Wilens 2005.

Methods	A multicentre, open‐label, cohort study of methylphenidate osmotic release oral system (OROS) use for 24 months
Participants	Number of participants screened: 436 Number of participants included: 407 Number of participants followed up: 289 (12 months), 229 (24 months) Number of withdrawals: 118 (12 months), 178 (24 moths) Diagnosis of ADHD: DSM‐IV (subtype: combined (75.5%), hyperactive‐impulsive (5.9%), inattentive (18.4%), not determined ( 0.2%)) Age: mean 9.2, range 6‐13 years old IQ: not stated Sex: 338 males, 69 females Methylphenidate‐naïve: none Ethnicity: white: 86%, African American: 5.7%, Asian: 0.7%, Hispanic:4.4%, others: 3.2% Country: USA Comorbidity: tics (11.8%) Comedication: none Sociodemographics: not stated Inclusion criteria ADHD diagnosis, as defined in Pelham 2001; Swanson 2003; Wolraich 2001, e.g. DSM‐IV Had participated in previous efficacy or pharmacokinetic studies of OROS methylphenidate Only children who had been receiving methylphenidate either with a positive response or without having experienced a significant adverse event based on parent or physician reports; ADHD; normal urinalysis, haematology, and blood chemistry values; parents/caregivers and school teachers had to be willing to complete all assessments Participants agreed to take the supplied study drug as their only medication for ADHD Exclusion criteria Clinically significant gastrointestinal problems History of hypertension, known hypersensitivity to methylphenidate, or a coexisting medical condition or concurrent medication likely to interfere with the safe administration of MPH Tourette syndrome, an ongoing seizure disorder, or a psychotic disorder Girls who had reached menarche Participants who were already receiving specific behavioural interventions for ADHD on an ongoing basis were permitted to enter the study, but new behavioural interventions could not be initiated during the study Any participants who developed systolic or diastolic blood pressure ≥ 95th percentile for age or sex or who had a blood pressure measurement ≥ 150 mmHg (systolic) or ≥ 100 mmHg (diastolic) were discontinued
Interventions	Methylphenidate type: extended release (OROS) Methylphenidate dosage: 18 mg/day, 36 mg/day, or 54 mg/day Mean methylphenidate dosage: 35 mg at study entry, 41 mg at the end of 12 months, and 44.2 mg at month 21/24 Administration schedule: once daily Duration of intervention: 21 to 24 months Treatment compliance: 86.4%
Outcomes	Non‐serious adverse events Growth (weight, height), rated objectively by observer at monthly visits for the first 12 months and then at 15, 18, 21, and 24 months Cardiac (heart rate, blood pressure), rated objectively by observer at monthly visits for the first 12 months and then at 15, 18, 21, and 24 months Sleep quality, tics, rated subjectively by parents at monthly visits for the first 12 months and then at 15, 18, 21, and 24 months Laboratory tests (urinalysis, haematology/complete blood counts, electrolytes, and liver function tests) were performed at baseline, at 6 and 12 months, and at the end of the study (21/24 months) At 12 months, 28 (6.9%) discontinued study medication prematurely because of adverse events. At 21/24 months, 38 discontinued study medication prematurely because of adverse events. From final: there was a 26% increase in mean daily dose over the study period, with most of the increase occurring during year 1. In general, treatment was well tolerated, with 31 (7.6%) participants discontinuing because of adverse events. Comparison of the baseline characteristics of participants discontinuing the study compared with those continuing with treatment for 21/24 months did not reveal any significant differences between the 2 groups for ADHD subtype, teacher and parent/caregiver IOWA Conners inattention/overactivity and oppositional/defiant baseline scores, previous stimulant exposure, presence of comorbidity, specific comorbidity, race, sex, or type of school classroom
Notes	Sample calculation: no Ethics approval: reviewed and approved by the institutional review board of participating centres prior to initiation of the study Funding: supported by McNeil Consumer & Specialty Pharmaceuticals Vested interests/authors' affiliations: all authors work for different medical companies Key conclusions of the study authors: sustained effectiveness of OROS methylphenidate was maintained for up to 24 months with minimal effects on growth, tics, vital signs, or laboratory test values, as demonstrated by stable IOWA Conners ratings and sustained improvements in peer interaction and Global Assessment Scale scores Comments from the study authors: the prospective trial was terminated by the sponsor (concomitant with US FDA approval) between 21 and 24 months of participation for administrative reasons that were not related to safety or effectiveness. Therefore, although data were available for a minority of participants at 24 months (n = 56), we refer to the final end point as 21/24 months Exclusion of methylphenidate non‐responders/children who have previously experienced adverse events on methylphenidate: yes. Included children had participated in previous controlled studies and were methylphenidate responders