International Study to Predict Optimised Treatment in Attention Deficit/Hyperactivity Disorder

This is a multi-center, open-label effectiveness trial to identify objective indicators of
treatment response in ADHD subjects (versus healthy controls) using cognitive and brain
function measures, brain structure and genetic measures in subjects diagnosed with ADHD.

At least 672 naïve and treatment experienced subjects with ADHD will be enrolled from
approximately 10 primary care centers. These patients are to be outpatients.

In addition, up to 672 healthy (non-ADHD) control subjects will be recruited who match the
enrolled ADHD subjects in race, age, gender and years of education.

Inclusion Criteria:

- Subjects who have signed an informed consent or assent form where required and/or
whose parent or legal guardian has provided written informed consent.

- Subjects who meet DSM-IV criteria for primary diagnosis of ADHD at study entry, as
determined by a psychiatrist, physician or clinical psychologist in conjunction with
the clinical work-up undertaken by trained research assistants, as defined by The Mini
International Neuropsychiatric Interview for Children and Adolescents (MINI Kid).

- Subjects who score at least 6 Inattentive or Hyperactive/impulsive items >1 on the
Attention Deficit / Hyperactivity Disorder Rating Scale.

- Subjects who are stimulant naïve or stimulant free (defined as no stimulant medication
in the previous 7 days*).

- Subjects who are 6-17 years of age (with an emphasis to enrol at least a third of the
subjects who are ≥ 13 years of age).

- Subjects who are fluent and literate in English (and/or Dutch in The Netherlands).

- coming off the stimulant medication for 7 days may place the participant at
increased risk, therefore, the participant may have this washout period reduced
to that defined in the drug package insert or 5 times the medication half life.

Exclusion Criteria:

- Known contra-indication or intolerance to the use of methylphenidate as defined in the
product package insert (including previous treatment failure at the highest
recommended dose).

- Pregnancy and females of child bearing potential who are not using a form of
contraception and are at risk of becoming pregnant during the study.

- Known medical condition, disease or neurological disorder which might, in the opinion
of investigator/s, interfere with the assessments to be made in the study or put ADHD
patients at increased risk when exposed to optimal doses of the drug treatment. For
example, a diagnosis of epilepsy would exclude a patient from this trial.

- History of physical brain injury or blow to the head that resulted in loss of
consciousness for at least 10 minutes or at least 5minutes within the last two years.
Prior treatment with methylphenidate or any other stimulant medication in the past 7
days.

- Known past or present substance dependence, including alcohol, as determined by The
Mini International Neuropsychiatric Interview for Children and Adolescents (MINI Kid).

- Participation in an investigational study within four months of the baseline visit in
which subjects have received an experimental drug/device that could affect the primary
end points of this study.

- Use of any psychological or counselling therapy or CNS medication that cannot be
washed out prior to participation or use of any psychological or counselling therapy
between the baseline and week 6 (or Early Termination) visits.

- Subjects who, in the opinion of the investigator, have a severe impediment to vision,
hearing and/or hand movement, which is likely to interfere with their ability to
complete the testing batteries.

- Subjects who, in the opinion of the investigator, are unable and/or unlikely to
comprehend and follow the study procedures and instructions.

- Presence of any other co-morbid primary DSM IV disorder.