Adult Study / OROS Methylphenidate Hydrochloride (HCL) (OROS MPH) in Adults With Attention Deficit Hyperactivity Disorder (ADHD)

The Adult ADHD Investigator Symptom Rating Score (AISRS) assesses 18 core ADHD symptoms corresponding to the DSM-IV diagnostic symptoms for adult subjects based on the investigator's rating for each of the symptoms using a four point scale (0=None, 1=Mild, 2=Moderate, and 3=Severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The AISRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms).

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set was defined as all randomized subjects who have received at least one dose of the study medication and have any post-baseline efficacy data (not including ASRS).

The Adult ADHD Self-Report Scale (ASRS) assesses 18 core ADHD symptoms corresponding to the DSM-IV diagnostic symptoms for adult subjects based on the subject's own rating for each of the symptoms using a four point scale (0=None, 1=Mild, 2=Moderate, and 3=Severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The ASRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms).

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Clinical Global Impression - Severity of Illness (CGI-S) is a clinician-rated subscale (low=0, high=7, higher score indicates increasing illness). The clinician rates the severity of the ADHD symptoms in relation to the clinician's total experience with ADHD subjects using a 7-point scale (1=normal, not at all ill, 2= borderline ill, 3= mildly ill, 4=moderately ill, 5= markedly ill, 6= severely ill, 7= among the most extremely ill subjects) in response to the question Considering your total clinical experience with this particular population, how ill is the subject at this time?.

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Stroop Test is a computerized measure of inhibition/disinhibition, executive function, reaction time, and information processing. The SAT is a computerized measure of the ability to shift from one instruction set to another quickly and accurately. The scores generated by the SAT are: correct matches, errors, and response time. The testing score is a measure of cognitive flexibility. Cognitive Flexibility Domain Score = SAT Correct Responses - SAT Errors - Stroop Commission Errors. Higher scores indicate better accuracy.

Time frame: Baseline, 4 hour timepoint for extended days or last non-missing value for non-extended days on day 42 or early discontinuation (endpoint)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The BRIEF-A, as completed by the DO, is a measure (low=61, high=225, lower scores indicate higher executive functioning) capturing views of an adult informant familiar with the subject's functioning. The BRIEF-A contains 75 scored items (1=never, 2=sometimes, 3=often) in nine non-overlapping clinical scales (Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials). The Behavioral Regulation Index (BRI), Metacognition Index (MI), and Global Executive Composite (GEC) are then derived.

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Dyadic Adjustment Scale (DAS) completed by DOs who were spouses or significant others assesses the relationship satisfaction or adjustment of partners in committed couple relationships. The 32-question DAS includes 4 empirically validated subscales that measure: dyadic satisfaction, dyadic consensus, dyadic cohesion and affectional expression. Possible responses include 5-, 6-, and 7-point Likert-scale questions and two yes/no items. The 10-question DAS subset, the Dyadic Satisfaction Subscale, was used in this study (low=0, high=50, higher score means better relationship satisfaction).

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The satisfaction with treatment questionnaire (low=0, high=20, a lower score indicates lower satisfaction with treatment) requires the subject's DO to answer 4 questions related to how much the subject's ADHD symptoms have changed since starting the medication, how much benefit was received from the medication, the extent, if any, the advantages outweighed the disadvantages, and overall satisfaction with the medication. Responses vary from extremely satisfied, very satisfied, satisfied, neutral, mildly dissatisfied, dissatisfied, very dissatisfied, or extremely dissatisfied.

Time frame: Endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set for non-missing response to this question

The Epworth Sleepiness Scale (ESS) is an 8-item self-rated questionnaire designed to assess the overall level of daytime sleepiness. Each item describes normal daily situations (i.e., watching TV, lying down in the afternoon, sitting inactive in a public place) and subjects rate the likelihood of dozing off or falling asleep in each situation. Responses use a 4-point rating scale (0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing). Item scores are summed to produce a total score (range of 0-24) with lower score suggesting more alertness.

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The BRIEF-A is a self-reported measure (low=61, high=225, lower scores indicate higher executive functioning) capturing views of the subject's own functioning in the everyday environment. The BRIEF-A contains 75 scored items (1=never, 2=sometimes, 3=often) in 9 non-overlapping clinical scales (Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials). The Behavioral Regulation Index (BRI), Metacognition Index (MI), and GEC are then derived.

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The AIM-A is a subject-reported measure (low=0, high=100, a higher score is more favorable) to assess the overall impact and role that ADHD may have in the conduct of tasks that are expected of adults. The AIM-A is comprised of four global quality of life items, five economic impact items, and five multi-item scales that describe important concepts. Items include: Living with ADHD; General Well-Being; Work, Home and School Performance and Daily Functioning; Relationships; and Communication; and Impact of Symptoms (emotional, degree of daily interference).

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The PSQI discriminates between good and poor sleepers. The self-administered scale contains 15 multiple-choice items concerning frequency of sleep disturbances and subjective sleep quality and 4 write-in items that inquire about typical bedtime, wake-up time, sleep latency, and sleep duration over the past month. The PSQI generates 7 scores corresponding to the different sleep domains. Each component score ranges from 0 to 3. Total sleep index is calculated by adding up the 7 component scores (low=0, high=21, the lower the score, the better in sleep quality).

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Symbol Digit Modalities Test (SDMT) is a computerized variant of the Wechsler Digit Symbol Substitution Test (DSST), but the position of symbols and digits is reversed. Scoring is the number of correct responses generated in 2 minutes. Processing Speed Domain = SDMT correct responses - SDMT errors. Higher scores indicate better functioning (i.e. information processing).

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

Stroop Test is a computerized measure of inhibition/disinhibition, executive function, reaction time, and information processing. The 1st part generates basic reaction time to colors. The 2nd part generates complex reaction time score to matching color names and font color. The 3rd part establishes a Stroop reaction time and an error score to unmatched color names/fonts. Reaction Time Domain Score = (Stroop Complex Reaction Time Correct + Stroop Reaction Time Correct)/2. Lower scores indicate better functioning (i.e. reaction time).

Time frame: Baseline, 4 hour timepoint for extended days or last non-missing value for non-extended days on day 42 or early discontinuation (endpoint)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

AISRS responder rate is defined as the percentage of subjects with AISRS \< 18 at endpoint.

Time frame: Endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set

The ADHD Rating Scale-IV (Significant Other) is an 18-item list of core ADHD symptoms corresponding to the DSM-IV diagnostic symptoms. Each item is rated on a four point Likert type scale (0 = never or rarely, 1 = sometimes, 2 = often, and 3 = very often). The subject's designated observer will complete this scale, with baseline assessment based on the subject's usual functioning when not on medication. The total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms).

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set and non-missing values at each timepoint. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Dyadic Adjustment Scale (DAS) assesses the relationship satisfaction or adjustment of partners in committed couple relationships. The 32-question DAS includes 4 empirically validated subscales that measure: dyadic satisfaction, dyadic consensus, dyadic cohesion and affectional expression. The response format varies across the entire scale and includes 5-, 6-, and 7-point Likert-scale questions and two yes/no items. The 10-question subset of the DAS, the Dyadic Satisfaction Subscale, was used in this study (low=0, high=50, higher score means better relationship satisfaction).

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The EWPS provides a measure of the subject's report of their overall productivity (low=0, high=100, a higher score indicates worsening work productivity and efficiency). There are 25 items (questions 15-39) on the scale that describe types of behaviors/ subjective feelings that are highly likely to reduce work productivity/efficiency. These 25 items are rated on a 5-point scale (0=never, 1=rarely, 2=sometimes, 3=often, to 4=almost always) indicating how often the behavior, feeling or attitude has been manifested in the past week. The total score is the sum of the 25 items.

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The satisfaction with treatment questionnaire (low=0, high=20, a lower score indicates lower satisfaction with treatment) requires subjects to answer 4 questions related to how much their ADHD symptoms have changed since starting the medication, how much benefit they received from the medication, the extent, if any, the advantages outweighed the disadvantages, and overall satisfaction with the medication. The responses for this question vary with range of satisfaction (e.g. extremely satisfied, very satisfied, satisfied, neutral, dissatisfied, very dissatisfied, or extremely dissatisfied).

Time frame: Endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set for non-missing response to this question

The Stroop Test is a computerized measure of inhibition/disinhibition, executive function, reaction time, and information processing. The Shifting Attention Test (SAT) a computerized measure of the ability to shift from one instruction set to another quickly and accurately. The Continuous Performance Test (CPT) is a computerized measure of vigilance or sustained attention/attention over time. Vigilance Domain (Complex Attention) Score = Stroop Commission Errors + SAT Errors + CPT Commission Errors + CPT Omission Errors. Lower scores indicate better functioning (i.e. sustained attention).

Time frame: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.