Trial Outcomes & Findings for Learning Impairments Among Survivors of Childhood Cancer (NCT NCT00576472)

NCT ID: NCT00576472

Last Updated: 2017-05-30

Results Overview

To compare the white matter volume of patients with those of sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 469 participants
• Primary outcome timeframe: Enrollment to evaluation of MRI, on average 12.8 months.
• Results posted on: 2017-05-30

Participant Flow

505 patients were enrolled from 3 institutions between January, 2000 and February, 2009. 91 siblings were enrolled as a control group.

Of 505 patients enrolled on the study, 36 were never assessed, and 469 participated in the initial screening. Of the 469 screened patients, 259 did not qualify for further medication phases, 75 qualified but refused to participate and 1 did not show for a scheduled appointment, leaving 134 patients to participate in the two-day MPH In-Lab Phase.

Participant milestones

Measure	Mild Intensity Intensity of prior CNS Therapy (systemic and/or intrathecal chemotherapy only)classified as mild.	Moderate Intensity Intensity of prior CNS Therapy (\< 24 Gy CRT with or without systemic and/or intrathecal chemotherapy)classified as moderate.	High Intensity Intensity of prior CNS Therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy) classified as high.	Screened/Didn't Qualify for Methylphenidate (MPH) In-Lab Phase Of the 469 screened patients, 259 did not qualify for further medication phases, 75 qualified but refused to participate and 1 did not show for a scheduled appointment, leaving 134 patients to participate in the two-day Methylphenidate (MPH) In-Lab Phase.	Group M/P Group M/P (patients received oral Methylphenidate (MPH) and then an oral placebo)	Group P/M Group P/M (patients received oral placebo and then Methylphenidate (MPH))	Completed MPH In-Lab Phase/Not Randomized for Cross Over Phase Patients who completed the MPH in Lab Phase but were not randomized for the MPH Cross-Over Phase	Placebo/Low Dose/Moderate Dose (PLM) The PLM group received a placebo on week one, low dose Methylphenidate (MPH) on week two, and a moderate dose of Methylphenidate (MPH) on week three.	Placebo/Moderate Dose/Low Dose (PML) The PML group received a placebo on week one, moderate dose Methylphenidate (MPH) on week two, and a low dose of Methylphenidate (MPH) on week three.	Low Dose/Moderate Dose/ Placebo (LMP) The LMP group received a low dose of Methylphenidate (MPH) on week one, a moderate dose of Methylphenidate (MPH) on week two, and a placebo on week three.	Low Dose/Placebo/Moderate Dose (LPM) The LPM group received a low dose of Methylphenidate (MPH) on week one, a placebo on week two, and a moderate dose of Methylphenidate (MPH) on week three.	Moderate Dose/Low Dose/Placebo (MLP) The MLP group received a moderate dose of Methylphenidate (MPH) on week one, a low dose of Methylphenidate (MPH) on week two, and a placebo on week three.	Moderate Dose/Placebo/Low Dose (MPL) The MPL group received a moderate dose of Methylphenidate (MPH) on week one, a placebo on week two, and a low dose of Methylphenidate (MPH) on week three.	Declined Methylphenidate (MPH) Home Maintenance Phase Patients who completed the Methylphenidate (MPH) Cross Over Phase but chose to decline participation in the Methylphenidate (MPH) Home Maintenance Phase.	Methylphenidate (MPH) Home Maintenance Phase Methylphenidate (MPH) was administered for 12 months during the Methylphenidate (MPH) Home Maintenance Phase.
Initial Screening STARTED	230	40	199	0	0	0	0	0	0	0	0	0	0	0	0
Initial Screening COMPLETED	230	40	199	0	0	0	0	0	0	0	0	0	0	0	0
Initial Screening NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
MPH In-Lab Phase STARTED	0	0	0	335	67	67	0	0	0	0	0	0	0	0	0
MPH In-Lab Phase COMPLETED	0	0	0	0	67	67	0	0	0	0	0	0	0	0	0
MPH In-Lab Phase NOT COMPLETED	0	0	0	335	0	0	0	0	0	0	0	0	0	0	0
MPH Cross Over Phase STARTED	0	0	0	0	0	0	12	20	18	22	23	18	21	0	0
MPH Cross Over Phase COMPLETED	0	0	0	0	0	0	0	20	16	22	22	17	21	0	0
MPH Cross Over Phase NOT COMPLETED	0	0	0	0	0	0	12	0	2	0	1	1	0	0	0
MPH Home Maintenance Phase STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	27	91
MPH Home Maintenance Phase COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	68
MPH Home Maintenance Phase NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	27	23

Reasons for withdrawal

Measure	Mild Intensity Intensity of prior CNS Therapy (systemic and/or intrathecal chemotherapy only)classified as mild.	Moderate Intensity Intensity of prior CNS Therapy (\< 24 Gy CRT with or without systemic and/or intrathecal chemotherapy)classified as moderate.	High Intensity Intensity of prior CNS Therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy) classified as high.	Screened/Didn't Qualify for Methylphenidate (MPH) In-Lab Phase Of the 469 screened patients, 259 did not qualify for further medication phases, 75 qualified but refused to participate and 1 did not show for a scheduled appointment, leaving 134 patients to participate in the two-day Methylphenidate (MPH) In-Lab Phase.	Group M/P Group M/P (patients received oral Methylphenidate (MPH) and then an oral placebo)	Group P/M Group P/M (patients received oral placebo and then Methylphenidate (MPH))	Completed MPH In-Lab Phase/Not Randomized for Cross Over Phase Patients who completed the MPH in Lab Phase but were not randomized for the MPH Cross-Over Phase	Placebo/Low Dose/Moderate Dose (PLM) The PLM group received a placebo on week one, low dose Methylphenidate (MPH) on week two, and a moderate dose of Methylphenidate (MPH) on week three.	Placebo/Moderate Dose/Low Dose (PML) The PML group received a placebo on week one, moderate dose Methylphenidate (MPH) on week two, and a low dose of Methylphenidate (MPH) on week three.	Low Dose/Moderate Dose/ Placebo (LMP) The LMP group received a low dose of Methylphenidate (MPH) on week one, a moderate dose of Methylphenidate (MPH) on week two, and a placebo on week three.	Low Dose/Placebo/Moderate Dose (LPM) The LPM group received a low dose of Methylphenidate (MPH) on week one, a placebo on week two, and a moderate dose of Methylphenidate (MPH) on week three.	Moderate Dose/Low Dose/Placebo (MLP) The MLP group received a moderate dose of Methylphenidate (MPH) on week one, a low dose of Methylphenidate (MPH) on week two, and a placebo on week three.	Moderate Dose/Placebo/Low Dose (MPL) The MPL group received a moderate dose of Methylphenidate (MPH) on week one, a placebo on week two, and a low dose of Methylphenidate (MPH) on week three.	Declined Methylphenidate (MPH) Home Maintenance Phase Patients who completed the Methylphenidate (MPH) Cross Over Phase but chose to decline participation in the Methylphenidate (MPH) Home Maintenance Phase.	Methylphenidate (MPH) Home Maintenance Phase Methylphenidate (MPH) was administered for 12 months during the Methylphenidate (MPH) Home Maintenance Phase.
MPH In-Lab Phase Declined participation in medication pha	0	0	0	75	0	0	0	0	0	0	0	0	0	0	0
MPH In-Lab Phase Lost to Follow-up	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
MPH In-Lab Phase Patients did not qualify - IQ < 50	0	0	0	4	0	0	0	0	0	0	0	0	0	0	0
MPH In-Lab Phase No attention/academic problems	0	0	0	245	0	0	0	0	0	0	0	0	0	0	0
MPH In-Lab Phase Psychiatric exclusion	0	0	0	10	0	0	0	0	0	0	0	0	0	0	0
MPH Cross Over Phase Withdrawal by Subject	0	0	0	0	0	0	6	0	0	0	0	0	0	0	0
MPH Cross Over Phase Ineligible due to disease	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0
MPH Cross Over Phase Physician Decision	0	0	0	0	0	0	4	0	0	0	0	0	0	0	0
MPH Cross Over Phase Did not complete cross over phase	0	0	0	0	0	0	0	0	2	0	1	1	0	0	0
MPH Home Maintenance Phase Did not meet response criteria	0	0	0	0	0	0	0	0	0	0	0	0	0	16	0
MPH Home Maintenance Phase Declined to participate	0	0	0	0	0	0	0	0	0	0	0	0	0	7	0
MPH Home Maintenance Phase Insufficient data	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0
MPH Home Maintenance Phase Side effects	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8
MPH Home Maintenance Phase Withdrawal by Subject	0	0	0	0	0	0	0	0	0	0	0	0	0	0	6
MPH Home Maintenance Phase Medical reasons	0	0	0	0	0	0	0	0	0	0	0	0	0	0	6
MPH Home Maintenance Phase Lost to Follow-up	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3

Baseline Characteristics

Learning Impairments Among Survivors of Childhood Cancer

Baseline characteristics by cohort

Measure	Mild n=230 Participants Intensity of prior Central Nervous System radiation therapy was considered mild.	Moderate n=40 Participants Intensity of prior Central Nervous System radiation therapy was considered moderate.	High n=199 Participants Intensity of prior Central Nervous System radiation therapy was considered high.	Not Randomized-In Lab Phase Patients not randomized for the MPH in Lab Phase	Group M/P Group M/P (patients receive oral Methylphenidate (MPH) and then an oral placebo)	Group P/M Group P/M (patients receive oral placebo and ten Methylphenidate (MPH))	Not Randomized-Cross Over Patients who completed the MPH in Lab Phase but were not randomized for the MPH Cross Over Phase	Placebo/Low Dose/Moderate Dose (PLM) The PLM group received a placebo on week one, low dose Methylphenidate (MPH) on week two, and a moderate dose of Methylphenidate (MPH) on week three.	Placebo/Moderate Dose/Low Dose (PML) The PML group received a placebo on week one, moderate dose Methylphenidate (MPH) on week two, and a lose dose of Methylphenidate (MPH) on week three.	Low Dose/Moderate Dose/ Placebo (LMP) The LMP group received a low dose of Methylphenidate (MPH) on week one, a moderate dose of Methylphenidate (MPH) on week two, and a placebo on week three.	Low Dose/Placebo/Moderate Dose (LPM) The LPM group received a low dose of Methylphenidate (MPH) on week one, a placebo on week two, and a moderate dose of Methylphenidate (MPH) on week three.	Moderate Dose/Low Dose/Placebo (MLP) The MLP group received a moderate dose of Methylphenidate (MPH) on week one, a low dose of Methylphenidate (MPH) on week two, and a placebo on week three.	Moderate Dose/Placebo/Low Dose (MPL) The MPL group received a moderate dose of Methylphenidate (MPH) on week one, a placebo on week two, and a low dose of Methylphenidate (MPH) on week three.	Declined Home Maintenance Phase Patients who completed the MPH Cross Over Phase but chose to decline participation in the Home Maintenance Phase.	Home Maintenance Phase Methylphenidate (MPH) was administered for 12 months during the duration of the Home Maintenance Phase.	Total n=469 Participants Total of all reporting groups
Age, Customized < 4 years of age	113 Participants n=5 Participants	23 Participants n=7 Participants	51 Participants n=5 Participants	—	—	—	—	—	—	—	—	—	—	—	—	187 Participants n=135 Participants
Age, Customized ≥ 4 years of age	117 Participants n=5 Participants	17 Participants n=7 Participants	148 Participants n=5 Participants	—	—	—	—	—	—	—	—	—	—	—	—	282 Participants n=135 Participants
Sex: Female, Male Female	98 Participants n=5 Participants	16 Participants n=7 Participants	90 Participants n=5 Participants	—	—	—	—	—	—	—	—	—	—	—	—	204 Participants n=135 Participants
Sex: Female, Male Male	132 Participants n=5 Participants	24 Participants n=7 Participants	109 Participants n=5 Participants	—	—	—	—	—	—	—	—	—	—	—	—	265 Participants n=135 Participants
Disease Group Acute Lymphoblastic Leukemia (ALL)	216 Participants n=5 Participants	39 Participants n=7 Participants	3 Participants n=5 Participants	—	—	—	—	—	—	—	—	—	—	—	—	258 Participants n=135 Participants
Disease Group Brain Tumors (BT)	14 Participants n=5 Participants	1 Participants n=7 Participants	196 Participants n=5 Participants	—	—	—	—	—	—	—	—	—	—	—	—	211 Participants n=135 Participants

PRIMARY outcome

Timeframe: Enrollment to evaluation of MRI, on average 12.8 months.

Population: Of the 505 patients enrolled, 106 did not have MRI acquired to measure brain volume, 16 were not evaluable: 6 had metal artifacts, 3 had motion artifacts, 1 had an acquisition error in MRI image, 4 had tumor on exam, and 2 had ischemic insults. 383 patients had evaluable MRI images. 67 of the 91 sibling controls had evaluable MRI images.

To compare the white matter volume of patients with those of sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

Outcome measures

Measure	Moderate Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=383 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=67 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Brain White Matter Volume for Patients Versus Sibling Controls	—	27 percentage Interval 26.5 to 27.5	30.3 percentage Interval 29.6 to 31.0	—

PRIMARY outcome

Timeframe: Enrollment to evaluation of MRI, on average 12.8 months.

Population: Of the 505 patients enrolled, 106 did not have MRI acquired to measure brain volume, 16 were not evaluable: 6 had metal artifacts, 3 had motion artifacts, 1 had an acquisition error in MRI image, 4 had tumor on exam, and 2 had ischemic insults. 383 patients had evaluable MRI images.

To compare the white matter volume of Acute Lymphoblastic Leukemia (ALL) patients with those of patients with malignant brain tumors using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

Outcome measures

Measure	Moderate Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=199 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=184 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Brain White Matter Volume for Patients With Acute Lymphoblastic Leukemia Versus Brain Tumors	—	28.4 percentage Interval 27.6 to 29.1	25.5 percentage Interval 25.0 to 26.0	—

PRIMARY outcome

Timeframe: Enrollment to evaluation of MRI, on average 12.8 months.

Population: Of the 505 patients enrolled, 106 did not have MRI acquired to measure brain volume, 16 were not evaluable: 6 had metal artifacts, 3 had motion artifacts, 1 had an acquisition error in MRI image, 4 had tumor on exam, and 2 had ischemic insults. 383 patients had evaluable MRI images. 67 of the 91 sibling controls had an evaluable MRI image.

To compare the white matter volume of patients by treatment intensity groups (mild, moderate, and high) and sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.

Outcome measures

Measure	Moderate Dose n=34 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=67 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=173 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity n=176 Participants High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Brain White Matter Volume for Treatment Intensity Groups and Sibling Controls	25.9 percentage Interval 24.3 to 27.5	30.3 percentage Interval 29.6 to 31.0	28.8 percentage Interval 28.0 to 29.7	25.4 percentage Interval 24.9 to 25.9

PRIMARY outcome

Timeframe: From beginning and at completion of Methylphenidate (MPH) Home Maintenance Phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 55 were screened at the beginning of the trial using the CTRS: ADHD T Score Questionnaire and 59 were screen at completion. 47 patients were analyzed.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-eight questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Methylphenidate (MPH) Home Maintenance Phase(baseline) and upon completion of the phase. Phase completion ranged between 11.44 and 24.36 months.

Outcome measures

Measure	Moderate Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=47 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Change From Methylphenidate (MPH) Home Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: ADHD T Score)	—	-7.17 T-score Interval -11.0 to -3.3	—	—

PRIMARY outcome

Timeframe: From beginning and at completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 55 were screened at the beginning of the trial using the CTRS: ADHD T Score Questionnaire and 59 were screened at completion. 47 patients were analyzed.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-eight questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Outcome measures

Measure	Moderate Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=47 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: Cognitive Problem T Score)	—	-3.34 T-score Interval -6.5 to -0.1	—	—

PRIMARY outcome

Timeframe: From beginning and at completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the CPRS: ADHD T Score Questionnaire and 68 were screen at completion. 68 patients were analyzed.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 and 24.36 months.

Outcome measures

Measure	Moderate Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=68 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score)	—	-8.74 T-score Interval -11.0 to -6.4	—	—

PRIMARY outcome

Timeframe: From beginning and at completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the CPRS: Cognitive Problem T Score Questionnaire and 68 were screened at completion. 68 patients were analyzed.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Outcome measures

Measure	Moderate Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=68 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conner's Parent Rating Scale (CPRS: Cognitive Problem T Score)	—	-9.56 T-score Interval -12.0 to -7.0	—	—

PRIMARY outcome

Timeframe: From beginning and at completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Social Skills Rating System (SSRS-P) and 68 were screened at completion. 68 patients were analyzed.

The Social Skills Rating System- Parent Version (SSRS-P) is a parent rating scale of social behaviors in reference to typically developing children. Thirty eight questions are rated 0 (Never) to 3 (very often). The social skills score is norm-referenced with a mean of 100±15 where a higher score is indicative of better skills. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Outcome measures

Measure	Moderate Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=68 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Social Skill Rating System (SSRS-P)	—	7.99 T-score Interval 4.4 to 11.6	—	—

PRIMARY outcome

Timeframe: From beginning and at completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Wechsler Individual Achievement Test (WIAT) REading: Composite Standard Score questionnaire and 68 were screened at completion. 68 patients were analyzed.

The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Reading Composite consists of Basic Reading (single word reading) and Reading Comprehension. Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Outcome measures

Measure	Moderate Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=68 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Reading: Composite Standard Score	—	-0.21 T-score Interval -2.3 to 1.9	—	—

PRIMARY outcome

Timeframe: From beginning and after completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Wechsler Individual Achievement Test (WIAT) Spelling: Standard Score System and 68 were screened at completion. 68 patients were analyzed.

The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Spelling score assesses the child's ability to spell words to dictation. Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Outcome measures

Measure	Moderate Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=68 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Spelling: Standard Score	—	-2.41 T-score Interval -3.9 to -0.9	—	—

PRIMARY outcome

Timeframe: From beginning and after completion of home maintenance phase, on average 16.3 months.

Population: 118 patients began the MPH Home Maintenance Phase of the trial. 68 completed the year long phase. 68 were screened at the beginning of the trial using the Wechsler Individual Achievement Test (WIAT) Math: Composite Standard Score System. 68 were screened at completion. 68 patients were analyzed.

The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Math Composite score assesses the child's ability to solve calculation problems (Numerical Operations) and solve applied, word problems (Math Reasoning). Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months

Outcome measures

Measure	Moderate Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=68 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Math: Composite Standard Score	—	0.22 T-score Interval -1.9 to 2.3	—	—

SECONDARY outcome

Timeframe: weekly during 3-week home crossover phase

Population: There were 122 patients treated in the home crossover period. Some patients had missing treatments and outcome assessments. A crossover design was used for better efficiency of test and better precision of estimation.

The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were done weekly during the 3-week Home Crossover Period with the best response being used as the measurement for the test.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Best Weekly Score Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score) During the 3-week Home Crossover Phase. Oppositional T Score	50.44 T score Interval 39.0 to 88.0	49.49 T score Interval 39.0 to 89.0	50.87 T score Interval 39.0 to 90.0	—
Best Weekly Score Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score) During the 3-week Home Crossover Phase. Cognitive Problems/Inattention T Score	51.72 T score Interval 41.0 to 90.0	55.64 T score Interval 41.0 to 90.0	53.14 T score Interval 41.0 to 87.0	—
Best Weekly Score Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score) During the 3-week Home Crossover Phase. Hyperactivity T Score	50.63 T score Interval 42.0 to 90.0	51.96 T score Interval 42.0 to 88.0	51.14 T score Interval 42.0 to 82.0	—
Best Weekly Score Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score) During the 3-week Home Crossover Phase. Adhd T Score	52.23 T score Interval 40.0 to 90.0	55.45 T score Interval 25.0 to 90.0	53.08 T score Interval 40.0 to 84.0	—

SECONDARY outcome

Timeframe: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Parent Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Cognitive Problem/Inattention Scale.	52.9854 Estimated T Score Standard Error 1.1368	57.6595 Estimated T Score Standard Error 1.1335	54.6491 Estimated T Score Standard Error 1.0969	—

SECONDARY outcome

Timeframe: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Parent Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Hyperactivity Scale.	51.5143 Estimated T Score Standard Error 1.0222	54.2138 Estimated T Score Standard Error 1.0193	52.2771 Estimated T Score Standard Error 0.9899	—

SECONDARY outcome

Timeframe: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Parent Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) ADHD Index.	53.5317 Estimated T Score Standard Error 1.0893	57.5805 Estimated T Score Standard Error 1.0861	54.4226 Estimated T Score Standard Error 1.0512	—

SECONDARY outcome

Timeframe: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Teacher Rating Scale-Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) Cognitive Problem/Inattention Scale.	59.6638 Estimated T Score Standard Error 1.0629	62.7053 Estimated T Score Standard Error 1.0602	59.3272 Estimated T Score Standard Error 1.0368	—

SECONDARY outcome

Timeframe: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Teacher Rating Scale-Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) Hyperactivity Scale.	52.6495 Estimated T Score Standard Error 1.1331	55.7638 Estimated T Score Standard Error 1.1300	52.1765 Estimated T Score Standard Error 1.1034	—

SECONDARY outcome

Timeframe: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The Conners' Teacher Rating Scale-Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) ADHD Index.	54.1974 Estimated T Score Standard Error 1.1084	58.7691 Estimated T Score Standard Error 1.1050	54.7438 Estimated T Score Standard Error 1.0720	—

SECONDARY outcome

Timeframe: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Parent (SSRS-P) - Social Skill.	101.8999 Estimated Standard Score Standard Error 1.7632	99.4412 Estimated Standard Score Standard Error 1.7590	101.5457 Estimated Standard Score Standard Error 1.7210	—

SECONDARY outcome

Timeframe: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Parent (SSRS-P) - Problem Behavior.	97.5709 Estimated Standard Score Standard Error 1.3446	97.4890 Estimated Standard Score Standard Error 1.3408	97.0891 Estimated Standard Score Standard Error 1.3021	—

SECONDARY outcome

Timeframe: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Teacher (SSRS-T) - Social Skill.	102.5281 Estimated Standard Score Standard Error 1.5012	97.6171 Estimated Standard Score Standard Error 1.5035	100.6957 Estimated Standard Score Standard Error 1.4591	—

SECONDARY outcome

Timeframe: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.

Population: 122 children began the Home Crossover Trial. 121 received all the placebo, 119 received all of the low dose, and 109 received all of the moderate dose.

The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

Outcome measures

Measure	Moderate Dose n=109 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Teacher (SSRS-T) - Problem Behavior.	97.3103 Estimated Standard Score Standard Error 1.3661	100.6084 Estimated Standard Score Standard Error 1.3671	98.6610 Estimated Standard Score Standard Error 1.3234	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Omission errors are the raw score for the number of targets presented where the subject did not respond. Accordingly, the range for this variable is 0-54 with a higher score indicative of worse performance or problems with sustained attention.

Outcome measures

Measure	Moderate Dose n=129 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=129 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=129 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Omission Errors.	0.2620 Estimated raw score Standard Error 0.6857	1.8889 Estimated raw score Standard Error 0.4923	1.6269 Estimated raw score Standard Error 0.4773	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Commission errors are the raw score for the numbers of nontargets presented where the subject incorrectly responded. Accordingly, the range for this variable is 0-6 with a higher score indicative of worse performance or impulsivity.

Outcome measures

Measure	Moderate Dose n=129 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=129 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=129 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Commission Errors.	0.1014 Estimated raw score Standard Error 0.3168	3.6984 Estimated raw score Standard Error 0.2274	3.5970 Estimated raw score Standard Error 0.2205	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Hit reaction time is average reaction time in milliseconds for all correct responses when targets were presented. There is no pre-defined range for reaction time; higher score is indicative of slower processing speed.

Outcome measures

Measure	Moderate Dose n=128 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=128 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=128 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Hit Reaction Time.	-4.7925 Estimated raw score Standard Error 14.0744	350.0590 Estimated raw score Standard Error 10.1432	354.8515 Estimated raw score Standard Error 9.7573	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. D' and β are derived variables from signal detection theory. D' is a measure of sensitivity of a person to the signal or target; a higher score is indicative of better performance or better sustained attention. D' was calculated as z(hit) - z(commission). Z-scores were calculated using the NORMSINV function in Microsoft Excel.

Outcome measures

Measure	Moderate Dose n=118 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=119 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=118 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for d' (Sensitivity).	-0.1163 Estimated raw score Standard Error 0.2307	1.6809 Estimated raw score Standard Error 0.1632	1.7972 Estimated raw score Standard Error 0.1632	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. D' and β are derived variables from signal detection theory. β is a measure of response tendency; higher scores indicate a more conservative response pattern. β was calculated using the formula = -d'*.5*(NORMSINV(hits)-NORMSINV(false alarms)). In the case where the false alarm rate = 0 or the hit rate = 1.0, we used the standard correction of 1/2N and 1- 1/2N, respectively.

Outcome measures

Measure	Moderate Dose n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=121 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=123 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Beta (Risk Taking).	-0.0346 Estimated raw score Standard Error 0.0453	0.2300 Estimated raw score Standard Error 0.0320	0.2647 Estimated raw score Standard Error 0.0320	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Trials 1-5 have a mean T Score of 50 and Standard Deviation of 10.

Outcome measures

Measure	Moderate Dose n=131 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=132 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=131 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) Over Five Learning Trials.	-1.2433 Estimated T Score Standard Error 2.2818	44.6970 Estimated T Score Standard Error 1.6195	45.9403 Estimated T Score Standard Error 1.6074	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Z Score for Short Delay Free Recall has a mean of 0 and a standard deviation of 1.

Outcome measures

Measure	Moderate Dose n=131 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=132 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=131 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) for Short Delay Free Recall.	-0.0278 Estimated Z Score Standard Error 0.2041	-0.3636 Estimated Z Score Standard Error 0.1449	-0.3358 Estimated Z Score Standard Error 0.1438	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Z Score for Long Delay Free Recall has a mean of 0 and a standard deviation of 1.

Outcome measures

Measure	Moderate Dose n=131 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=131 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=131 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) for Long Delay Free Recall.	-0.1603 Estimated Z Score Standard Error 0.2083	-0.3692 Estimated Z Score Standard Error 0.1484	-0.2090 Estimated Z Score Standard Error 0.1462	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Word Naming Time have a mean of 50 and a standard deviation of 10.

Outcome measures

Measure	Moderate Dose n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Word Naming Time.	1.1585 Estimated T Score Standard Error 1.4333	39.0156 Estimated T Score Standard Error 1.0095	37.8571 Estimated T Score Standard Error 1.0175	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Color Naming Time have a mean of 50 and a standard deviation of 10.

Outcome measures

Measure	Moderate Dose n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Color Naming Time.	0.8142 Estimated T Score Standard Error 1.4507	40.7031 Estimated T Score Standard Error 1.0218	39.8889 Estimated T Score Standard Error 1.0299	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Ink Color Naming Time have a mean of 50 and a standard deviation of 10.

Outcome measures

Measure	Moderate Dose n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Ink Color Naming Time.	3.3157 Estimated T Score Standard Error 1.4662	45.1094 Estimated T Score Standard Error 1.0327	41.7937 Estimated T Score Standard Error 1.0409	—

SECONDARY outcome

Timeframe: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.

Population: A mixed model was used to estimate the means of MPH and Placebo accounting for carry-over effects in the In-Lab crossover phase.

Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Interference Score have a mean of 50 and a standard deviation of 10.

Outcome measures

Measure	Moderate Dose n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 109 received the moderate dose. . T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Placebo n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 121 received the placebo. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	Low Dose n=126 Participants Children qualifying for the 3-week, randomized Home MPH Crossover Trial will receive a combination of placebo, a low dose condition (0.3 mg/kg MPH; 10 mg maximum), and a moderate dose condition (0.6 mg/kg MPH; 20 mg maximum). There are six possible combinations of placebo (P), low dose MPH (LD), and moderate dose MPH (MD). Of the 122 children who began the Home Crossover Trial, 119 received the low dose. T Scores were estimated using a mixed model to account for carry-over effects. Mean and standard error were estimated by eliminating the effect of the carry-over from the directly measured mean.	High Treatment Intensity High intensity central nervous system therapy (\>24 Gy CRT with or without systemic and/or intrathecal chemotherapy.
Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Interference Score.	2.0526 Estimated T Score Standard Error 1.2593	52.6875 Estimated T Score Standard Error 0.8870	50.6349 Estimated T Score Standard Error 0.8940	—

Adverse Events

Mild

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Moderate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

High

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Heather Conklin PhD

St. Jude Children's Research Hospital

Phone: 1-866-278-5833

Email: info@stjude.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place