNegative score change indicates improved early morning functional impairment, as measured by the PREMB-R AM.
Figure 4.
Figure 4.
Cumulative percentages of participants with specified changes from baseline in PREMB-R PM score anchored to CGI-I after 3 weeks of treatment.a Note. CGI-I = Clinical Global Impression–Improvement; CI = confidence interval; DR/ER-MPH = delayed-release and extended-release methylphenidate; PREMB-R PM = Parent Rating of Evening and Morning Behavior–Revised, Evening subscale. aNegative score change indicates improved late afternoon/evening functional impairment, as measured by the PREMB-R PM.
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